WorldWideScience

Sample records for monotherapy aed polytherapy

  1. QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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    Piccinelli Marco

    2005-01-01

    Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

  2. Effects of monotherapy and polytherapy on the blink reflex in epileptic patients.

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    Lancman, M E; Cristiano, E; Golimstok, A; Granillo, R J

    1993-01-01

    We performed the blink reflex (BR) in 20 normal volunteers, 13 epileptic patients receiving antiepileptic drug (AED) monotherapy, and 13 epileptic patients receiving AED polytherapy. Comparison of R1, ipsilateral and contralateral R2 and VIIth nerve latencies in the three groups showed no statistically significant differences R1 and VIIth nerve latencies among the three groups. There were statistically significant differences between the polytherapy group and the monotherapy and control groups in comparisons of ipsilateral and contralateral R2. There were no significant differences between the monotherapy group and the control group for ipsilateral and contralateral R2. We hypothesized that AED polytherapy might interfere with synaptic transmission in the polysynaptic pathway of the blink reflex, prolonging the latency of R2. These results provide further evidence of the pathophysiologic effects associated with polytherapy in epileptic patients.

  3. QTc and psychopharmacs: are there any differences between monotherapy and polytherapy

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    Sisek-Šprem Mirna

    2007-05-01

    Full Text Available Abstract Background Some psychotropic drugs are connected with prolongation of QT interval, increased risk of cardiac arrhythmias and greater incidence of sudden death, especially when used in combination. Concomitant use of antipsychotics and antidepressants is not rare in our clinical practice. The study compares the length of QT interval in patients on monotherapy with an antipsychotic or an antidepressant and patients taking polytherapy (an antipsychotic agent combined with an antidepressant. Methods Sixty-one hospitalized women who met the ICD-10 criteria for schizophrenia, schizoaffective psychosis, delusional disorder and mood disorder were included in the study. The monotherapy group was consisted of thirty-two women treated with an antipsychotic or an antidepressant while the polytherapy group was composed of twenty-nine women treated with an antipsychotic agent plus an antidepressant. Two electrocardiograms (ECGs were obtained for each patient: the first was carried out before the treatment and the second after two weeks of treatment. Statistical analysis was carried out by SPSS program and included unpaired and paired t test and Fisher's exact test. Results Mean baseline QTc values did not differ between the groups (439 ± 22 ms was the same value found in the both groups; unpaired t test, p > 0.5. Mean QTc intervals after two weeks of treatment were also similar (439 ± 24 ms in the monotherapy group and 440 ± 20 ms in the polytherapy group; unpaired t test, p > 0.5. Fisher's exact test did not reveal significant difference in the number of patients with borderline (451–470 ms or prolonged (> 470 ms QTc between groups, neither before treatment nor after two weeks of treatment. Twenty two women of the total of sixty one patients (36% had QTc > 450 ms before applying therapy. Conclusion We did not find significant QT prolongation in our patients after two weeks of treatment with antipsychotics and/or antidepressants. The QTc

  4. The impact of antipsychotic polytherapy costs in the public health care in Sao Paulo, Brazil.

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    Denise Razzouk

    Full Text Available Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce.To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil.A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider's perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated.147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs.Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially

  5. An effective initial polytherapy for children with West syndrome

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    Feiyong Jia; Huiyi Jiang; Lin Du; Ning Li; Ji Sun; Chunbo Niu

    2013-01-01

    Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.

  6. RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK–positive lung cancer

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    Hrustanovic, Gorjan; Olivas, Victor; Pazarentzos, Evangelos; Tulpule, Asmin; Asthana, Saurabh; Blakely, Collin M; Okimoto, Ross A; Lin, Luping; Neel, Dana S; Sabnis, Amit; Flanagan, Jennifer; Chan, Elton; Varella-Garcia, Marileila; Aisner, Dara L; Vaishnavi, Aria; Ou, Sai-Hong I; Collisson, Eric A; Ichihara, Eiki; Mack, Philip C; Lovly, Christine M; Karachaliou, Niki; Rosell, Rafael; Riess, Jonathan W; Doebele, Robert C; Bivona, Trever G

    2016-01-01

    One strategy for combating cancer-drug resistance is to deploy rational polytherapy up front that suppresses the survival and emergence of resistant tumor cells. Here we demonstrate in models of lung adenocarcinoma harboring the oncogenic fusion of ALK and EML4 that the GTPase RAS–mitogen-activated protein kinase (MAPK) pathway, but not other known ALK effectors, is required for tumor-cell survival. EML4-ALK activated RAS-MAPK signaling by engaging all three major RAS isoforms through the HELP domain of EML4. Reactivation of the MAPK pathway via either a gain in the number of copies of the gene encoding wild-type K-RAS (KRASWT) or decreased expression of the MAPK phosphatase DUSP6 promoted resistance to ALK inhibitors in vitro, and each was associated with resistance to ALK inhibitors in individuals with EML4-ALK–positive lung adenocarcinoma. Upfront inhibition of both ALK and the kinase MEK enhanced both the magnitude and duration of the initial response in preclinical models of EML4-ALK lung adenocarcinoma. Our findings identify RAS-MAPK dependence as a hallmark of EML4-ALK lung adenocarcinoma and provide a rationale for the upfront inhibition of both ALK and MEK to forestall resistance and improve patient outcomes. PMID:26301689

  7. Effects of polytherapy with phenytoin, carbamazepine, and stiripentol on formation of 4-ene-valproate, a hepatotoxic metabolite of valproic acid.

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    Levy, R H; Rettenmeier, A W; Anderson, G D; Wilensky, A J; Friel, P N; Baillie, T A; Acheampong, A; Tor, J; Guyot, M; Loiseau, P

    1990-09-01

    The incidence of valproic acid hepatotoxicity has been reported to increase in patients who are receiving polytherapy. A minor valproic acid metabolite, 2-propyl-4-pentenoic acid (4-ene-VPA), formed by a cytochrome P450-mediated reaction, has been shown to be a potent inducer of microvesicular steatosis in rats. This study tested the hypothesis that formation of 4-ene-VPA would be increased in patients taking valproic acid with carbamazepine or with phenytoin but decreased with coadministration of an inhibitor of cytochrome P450 (the antiepileptic drug stiripentol in 300 to 1200 mg daily doses) in healthy subjects. Blood and urine samples in the studies were collected during a dosing interval at steady state. Valproic acid was assayed in plasma by capillary gas chromatography; valproic acid and 15 metabolites were measured in urine by gas chromatography/mass spectrometry. The formation clearance (CLf) of 4-ene-VPA was increased twofold in the valproic acid-carbamazepine and valproic acid-phenytoin groups. In the valproic acid/stiripentol studies, the CLf of 4-ene-VPA decreased by 32% in the 1200 mg/day stiripentol study. Similar findings were obtained at 600 and 300 mg/day stiripentol. These findings provide evidence supporting a role for cytochrome P450 in the formation of the hepatotoxic metabolite, 4-ene-VPA, in humans. The increased formation of 4-ene-VPA associated with carbamazepine and phenytoin is striking in relation to the epidemiologic finding of increased incidence of valproic acid-related hepatotoxicity during polytherapy with P450 inducers.

  8. Antiandrogen monotherapy

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    Kolvenbag, G J; Iversen, P; Newling, D W

    2001-01-01

    Nonsteroidal antiandrogens are generally used in conjunction with castration as combined androgen blockade. However, the changing profile of patients with prostate cancer has made monotherapy with a nonsteroidal antiandrogen an attractive alternative therapeutic approach, offering potential quali...

  9. Antiandrogen monotherapy

    DEFF Research Database (Denmark)

    Kolvenbag, G J; Iversen, P; Newling, D W

    2001-01-01

    Nonsteroidal antiandrogens are generally used in conjunction with castration as combined androgen blockade. However, the changing profile of patients with prostate cancer has made monotherapy with a nonsteroidal antiandrogen an attractive alternative therapeutic approach, offering potential quality......-of-life benefits (sexual interest and physical capacity), with preliminary data suggesting that the risk of osteoporosis may also be reduced by bicalutamide 150-mg monotherapy compared with castration. In general, bicalutamide is well tolerated, with a predictable adverse-effect profile. Breast pain (40......%) and gynecomastia (49%) are the most common adverse events seen during monotherapy with this drug. In summary, the availability of bicalutamide 150-mg monotherapy broadens treatment options for men with locally advanced prostate cancer, offering a viable and attractive alternative to castration in this patient...

  10. Gestation-induced changes in lamotrigine pharmacokinetics : A monotherapy study

    NARCIS (Netherlands)

    de Haan, GJ; Edelbroek, P; Segers, J; Engelsman, M; Lindhout, D; Devile-Notschaele, M; Augustijn, P

    2004-01-01

    The authors describe 12 pregnancies in women with epilepsy using lamotrigine (LTG) monotherapy. A seizure increase in nine pregnancies was probably related to a gradual decline of LTG level-to-dose ratio to 40% of baseline. After delivery, LTG kinetics returned swiftly to baseline, causing toxic sid

  11. PRESCRIPTION AUDIT OF ACNE VULGARIS IN SKIN OUTPATIENT DEPARTMENT OF A TERTIARY CARE TEACHING HOSPITAL

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    Vishal Prakash

    2014-10-01

    Full Text Available : OBJECTIVE: To evaluate prescribing pattern in acne vulgaris cases at a tertiary care teaching hospital in south India. METHODS: Prescriptions of 120 patients of acne vulgaris who attended Dermatology OPD of a tertiary care teaching hospital were selected for study and their drug data were analyzed. RESULTS: Topical Benzoyl peroxide, adapalene, ketoconazole were prescribed as monotherapy, while aloevera, liquid paraffin and white soft paraffin as polytherapy. Azithromycin, antibiotics, anti histaminics were prescribed as systemic monotherapy and polytherapy. Statistical analysis revealed p-value was > 0.05. CONCLUSIONS: Prescription patterns were in consensus with the general guidelines, with few changes, in the choice of established therapeutic agents.

  12. Dose-dependent teratogenicity of valproate in mono- and polytherapy

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    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2015-01-01

    OBJECTIVE: To assess the risk of major congenital malformations (MCMs) in association with maternal use of valproic acid (VPA) in monotherapy or adjunctive therapy, and its relationship with dose. METHODS: The analysis was based on prospectively acquired data from EURAP, a registry enrolling wome...

  13. Successful Ziprasidone Monotherapy in a Case of Delusional Parasitosis: A One-Year Followup

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    Domenico De Berardis

    2013-01-01

    Full Text Available Delusional parasitosis is characterized by the false idea that own body is infested by invisible mites, insects, or other parasites. This case report describes a 24-year-old woman with delusional parasitosis who was treated with ziprasidone monotherapy (120 mg/day with a complete remission of delusion and followed for one year without symptom recurrences. These findings, although preliminary, indicate that further investigation of ziprasidone monotherapy for the treatment of delusional parasitosis is warranted in further trials.

  14. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy.

    NARCIS (Netherlands)

    E.B. Samren (Bettina); C.M. van Duijn (Cock); S. Koch; V.K. Hiilesma; H. Klepel; A.H. Bardy; B. Mannegetta; A.W. Deichl; E. Gaily; M.L. Granstrom; H. Meinardi; D.E. Grobbee (Diederick); D. Lindhout (Dick); A. Hofman (Albert)

    1997-01-01

    textabstractPURPOSE: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy. METHODS: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy

  15. Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.

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    Rui Li

    Full Text Available Clostridium difficile infection (CDI has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients.A comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs with 95% confidence intervals (95% CIs were calculated and reported.Of the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00, p = 0.05 or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96, p = 0.83; however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80, p = 0.006. No statistically significant difference in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40, 2.45, p = 0.98 or severe CDI (OR = 0.98, 95% CI (0.63, 1.53, p = 0.94 or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26, p = 0.56. In addition, there was no significant difference in the rate of adverse events (AEs between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74, p = 0.41. In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51, p < 0.0001.Metronidazole and vancomycin are equally effective for the

  16. Polytherapy with two or more antihypertensive drugs to lower blood pressure in elderly Ontarians. Room for improvement

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    Campbell, Norman RC; McAlister, Finlay A; Duong-Hua, Minh; Tu, Karen

    2007-01-01

    BACKGROUND: Although guidelines now recommend polytherapy to achieve blood pressure targets, little is know about which antihypertensive drugs are combined in clinical practice. OBJECTIVE: To examine current practices for the coprescribing of antihypertensive agents. METHODS: A population-based cohort study was performed using linked administrative databases on all Ontario residents 66 years of age or older who were newly treated for hypertension between July 1, 1994, and March 31, 2002, and did not have diabetes or other relevant comorbidities. All patients were followed for two years to determine which antihypertensives were prescribed concurrently. RESULTS: Of the 166,018 patients in the described cohort, 1819 (1%) were prescribed a combination therapy tablet as their first-line therapy. The number of patients prescribed antihypertensive polytherapy within the first two years of diagnosis increased from 2071 (21%) of the 9825 hypertensive patients starting treatment in the second half of 1994 to 2578 (37%) of the 6988 hypertensive patients beginning treatment in the first quarter of 2002 (P<0.0001). Overall, 11,003 (27%) of polytherapy prescriptions were for drugs without additive hypotensive effects when combined and this proportion did not change over time. CONCLUSIONS: Although there has been an increase in the use of polytherapy in elderly hypertensive patients without comorbidities in Ontario over the past decade, more than one-quarter of the two drugs prescribed together have not been proven to have additive hypotensive effects. Because this likely contributes to suboptimal blood pressure control rates, future guidelines and educational programs should devote increased attention to the choice of optimal polytherapy combinations. PMID:17703255

  17. Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

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    Kaisary, A V; Iversen, P; Tyrrell, C J

    2001-01-01

    with a prostate specific antigen (PSA) level 400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203.......Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non......-steroidal antiandrogens, bicalutamide ('Casodex'), flutamide and nilutamide, only bicalutamide has been compared with castration in large, controlled, randomised, Phase III trials in M1 patients. A post-hoc analysis of these studies indicated that bicalutamide 150 mg/day monotherapy may be of benefit to M1 patients...

  18. Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

    DEFF Research Database (Denmark)

    Kaisary, A V; Iversen, P; Tyrrell, C J;

    2001-01-01

    with a prostate specific antigen (PSA) level 400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203.......Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non...

  19. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

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    Ye W

    2012-01-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical

  20. Fixed-dose combination vs monotherapy in hypertension: a meta-analysis evaluation.

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    Hilleman, D E; Ryschon, K L; Mohiuddin, S M; Wurdeman, R L

    1999-07-01

    Fixed-dose combination antihypertensive therapy has received interest since the publication of the JNC-VI report. Relatively few head-to-head comparative studies between fixed-dose combinations and first-line monotherapies for hypertension have been published. The objective of this study was to conduct a meta-analysis of various first-line monotherapies and the fixed-dose combination of amlodipine/benazepril. The results of the meta-analysis were used to compare the efficacy and safety of the first-line monotherapies with amlodipine/benazepril. The meta-analysis included 82 studies that included 110 treatment groups (cohorts). The study compared nine different monotherapies and one combination therapy (amlodipine/benazepril). Of the 82 studies, 22 were placebo-controlled and 60 were active treatment controlled. The mean absolute decrease in supine diastolic blood pressure (BP) ranged from 9.7 to 13.3 mm Hg with verapamil showing the greatest effect and captopril the least (13.3 +/- 3.0 mm Hg; 9.7 +/- 2.9 mm Hg, respectively). When studies were weighted by sample size, atenolol, verapamil, lisinopril and amlodipine/benazepril showed the greatest BP effect. When studies were weighted by variance, amlodipine/benazepril and atenolol showed the greatest BP effect. The percentage of patients controlled on therapy ranged from 54% to 79%. Lisinopril and amlodipine/benazepril showed the greatest percent controlled. The overall incidence of adverse effects ranged from 12.1% to 41.8% with lisinopril having the lowest and nifedipine having the highest incidence. The overall incidence of adverse effects resulting in drug discontinuance ranged from 1.3% to 10.7%, with amlodipine/benazepril having the lowest and nifedipine having the highest incidence. The results of the meta-analysis indicate that amlodipine/benazepril produces above average reductions in BP with a lower than average incidence of overall side effects and the lowest incidence of adverse effects resulting in drug

  1. Barnidipine monotherapy and combination therapy in older patients with essential hypertension: a long-term study.

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    Naber, F B; Häge, R; Mortelmans, J

    2000-11-01

    The long-term (2 year) safety and efficacy of barnidipine was assessed in an open-label, dose-titration, multicentre study of 236 patients aged > or = 75 years with a sitting diastolic blood pressure (DBP) > or = 95 mmHg. All eligible patients started treatment with barnidipine 10 mg once daily. After at least 4 weeks treatment, the dose of barnidipine was titrated upwards to 20 mg daily in patients who did not achieve normalisation of blood pressure (sitting DBP Barnidipine monotherapy was the final treatment in 74% of patients in the ITT population (50% barnidipine 10 mg, 24% barnidipine 20 mg). The overall response rate was 84.1% at endpoint. Overall mean sitting DBP decreased by 18.4 mmHg from 102.1 mmHg at baseline to 83.7 mmHg at endpoint. Although a total of 82.2% of patients reported at least one adverse event, only 37.4% of patients experienced an adverse event that was possibly or probably related to the study medication. Many patients experienced adverse events associated with co-existing diseases common in older people. It can be concluded that barnidipine as monotherapy or in combination with ACE inhibitors or diuretics is safe and effective in older patients with essential hypertension.

  2. Combination antibiotic therapy versus monotherapy for Pseudomonas aeruginosa bacteraemia: a meta-analysis of retrospective and prospective studies.

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    Hu, Yangmin; Li, Leiqing; Li, Wenlu; Xu, Huimin; He, Ping; Yan, Xiaofeng; Dai, Haibin

    2013-12-01

    The choice of antibiotic monotherapy or combination therapy to treat Pseudomonas aeruginosa bacteraemia is controversial. The aim of this review was to compare both types of therapy to determine which delivers the best outcome for P. aeruginosa bacteraemia. We systematically searched electronic bibliographic databases, including PubMed, Ovid EMBASE and The Cochrane Library, for clinical studies that compared combination therapy with monotherapy in the treatment of P. aeruginosa bacteraemia. Eligible articles were analysed using Stata(®)/SE software v.12.0. Stratification analysis was conducted by study design and treatment type. Publication bias was assessed using Begg's funnel plot and Egger's test. Ten studies (eight retrospective and two prospective) involving 1239 patients were analysed. We found no difference between combination therapy and monotherapy when the data were combined (odds ratio = 0.89, 95% confidence interval 0.57-1.40; P = 0.614) or when data were analysed in subgroups. Neither combination therapy nor monotherapy treatment appears to have a significant effect on mortality rates in patients with P. aeruginosa bacteraemia. Further studies evaluating the effects of combination therapy or monotherapy in more specialised cases, such as when encountering a multidrug-resistant organism, are necessary.

  3. Failure of a monotherapy strategy for difficult chronic prostatitis/chronic pelvic pain syndrome.

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    Nickel, J Curtis; Downey, Joe; Ardern, Dale; Clark, Janet; Nickel, Kyle

    2004-08-01

    We determined the effect of a best evidence based monotherapeutic strategy for patients diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) referred to a specialized prostatitis clinic. Patients with CP/CPPS referred by urologists after failure of prescribed therapy for evaluation and treatment at Queen's University prostatitis research clinic were extensively evaluated, aggressively treated following a standardized treatment algorithm and followed for 1 year using a validated prostatitis specific symptom and quality of life instrument, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). All patients underwent a standardized protocol for CP/CPPS including a history, physical examination, standard 4-glass test, plus urethral swab and semen for microscopy and culture, uroflowmetry and residual urine determination. Treatment followed a best evidence based strategy with a standardized monotherapy based algorithm. A total of 100 consecutive patients with CP/CPPS (average age 42.2 years, range 20 to 70 and average symptom duration 6.5 years, range 0.5 to 39) had 1-year followup after initial evaluation. Patients were prescribed treatment based on documentation of "failed," "successful" and "never tried" therapies based on a standardized treatment algorithm. Patients treated successfully were continued on the prescribed therapy, while therapy was discontinued and new therapy instituted (based on algorithm) in those in whom the initially prescribed therapy failed. At 1 year there was a statistically significant decrease in total NIH-CPSI (23.3 to 19.5, p = 0.0004), pain (11.0 to 9.4, p = 0.03) and quality of life (7.7 to 6.1, p quality of life domain (43% of patients had greater than 25% improvement in quality of life). Of the patients 35% had a significant decrease of greater than 6 points in total NIH-CPSI. A clear, clinically significant improvement in total NIH-CPSI (greater than 50% decrease) was noted in 19

  4. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody.

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    Corti, Davide; Misasi, John; Mulangu, Sabue; Stanley, Daphne A; Kanekiyo, Masaru; Wollen, Suzanne; Ploquin, Aurélie; Doria-Rose, Nicole A; Staupe, Ryan P; Bailey, Michael; Shi, Wei; Choe, Misook; Marcus, Hadar; Thompson, Emily A; Cagigi, Alberto; Silacci, Chiara; Fernandez-Rodriguez, Blanca; Perez, Laurent; Sallusto, Federica; Vanzetta, Fabrizia; Agatic, Gloria; Cameroni, Elisabetta; Kisalu, Neville; Gordon, Ingelise; Ledgerwood, Julie E; Mascola, John R; Graham, Barney S; Muyembe-Tamfun, Jean-Jacques; Trefry, John C; Lanzavecchia, Antonio; Sullivan, Nancy J

    2016-03-18

    Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible.

  5. Cinacalcet Monotherapy in Neonatal Severe Hyperparathyroidism: A Case Study and Review

    Science.gov (United States)

    Gannon, Anthony W.; Monk, Heather M.

    2014-01-01

    Context: Neonatal severe hyperparathyroidism (NSHPT) is a severe form of familial hypocalciuric hypercalcemia characterized by severe hypercalcemia and skeletal demineralization. In most cases, NSHPT is due to biallelic loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR), but some patients have heterozygous mutations. Conventional treatment consists of iv saline, bisphosphonates, and parathyroidectomy. Objective: The aim of this project was to characterize the molecular basis for NSHPT in an affected newborn and to describe the response to monotherapy with cinacalcet. Methods: Clinical and biochemical features were monitored as cinacalcet therapy was initiated and maintained. Genomic DNA was obtained from the proband and parents. The CASR gene was amplified by PCR and sequenced directly. Results: The patient was a full-term male who developed hypotonia and respiratory failure soon after birth. He was found to have multiple fractures and diffuse bone demineralization, with a marked elevation in serum ionized calcium (1.99 mmol/L) and elevated serum levels of intact PTH (1154 pg/mL); serum 25-hydroxyvitamin D was low, and fractional excretion of calcium was reduced. The serum calcium level was not reduced by iv saline infusion. Based on an extensive family history of autosomal dominant hypercalcemia, a diagnosis of NSHPT was made, and cinacalcet therapy was initiated with a robust and durable effect. Molecular studies revealed a heterozygous R185Q missense mutation in the CASR in the patient and his father, whereas normal sequences for the CASR gene were present in the patient's mother. Conclusions: We describe the first use of cinacalcet as monotherapy for severe hypercalcemia in a newborn with NSHPT. The rapid and durable response to cinacalcet suggests that a trial of calcimimetic therapy should be considered early in the course of NSHPT. PMID:24203066

  6. Efficacy of Quetiapine Monotherapy in Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Villarreal, Gerardo; Hamner, Mark B; Cañive, José M; Robert, Sophie; Calais, Lawrence A; Durklaski, Valerie; Zhai, Yusheng; Qualls, Clifford

    2016-12-01

    This was a 12-week randomized, placebo-controlled trial to assess the efficacy of quetiapine monotherapy in the treatment of posttraumatic stress disorder (PTSD). Eighty patients were randomly assigned to treatment with either quetiapine or placebo. The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS). Secondary efficacy measures included the CAPS subscales, the Davidson Trauma Scale, the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scales for severity of Illness and improvement, the Hamilton Depression Rating Scale (HAM-D), and the Hamilton Anxiety Rating Scale (HAM-A). Safety measurements included adverse events, vital signs, the Abnormal Involuntary Movement Scale, the Barnes Akathisia Scale, the Simpson-Angus Scale, and the Arizona Sexual Experiences Scale. After a 1-week placebo run-in, quetiapine was started at a daily dosage of 25 mg and increased to a maximum of 800 mg; the average was 258 mg (range, 50-800 mg). Reductions in CAPS total, re-experiencing, and hyperarousal scores were significantly greater for the quetiapine group than for the placebo group. Greater improvements were also observed for quetiapine in scores on the Davidson Trauma Scale, CGI severity and improvement ratings, PANSS positive symptom and general psychopathology subscales, HAM-A, and HAM-D than for placebo. Adverse events were generally mild and expected based on prior studies of quetiapine in this and other patient population. There were no differences in safety measures between groups. Quetiapine monotherapy was efficacious in the treatment of PTSD. These findings suggest quetiapine as a single agent is effective in treating military PTSD.

  7. A prospective open-label trial of lamotrigine monotherapy in children and adolescents with bipolar disorder.

    Science.gov (United States)

    Biederman, Joseph; Joshi, Gagan; Mick, Eric; Doyle, Robert; Georgiopoulos, Anna; Hammerness, Paul; Kotarski, Meghan; Williams, Courtney; Wozniak, Janet

    2010-04-01

    To evaluate the safety and efficacy of lamotrigine monotherapy as an acute treatment of bipolar mood elevation in children with bipolar spectrum disorders. This was a 12-week, open-label, prospective trial of lamotrigine monotherapy to assess the effectiveness and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), Children's Depression Rating Scale (CDRS), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. Thirty-nine children with bipolar disorder (YMRS at entry: 31.6 +/- 5.5) were enrolled in the study and 22 (56%) completed the 12-week trial. Lamotrigine was slowly titrated to an average endpoint dose of 160.7 +/- 128.3 in subjects children 12-17 years of age (N = 17). Treatment with lamotrigine was associated with statistically significant levels of improvement in mean YMRS scores (-14.9 +/- 9.7, P disorder (ADHD), and psychotic symptoms. Lamotrigine was generally well tolerated with marginal increase in body weight (47.0 +/- 18.0 kg vs. 47.2 +/- 17.9 kg, P= 0.6) and was not associated with abnormal changes in laboratory parameters. Several participants were discontinued due to skin rash; in all cases, the rash resolved shortly after discontinuation of treatment. No patient developed Steven Johnson syndrome. Open-label lamotrigine treatment appears to be beneficial in the treatment of bipolar disorder and associated conditions in children. Future placebo-controlled, double-blind studies are warranted to confirm these findings.

  8. 3-D conformal HDR brachytherapy as monotherapy for localized prostate cancer. A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Martin, T.; Baltas, D.; Kurek, R.; Roeddiger, S.; Kontova, M.; Anagnostopoulos, G.; Skazikis, G.; Zamboglou, N. [Dept. of Radiation Oncology, Klinikum Offenbach, Offenbach/Main (Germany); Dannenberg, T.; Buhleier, T.; Tunn, U. [Dept. of Urology, Klinikum Offenbach, Offenbach/Main (Germany)

    2004-04-01

    Purpose: pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose-rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning. Patients and methods: between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) {<=} 10 ng/ml, Gleason score {<=} 7 and clinical stage {<=} T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT trademark was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (D{sub ref}) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D{sub 90}, D{sub 10} urethra, and D{sub 10} rectum. Acute toxicity was evaluated using the CTC (common toxicity criteria) scales. Results: median D{sub 90} was 106% of D{sub ref} (range: 93-115%), median D{sub 10} urethra 159% of D{sub ref} (range: 127-192%), and median D{sub 10} rectum 55% of D{sub ref} (range: 35-68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred. Conclusion: 3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control. (orig.)

  9. Who continues to stock oral artemisinin monotherapy? Results of a provider survey in Myanmar.

    Science.gov (United States)

    Thein, Si Thu; Sudhinaraset, May; Khin, Hnin Su Su; McFarland, Willi; Aung, Tin

    2016-06-22

    Artemisinin-based combination therapy (ACT) is a key strategy for global malaria elimination efforts. However, the development of artemisinin-resistant malaria parasites threatens progress and continued usage of oral artemisinin monotherapies (AMT) predisposes the selection of drug resistant strains. This is particularly a problem along the Myanmar/Thailand border. The artemisinin monotherapy replacement programme (AMTR) was established in 2012 to remove oral AMT from stocks in Myanmar, specifically by replacing oral AMT with quality-assured ACT and conducting behavioural change communication activities to the outlets dispensing anti-malarial medications. This study attempts to quantify the characteristics of outlet providers who continue to stock oral AMT despite these concerted efforts. A cross-sectional survey of all types of private sector outlets that were stocking anti-malarial drugs in 13 townships of Eastern Myanmar was implemented from July to August 2014. A total of 573 outlets were included. Bivariate and multivariable logistic regressions were conducted to assess outlet and provider-level characteristics associated with stocking oral AMT. In total, 2939 outlets in Eastern Myanmar were screened for presence of any anti-malarial drugs in August 2014. The study found that 573 (19.5 %) had some kind of oral anti-malarial drug in stock at the time of survey and among them, 96 (16.8 %) stocked oral AMT. In bivariate analyses, compared to health care facilities, itinerant drug vendors, retailers and health workers were less likely to stock oral AMT (33.3 vs 12.9, 10.0, 8.1 %, OR = 0.30, 0.22, 0.18, respectively). Providers who cut blister pack or sell partial courses (40.6 vs 11.7 %, OR 5.18, CI 3.18-8.44) and those who based their stock decision on consumer demand (32.8 vs 12.1 %, OR 3.54, CI 2.21-5.63) were more likely to stock oAMT. Multivariate logistic regressions produced similar significant associations. Private healthcare facilities and drug

  10. Relative efficacy of bivalirudin versus heparin monotherapy in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: a network meta-analysis

    Science.gov (United States)

    Kinnaird, Tim; Medic, Goran; Casella, Gianni; Schiele, Francois; Kaul, Upendra; Radke, Peter W; Eijgelshoven, Indra; Bergman, Gert; Chew, Derek P

    2013-01-01

    In the absence of head-to-head clinical data, the objective of this study was to indirectly compare the efficacy and safety of a bivalirudin-based anticoagulation strategy with that of heparin monotherapy in patients with ST-elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention. A systematic literature review was performed to identify randomized controlled trials to build a network of bivalirudin and heparin monotherapy strategies in STEMI patients using heparin, with glycoprotein IIb/IIIa inhibitor as a common reference strategy. At 30 days, the bivalirudin-based strategy was expected to result in lower mortality rates than heparin monotherapy (odds ratio [OR], 0.55; credible limit [CrL], 0.32–0.95). This relationship was sustained at 1 year. At 30 days, the risk for stroke (OR, 0.88; CrL, 0.37–2.13), myocardial infarction (OR, 0.79; CrL, 0.40–1.55), and thrombolysis in myocardial infarction major and minor bleedings (OR, 0.66; CrL, 0.45–0.98) tended to be numerically reduced with bivalirudin in comparison with heparin monotherapy. For patients with STEMI intended for primary percutaneous coronary intervention, bivalirudin is associated with lower mortality rates in comparison with heparin monotherapy. This study suggests that bivalirudin is more effective and safer than heparin monotherapy and should therefore be preferred over heparin monotherapy. PMID:24124401

  11. Interstitial lung disease associated with trastuzumab monotherapy: A report of 3 cases

    Science.gov (United States)

    Sugaya, Akinori; Ishiguro, Shingo; Mitsuhashi, Shoichi; Abe, Masahiro; Hashimoto, Ikuta; Kaburagi, Takayuki; Kojima, Hiroshi

    2017-01-01

    We herein report 3 cases of female patients with breast cancer who developed interstitial lung disease (ILD) during trastuzumab monotherapy in an adjuvant setting. Prior chemotherapy included 4 cycles of epirubicin and cyclophosphamide in patients 1 and 2, and 4 cycles of docetaxel, cyclophosphamide and trastuzumab in patient 3. Patient 1 presented with a cough and fever after the fourth cycle of trastuzumab. Patient 2 experienced rapid deterioration of oxygen saturation without subjective symptoms within 3 h of the first administration of trastuzumab. Patient 3 was unexpectedly diagnosed with organizing pneumonia in a scheduled computed tomography (CT) scan after the first course of trastuzumab. Based on clinical data, such as decreased PaO2 level, increased serum levels of KL-6 and/or lactate dehydrogenase, and findings on chest CT, these patients were diagnosed with drug-induced ILD. Considering the clinical course, trastuzumab was incriminated as the cause of ILD, particularly in patients 1 and 2. All 3 patients improved due to the timely diagnosis, discontinuation of trastuzumab and immediate administration of corticosteroid therapy. Although ILD is a rare adverse event associated with trastuzumab, it may cause rapid deterioration without preceding symptoms. Close observation and early diagnosis are required to avoid an unfavorable outcome.

  12. Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial

    Science.gov (United States)

    Wood, John C.; Glynos, Tara; Thompson, Alexis; Giardina, Patricia; Harmatz, Paul; Kang, Barinder P.; Paley, Carole; Coates, Thomas D.

    2011-01-01

    The US04 trial was a multicenter, open-label, single arm trial of deferasirox monotherapy (30–40 mg/kg/day) for 18 months. Cardiac iron response was bimodal with improvements observed in patients with mild to moderate initial somatic iron stores; relationship of cardiac response to labile plasma iron is now presented. Labile plasma iron was measured at baseline, six months, and 12 months. In patients having a favorable cardiac response at 18 months, initial labile plasma iron was elevated in only 31% of patients at baseline and no patient at six or 12 months. Cardiac non-responders had elevated labile plasma iron in 50% of patients at baseline, 50% patients at six months, and 38% of patients at 12 months. Risk of abnormal labile plasma iron and cardiac response increased with initial liver iron concentration. Persistently increased labile plasma iron predicts cardiac non-response to deferasirox but labile plasma iron suppression does not guarantee favorable cardiac outcome. Study registered at www.clinicaltrials.gov (NCT00447694). PMID:21393329

  13. The Effects of Topical Antiglaucoma Drugs as Monotherapy on the Ocular Surface: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Sevda Aydin Kurna

    2014-01-01

    Full Text Available Purpose. The aim was to compare the effects of antiglaucoma eye drops on the tear functions and ocular surface. Method. Eighty-five eyes of 43 patients with glaucoma were included into this randomized prospective study. Timolol without preservative (1, timolol with benzododecinium bromide (2, latanoprost (3, bimatoprost (4, travoprost with benzalkonium chloride (5, and brimonidine with purite (6 were given to 6 groups. Schirmer I, tear film breakup time (TBUT, staining scores, and impression cytology samples were evaluated before and during 12-month-follow-up period. Results. At the end of 12 months, there was no detected change in Schirmer I and TBUT tests indicating dry eye. Corneal staining scores were higher in groups 1 and 2, while conjunctival staining scores were higher in group 6. Goblet cell count decreased in groups 1 and 5 in superior and inferior, group 2 in superior, and groups 3 and 6 in inferior conjunctiva. Squamous metaplasia grades showed a significant increase in groups 1 and 2 at 3rd, 6th, and 12th month controls (P<0.05. Conclusion. We observed nonserious impact on tear functions and ocular surface with antiglaucoma monotherapy. Beta blockers induced more damage on the ocular surface suggesting the role of the dosing and active substances beside preservatives.

  14. The Effects of Topical Antiglaucoma Drugs as Monotherapy on the Ocular Surface: A Prospective Study

    Science.gov (United States)

    Aydin Kurna, Sevda; Acikgoz, Semih; Ozbay, Nurver; Sengor, Tomris; Olcaysu, Osman Okan

    2014-01-01

    Purpose. The aim was to compare the effects of antiglaucoma eye drops on the tear functions and ocular surface. Method. Eighty-five eyes of 43 patients with glaucoma were included into this randomized prospective study. Timolol without preservative (1), timolol with benzododecinium bromide (2), latanoprost (3), bimatoprost (4), travoprost with benzalkonium chloride (5), and brimonidine with purite (6) were given to 6 groups. Schirmer I, tear film breakup time (TBUT), staining scores, and impression cytology samples were evaluated before and during 12-month-follow-up period. Results. At the end of 12 months, there was no detected change in Schirmer I and TBUT tests indicating dry eye. Corneal staining scores were higher in groups 1 and 2, while conjunctival staining scores were higher in group 6. Goblet cell count decreased in groups 1 and 5 in superior and inferior, group 2 in superior, and groups 3 and 6 in inferior conjunctiva. Squamous metaplasia grades showed a significant increase in groups 1 and 2 at 3rd, 6th, and 12th month controls (P < 0.05). Conclusion. We observed nonserious impact on tear functions and ocular surface with antiglaucoma monotherapy. Beta blockers induced more damage on the ocular surface suggesting the role of the dosing and active substances beside preservatives. PMID:25009742

  15. A comparative study of thyroid status of patients on phenytoin, carbamazepine and valproate monotherapy

    Directory of Open Access Journals (Sweden)

    Dinesh K. Dhodi

    2016-04-01

    Conclusions: Valproate monotherapy does not alter serum levels of thyroid hormones. On the contrary, alterations of thyroid hormone function were seen in patients treated with carbamazepine and phenytoin. However, all the patients were euthyroid and were not associated with clinical or even subclinical hypothyroidism. [Int J Basic Clin Pharmacol 2016; 5(2.000: 362-365

  16. Ribavirin monotherapy for chronic hepatitis C

    DEFF Research Database (Denmark)

    Brok, J; Gluud, L L; Gluud, C

    2005-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades. Ribavirin monotherapy may represent a treatment for some patients.......Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades. Ribavirin monotherapy may represent a treatment for some patients....

  17. Ribavirin monotherapy for chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2006-01-01

    Adding ribavirin to interferon improves treatment response for patients with chronic hepatitis C, but the effects of ribavirin monotherapy are unclear. We conducted a systematic review to assess the benefits and harms of ribavirin monotherapy for patients with chronic hepatitis C....

  18. Antidepressant monotherapy and combination of antidepressants in the treatment of resistant depression in current clinical practice: A retrospective study.

    Science.gov (United States)

    Bares, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Höschl, Cyril

    2010-11-01

    Abstract Objectives. The aim of this study was to compare efficacy of antidepressant monotherapies and combinations of antidepressants in the treatment of resistant patients in current clinical practice. Methods. We reviewed chart documents of resistant depressive inpatients treated at least 4 weeks with a new treatment. Depressive symptoms and clinical status were assessed using Montgomery and Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory-Short Form and Clinical Global Impression at the baseline, week 2 and in the end of treatment. Results. We identified 81 patients (27 with combinations and 51 with monotherapies) that were suitable for analyses. The combination group achieved higher reduction of MADRS score (14.6 vs 10.2 pts., p=0.02) and response rate (≥ 50% reduction of MADRS, 67% vs 39%, p=0.03). Number needed to treat for response was 4. Conclusions. Based on our results, we suggest that combination of antidepressants might be more effective than monotherapy in clinical practice.

  19. Monotherapy with lanreotide depot for acromegaly: long-term clinical experience in a pituitary center.

    Science.gov (United States)

    Sagvand, Babak Torabi; Khairi, Shafaq; Haghshenas, Arezoo; Swearingen, Brooke; Tritos, Nicholas A; Miller, Karen K; Klibanski, Anne; Nachtigall, Lisa B

    2016-08-01

    Long-acting somatostatin analogs are one of the main classes of medical therapy used for acromegaly and most patients require ongoing treatment. Few studies have evaluated the long-term efficacy and safety of lanreotide depot beyond 2 years. The goal of this study was to provide a long-term longitudinal assessment of efficacy and safety of lanreotide depot in lanreotide responders compared to a surgically cured control group. In this retrospective longitudinal case-control study, patients with acromegaly receiving lanreotide depot monotherapy continuously for at least 24 months (N = 24) and surgically cured patients (N = 39) were compared. Serum IGF-1, pituitary MRIs, lanreotide dose, co-morbidities and adverse effects were assessed longitudinally. In the lanreotide group, IGF-1 remained normal and unchanged over 6 years; comparable to the surgery only group. There was no difference in prevalence of normal IGF-1 between the lanreotide and surgery only groups at 6 months (100 vs. 97 %), 6 years (89 vs. 90 %) and at last follow-up (96 vs. 92 %). Tumor size remained stable (79 %) or decreased (21 %) in the lanreotide group. In the surgery only group, tumor size remained unchanged in all patients. Hemoglobin A1C did not differ between lanreotide and surgery only groups (baseline 5.8 vs. 6.1 %; last follow-up 6.0 vs. 5.7 %). Two (8 %) of the lanreotide and none of the surgery only group developed new diabetes mellitus. Lanreotide depot maintains normalization of IGF-1 in 89 % of responders after 6 years, comparable to surgically cured controls, and controlled tumor size in all without significant adverse effects.

  20. Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected non-responders and relapsers after interferon alfa-2a monotherapy

    Institute of Scientific and Technical Information of China (English)

    Perdita Wietzke-Braun; Volker Meier; Felix Braun; Giuliano Ramadori

    2001-01-01

    AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be

  1. Real-world effectiveness of antipsychotic monotherapy vs. polypharmacy in schizophrenia: to switch or to combine? A nationwide study in Hungary.

    Science.gov (United States)

    Katona, Lajos; Czobor, Pál; Bitter, István

    2014-01-01

    Leading guidelines recommend antipsychotic (AP) monotherapy for schizophrenia, nonetheless the combination of antipsychotics (polypharmacy) is common practice worldwide. We conducted a nationwide population-based study to investigate the comparative effectiveness of monotherapy versus polypharmacy in schizophrenia and other psychotic disorders. Data was collected from the Hungarian National Health Insurance Fund's database and a non-interventional retrospective-prospective parallel arm study was designed with a monotherapy arm (MA, switch to a new antipsychotic after >60 days of monotherapy, N=5480) and a polypharmacy arm with two APs (PA, addition of a second antipsychotic after >60 days of monotherapy, N=7901). The analyses focused on therapy changers, who started a new monotherapy or added a new AP to the existing one. Polypharmacy combinations with more than two APs were not investigated. Fourteen APs were investigated representing the majority of marketed antipsychotics of Hungary in the period of 1/2007-12/2009. The principal endpoint was the time to all-cause treatment discontinuation during a one-year observation period. Kaplan-Meier survival analysis and Cox proportional hazards model were applied with propensity score adjustment. The principal outcome measure time to all-cause discontinuation indicated superiority for monotherapy over polypharmacy for the majority of (oral and depot) second generation APs (SGAs). For first generation APs (FGAs), oral formulations did not show a difference between monotherapy and polypharmacy, while depot formulations exhibited polypharmacy advantage. For the four most frequently used oral SGAs, the median times to all-cause discontinuation for monotherapy and polypharmacy, respectively, were 192 and 100 days for aripiprazole; 222 and 86 days for olanzapine; 176 and 91 days for quetiapine; and 157 and 93 days for risperidone. For mortality and hospitalization, a significant overall advantage of polypharmacy was detected

  2. Polypharmacy (or polytherapy) in the treatment of heart failure.

    Science.gov (United States)

    Cleland, J G; Baksh, A; Louis, A

    2000-01-01

    There is now conclusive evidence that most patients with heart failure due to left ventricular systolic dysfunction should be treated with angiotensin converting enzyme (ACE) inhibitors and beta-blockers. They will also need diuretics for the control of fluid retention. There is also a powerful case for adding spironolactone to the treatment of patients with more severe symptoms. Many doctors would also use digoxin and, especially if coronary disease is present, aspirin or warfarin. Most patients also have other chronic diseases, such as diabetes, arthritis, depression and dyspepsia, and each of these may provoke the prescription of yet another agent. Many patients will receive prescriptions to treat the side-effects of their therapy. Finding a sure path through the morass of pharmacotherapy is a daunting task. Polypharmacy is having a negative impact on new drug research in an area where there are in fact remarkably few really effective treatments and the therapeutic problem is only partially solved. This paper discusses some of the issues surrounding polypharmacy in heart failure and how to resolve them, using an illustrative case history. It highlights the potential benefits of polypharmacy with effective drugs and the gross over-use of ineffective treatments in heart failure. The major problem with polypharmacy in heart failure is not the heart failure treatment itself, but the drugs for other concomitant conditions, the effectiveness of which is often not supported by an appropriate evidence base and for which alternative, less noxious management strategies often exist. Polypharmacy may be deleterious not only because of the increased potential for side-effects and drug interactions but also because taking unnecessary therapy reduces compliance with effective drugs.

  3. The difficulties of polytherapy: examples from antimicrobial chemotherapy.

    Science.gov (United States)

    Mazzei, Teresita

    2011-10-01

    Medical therapy in patients with more than one pathology means using more pharmaceuticals, which results in a higher risk of drug interactions which are modifications in the action of one drug when it is administered in the presence of another. The consequences can be diminished therapeutic effect or increased adverse reactions. The pharmacological interactions can be either physico-chemical, pharmacokinetic or pharmacodynamic, on the basis of their mechanisms. Pharmacokinetic interactions are the most important and can emerge during various phases of absorption, distribution, metabolism and drug elimination. The absorption of many antimicrobial agents can be modified through various mechanisms. Some drugs (for example the anticholinergics and opiates) or food can slow gastric motility, slowing the absorption and reducing maximum concentrations of the antibiotic. Variations in gastric pH can alter the solubility or chemical stability of molecules such as the beta-lactams, the natural macrolides and some azoles. The bioavailability of these drugs can be reduced due to molecules used to raise gastric pH. Antibiotics such as tetracycline or the fluoroquinolones have reduced bioavailability due to chelation from bi- and trivalent cations. The primary number of clinically relevant pharmacological interactions is correlated with modifications of biotransformation of drugs due to Cytochrome P450 (CYP) hepatic enzymes which are involved in oxidative drug processes, including lipophilic antimicrobial drugs such as the macrolides, the fluoroquinolones (to be considered amphoteric) and the antifungal azole derivatives. CYP3A is probably one of the most important isoenzymes since it contributes to at least the partial transformation of 60% of drugs that undergo oxidation: erythromycin and clarithromycin are CYP3A4 substrates. Many isoenzymes can also be inhibited by antimicrobial drugs, including both antibacterials and antifungals (for example the macrolides, fluoroquinolones

  4. Effect of narrow band ultraviolet B phototherapy as monotherapy or combination therapy for vitiligo: a meta-analysis.

    Science.gov (United States)

    Li, Ronghua; Qiao, Meng; Wang, Xiaoyan; Zhao, Xintong; Sun, Qing

    2017-01-01

    The treatment of vitiligo is still one of the most difficult dermatological challenges, although there are many therapeutic options. Narrow band ultraviolet B (NB-UVB) phototherapy is considered to be a very important modality for generalized vitiligo. The aim of this study was to explore whether a combination of NB-UVB and topical agents would be superior to NB-UVB alone for treating vitiligo. We searched the electronic databases such as PUBMED, EMBASE, Cochrane Library, and Web of Science. The primary outcome was the proportion of ≥50% repigmentation (a clinical significance), and secondary outcome was the proportion of ≥75% repigmentation (an excellent response). Seven randomized controlled trials (RCTs) involving 240 patients (413 lesions) were included in this meta-analysis. The study showed no significant difference between NB-UVB combination therapy (NB-UVB and topical calcineurin inhibitor or vitamin D analogs) and NB-UVB monotherapy in the outcomes of ≥50% repigmentation and ≥75% repigmentation. However, lesions located on the face and neck had better results in ≥50% repigmentation (RR = 1.40, 95% CI 1.08-1.81) and ≥75% repigmentation (RR = 1.88, 95% CI 1.10-3.20) with NB-UVB and topical calcineurin inhibitor combination therapy vs. NB-UVB monotherapy. The meta-analysis suggested that adding neither topical calcineurin inhibitors nor topical vitamin-D3 analogs on NB-UVB can yield significantly superior outcomes than NB-UVB monotherapy for treatment of vitiligo. However, addition of topical calcineurin inhibitors to NB-UVB may increase treatment outcomes in vitiligo affecting face and neck. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Curcumin analog DM-1 in monotherapy or combinatory treatment with dacarbazine as a strategy to inhibit in vivo melanoma progression.

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    Fernanda Faião-Flores

    Full Text Available Malignant melanoma is a highly aggressive form of skin cancer with a high mortality rate if not discovered in early stages. Although a limited number of treatment options for melanoma currently exist, patients with a more aggressive form of this cancer frequently decline treatment. DM-1 is a sodium phenolate and curcumin analog with proven anticancer, anti-proliferative and anti-metastatic properties. In this paper, the DM-1 compound showed in vivo antitumor activity alone or in combination with chemotherapeutic DTIC in B16F10 melanoma-bearing mice. Beneficial effects such as melanoma tumor burden reduction with pyknotic nuclei, decreased nuclei/cytoplasmic ratio and nuclear degradation occurred after DM-1 treatment. No toxicological changes were observed in the liver, kidneys, spleen and lungs after DM-1 monotherapy or DTIC combined therapy. DTIC+DM-1 treatment induced the recovery of anemia arising from melanoma and immunomodulation. Both DM-1 treatment alone and in combination with DTIC induced apoptosis with the cleavage of caspase-3, -8 and -9. Furthermore, melanoma tumors treated with DM-1 showed a preferential apoptotic intrinsic pathway by decreasing Bcl-2/Bax ratio. Considering the chemoresistance exhibited by melanoma towards conventional chemotherapy drugs, DM-1 compound in monotherapy or in combination therapy provides a promising improvement in melanoma treatment with a reduction of side effects.

  6. Curcumin Analog DM-1 in Monotherapy or Combinatory Treatment with Dacarbazine as a Strategy to Inhibit In Vivo Melanoma Progression

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    Faião-Flores, Fernanda; Quincoces Suarez, José Agustín; Fruet, Andréa Costa; Maria-Engler, Silvya Stuchi; Pardi, Paulo Celso; Maria, Durvanei Augusto

    2015-01-01

    Malignant melanoma is a highly aggressive form of skin cancer with a high mortality rate if not discovered in early stages. Although a limited number of treatment options for melanoma currently exist, patients with a more aggressive form of this cancer frequently decline treatment. DM-1 is a sodium phenolate and curcumin analog with proven anticancer, anti-proliferative and anti-metastatic properties. In this paper, the DM-1 compound showed in vivo antitumor activity alone or in combination with chemotherapeutic DTIC in B16F10 melanoma-bearing mice. Beneficial effects such as melanoma tumor burden reduction with pyknotic nuclei, decreased nuclei/cytoplasmic ratio and nuclear degradation occurred after DM-1 treatment. No toxicological changes were observed in the liver, kidneys, spleen and lungs after DM-1 monotherapy or DTIC combined therapy. DTIC+DM-1 treatment induced the recovery of anemia arising from melanoma and immunomodulation. Both DM-1 treatment alone and in combination with DTIC induced apoptosis with the cleavage of caspase-3, -8 and -9. Furthermore, melanoma tumors treated with DM-1 showed a preferential apoptotic intrinsic pathway by decreasing Bcl-2/Bax ratio. Considering the chemoresistance exhibited by melanoma towards conventional chemotherapy drugs, DM-1 compound in monotherapy or in combination therapy provides a promising improvement in melanoma treatment with a reduction of side effects. PMID:25742310

  7. Adverse events of statin-fenofibric acid versus statin monotherapy: a meta-analysis of randomized controlled trials.

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    Geng, Qiang; Ren, Jingyi; Chen, Hong; Lee, Chongyou; Liang, Wenqing

    2013-03-01

    Patients with mixed dyslipidemia can benefit from the combination of fenofibric acid (FA) with statins, but concerns about adverse events make physicians reluctant to prescribe the combination therapy. In the present study, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse events in patients taking statins and FA. Medline, Embase and the Cochrane Library were searched to identify studies that reported adverse events. Finally, five trials covering 2704 patients were selected in this study. There were significant decreases in TG and increases in HDL-C in patients receiving combination therapy compared with statin monotherapy. The incidence of hepatic toxicity (OR, 3.57; 95% CI, 1.17-10.83; P statin group than in the corresponding statin monotherapy. The incidence of CK elevations and muscle-associated AEs was not statistically different between the two groups. The adverse events in the FA + moderate-dose statin group were almost identical to those in the FA + low-dose statin group. In conclusion, combination therapy could improve the blood lipid profile. Addition of FA to statins therapy is more frequently associated with hepatic and renal toxicity than muscle-associated AEs. Therefore patients taking the combination of FA with statins should have liver enzyme and renal function monitored. However, we still need large-scale and long follow-up period RCTs to definitively confirm the adverse events of FA-statin therapy.

  8. Quetiapine monotherapy for bipolar depression

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    Michael E Thase

    2008-03-01

    Full Text Available Michael E ThaseDepartments of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; the Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA; and the University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: Bipolar depression is more common, disabling, and difficult-to-treat than the manic and hypomanic phases that define bipolar disorder. Unlike the treatment of so-called “unipolar” depressions, antidepressants generally are not indicated as monotherapies for bipolar depressions and recent studies suggest that - even when used in combination with traditional mood stabilizers – antidepressants may have questionable value for bipolar depression. The current practice is that mood stabilizers are initiated first as monotherapies; however, the antidepressant efficacy of lithium and valproate is modest at best. Within this context the role of atypical antipsychotics is being evaluated. The combination of olanzapine and the antidepressant fluoxetine was the first treatment to receive regulatory approval in the US specifically for bipolar I depression. Quetiapine was the second medication to be approved for this indication, largely as the result of two pivotal trials known by the acronyms of BOLDER (BipOLar DEpRession I and II. Both studies demonstrated that two doses of quetiapine (300 mg and 600 mg given once daily at bedtime were significantly more effective than placebo, with no increased risk of patients switching into mania. Pooling the two studies, quetiapine was effective for both bipolar I and bipolar II depressions and for patients with (and without a history of rapid cycling. The two doses were comparably effective in both studies. Although the efficacy of quetiapine monotherapy has been established, much additional research is necessary. Further studies are needed to more fully investigate dose-response relationships and comparing quetiapine monotherapy to other mood stabilizers

  9. The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial: a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection.

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    Paton, Nicholas I; Stöhr, Wolfgang; Oddershede, Lars; Arenas-Pinto, Alejandro; Walker, Simon; Sculpher, Mark; Dunn, David T

    2016-03-01

    Standard-of-care antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection uses a combination of drugs, until now considered essential to minimise treatment failure and development of drug resistance. Protease inhibitors (PIs) are potent with a high genetic barrier to resistance and have the potential for use as monotherapy after viral load (VL) suppression achieved on combination therapy. However, longer-term resistance and toxicity risks are uncertain. To compare the effectiveness, toxicity profile and cost-effectiveness of PI monotherapy with those of standard-of-care triple therapy in a pragmatic long-term clinical trial. Open-label, parallel-group, randomised controlled trial. Forty-three HIV clinical centres in the UK NHS. HIV-positive adults taking standard combination ART with a suppressed VL for ≥ 6 months. Patients were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected ritonavir-boosted PI monotherapy (PI-mono), with prompt return to combination therapy in the event of VL rebound. The primary outcome was reduction of future drug options, defined as new intermediate-/high-level resistance to one or more drugs to which the patient's virus was considered to be sensitive at trial entry (non-inferiority comparison, 10% margin). Secondary outcomes included confirmed virological rebound, serious drug- or disease-related complications, total grade 3 or 4 adverse events (AEs), neurocognitive function change, cluster of differentiation 4 (CD4) cell count change, change in health-related quality of life, cardiovascular risk change, health-care costs and health economic analysis. In total, 587 participants were randomised (77% male, 68% white) to OT (n = 291) or PI-mono (n = 296) and followed for a median of 44 months, of whom 2.7% withdrew/were lost to follow-up. One or more episodes of confirmed VL rebound were observed in eight patients (Kaplan-Meier estimate 3.2%) in the OT group and

  10. PDE-5 inhibitors in monotherapy versus combination therapy in a sample of 1200 patients with erectile dysfunction

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    Luis Labairu-Huerta

    2015-09-01

    Full Text Available Objectives: To compare the effectiveness in the treatment of erectile dysfunction when using PDE-5 inhibitors (PDE5i, alprostadil (PG-E1 and testosterone (TES in monotherapy or combination therapy. Material and Methods: Observational multicentre retrospective study of men diagnosed and treated for ED between January 2008 and January 2014. Age, social and employment situation, pathological medical history, risk factors, usual treatments, IIEF-5 at the first consultation and at first and each 6 months follow-ups, physical examination, calculated total and free testosterone and received treatment were analysed. Descriptive statistics, one-way ANOVA analysis, Chi2 for qualitative data, t-test, Fisher's exact test and Pearson's correlation coefficient were used; p < 0.05 is considered significant. Results: Average age was 58.61 years, SD5.02, average follow- up time 48.21 months, SD 6.21, range 6-174 months. Out of the patients 76.12% were married, 9.81% divorced/separated, 10.04% single, 4.03% widowed; 85.14% of the total in stable partnership but 66.16% were not accompanied by their partners. In total 844 patients received monotherapy (597 PDE5i; 62 PG-E1; 36 TES; 27 penile prosthesis; 121 psychotherapy/alternative therapies and 357 combination therapy (167 PDE5i+TES; 124 PDE5i+PGE1; 66 PG-E1+TES. There was a homogeneous distribution between risk factors and medical history groups. Satisfactory response according to IIEF-5 was achieved for 72.33% of patients on PDE5i monotherapy, 46.65% of patients on PDE5i+PG-E1 combination therapy and 83.41% of patients on PDE5i+TES. Conclusions: The best therapeutic success for ED in this series was achieved through a combination of testosterone+PDE-5 inhibitors without increasing morbidity and maintaining the response over time. Larger studies with longer follow-up will corroborate these findings.

  11. Romidepsin Used as Monotherapy in Sequence with Allogeneic Stem Cell Transplant in a Patient with Peripheral T-Cell Lymphoma

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    Nicholas Finn

    2014-01-01

    Full Text Available Despite advances in the field, a clear treatment algorithm for most peripheral T-cell lymphoma (PTCL subtypes remains to be defined. Generating reliable randomized data for this type of pathology remains a challenge because of the relative rarity of the disease and the heterogeneity of subtypes. Newer agents, such as the class-I selective histone deacetylase inhibitor romidepsin, have demonstrated efficacy and manageable toxicity in the relapsed and refractory setting. Whether novel agents should be used in conjunction with more conventional cytotoxic therapies or in sequence with a transplant strategy is unknown at this time. Here we report the successful use of romidepsin monotherapy as a bridge to allogeneic stem cell transplantation in a patient who had previously relapsed after several lines of conventional cytotoxic therapy for PTCL. Romidepsin provided the patient with sufficient disease control to proceed to transplantation while remaining in complete remission.

  12. Effect of Combined versus Monotherapy with Deferoxamine and Deferiprone in Iron Overloaded Thalassemia Patients: a Randomized Clinical Trial

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    Sasan Hejazi

    2016-06-01

    Full Text Available Background: Patients with transfusional iron overload have depended on iron chelation therapy and improving chelation regimens have been of the highest priority. The aim of this study was to compare effect of combined versus monotherapy with Deferoxamine (DFO and Deferiprone (DFP in iron overloaded beta thalassemia (BT major patients Materials and Methods We studied 36 BT major patients (mean age 7.6±4.6; range 3–16 years attending the Ormieh Motahari hospital for regular transfusional support. Patients were randomly allocated to receive one of the following two treatments: DFO in combination with DFP (n=12, DFO alone (n=12 and DFP alone (n=12. Serum ferritin level, liver enzymes, blood urea nitrogen, and creatinine and side effects were monitored over a 12 months period. Results: After one year, serum ferritin decreased more significantly in patients on DFO+DFP therapy compared to patients who only received DFO or DFP alone (P

  13. Short term outcomes of topiramate monotherapy as a first-line treatment in newly diagnosed West syndrome

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    Gyu Min Lee

    2011-09-01

    Full Text Available Purpose : To investigate the efficacy of topiramate monotherapy in West syndrome prospectively. Methods : The study population included 28 patients (15 male and 13 female children aged 2 to 18 months diagnosed with West syndrome. After a 2-week baseline period for documentation of the frequency of spasms, topiramate was initiated at 2 mg/kg/day. The dose was increased by 2 mg/kg every week to a maximum of 12 mg/ kg/day. Clinical assessment was based on the parents’ report and a neurological examination every 2 weeks for the first 2 months of treatment. The baseline electroencephalograms (EEGs were compared with the post-treatment EEGs at 2 weeks and 1 month. Results : West syndrome was considered to be cryptogenic in 7 of the 28 patients and symptomatic in 21 patients. After treatment, 11 patients (39% became spasm-free, 6 (21% had more than 50% spasmsreduction, 3 (11% showed less than 50% reduction, and 8 (29% did not respond. The effective daily dose for achieving more than 50% reduction in spasm frequency, including becoming spasm-free, was found to be 5.8±1.1 mg/kg/day. Nine patients (32% showed complete disappearance of spasms and hypsarrhythmia, and 11 (39% showed improved EEG results. Despite adverse events (4 instances of irritability, 3 of drowsiness, and 1 of decreased feeding, no patients discontinued the medication. Conclusion : Topiramate monotherapy seems to be effective and well tolerated as a first line therapy for West syndrome and is not associated with serious adverse effects.

  14. High-dose rate brachytherapy as monotherapy in prostate cancer: A systematic review of its safety and efficacy.

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    Sánchez-Gómez, L M; Polo-deSantos, M; Rodríguez-Melcón, J I; Angulo, J C; Luengo-Matos, S

    2017-03-01

    High-dose rate brachytherapy (HDR-BT) is an increasingly popular treatment for patients with localised prostate cancer (PC). To assess the safety and efficacy of HDR-BT as monotherapy in PC. A systematic literature review was conducted through searches on MEDLINE (PubMed), Cochrane Library, CDR, ClinicalTrials and EuroScan. We assessed safety and efficacy indicators. We selected 2 reviews and 12 uncontrolled studies, included in these 2 reviews. In terms of efficacy, local control in 6 studies was 97-100%. The biochemical progression-free survival varied as follows: 85-100% for low risk and 79-92% for high risk. Survival free of metastases was >95% at 8 years, except in one study where the survival rate was 87% at 5 years. The overall survival was ≥95% in 8 studies. In terms of safety, most of the studies recorded acute and long-term genitourinary and gastrointestinal complications, especially grade ≥2. Only 3 studies found grade 4 complications. All studies, except for one without complications, observed genitourinary complications that were more frequent and severe than the gastrointestinal complications. Two studies assessed the quality of life and showed an initial reduction in various domains and subsequent partial or total recovery, except in the sexual domain. HDR-BT is effective as monotherapy, especially in cases of low to intermediate risk. There is insufficient information on high-risk patients. The short to medium-term toxicity was acceptable. Further research needs to be funded to provide more information on the long-term safety and efficacy of this treatment. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. A longitudinal trial comparing chloroquine as monotherapy or in combination with artesunate, azithromycin or atovaquone-proguanil to treat malaria.

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    Miriam K Laufer

    Full Text Available BACKGROUND: The predominance of chloroquine-susceptible falciparum malaria in Malawi more than a decade after chloroquine's withdrawal permits contemplation of re-introducing chloroquine for targeted uses. We aimed to compare the ability of different partner drugs to preserve chloroquine efficacy and prevent the re-emergence of resistance. METHODOLOGY/PRINCIPAL FINDINGS: Children with uncomplicated malaria were enrolled at a government health center in Blantyre, Malawi. Participants were randomized to receive chloroquine alone or combined with artesunate, azithromycin or atovaquone-proguanil for all episodes of uncomplicated malaria for one year. The primary outcome was incidence of clinical malaria. Secondary endpoints included treatment efficacy, and incidence of the chloroquine resistance marker pfcrt T76 and of anemia. Of the 640 children enrolled, 628 were included in the intention-to-treat analysis. Malaria incidence (95% confidence interval was 0.59 (.46-.74, .61 (.49-.76, .63 (.50-.79 and .68 (.54-.86 episodes/person-year for group randomized to receive chloroquine alone or in combination with artesunate, azithromycin or atovaquone-proguanil respectively and the differences were not statistically significant. Treatment efficacy for first episodes was 100% for chloroquine monotherapy and 97.9% for subsequent episodes of malaria. Similar results were seen in each of the chloroquine combination groups. The incidence of pfcrt T76 in pure form was 0%; mixed infections with both K76 and T76 were found in two out of 911 infections. Young children treated with chloroquine-azithromycin had higher hemoglobin concentrations at the study's end than did those in the chloroquine monotherapy group. CONCLUSION/SIGNIFICANCE: Sustained chloroquine efficacy with repeated treatment supports the eventual re-introduction of chloroquine combinations for targeted uses such as intermittent preventive treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT00379821.

  16. A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy.

    Science.gov (United States)

    Fredsø, N; Sabers, A; Toft, N; Møller, A; Berendt, M

    2016-02-01

    Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided into three daily dosages) or phenobarbital (4 mg/kg/day divided twice daily). Control visits were at days 30, 60 and then every 3 months for up to 1 year. Two or more seizures within 3 months led to an increase in drug dosage (levetiracetam: 10 mg/kg/day, phenobarbital: 1 mg/kg/day). Five of six levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2-5 months due to insufficient seizure control. In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs there were significantly (P = 0.013) fewer seizures after treatment. Five phenobarbital treated dogs were classified as true responders (≥50% reduction in seizures/month) whereas none of the levetiracetam treated dogs fulfilled this criterion. Adverse effects were reported in both groups but were more frequent in the phenobarbital group. In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy.

  17. High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

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    Barkati, Maroie [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Williams, Scott G., E-mail: scott.williams@petermac.org [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Dyk, Sylvia van [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); See, Andrew [Ballarat Austin Radiation Oncology Centre, Ballarat (Australia); Duchesne, Gillian M. [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia)

    2012-04-01

    Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

  18. Stereotactic body radiotherapy with a focal boost to the MRI-visible tumor as monotherapy for low- and intermediate-risk prostate cancer: Early results

    NARCIS (Netherlands)

    S. Aluwini (Shafak); P.H. van Rooij (Peter); M.S. Hoogeman (Mischa); W.J. Kirkels (Wim); I.-K.K. Kolkman-Deurloo (Inger-Karina); C.H. Bangma (Chris)

    2013-01-01

    textabstractBackground: There is growing evidence that prostate cancer (PC) cells are more sensitive to high fraction dose in hypofractionation schemes. High-dose-rate (HDR) brachytherapy as monotherapy is established to be a good treatment option for PC using extremely hypofractionated schemes. Thi

  19. Linagliptin and pioglitazone combination therapy versus monotherapy with linagliptin or pioglitazone: A randomised, double-blind, parallel-group, multinational clinical trial.

    Science.gov (United States)

    Nauck, Michael Albrecht; di Domenico, Maximiliano; Patel, Sanjay; Kobe, Maureen; Toorawa, Robert; Woerle, Hans-Juergen

    2016-07-01

    Linagliptin plus pioglitazone single-pill combinations were evaluated. Patients (n = 936) with insufficient glycaemic control, despite lifestyle interventions, were randomised for 30 weeks to either monotherapy with linagliptin 5 mg; pioglitazone 15, 30 or 45 mg; or single-pill combination with linagliptin 5 mg plus pioglitazone 15, 30 or 45 mg. An extension (⩽54 weeks) planned to evaluate linagliptin plus pioglitazone 30 or 45 mg single-pill combinations was not completed due to a protocol amendment. Adjusted mean (95% confidence interval) differences in HbA1c change from baseline at week 30 for linagliptin plus pioglitazone 15, 30 and 45 mg were -0.17% (-0.41, 0.07), -0.37% (-0.60, -0.14) and -0.41% (-0.64, -0.18) versus pioglitazone monotherapies, respectively, and -0.44% (-0.67, -0.20), -0.68% (-0.91, -0.44) and -0.89% (-1.12, -0.66) versus linagliptin monotherapy, respectively. Single-pill combinations were generally well tolerated. Hypoglycaemia frequency was ⩽1.5% per group. Linagliptin plus pioglitazone combinations were efficacious, with safety profiles comparable to the individual monotherapies.

  20. Relative efficacy of bivalirudin versus heparin monotherapy in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: a network meta-analysis

    Directory of Open Access Journals (Sweden)

    Kinnaird T

    2013-10-01

    Full Text Available Tim Kinnaird,1 Goran Medic,2 Gianni Casella,3 Francois Schiele,4 Upendra Kaul,5 Peter W Radke,6 Indra Eijgelshoven,2 Gert Bergman,2 Derek P Chew71Cardiff and Vale University Health Board, Cardiff, UK; 2Mapi-Health Economics Outcomes Research and Strategic Market Access, Houten, the Netherlands; 3Ospedale Maggiore, Unità Operativa di Cardiologia, Bologna, Italy; 4Hôpital Jean Minjoz, Besançon Cedex, France; 5Fortis Escorts Heart Institute and Research Centre, Okhla Road, New Delhi, India; 6Schön Klinik Neustadt, Neustadt, Germany; 7Flinders University; Department of Cardiovascular Medicine, Southern Adelaide Health Service, Bedford Park, SA, AustraliaAbstract: In the absence of head-to-head clinical data, the objective of this study was to indirectly compare the efficacy and safety of a bivalirudin-based anticoagulation strategy with that of heparin monotherapy in patients with ST-elevation myocardial infarction (STEMI intended for primary percutaneous coronary intervention. A systematic literature review was performed to identify randomized controlled trials to build a network of bivalirudin and heparin monotherapy strategies in STEMI patients using heparin, with glycoprotein IIb/IIIa inhibitor as a common reference strategy. At 30 days, the bivalirudin-based strategy was expected to result in lower mortality rates than heparin monotherapy (odds ratio [OR], 0.55; credible limit [CrL], 0.32–0.95. This relationship was sustained at 1 year. At 30 days, the risk for stroke (OR, 0.88; CrL, 0.37–2.13, myocardial infarction (OR, 0.79; CrL, 0.40–1.55, and thrombolysis in myocardial infarction major and minor bleedings (OR, 0.66; CrL, 0.45–0.98 tended to be numerically reduced with bivalirudin in comparison with heparin monotherapy. For patients with STEMI intended for primary percutaneous coronary intervention, bivalirudin is associated with lower mortality rates in comparison with heparin monotherapy. This study suggests that bivalirudin is

  1. Psychomotor symptoms and treatment outcomes of ziprasidone monotherapy in patients with major depressive disorder: a 12-week, randomized, double-blind, placebo-controlled, sequential parallel comparison trial.

    Science.gov (United States)

    Jeon, Hong Jin; Fava, Maurizio; Mischoulon, David; Baer, Lee; Clain, Alisabet; Doorley, James; DiPierro, Moneika; Cardoos, Amber; Papakostas, George I

    2014-11-01

    The aim of this study was to evaluate efficacy of ziprasidone monotherapy for major depressive disorder (MDD) with and without psychomotor symptoms. In accordance with the sequential parallel comparison design, 106 MDD patients (age 44.0±10.7 years; female, 43.4%) were recruited and a post-hoc analysis was carried out on 12-week double-blind treatment with either ziprasidone (40-160 mg/day) or placebo, divided into two phases of 6 weeks each to the assigned treatment sequences, drug/drug, placebo/placebo, and placebo/drug. Psychomotor symptoms were evaluated on the basis of the Mini-International Neuropsychiatric Interview at baseline. Efficacy assessments, on the basis of the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Quick Inventory of Depressive Symptomatology Scale, Self-Rated (QIDS-SR), were performed every week throughout the trial. In phase I, ziprasidone monotherapy produced significant improvement in patients with psychomotor symptoms compared with placebo on the basis of HDRS-17 (F=5.95, P=0.017) and QIDS-SR (F=5.26, P=0.025) scores, whereas no significant changes were found in HDRS-17 (F=2.32, P=0.15) and QIDS-SR (F=3.70, P=0.074) scores in patients without psychomotor symptoms. In phase II, ziprasidone monotherapy produced no significant differences compared with placebo. In the pooled analysis, ziprasidone monotherapy showed significance according to QIDS-SR (Z=2.00, P=0.046) and a trend toward statistical significance according to the HDRS-17 (Z=1.66, P=0.10) in patients with psychomotor symptoms. Ziprasidone monotherapy may produce significant improvement compared with placebo in MDD patients with psychomotor symptoms.

  2. Is combined treatment more effective than switching to monotherapy in patients with resistant depression? A retrospective study.

    Science.gov (United States)

    Bares, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Sos, Peter

    2009-01-01

    The aim of this retrospective study was to compare the efficacy of combination therapy (combinations of antidepressants and various augmentations) and antidepressant monotherapy in the treatment of patients, who failed to respond at least to one previous antidepressant trial in the routine clinical practice. We reviewed chart documents of patients hospitalized at Prague Psychiatric Center for depressive disorder from June 2005 to June 2007 and finished at least 4 weeks of new treatment. Depressive symptoms and overall clinical status were assessed using Montgomery and Asberg Depression Rating Scale, Clinical Global Impression and Beck Depression Inventory - Short Form at the baseline and in the end of treatment. We identified 49 inpatients (24-combined treatment, 25-monotherapy), who were suitable for analyses. Both groups were equal in baseline characteristics and in the duration of index episode treatment. The combined treatment was superior to the monotherapy switch in the MADRS median score reduction (16 vs. 9 points, p=0.01). The combined group achieved higher response rate compared to monotherapy group (67% vs. 36%, p=0.05). Number need to treat for response was 3.3 (95% CI, 1.85-37.3). The findings of this study suggest that combined treatment is more efficacious than switch to monotherapy in the treatment of resistant depression.

  3. Trastuzumab as a preoperative monotherapy does not inhibit HER2 downstream signaling in HER2-positive breast cancer

    Science.gov (United States)

    Lion, Maëva; Harlé, Alexandre; Salleron, Julia; Ramacci, Carole; Campone, Mario; Merlin, Jean-Louis

    2016-01-01

    Human epidermal growth factor 2 (HER2) is overexpressed in 15–20% of breast carcinomas. The overexpression of HER2 was previously associated with a poor prognosis until the development of the first anti-HER2 therapy, trastuzumab, which drastically improves the prognosis of HER2-overexpressing breast cancers. However, its mechanism of action remains not fully understood. Several studies have proposed that the behavior and mechanism of action of trastuzumab may be drastically altered in vitro and in vivo. The present study assesses the ability of trastuzumab to inhibit the phosphorylation of the key-proteins of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin and Ras/Raf/mitogen-activated protein kinase (MAPK) signaling pathways in vitro, in breast cancer cell lines and in tumor biopsies obtained from patients treated with trastuzumab preoperative monotherapy as part of the Unicancer GEP04 RADHER phase II clinical trial. HER2-positive SKBR3 and HER2-negative MCF-7 cell lines were exposed to trastuzumab for 72 h. In total, 41 patients received trastuzumab alone for 6 weeks of preoperative treatment. Biopsies were collected at the baseline and at surgery. A total of 19 pairs of associated baseline and surgery tumor specimens were eligible for protein extraction and comparative phosphoprotein expression analysis, prior to and subsequent to treatment. The expression of phosphoproteins was quantitatively assessed using a multiplex immunoassay. In the SKBR3 cell line, a statistically significant decrease of the expression level of phosphorylated (p-)AKT, p-ribosomal protein S6 kinase B1, p-extracellular signal regulated kinase 1/2 and p-mitogen-activated protein kinase kinase 1 was observed after exposure to trastuzumab. In contrast, no statistically significant variations for levels expression of these phosphoproteins were observed in patients following treatment. The lack of downregulation of PI3K and MAPK pathways could probably

  4. Current status of artemisinin-resistant falciparum malaria in South Asia: a randomized controlled artesunate monotherapy trial in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Peter Starzengruber

    Full Text Available OBJECTIVE: Recent reports indicate that first cases of genuine artemisinin resistance have already emerged along the Thai-Cambodian border. The main objective of this trial was to track the potential emergence of artemisinin resistance in Bangladesh, which in terms of drug resistance forms a gateway to the Indian subcontinent. METHODS: We conducted an open-label, randomized, controlled 42-day clinical trial in Southeastern Bangladesh to investigate the potential spread of clinical artemisinin resistance from Southeast Asia. A total of 126 uncomplicated falciparum malaria patients were randomized to one of 3 treatment arms (artesunate monotherapy with 2 or 4 mg/kg/day once daily or quinine plus doxycycline TID for 7 days. Only cases fulfilling a stringent set of criteria were considered as being artemisinin-resistant. FINDINGS: The 28-day and 42-day cure rates in the artesunate monotherapy (2 and 4 mg/kg and quinine/doxycyline arms were 97.8% (95% confidence interval, CI: 87.8-99.8%, 100% (95% CI: 91.1-100%, and 100% (95% CI: 83.4-100%, respectively. One case of re-infection was seen in the artesunate high dose arm, and a single case of recrudescence was observed in the low dose group on day 26. No differences in median parasite and fever clearance times were found between the 2 artesunate arms (29.8 h and 17.9 h vs. 29.5 h and 19.1 h. Not a single case fulfilled our criteria of artemisinin resistance. Parasite clearance times were considerably shorter and ex vivo results indicate significantly higher susceptibility (50% inhibitory concentration for dihydroartemisinin was 1.10 nM; 95% CI: 0.95-1.28 nM to artemisinins as compared to SE-Asia. CONCLUSION: There is currently no indication that artemisinin resistance has reached Bangladesh. However, the fact that resistance has recently been reported from nearby Myanmar indicates an urgent need for close monitoring of artemisinin resistance in the region. TRIAL REGISTRATION: ClinicalTrials.gov NCT

  5. Cancer risk in patients aged 30 years and above with type 2 diabetes receiving antidiabetic monotherapy: a cohort study using metformin as the comparator

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    Chen YC

    2015-08-01

    Full Text Available Yu-Ching Chen,1 Victor C Kok,1,2 Ching-Hsuan Chien,1 Jorng-Tzong Horng,1,3 Jeffrey J P Tsai11Department of Biomedical Informatics, Asia University, Taichung, 2Department of Internal Medicine, Kuang Tien General Hospital, Taichung, 3Department of Computer Science and Information Engineering, National Central University, Jhongli, TaiwanIntroduction: Accumulating evidence suggests that metformin reduces incident cancer development. Few cohort studies have evaluated the risk of subsequent cancer development in diabetic cohorts receiving antidiabetic monotherapy. We conducted a population-based study in patients with new-onset type 2 diabetes treated with antidiabetic monotherapy.Methods: We identified a cohort of patients with type 2 diabetics aged ≥30 years receiving hypoglycemic monotherapy (n=7,325 from the 1998–2007 Longitudinal Health Insurance Dataset. Patients were grouped according to the antidiabetic therapy they received into metformin (n=2,223, sulfonylurea (n=3,965, glitazone (n=53, meglitinide (n=128, acarbose (n=150, and insulin (n=806 groups. Patients with preexisting cancer were excluded. All patients were followed up until cancer development, dropout, death, or until December 31, 2008. Cox’s model was used to estimate multivariable hazard ratios (HRs adjusted for age, sex, Charlson comorbidity index, smoking-related comorbidities, alcohol use disorders, morbid obesity, pancreatitis, hypertension, monthly income, and urbanization level. The log-rank test was used to compare cumulative cancer incidence. Two-sided P-values <0.05 were required to reject the null hypothesis.Results: The overall median follow-up duration was 2.5 years (interquartile range, 3.6 years. Totally, 367 and 124 cancers developed in the sulfonylurea and metformin groups, respectively, representing an adjusted HR of 1.36 (95% confidence interval [CI], 1.11–1.67; P<0.005. No significant differences were observed between other groups. Increased adjusted HRs

  6. Conversion to lanthanum carbonate monotherapy effectively controls serum phosphorus with a reduced tablet burden: a multicenter open-label study

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    Matalon Albert

    2011-09-01

    Full Text Available Abstract Background Lanthanum carbonate (FOSRENOL® is an effective, well-tolerated phosphate binder. The ability of lanthanum to reduce serum phosphorus levels to ≤5.5 mg/dL in patients with end-stage renal disease (ESRD was assessed in a clinical practice setting. Methods A 16-week, phase IV study enrolled 2763 patients at 223 US sites to evaluate the efficacy of lanthanum carbonate in controlling serum phosphorus in patients with ESRD, and patient and physician satisfaction with, and preference for, lanthanum carbonate after conversion from other phosphate-binder medications. Patients received lanthanum carbonate prescriptions from physicians. These prescriptions were filled at local pharmacies rather than obtaining medication at the clinical trial site. Changes from serum phosphorus baseline values were analyzed using paired t tests. Patient and physician preferences for lanthanum carbonate versus previous medications were assessed using binomial proportion tests. Satisfaction was analyzed using the McNemar test. Daily dose, tablet burden, and laboratory values including albumin-adjusted serum calcium, calcium × phosphorus product, and parathyroid hormone levels were secondary endpoints. Results Serum phosphorus control (≤5.5 mg/dL was effectively maintained in patients converting to lanthanum carbonate monotherapy; 41.6% of patients had controlled serum phosphate levels at 16 weeks. Patients and physicians expressed markedly higher satisfaction with lanthanum carbonate, and preferred lanthanum carbonate over previous medication. There were significant reductions in daily dose and daily tablet burden after conversion to lanthanum carbonate. Conclusions Serum phosphorus levels were effectively maintained in patients converted from other phosphate-binder medications to lanthanum carbonate, with increased satisfaction and reduced tablet burden. Trial Registration ClinicalTrials.gov: NCT0016012

  7. Antidepressant monotherapy compared with combinations of antidepressants in the treatment of resistant depressive patients: a randomized, open-label study.

    Science.gov (United States)

    Bares, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Cermak, Jan; Kozeny, Jiri; Höschl, Cyril

    2013-02-01

    This randomized, 6-week, open-label study compared efficacy of CAD and antidepressant monotherapies (ADM) that had been chosen according to clinical judgment of the attending psychiatrist. A total of 60 inpatients (intent-to-treat analysis) with depressive disorder (≥ 1 unsuccessful antidepressant treatment) were randomly assigned to the interventions. The responders who completed the acute phase of study, were evaluated for relapse within 2 months of follow-up treatment. The primary outcome measure was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) and response was defined as a ≥ 50% reduction of MADRS score. Mean changes in total MADRS score from baseline to week 6 for patients in both treatment modalities were not different (ADM = 13.2 ± 8.6 points; CAD = 14.5 ± 9.5 points; P = 0.58). The analysis of covariance performed for significantly higher value of imipramine equivalent dose in CAD group showed only a non-significant between-group difference for total MADRS change (P = 0.17). There were also no differences between groups in response rate (ADM = 48%; CAD = 58%) and number of drop-outs in acute treatment as well as proportion of responders' relapses in the follow-up. Both treatment modalities produced clinically relevant reduction of depressive symptomatology in acute treatment of patients with resistant depression and their effect was comparable.

  8. A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy

    DEFF Research Database (Denmark)

    Fredsø, N.; Sabers, A.; Toft, Nils;

    2016-01-01

    Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to inves......Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study...... was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided...... levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2-5 months due to insufficient seizure control.In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital...

  9. Effects of interferon β-1a and interferon β-1b monotherapies on selected serum cytokines and nitrite levels in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Stępień, Adam; Chalimoniuk, Małgorzata; Lubina-Dąbrowska, Natalia;

    2013-01-01

    Interferon (IFN)β treatment is a mainstay of relapsing-remitting multiple sclerosis (RRMS) immunotherapy. Its efficacy is supposedly a consequence of impaired trafficking of inflammatory cells into the central nervous system and modification of the proinflammatory/antiinflammatory cytokine balance....... However, the effects of long-term monotherapy using various IFNβ preparations on cytokine profiles and the relevance of these effects for the therapy outcome have not yet been elucidated....

  10. EQ-5D utility, response and drug survival in rheumatoid arthritis patients on biologic monotherapy: A prospective observational study of patients registered in the south Swedish SSATG registry

    Science.gov (United States)

    Jørgensen, Tanja Schjødt; Turesson, Carl; Kapetanovic, Meliha; Englund, Martin; Turkiewicz, Aleksandra; Christensen, Robin; Bliddal, Henning; Geborek, Pierre; Kristensen, Lars Erik

    2017-01-01

    Objectives Biologic agents have dramatically changed treatment of rheumatoid arthritis (RA). To date only scarce head-to-head data exist especially when the biological therapies are given as monotherapy without concomitant disease modifying drugs (DMARDs). Thus the objective of the current study is to evaluate treatment response of all available biological therapies with special focus on utility (EQ-5D-3L) and drug survival of biologic DMARDs (bDMARDs) prescribed as monotherapy in RA patients in southern Sweden. Materials and methods All RA patients registered in a regional database as initiating bDMARD as monotherapy, i.e. without concomitant conventional synthetic DMARDs (csDMARDs), from 1st of January 2006 through 31st of December 2012, were included. Patients were followed from initiation of the first dose of bDMARD monotherapy treatment until withdrawal from treatment, loss of follow-up or 31st of December 2012. Descriptive statistics for utility (EQ-5D-3L), effectiveness, and drug survival of bDMARD monotherapy were calculated. Results During the study period, a total of 554 patients were registered in SSATG as initiating bDMARD monotherapy. Most of the patients were women (81%), with a mean age of 57 years. The average disease duration was more than 12 years, and on average the patients had previously been treated with approximately four different csDMARDs. Fifty-five percent of the patients were initiating their first bDMARD, 26% their second, and 19% their third or more. At baseline the average EQ-5D-3L was 0.34. Most patients had moderate to high disease activity, with a mean DAS28 of 5.0, and were substantially disabled, with an average HAQ score of 1.4. At 6 months´ follow-up, the EQ-5D-3L in patients still on the biologic drug had increased by mean 0.23 (SD 0.4) with no differences between type of bDMARD (p = 0.49). The mean change in EQ-5D-3L ranged from 0.11 (rituximab and infliximab) to 0.42 (tocilizumab). Although the changes were numerically

  11. S-1 monotherapy versus S-1 combination therapy in gemcitabine-refractory advanced pancreatic cancer: A meta-analysis (PRISMA) of randomized control trials.

    Science.gov (United States)

    Zhong, Sheng; Qie, Shuai; Yang, Liu; Yan, Qi; Ge, Linna; Wang, Zhongfeng

    2017-07-01

    Pancreatic cancer (PC) is one of the most lethal digestive system tumors. Most new cases are diagnosed based on metastasis or local aggression and are known as "advanced PC." Recently, studies investigating S-1 have indicated that it has a better clinical curative effect on PC. We conducted a meta-analysis to evaluate the efficacy and safety of S-1 monotherapy compared with S-1 combination regimens in patients with gemcitabine (GEM)-refractory PC. Trials published between 1978 and 2016 were identified by an electronic search of public databases (Medline, Embase, and the Cochrane Library). All prospective studies were independently identified by 2 authors for inclusion. The response rate (RR), progression-free and overall survival (PFS and OS, respectively), and the primary toxicities were extracted for the meta-analysis. Four randomized controlled trials consisting of 623 patients were included in the analysis, among which 315 patients underwent S-1 monotherapy and 308 patients underwent S-1 combination therapy. The pooled data showed a significantly higher response rate and longer PFS in the S-1 combination group than in the S-1 monotherapy group (RR, 1.75; 95% confidence interval [CI], 1.19-2.57; P = .005 and hazard ration [HR], 0.75; 95% CI, 0.62-0.91; P = .005). There were no significant differences in OS or adverse events. Compared with the S-1 monotherapy group, the S-1 combination group had a higher response rate and longer PFS. Both groups had few adverse events, which were balanced between the groups. The subgroup analysis suggested that S-1 combination regimens with leucovorin or irinotecan (CPT-11) provided promising efficacy. These promising combination regimens should be considered for patients with advanced PC who choose S-1 as their second-line therapy.

  12. Long-Lasting Tumor Response in Patients with Panitumumab Monotherapy for Chemorefractory Metastatic Colorectal Carcinoma – A Report of Two Cases

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    G. Ramadori

    2010-05-01

    Full Text Available Background: Second as well as higher-line therapies have a significant influence on progression-free and overall survival of metastatic colorectal cancer patients. However, treatment of late-stage disease remains suboptimal. Therefore, the introduction of new, effective and well-tolerated agents is of major importance. Case Reports: Here we describe the cases of 2 patients with metastatic KRAS wild-type colorectal cancer who received a fourth-line monotherapy with panitumumab after failure of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab. Results: Both patients achieved a partial remission, and for 11.5 and 18 months, respectively, they had a stable disease with initial reduction in the tumor marker carcinoembryonic antigen. Both patients reported a good tolerability of the treatment with improved quality of life (compared to receiving combined chemotherapy. Conclusion: Panitumumab monotherapy is an effective and well tolerated treatment of metastatic colorectal cancer in extensively pretreated KRAS wild-type patients. Our data have shown a response to panitumumab monotherapy for more than 11 months.

  13. Results from a 12 months, randomized, clinical trial comparing an olmesartan/amlodipine single pill combination to olmesartan and amlodipine monotherapies on blood pressure and inflammation.

    Science.gov (United States)

    Derosa, Giuseppe; Cicero, Arrigo F G; Carbone, Anna; Querci, Fabrizio; Fogari, Elena; D'Angelo, Angela; Maffioli, Pamela

    2014-01-23

    Hypertension affects nearly 1 in 3 adults in the United States, and it is an important modifiable risk factor for coronary artery disease, heart failure, renal failure, and stroke. The aim of this study was to evaluate the effects of a fixed-dose olmesartan/amlodipine combination on blood pressure control, lipid profile, insulin sensitivity, and inflammation compared to singles monotherapies. We randomized 276 hypertensive patients to olmesartan 20 mg, amlodipine 10mg or a single pill containing a fixed-dose olmesartan/amlodipine combination 20/5mg for 12 months. We evaluated: body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, omentin, chemerin, high sensitivity C-reactive protein (Hs-CRP). At baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp to assess insulin sensitivity (M value). Olmesartan/amlodipine combination was more effective than amlodipine or olmesartan in reducing blood pressure. Olmesartan/amlodipine combination, but not amlodipine, decreased FPG after 12 months. Olmesartan/amlodipine combination better decreased FPI and HOMA index and increased M value compared to olmesartan and amlodipine monotherapies. Olmesartan/amlodipine significantly decreased chemerin and omentin compared to olmesartan and amlodipine. Other than to be more effective in reducing blood pressure, olmesartan/amlodipine single pill combination gave also a major increase of insulin sensitivity and a decrease of inflammatory markers compared to single monotherapies. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Antiandrogen monotherapy: indications and results

    DEFF Research Database (Denmark)

    Iversen, Peter

    2002-01-01

    with castration, in terms of sexual interest and physical capacity, in patients with either M0 and M1 stage disease. Data from a small subgroup of patients with stage M0 disease suggest that bicalutamide may also reduce the risk of osteoporosis compared with castration. Long-term therapy with bicalutamide 150-mg......Many patients with prostate cancer for whom hormonal therapy is indicated are still physically and sexually active; quality of life is therefore a vital issue when considering treatment options. Traditional castration-based therapies, although effective, have implications with respect to quality...... of life, causing loss of libido, impotence, fatigue, and reduced bone mineral density. Monotherapy with a nonsteroidal antiandrogen is an attractive therapeutic alternative to castration, offering effective therapy with potential quality-of-life benefits. Of the available nonsteroidal antiandrogens...

  15. Combination antibiotic treatment versus monotherapy for multidrug-resistant, extensively drug-resistant, and pandrug-resistant Acinetobacter infections: a systematic review.

    Science.gov (United States)

    Poulikakos, P; Tansarli, G S; Falagas, M E

    2014-10-01

    Controversy surrounds combination treatment or monotherapy against multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Acinetobacter infections in clinical practice. We searched the PubMed and Scopus databases for studies reporting on the clinical outcomes of patients infected with MDR, XDR, and PDR Acinetobacter spp. with regard to the administered intravenous antibiotic treatment. Twelve studies reporting on 1,040 patients suffering from 1,044 infectious episodes of MDR Acinetobacter spp. were included. The overall mortality between studies varied from 28.6 to 70 %; from 25 to 100 % in the monotherapy arm and from 27 to 57.1 % in the combination arm. Combination treatment was superior to monotherapy in three studies, where carbapenem with ampicillin/sulbactam (mortality 30.8 %, p = 0.012), carbapenem with colistin (mortality 23 %, p = 0.009), and combinations of colistin with rifampicin, sulbactam with aminoglycosides, tigecycline with colistin and rifampicin, and tigecycline with rifampicin and amikacin (mortality 27 %, p Acinetobacter spp. resistant at least to carbapenems. The benefit was not validated in the remaining studies. Clinical success varied from 42.4 to 76.9 % and microbiological eradication varied from 32.7 to 67.3 %. Adverse events referred mainly to polymixins nephrotoxicity that varied from 19 to 50 %. The emergence of resistance was noted with tigecycline regimens in off-label uses in three studies. The available data preclude a firm recommendation with regard to combination treatment or monotherapy. For the time being, combination treatment may be preferred for severely ill patients. We urge for randomized controlled trials examining the optimal treatment of infections due to MDR, XDR, and PDR Acinetobacter spp.

  16. A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Tyrrell, C J; Kaisary, A V; Iversen, P;

    1998-01-01

    To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer.......To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer....

  17. Efficacy of Tenofovir-Based Combination Therapy versus Tenofovir Monotherapy in Chronic Hepatitis B Patients Presenting with Suboptimal Responses to Pretreatment: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ling Chen

    2016-01-01

    Full Text Available Background/Aims. It remains unclear whether tenofovir disoproxil fumarate- (TDF- based combination therapy produces better outcomes than TDF monotherapy in chronic hepatitis B (CHB patients. The aim of this study was to compare the efficacy of the two regimens by performing a meta-analysis. Methods. A comprehensive literature search was performed on the comparison of TDF-based combination therapy and monotherapy for CHB patients in the PubMed, Embase, Web of Science, and the Cochrane Libraries. Both dichotomous and continuous variables were extracted and pooled outcomes were expressed as risk ratio (RR or standard mean difference (SMD. Results. Nine eligible studies (1089 subjects in total were included in our analysis. The proportion of patients with undetectable HBV DNA at 24, 48, and 96 weeks were similar between the two comparable groups (62.5% versus 70.9%, P=0.086; 78.1% versus 83.7%, P=0.118; 86.4% versus 87.9%, P=0.626, resp.. HBV DNA reduction, rates of ALT normalization, hepatitis B e antigen (HBeAg loss, and HBeAg seroconversion were also similar between the two groups. Conclusions. On the current data, TDF-based combination therapy seemed to be no better than those achieved by monotherapy. Further studies are needed to verify this comparison.

  18. Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment option for first-line monotherapy in advanced prostate cancer.

    Science.gov (United States)

    Kitamura, T

    2001-02-01

    Estramustine phosphate sodium (EMP) was first introduced in the early 1970s for the treatment of prostate cancer, when EMP was supposed to have the dual effect of estrogenic activity and cytotoxicity. For the following decades, it was used mainly in hormone-refractory cases, with a conventional dosage of 4-9 capsules/day, which showed a 30-35% objective response rate. However, a very limited number of cases have been reported that used EMP as a first-line monotherapy in the conventional dosage. One study showed a response rate of 82%, which is at least as effective as conventional estrogen (diethylstilbestrol; DES) monotherapy. Nevertheless, EMP was almost abandoned for the treatment of prostate cancer because of severe adverse side-effects, especially in the cardiovascular system and gastrointestinal tract. Recently, two facts have become evident. First, EMP interferes with cellular microtubule dynamics but does not show alkylating effects. Second, EMP is able to produce a complex with calcium when dairy products are taken concomitantly with EMP, resulting in a decrease in the absorption rate of EMP from the gut. Many clinical trials have been undertaken without warning against concomitant dairy product intake since the introduction of EMP. This fact will jeopardize almost all the clinical trials performed before 1990. It is considered that response rates have been underestimated and better results could have been obtained because side-effects decrease dose-dependently. Low-dose EMP monotherapy (2 capsules/day) has been performed infrequently in previously untreated advanced prostate cancer. The only large trial by the European Organization for Research and Treatment of Cancer in 1984 was biased in selecting patients. Nevertheless, the response rate of EMP is comparable to that of DES. In this study, the adverse side-effects of EMP were less than that of DES. Recently, a study was conducted at the University of Tokyo of 11 patients with advanced prostate cancer on

  19. Association between Insulin Monotherapy versus Insulin plus Metformin and the Risk of All-Cause Mortality and Other Serious Outcomes: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Sarah E Holden

    Full Text Available To determine if concomitant metformin reduced the risk of death, major adverse cardiac events (MACE, and cancer in people with type 2 diabetes treated with insulin.For this retrospective cohort study, people with type 2 diabetes who progressed to insulin with or without metformin from 2000 onwards were identified from the UK Clinical Practice Research Datalink (≈7% sample of the UK population. The risks of all-cause mortality, MACE and incident cancer were evaluated using multivariable Cox models comparing insulin monotherapy with insulin plus metformin. We accounted for insulin dose.12,020 subjects treated with insulin were identified, including 6,484 treated with monotherapy. There were 1,486 deaths, 579 MACE (excluding those with a history of large vessel disease, and 680 cancer events (excluding those in patients with a history of cancer. Corresponding event rates were 41.5 (95% CI 39.4-43.6 deaths, 20.8 (19.2-22.5 MACE, and 21.6 (20.0-23.3 cancer events per 1,000 person-years. The adjusted hazard ratios (aHRs for people prescribed insulin plus metformin versus insulin monotherapy were 0.60 (95% CI 0.52-0.68 for all-cause mortality, 0.75 (0.62-0.91 for MACE, and 0.96 (0.80-1.15 for cancer. For patients who were propensity-score matched, the corresponding aHRs for all-cause mortality and cancer were 0.62 (0.52-0.75 and 0.99 (0.78-1.26, respectively. For MACE, the aHR was 1.06 (0.75-1.49 prior to 1,275 days and 1.87 (1.22-2.86 after 1,275 days post-index.People with type 2 diabetes treated with insulin plus concomitant metformin had a reduced risk of death and MACE compared with people treated with insulin monotherapy. There was no statistically significant difference in the risk of cancer between people treated with insulin as monotherapy or in combination with metformin.

  20. Comparative efficacy of long-acting β2-agonists as monotherapy for chronic obstructive pulmonary disease: a network meta-analysis

    Directory of Open Access Journals (Sweden)

    Donohue JF

    2017-01-01

    Full Text Available James F Donohue,1 Keith A Betts,2 Ella Xiaoyan Du,2 Pablo Altman,3 Pankaj Goyal,4 Dorothy L Keininger,4 Jean-Bernard Gruenberger,4 James E Signorovitch5 1Department of Pulmonary Diseases and Critical Care Medicine, The University of North Carolina, Chapel Hill, NC, 2Analysis Group, Inc., Los Angeles, CA, 3Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 4Novartis Pharma AG, Basel, Switzerland; 5Analysis Group, Inc., Boston, MA, USA Purpose: Long-acting β2-agonists (LABAs have demonstrated efficacy in patients with COPD in clinical trials. The purpose of this study was to assess the comparative efficacy of all available dosages of all LABA monotherapies using a network meta-analysis.Methods: A systematic literature review identified 33 randomized controlled trials of LABA monotherapies (salmeterol 50 µg twice daily [BID]; formoterol 12 µg BID; indacaterol 75, 150, and 300 µg once daily [OD]; olodaterol 5 and 10 µg OD, and vilanterol 25 µg OD. Clinical efficacy was evaluated at 12 and 24 weeks in terms of trough forced expiratory volume in 1 second (FEV1, transition dyspnea index focal score, St George’s Respiratory Questionnaire total score, and rate of COPD exacerbations. The relative effectiveness of all LABA monotherapies was estimated by Bayesian network meta-analysis.Results: At 12 and 24 weeks, indacaterol 300 and 150 µg OD were associated with statistically significant improvement in trough FEV1 compared to all other LABA monotherapies; vilanterol 25 µg OD was superior to formoterol 12 µg BID. At 12 weeks, indacaterol 75 µg OD was associated with significant improvement in trough FEV1 compared to formoterol 12 µg BID and olodaterol (5 and 10 µg OD; salmeterol 50 µg BID was superior to formoterol 12 µg BID and olodaterol 5 µg OD. Indacaterol 300 µg OD was also associated with significant improvement in transition dyspnea index focal score compared to all other LABAs at 12 or 24 weeks. Indacaterol 150 µg OD had

  1. Systemic corticosteroid monotherapy for clinically diagnosed acute rhinosinusitis: a randomized controlled trial

    NARCIS (Netherlands)

    Venekamp, R.P.; Bonten, M.J.; Rovers, M.M.; Verheij, T.J.; Sachs, A.P.

    2012-01-01

    BACKGROUND: Patients with acute rhinosinusitis are frequently encountered in primary care. Although corticosteroids are being increasingly used for symptom control, evidence supporting their use is inconclusive. We conducted a randomized controlled trial to examine the effectiveness of systemic cort

  2. A COMPARATIVE STUDY OF REPAGLINIDE VERSUS GLIMEPIRIDE MONOTHERAPY IN TYPE - 2 DIABETES MELLITUS PATIENT

    Directory of Open Access Journals (Sweden)

    Sudheer

    2015-10-01

    Full Text Available Diabetes mellitus refers to a group of common metabolic disorder that share the phenotype of hyperglycaemia. Insulin resistance and abnormal insulin secretion is central to the development of type 2 DM the primary effect is controversial. Present study is a prospective study conducted to evaluate and compare the effect of glimepiride and Repaglinide in patient with type – 2 DM attending general medicine between O ct . 2013 to O ct . 2015. Both the drugs have same glycaemic profile and lipid profile but there is significant difference in the change in PPBs and HbA1c % but a study with more no of patient is required to evaluate it more effectively

  3. Neural correlates of delusional infestation responding to aripiprazole monotherapy: a case report

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    Ponson L

    2015-02-01

    Full Text Available Laura Ponson,1,2 Frédéric Andersson,1 Wissam El-Hage1,2 1Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR U930, Tours, France, 2CHRU de Tours, Clinique Psychiatrique Universitaire, Tours, France Background: The pathophysiology and appropriate pharmacological interventions for delusional infestation remain unknown.Case presentation: Here, we report a case of primary delusional infestation successfully treated with aripiprazole. We performed functional magnetic resonance imaging (fMRI to investigate brain structures and functional modifications. Before antipsychotic treatment, pre- versus post-treatment fMRI images revealed a marked increase in brain activation in the supplementary motor area (SMA.Conclusion: Our results highlight the efficacy and safety of aripiprazole in the treatment of delusional infestation and the possible role of SMA dysfunction in delusional infestation. Indeed, our results suggest that psychiatric improvement of delusional infestation is associated with normalization of brain activity, particularly in the SMA. Keywords: supplementary motor area, antipsychotics, fMRI

  4. [Topiramate in monotherapy or in combination as a cause of metabolic acidosis in adults with epilepsy].

    Science.gov (United States)

    Ruiz-Granados, Velvet J; Márquez-Romero, Juan M

    2015-02-16

    Objetivo. Determinar la frecuencia de acidosis metabolica y sus factores relacionados en pacientes tratados con topiramato solo o como adyuvante para el tratamiento de epilepsia. Pacientes y metodos. Analisis transversal de la gasometria arterial de pacientes epilepticos que recibieron topiramato durante 2010 en la clinica de epilepsia del Centro Medico Nacional 20 de Noviembre en Mexico. Se registraron datos clinicos concernientes a la epilepsia y su tratamiento, asi como de los sintomas comunes de acidosis metabolica. Resultados. Se estudiaron 32 adultos con epilepsia, quienes recibieron topiramato en monoterapia o en combinacion por lo menos durante un mes. Se encontro acidosis metabolica en todos los pacientes (HCO3 < 22 Eq/L); nueve tomaron solo topiramato y 23 tomaron por lo menos dos farmacos antiepilepticos (FAE). Todos los pacientes fueron asintomaticos. No se encontro correlacion entre los niveles de bicarbonato y la dosis del medicamento o la duracion del tratamiento. La dosis fue significativamente mayor en el grupo de monoterapia y el nivel de bicarbonato fue mas bajo en los pacientes que tomaban mas de un FAE. Conclusiones. El uso concomitante de FAE incrementa los efectos conocidos del topiramato sobre los niveles sericos de bicarbonato y la presencia de acidosis metabolica; estos efectos parecen ser independientes del numero de FAE utilizados.

  5. Efficacy and Safety of Switching Latanoprost Monotherapy to Bimatoprost Monotherapy or Combination of Brinzolamide and Latanoprost

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    Imasawa, Mitsuhiro; Tanabe, Joji; Kashiwagi, Fumiko; Kashiwagi, Kenji

    2016-01-01

    Purpose: To prospectively assess the efficacy and safety of switching to bimatoprost monotherapy or brinzolamide and latanoprost combination therapy in patients who had been receiving latanoprost monotherapy. Methods: A prospective, open-label study was conducted. Patients with primary open-angle glaucoma or ocular hypertension who had been receiving latanoprost monotherapy for three months or more were enrolled. Bimatoprost was substituted for latanoprost in one eye (BIM group), and brinzolamide was added to the latanoprost in the other eye (BRZ group) simultaneously. The patients underwent examinations at 6 weeks (visit 1) and 12 weeks (visit 2) after changing therapies. Subsequently, the treatments were returned to latanoprost monotherapy. The patients underwent another examination 6 weeks (visit 3) after the return to latanoprost. The parameters examined were intraocular pressure (IOP), conjunctival hyperemia, and corneal epithelial damage. Results: Twenty-six patients (13 men and 13 women) completed the protocol. Both groups showed a significant IOP reduction at visits 1 and 2 compared with the baseline, with a similar magnitude (BIM group: P = 0.016 at visit 1, P = 0.025 at visit 2, BRZ group: P = 0.0006 at visit 1, P = 0.028 at visit 2). The IOPs at the baseline and on visit 3 were similar in both groups (P = 0.7). The two groups showed no changes in either conjunctival hyperemia or corneal epithelial damage compared with the baseline. Conclusion: Bimatoprost monotherapy and brinzolamide adjunctive to latanoprost similarly reduced the IOP, with no additive adverse effects, compared with latanoprost monotherapy. PMID:27073587

  6. Treatment profiles in a Danish psychiatric university hospital department

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    Okkels, Niels; Mogensen, Rasmus Beyer; Crean, Lea Catherine

    2017-01-01

    -eight patients (94%) used psychotropic medication, 37 (19%) as monotherapy, and 148 (74%) in combination with non-pharmacological therapy. Ninety-seven (49%) had psychotherapy and 104 (52%) social support. Among inpatients, 21 (64%) had physical therapy, and 10 (30%) electroconvulsive therapy. In total, 163 (82......%) had non-pharmacological therapy. Fifty-two (26%) patients had monotherapy, and 148 (74%) polytherapy. Mean number of treatment modalities used per patient was 2.07 for all patients and 3.23 for inpatients. CONCLUSIONS: In this department, polytherapy including non-pharmacological modalities is applied...

  7. Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy:A randomized controlled trial

    Institute of Scientific and Technical Information of China (English)

    Giuseppe Alaimo; Vito Di Marco; Donatella Ferraro; Rosa Di Stefano; Salvatore Porrovecchio; Francesca D'Angelo; Vincenza Calvaruso; Antonio Craxì; Piero Luigi Almasio

    2006-01-01

    AIM:To assess the efficacy of different schedules of consensus interferon (CIFN) plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon (rIFN) monotherapy.METHODS:Forty-five patients (34 males and 11 females) with chronic hepatitis due to hepatitis C virus (HCV) genotype 1 who relapsed after a previous course of rIFN monotherapy were randomized to receive 9 μg CIFN three times per week for 52 wk (group A, n = 22)or 18 μg CIFN three times per week for 52 wk (group B, n = 23) in combination with ribavirin 800 to 1200 mg daily for 52 wk (according to body weight). Virological response was evaluated at week 24 (EVR), at the end of treatment (ETR) and at 76 wk (SVR).RESULTS:By intention-to-treat analysis, subjects in group A had an EVR in 35% of cases, an ETR in 35% and a SVR in 27.3% of cases. Subjects in group B had an EVR in 32% of cases, an ETR in 35% and a SVR in 26.1% of cases. Treatment was stopped because of adverse effects (mostly intolerance) in 15 patients (6 in group A and 9 in group B). IFN dose reduction was needed in 2 patients (1 in group A and 1 in group B).Ribavirin dose was reduced in 2 patients in group A and 1 in group B respectively. Among the 15 subjects who received at least 80% of the intended schedule, the rate of SVR was 80% (6 in group A and 6 in group B).CONCLUSION: CIFN in combination with ribavirin when given to HCV genotype 1 relapsers after rIFN monotherapy obtains an unsatisfactory rate of sustained viral clearance independently of dosage of the drug. This may be due to its scarce tolerability.

  8. Randomized trial of DRV/r or LPV/r QD monotherapy vs maintaining a PI/r-based antiretroviral regimen in persons with suppressed HIV replication

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    Carmela Pinnetti

    2014-11-01

    Full Text Available Introduction: PI/r monotherapy has been suggested as an attainable maintenance strategy in patients achieving stable HIV suppression in plasma. The objective of trial was to compare the virological outcome of two different PI/r QD monotherapy strategies (LPV/r or DRV/r with maintaining a triple PI/r-based ARV regimen. Material and Methods: Phase III, open-label, non-inferiority (−12% margin, randomized trial of HIV adults with HIV-RNA 100 cell/mm3, without previous PIs virological failure. Eligible patients were randomized to continue PI/r+2NRTIs (Arm A, to switch to LPV/r 800/200 mg QD monotherapy (Arm B, or to switch to DRV/r 800/100 mg QD monotherapy (Arm C. Primary endpoint was proportion of patients with plasma HIV-1 RNA <50 cp/mL (TLOVR at 48w by intent to treat (ITT analysis (missing/re-induction=failure. FDA snapshot and ITT switch-included analysis (ITT-SI were also used. In ITT-SI, patients who had <50 copies/mL at 96w were counted as successes even if they had confirmed HIV-RNA elevations and had subsequently successfully intensified by NRTI. Results: Due to slow recruitment, only 103 patients were included. No differences were observed between the three arms with respect to gender, age, HIV transmission, CD4 nadir and at screening. At randomization, 61 patients were receiving TDF/FTC (60%, 19 ZDV/3TC (18%, 8 ABV/3TC (8%, 75 LPV/r (73%, 13 ATV/r (13%, 4 DRV/r (4%. Differences in proportion of virological success by groups using Arm A as comparator according to FDA TLOVR were reported in Figure 1. Similar results were obtained by Snapshot analysis. Of 14 patients with virological failure, 8 patients restarted triple therapy with 2NRTI and 7/8 regained a VL <50 cp/mL over time. According to ITT-SI analysis, 96 week differences [95% CI] were −5.7 [−29.6; +18.2] in Arm B, and +19.6 [−1.6; +40.8] in Arm C. A GRT was performed in 6/14 patients (one not amplifiable; four without mutations; one showed E138A. Conclusions: Compared to

  9. Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3-T 1H-MRS Study.

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    Machado-Vieira, Rodrigo; Zanetti, Marcus V; Otaduy, Maria C; De Sousa, Rafael T; Soeiro-de-Souza, Marcio G; Costa, Alana C; Carvalho, Andre F; Leite, Claudia C; Busatto, Geraldo F; Zarate, Carlos A; Gattaz, Wagner F

    2017-02-01

    Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using proton magnetic resonance spectroscopy (H-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using H-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3-T H-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy. Twenty medication-free outpatients with short length of BD (80% drug-naive) in a current major depressive episode were matched with control subjects. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood level, 0.48 ± 0.19 mmol/L). Cingulate cortex lactate was measured before (week 0) and after lithium therapy (week 6) using H-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome. Subjects with BD depression showed a significantly higher CC lactate in comparison to control subjects. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared with baseline (P = 0.002). CC Lactate levels was associated with family history of mood disorders and plasma lithium levels. This is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium's therapeutic actions.

  10. Use of Fibrates Monotherapy in People with Diabetes and High Cardiovascular Risk in Primary Care: A French Nationwide Cohort Study Based on National Administrative Databases.

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    Ronan Roussel

    Full Text Available According to guidelines, diabetic patients with high cardiovascular risk should receive a statin. Despite this consensus, fibrate monotherapy is commonly used in this population. We assessed the frequency and clinical consequences of the use of fibrates for primary prevention in patients with diabetes and high cardiovascular risk.Retrospective cohort study based on nationwide data from the medical and administrative databases of French national health insurance systems (07/01/08-12/31/09 with a follow-up of up to 30 months.Lipid-lowering drug-naive diabetic patients initiating fibrate or statin monotherapy were identified. Patients at high cardiovascular risk were then selected: patients with a diagnosis of diabetes and hypertension, and > 50 (men or 60 (women, but with no history of cardiovascular events. The composite endpoint comprised myocardial infarction, stroke, amputation, or death.Of the 31,652 patients enrolled, 4,058 (12.8% received a fibrate. Age- and gender-adjusted annual event rates were 2.42% (fibrates and 2.21% (statins. The proportionality assumption required for the Cox model was not met for the fibrate/statin variable. A multivariate model including all predictors was therefore calculated by dividing data into two time periods, allowing Hazard Ratios to be calculated before (HR 540 of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR 540 = 1.73 (1.28-2.32.Fibrate monotherapy is commonly prescribed in diabetic patients with high cardiovascular risk and is associated with poorer outcomes compared to statin therapy.

  11. Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen-negative hepatitis B treatment:a meta-analysis of randomized controlled trials

    Institute of Scientific and Technical Information of China (English)

    YuShi; Yi-HuaWu; Zhe-YueShu; Wan-JunZhang; JunYang; ZhiChen

    2010-01-01

    BACKGROUND: It has been demonstrated that only a minority of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) obtain a sustained response after either interferon (IFN) or nucleos(t)ide analogue monotherapy. Therefore, combination therapy of drugs with synergistic antiviral effects was proposed to have a sustained response in these patients. We compared the effect and safety of lamivudine monotherapy and its combination with IFN including conventional interferon (CON-IFN) and pegylated interferon (PEG-IFN) for HBeAg-negative CHB patients. DATA  SOURCES: A group of three independent reviewers identified 9 eligible randomized controlled trials through electronic searches (MEDLINE, OVID, EMBASE, the Cochrane Library Clinical Trials Registry, and the Chinese Medical Database), manual searches, and contact with experts. Sustained virological and biochemical responses were defined as primary efficacy measures. We performed quantitative meta-analyses to assess differences between CON-IFN plus lamivudine combination and lamivudine monotherapy groups. RESULTS: No greater sustained virological and biochemical rates were found in patients receiving CON-IFN/lamivudine combination therapy [29.1% vs. 26.7%, odds ratio (OR)=0.98, 95% confidence interval (CI) 0.65-1.50, P=0.94, and 41.8%vs. 40.3%, OR=1.13, 95% CI 0.78-1.65, P=0.51, respectively], though a reduced YMDD mutation rate was achieved in the combination group [8.39% vs. 30.0%, OR=0.16, 95% CI 0.076-0.33, P CONCLUSIONS: Addition of CON-IFN to lamivudine did not improve treatment efficacy but suppressed YMDD mutation by lamivudine. Combination of PEG-IFN and lamivudine might increase the sustained response, and further clinical trials are needed for confirmation.

  12. High-intensity Statin Treatments in Clinically Stable Patients on Aspirin Monotherapy 12 Months After Drug-eluting Stent Implantation: A Randomized Study.

    Science.gov (United States)

    Im, Eui; Cho, Yun-Hyeong; Suh, Yongsung; Cho, Deok-Kyu; Her, Ae-Young; Kim, Yong Hoon; Lee, Kyounghoon; Kang, Woong Chol; Yun, Kyeong Ho; Yoo, Sang-Yong; Cheong, Sang-Sig; Shin, Dong-Ho; Ahn, Chul-Min; Kim, Jung-Sun; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2017-07-14

    Current guidelines on the treatment of blood cholesterol recommend continuous maintenance of high-intensity statin treatment in drug-eluting stent (DES)-treated patients. However, high-intensity statin treatment is frequently underused in clinical practice after stabilization of DES-treated patients. Currently, the impact of continuous high-intensity statin treatment on the incidence of late adverse events in these patients is unknown. We investigated whether high-intensity statin treatment reduces late adverse events in clinically stable patients on aspirin monotherapy 12 months after DES implantation. Clinically stable patients who underwent DES implantation 12 months previously and received aspirin monotherapy were randomly assigned to receive either high-intensity (40mg atorvastatin, n = 1000) or low-intensity (20mg pravastatin, n = 1000) statin treatment. The primary endpoint was adverse clinical events at 12-month follow-up (a composite of all death, myocardial infarction, revascularization, stent thrombosis, stroke, renal deterioration, intervention for peripheral artery disease, and admission for cardiac events). The primary endpoint at 12-month follow-up occurred in 25 patients (2.5%) receiving high-intensity statin treatment and in 40 patients (4.1%) receiving low-intensity statin treatment (HR, 0.58; 95%CI, 0.36-0.92; P = .018). This difference was mainly driven by a lower rate of cardiac death (0 vs 0.4%, P = .025) and nontarget vessel myocardial infarction (0.1 vs 0.7%, P = .033) in the high-intensity statin treatment group. Among clinically stable DES-treated patients on aspirin monotherapy, high-intensity statin treatment significantly reduced late adverse events compared with low-intensity statin treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01557075. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  13. Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.

    Science.gov (United States)

    Berna, F; Misdrahi, D; Boyer, L; Aouizerate, B; Brunel, L; Capdevielle, D; Chereau, I; Danion, J M; Dorey, J M; Dubertret, C; Dubreucq, J; Faget, C; Gabayet, F; Lancon, C; Mallet, J; Rey, R; Passerieux, C; Schandrin, A; Schurhoff, F; Tronche, A M; Urbach, M; Vidailhet, P; Llorca, P M; Fond, G

    2015-12-01

    The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

  14. Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis

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    Hu Peng

    2011-08-01

    Full Text Available Abstract Background Chronic hepatitis B virus (HBV infection represents a serious global health problem and resistance to lamivudine (LAM has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV and adding adefovir (ADV or tenofovir (TFV. At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB. The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance. Methods We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD in HBV DNA levels and safety were reviewed. Results Six eligible trials (451 patients in total were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated. Conclusions LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.

  15. Treatment response in relation to subthreshold bipolarity in patients with major depressive disorder receiving antidepressant monotherapy: a post hoc data analysis (KOMDD study

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    Park YM

    2016-05-01

    Full Text Available Young-Min Park,1 Bun-Hee Lee2 1Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, 2Department of Psychiatry, Seoul Eunpyeong Hospital, Seoul, Republic of Korea Background: The aim of this observational study was to determine whether subthreshold bipolarity affects treatment response and remission in patients with major depressive disorder receiving antidepressant (AD monotherapy over a 6-month follow-up period. Methods: Seventy-eight patients with major depressive disorder were stratified into two subgroups according to the presence of subthreshold bipolarity, identified using the Korean version of the Mood Disorder Questionnaire (K-MDQ, which classifies patients as positive for a screening of bipolarity based on the cutoff for the total K-MDQ score (ie, 7 points. They received AD monotherapy such as escitalopram, sertraline, paroxetine, or tianeptine for 6 months. The Beck Depression Inventory (BDI, Hamilton Depression Rating Scale (HAMD, Hamilton Anxiety Scale, and Beck Scale for Suicide Ideation were applied at baseline, 1 week, 3 weeks, 2 months, 3 months, and 6 months. Results: The mean HAMD, BDI, and Beck Scale for Suicide Ideation scores were higher in the bipolarity group than in the nonbipolarity group at 3 weeks. The mean BDI score was also higher in the bipolarity group than in the nonbipolarity group at 6 months. Evaluation of the ratio of improvement for each scale revealed different patterns of percentage changes between the two groups over the 6-month follow-up period. Furthermore, the response and remission rates (as assessed using BDI and HAMD scores were higher in the nonbipolarity group than in the bipolarity group, with the exception of HAMD scores at the 3-week follow-up time point. Conclusion: The findings of this study showed that depressed patients with bipolarity had a worse response to AD monotherapy than did those without bipolarity. Keywords: subthreshold bipolarity

  16. Alternating Acetaminophen and Ibuprofen versus Monotherapies in Improvements of Distress and Reducing Refractory Fever in Febrile Children: A Randomized Controlled Trial.

    Science.gov (United States)

    Luo, Shuanghong; Ran, Mengdong; Luo, Qiuhong; Shu, Min; Guo, Qin; Zhu, Yu; Xie, Xiaoping; Zhang, Chongfan; Wan, Chaomin

    2017-05-18

    No evidence can be found in the medical literature about the efficacy of alternating acetaminophen and ibuprofen treatment in children with refractory fever. Our objective was to assess the effect of alternating acetaminophen and ibuprofen therapy on distress and refractory fever compared with acetaminophen or ibuprofen as monotherapy in febrile children. A total of 474 febrile children with axillary temperature ≥38.5 °C and fever history ≤3 days in a tertiary hospital were randomly assigned to receive either (1) alternating acetaminophen and ibuprofen (acetaminophen 10 mg/kg per dose with shortest interval of 4 h and ibuprofen 10 mg/kg per dose with shortest interval of 6 h and the shortest interval between acetaminophen and ibuprofen ≥2 h; n = 158), (2) acetaminophen monotherapy (10 mg/kg per dose with shortest interval of 4 h; n = 158), or (3) ibuprofen monotherapy (10 mg/kg per dose with shortest interval of 6 h; n = 158). The mean Non-Communicating Children's Pain Checklist (NCCPC) score was measured every 4 h, and axillary temperatures were measured every 2 h. In total, 471 children were included in an intention-to-treat analysis. No significant clinical or statistical difference was found in mean NCCPC score or temperature during the 24-h treatment period in all febrile children across the three groups. Although the proportion of children with refractory fever for 4 h and 6 h was significantly lower in the alternating group than in the monotherapy groups (4 h: 11.54% vs. 26.58% vs. 21.66%, respectively [p = 0.003]; 6 h: 3.85% vs. 10.13% vs. 17.83%, respectively [p acetaminophen and ibuprofen can reduce the proportion of children with refractory fever, but if one cycle of alternating therapy cannot reduce febrile distress as defined by NCCPC score, two or more cycles of alternating therapy may have minimal to no clinical efficacy in some cases. The trial was registered with the Chinese Clinical Trial Registry as Chi

  17. Effect of candesartan monotherapy on lipid metabolism in patients with hypertension: a retrospective longitudinal survey using data from electronic medical records

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    Nishida Yayoi

    2010-08-01

    Full Text Available Abstract Background Studies focusing on the add-on effects of angiotensin II type 1 receptor blockers (ARBs other than their antihypertensive effect are receiving attention. However, the effects of prolonged administration of ARBs on lipid metabolism in clinical cases are unclear. Our aims were to survey the changes in plasma lipid profile in patients with hypertension over a one-year period, and to examine the correlations between these values and the time after the start of ARB monotherapy with candesartan. Methods We carried out candesartan monotherapy in patients with mild to moderate hypertension and examined the longitudinal changes in plasma lipid profile. Data from 405 patients for triglyceride (TG, 440 for total cholesterol (TC, 313 for high density lipoprotein cholesterol (HDL-C and 304 for low density lipoprotein cholesterol (LDL-C were obtained from the electronic medical records (EMRs in the Clinical Data Warehouse (CDW of Nihon University School of Medicine (NUSM. The inverse probability of treatment weighting (IPTW method (calculated from the inverse of the propensity score was used to balance the covariates and reduce bias in each treatment duration. Linear mixed effects models were used to analyse the relationship between these longitudinal data of blood examinations and covariates of patient sex, age, diagnosis of diabetes mellitus (DM and duration of candesartan monotherapy. Results Plasma HDL-C level was associated with sex, duration of treatment, and interaction of sex and treatment duration, but not with age or diagnosis of DM. HDL-C level was significantly decreased during the 6~9 months period (p = 0.0218 compared with baseline. TG and TC levels were associated with sex, but not with age, diagnosis of DM or treatment duration. LDL-C level was not associated with any covariate. Analysis of the subjects divided by sex revealed a decrease in HDL-C in female subjects (during the 6~9 months period: p = 0.0054, but not in male

  18. Ribavirin monotherapy for chronic hepatitis C

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise Lotte; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatitis C is a major cause of liver-related morbidity and mortality. A high proportion of patients never experience symptoms. Peginterferon plus ribavirin is the recommended treatment for chronic hepatitis C. However, ribavirin monotherapy may be considered for some patients....... OBJECTIVES: To assess the beneficial and harmful effects of ribavirin monotherapy for patients with chronic hepatitis C. SEARCH STRATEGY: We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until March 2009....... SELECTION CRITERIA: We included all randomised trials irrespective of blinding, language, or publication status comparing ribavirin versus no intervention, placebo, or interferon for chronic hepatitis C. DATA COLLECTION AND ANALYSIS: The primary outcome measures were serum sustained virological response...

  19. AN OBSERVATIONAL STUDY COMPARING SITAGLIPTIN TO METFORMIN AS A INITIAL MONOTHERAPY IN TYPE 2 DIABETES MELLITUS PATIENTS

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    Mohd

    2014-02-01

    Full Text Available AIM: An Observational study Comparing sitagliptin to metformin as an initial monotherapy in type 2 diabetes mellitus patients . METHOD : In this observational study we have selected 100 patients which divided into two groups; first group was on sitagliptin and second group was on metformin. The criterion for inclusion in the study was 1 Age group of 18 – 78 years 2 HbA1c of 6.5 – 9.0%. G roup A was started on sitagliptin 50 to 100 mg. Group B patients were started on Metformin , dosage of 500 mg once a day and the dose was increased to a of maximum of 2000 mg; and this study was done for 12 weeks. RESULTS AND STATISTICAL ANALYSIS : Group A c omprises 50 patients whose baseline FBS , PPBS , HbA1C was determined , Group B comprises 50 patients whose baseline FBS , PPBS , HbA1C was determined. The results of HbA1c obtained before and after the sitagliptin and metformin therapy was analyzed using SPSS V 20 software using paired t test and chi square analysis. It was observed that the mean baseline hba1c in the group A patients was 7.8 % and in group B was 7.95% whereas the mean HbA1c after 12 weeks of therapy was 7.44% and 7.73% respectively in the Grou p A and B. There was a significant decrease in Hba1c in both groups with t ( 49 value Group A (7.89 , p <0.001 Group B (3.48 , p 0.001. There was a significantly positive correlation (p<0.001 in two groups , A (r = 0.903 having higher positive correlation than group B (r= 0.748 , whereas the mean difference in Hba1c was higher for group A (0.36 compared to group B (0 , 21 suggesting a greater decrease in Hba1c with sitagliptin compared to metformin , as the mean difference was significant the effect size ( d was calculated it was observed that the effect size for group A was (d= 1.16 larger than group B (d= 0.49. Occurrence of Various symptoms such as nausea , headache and diarrhoea were seen in two groups and it was observed that nausea was greater in gro up A (16% compared to B (8% , the

  20. Chlorhexidine monotherapy with adjunctive topical corticosteroids for acanthamoeba keratitis

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    Firoozeh Rahimi

    2015-01-01

    Conclusion: Chlorhexidine is effective for monotherapy in AK and could be a good choice for initiating treatment. After the initial response to anti-Acanthamoeba agents, corticosteroids can be used as adjunctive therapy depending on the clinical condition.

  1. The AMBITION trial: tocilizumab monotherapy for rheumatoid arthritis.

    Science.gov (United States)

    Jones, Graeme

    2010-03-01

    Recent years have seen many exciting developments in the treatment of inflammatory arthritis. Tocilizumab (TCZ) is a compound that inhibits the IL-6 receptor. Following initial studies in Japan, it has been extensively studied in five multicenter clinical trials. This report concentrates on the Actemra Versus Methotrexate Double-blind Investigative Trial in Monotherapy (AMBITION), which compared TCZ monotherapy (8 mg/kg every 4 weeks) with methotrexate monotherapy over 24 weeks. TCZ was shown to be the first biologic agent that is superior to methotrexate across a whole range of clinical outcomes measures with a rapid onset of effect. Significant liver toxicity was less common in the TCZ group. However, increases in lipids and decreases in neutrophils and skin infections were more common in the TCZ arm. Long-term efficacy and safety follow-up is ongoing. This trial supports the use of TCZ as monotherapy and suggests it should be regarded as a first-line biologic therapy.

  2. Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

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    Maneeton Narong

    2012-09-01

    Full Text Available Abstract Background Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect. Objectives This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD. Only the randomized controlled trials (RCTs comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012. Data sources MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. Study eligible criteria, participants and interventions Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i depression severity, ii response rate, iii overall discontinuation rate, or iv discontinuation rate due to adverse events. No language restriction was applied. Study appraisal and synthesis methods All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs and weighted mean differences (WMDs with 95% confidence intervals (CIs were computed by using a random effect model. Results A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR. The pooled mean change scores of the Montgomery-Asberg Depression

  3. [A case of recurrent non-small cell lung cancer successfully treated with multiple modality therapies including S-1 monotherapy as fifth-line chemotherapy hospital)].

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    Yokosuka, Tetsuya; Kobayashi, Toshiko; Enomoto, Tatsuji; Takeda, Atsuya

    2013-09-01

    An 80-year-old man with no complaint was referred to our department because of high serum CEA level. He was diagnosed as non-small cell lung cancer(adenocarcinoma)of the left lower lobe(c-T2aN0M0, stage I B), and therefore the left lower lobectomy with lymph node dissection was performed. Pathological staging was p-T2aN1(#10)M0, stage II A, and EGFR mutation was negative. Adjuvant chemotherapy with UFT was started, but multiple hilar and mediastinal lymph nodes metastases soon appeared. Carboplatin(CBDCA)+paclitaxel(PTX), erlotinib, and docetaxel(DOC)were attempted after that, but the lymph nodes increased in size and the CEA level was up to 159.8 ng/mL. At about the same time, brain and pulmonary metastases were recognized. After radiation for the chest lymph nodes and stereotactic radiosurgery(SRS)for the brain metastasis, oral S-1 monotherapy was introduced. Soon after, the lymph nodes shrinked and the CEA level decreased. Also, the pulmonary metastasis disappeared. Although a right supraclavicular lymph node metastasis was resected during the clinical course, the S-1 monotherapy has been continued with no serious adverse event. He is well(PS 0)without recurrent lesion, and his serum CEA level is within the normal limit.

  4. Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

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    Qing-Yi Zeng

    Full Text Available To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs for monotherapy of adult patients with focal epilepsy in routine clinical practice.Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ, valproate (VPA, lamotrigine (LTG, topiramate (TPM, or oxcarbazepine (OXC as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD, were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.This study included 654 patients: CBZ (n=125, VPA (n=151, LTG (n=135, TPM (n=76, and OXC (n=167. The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]; TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74], and OXC was better than VPA (0.86 [0.78-0.96]. After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82] and OXC (LTG vs. OXC, 0.76 [0.63-0.93]; OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40].LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

  5. Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

    Science.gov (United States)

    Zeng, Qing-Yi; Fan, Tian-Tian; Zhu, Pan; He, Ru-Qian; Bao, Yi-Xin; Zheng, Rong-Yuan; Xu, Hui-Qin

    2015-01-01

    To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice. Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure. This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]). LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

  6. Cefepime Monotherapy is as Effective as Ceftriaxone Plus Amikacin in Pediatric Patients with Cancer and High-Risk Febrile Neutropenia: A Randomized Comparison

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    Carlos Alberto Pires Pereira

    2008-01-01

    Full Text Available The empirical use of antibiotic therapies is widely accepted in patients with fever and neutropenia during cancer chemotherapy. The use of intravenous monotherapy with broad-spectrum antibiotics in patients with high-risk of complications is an appropriate alternative. However, few data are available in pediatric patients. We conducted a prospective, randomized, open study in patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients were randomized to receive cefepime (CFP or ceftriaxone plus amikacin (CFT+AK. A total of 57 patients with 125 episodes of fever and neutropenia were evaluated (CFP, 62 and CFT + AK, 63 episodes. The mean neutrophil count at admission was 118.6 cells mm-3 (CFP and 107 cells mm-3 (CFT+AK. The mean duration of neutropenia was 9.0 days (CFP and 8.0 days (CFT+AK. Analyzing only the first episodes of each patient, CFP treatment was successful in 65.5% of the episodes and CFT+AK were successful in 64.3%. Overall rates of success with modification were 90% (CFP and 89% (CFT+AK. No major treatment-emergent toxicity was reported. Monotherapy with CFP seems to be as effective and safe as the combination of CFT+AK for initial empirical therapy in children and adolescents with NF.

  7. Monotherapy with anti-CD20 monoclonal antibody in a heart transplant recipient with sick sinus syndrome and posttransplantation lymphoproliferative disorder: a case report.

    Science.gov (United States)

    Yang, Hsiang-Yu; Ke, Hung-Yen; Hong, Gou-Jieng; Tsai, Yi-Ting; Lin, Chih-Yuan; Li, Chung-Yi; Tsai, Chien-Sung

    2009-10-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with an incidence of 0.8% to 20% in heart transplant (HTx) recipients, and standard treatment may be too toxic in some cases. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies and has been demonstrated effective in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Cardiotoxicity with CHOP remains a major concern for treating HTx recipients with PTLD, however. We present a case of an HTx recipient with sick sinus syndrome and PTLD who was successfully treated with rituximab alone, avoiding the cardiotoxicity of CHOP. The cardiotoxicity induced by CHOP should be kept in mind in HTx recipients with PTLD, especially when there is an existing heart problem in such recipients. Monotherapy with rituximab can be considered a safe choice.

  8. Combination therapy of fenofibrate and ursodeoxycholic acid in patients with primary biliary cirrhosis who respond incompletely to UDCA monotherapy: a meta-analysis

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    Zhang Y

    2015-05-01

    Full Text Available Yan Zhang,1,2,* Sainan Li,1,* Lei He,1 Fan Wang,1 Kan Chen,1 Jingjing Li,1 Tong Liu,1 Yuanyuan Zheng,1 Jianrong Wang,1,3 Wenxia Lu,1,3 Yuqing Zhou,1,4 Qin Yin,1,4 Yujing Xia,1 Yingqun Zhou,1 Jie Lu,1 Chuanyong Guo1 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 2Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 3The First Clinical Medical College of Nanjing Medical University, Nanjing, 4The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Background: Although the effectiveness of treatment with ursodeoxycholic acid (UDCA and fenofibrate for primary biliary cirrhosis (PBC has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out.Methods: A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches.Results: Six trials, which included 84 patients, were assessed. Combination therapy with UDCA and fenofibrate was more effective than UDCA monotherapy in improving alkaline phosphatase (mean difference [MD]: -90.44 IU/L; 95% confidence interval [CI]: -119.95 to -60.92; P<0.00001, gamma-glutamyl transferase (MD: -61.58 IU/L; 95% CI: -122.80 to -0.35; P=0.05, immunoglobulin M (MD: -38.45 mg/dL; 95% CI: -64.38 to -12.51; P=0.004, and triglycerides (MD: -0.41 mg/dL; 95% CI: -0.82 to -0.01; P=0.05. However, their effects on pruritus (odds ratio [OR]: 0.39; 95% CI: 0.09–1.78; P=0.23, total bilirubin (MD: -0.05 mg/dL; 95% CI: -0.21 to 0.12; P=0.58, and alanine aminotransferase (MD: -3.31 IU/L; 95% CI: -14.60 to 7.97; P=0.56 did not differ significantly. This meta-analysis revealed no significant differences in the incidence of adverse events (OR: 0.21; 95% CI: 0.03–1.25; P=0.09 between patients treated with

  9. Real‑life cost and cost‑effectiveness for tiotropium 18 μg od monotherapy in moderate and severe COPD patients: a 48‑month survey

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    Massimiliano Povero

    2014-06-01

    Full Text Available BACKGROUND: Tiotropium monotherapy enables a significant minimization of morbidity in COPD. OBJECTIVE: to evaluate and compare cost and cost‑effectiveness of tiotropium monotherapy administrated for 24 months (18 μg od in mild‑to‑moderate and severe chronic obstructive pulmonary disease (COPD. METHODS: Clinical outcomes (days in hospital; visits in general ward; cycles of systemic steroids; cycles of antibiotics and maintenance therapy drugs were evaluated in two groups of patients corresponding to predicted FEV1 baseline values ≤ 50% (A and > 50% (B from the Italian NHS perspective. In order to perform cost‑effectiveness analysis, FEV1 value, available for each patient, was converted in SGRQ score using a published multivariate linear model. Utilities were then obtained through the Ståhl equation. RESULTS: The comparison between 24 months of standard therapy and subsequent 24‑month period of tiotropium monotherapy showed that hospitalization cost, which represents the driving treatment cost, drops from 77% to 69% (A and from 67% to 33% (B of the total cost. Differently, maintenance therapy cost increased but the amount was more than offset by the savings accruing from the shortening of hospitalization. Furthermore, cost‑effectiveness results revealed a mean savings of about 216 € (A and 961 € (B other than a mean gain of 0.07 QALY (A and 0.02 QALY (B. Dominance of tiotropium (calculated only within patients completing treatment course revealed that in almost 29% (A and 36% (B of subjects tiotropium strategy is dominant while only in 2% (A and 7% (B of cases is associated to costs increment and worsening on quality of life. The dominance was systematic in severe COPD. Statistical analyses confirm such trend. CONCLUSIONS: Results of the present study suggest that tiotropium used as unique treatment in COPD systematically consents significant costs savings together with positive effects on evaluated quality. These effects prove

  10. Primary Cutaneous Cryptococcosis Treated with Debridement and Fluconazole Monotherapy in an Immunosuppressed Patient: A Case Report and Review of the Literature

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    Jennifer Wang

    2015-01-01

    Full Text Available Cryptococcus neoformans is an opportunistic yeast present in the environment. Practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with AIDS or other conditions of immunocompromise. There is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. We report a case of primary cutaneous cryptococcosis (PCC in a patient who had been immunosuppressed by chronic high-dose corticosteroid for the treatment of severe asthma. This case highlights the importance of early recognition of aggressive cellulitis that fails standard empiric antibiotic treatment in an immunocompromised patient. It also demonstrates successful treatment of PCC with a multispecialty approach including local debridement and fluconazole monotherapy.

  11. Early Relapse of Unresectable Gallbladder Cancer after Discontinuation of Gemcitabine Monotherapy Administered for 5 Years in a Patient Who Had Complete Response to the Treatment

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    Koichi Suyama

    2013-10-01

    Full Text Available The tumor shrinkage effect of gemcitabine is considered to be limited in cases of advanced gallbladder cancer, and there are few reports of complete response to gemcitabine therapy in patients with this cancer. Therefore, the treatment continuation strategy in these patients, after a complete response has been achieved, still remains to be established. Here, we present the case of a 77-year-old patient with unresectable gallbladder cancer, who after showing complete response to gemcitabine monotherapy administered for 5 years, showed early relapse within only 11 months of discontinuation of the drug. Thus, it is necessary to establish a suitable treatment continuation strategy for patients who show complete response to gemcitabine treatment.

  12. Refining criteria for selecting candidates for a safe lopinavir/ritonavir or darunavir/ritonavir monotherapy in HIV-infected virologically suppressed patients.

    Science.gov (United States)

    Gianotti, Nicola; Cozzi-Lepri, Alessandro; Antinori, Andrea; Castagna, Antonella; De Luca, Andrea; Celesia, Benedetto Maurizio; Galli, Massimo; Mussini, Cristina; Pinnetti, Carmela; Spagnuolo, Vincenzo; d'Arminio Monforte, Antonella; Ceccherini-Silberstein, Francesca; Andreoni, Massimo

    2017-01-01

    The primary objective of this study was to estimate the incidence of treatment failure (TF) to protease inhibitor monotherapies (PI/r-MT) with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r). A multicenter cohort of HIV-infected patients with viral load (VL) ≤50 copies/mL, who underwent a switch from any triple combination therapy to PI/r-MT with either LPV/r or DRV/r. VL was assessed in each center according to local procedures. Residual viremia was defined by any HIV-RNA value detectable below 50 copies/mL by a Real-Time PCR method. Standard survival analysis was used to estimate the rate of TF (defined by virological failure or interruption of monotherapy or reintroduction of combination therapy). A multivariable Cox regression analysis with automatic stepwise procedures was used to identify factors independently associated with TF among nadir and baseline CD4+ counts, residual viremia, time spent with HIV-RNA copies/mL before switch, history of virological failure, HCV co-infection, being on a PI/r and hemoglobin concentrations at baseline. Six hundred ninety patients fulfilled the inclusion criteria and were included in this analysis. Their median follow-up was 20 (10-37) months. By month 36, TF occurred in 176 (30.2%; 95% CI:25.9-34.5) patients. Only CD4+ nadir counts (adjusted hazard ratio [aHR] = 2.03 [95% CI: 1.35, 3.07] for counts ≤100 vs. >100 cells/μL) and residual viremia (aHR = 1.48 [95% CI: 1.01-2.17] vs. undetectable VL) were independently associated to TF. Residual viremia and nadir CD4+ counts <100 cells/μL should be regarded as the main factors to be taken into account before considering switching to a PI/r-MT.

  13. Effectiveness of bromocriptine monotherapy or combination treatment with clomiphene for infertility in women with galactorrhea and normal prolactin: A systematic review and meta-analysis.

    Science.gov (United States)

    Xue, Tao; Li, Shang-Wei; Wang, Yan

    2010-08-01

    Among women with unexplained infertility, 28% to 55% of patients with galactorrhea are normoprolactinemic. Bromocriptine, a common treatment for infertile women with hyperprolactinemia, has been used in the treatment of unexplained subfertility in women with galactorrhea and normal prolactin; however, its effectiveness and safety profile have never been determined. The aim of this study was to determine the relative effectiveness and safety profile of bromocriptine monotherapy or as an adjunct to clomiphene citrate in women with galactorrhea and normal prolactin levels. We conducted a search of the Cochrane Subfertility Review Group specialized register of controlled trials (March 2010), CENTRAL (The Cochrane Library, Issue 3, 2010), MEDLINE (1950-March 2010), EMBASE (1980-March 2010), and the China Biological Medicine Database (inception to March 2010) for relevant randomized controlled trials (RCTs) using the following terms: controlled, randomized, blinded, clinical trials, humans, galactorrhea, prolactin, bromocriptine, infertility, and subfertility. Additionally, reference lists of identified articles were searched for relevant articles. Of the 8 studies identified, 5 were excluded after full-text review for the following reasons: lack of a placebo group (2); difference in cointerventions (1); difference in end points (1); and systematic review (1). Therefore, 3 RCTs were included in this review. Bromocriptine administered in combination with clomiphene was found to be associated with a higher accumulative pregnancy rate compared with clomiphene monotherapy (fixed odds ratio [OR], 5.33; 95% CI, 2.62-10.88), and a lower miscarriage rate (fixed OR, 0.20; 95% CI, 0.05-0.76). Only 1 trial reported live birth as an outcome, and multiple pregnancy rates were poorly reported. Patient-reported adverse effects were mentioned in the studies, but reports were often incomplete. This review suggests the effectiveness of bromocriptine with clomiphene for infertility in

  14. Comparison of amlodipine and benazepril monotherapy to amlodipine plus benazepril in patients with systemic hypertension: a randomized, double-blind, placebo-controlled, parallel-group study. The Benazepril/Amlodipine Study Group.

    Science.gov (United States)

    Frishman, W H; RAM, C V; McMahon, F G; Chrysant, S G; Graff, A; Kupiec, J W; Hsu, H

    1995-11-01

    A single-blind, run-in, randomized, double-blind, parallel-group, placebo-controlled comparison trial was conducted to assess the safety and efficacy of low-dose amlodipine 2.5 mg daily, low-dose benazepril 10 mg daily, and the combination of the two drugs at the same doses used once daily in patients (n = 401) with mild to moderate (stages I and II) systemic hypertension. Both monotherapy regimens were shown to significantly reduce both systolic and diastolic blood pressure compared with baseline placebo values, and the combination regimen was shown to be superior in lowering systolic and diastolic blood pressure when compared with either of the monotherapy regimens. The combination therapy also resulted in a greater percentage of patients having successful clinical response in mean sitting diastolic blood pressure. The amlodipine and benazepril regimen was also shown to be associated with a similar incidence of adverse experiences as the active monotherapy or placebo regimens, although the group given combination therapy appeared to have a lower incidence of edema than the group given amlodipine alone. Low-dose amlodipine (2.5 mg) plus benazepril (10 mg) provides greater blood-pressure-lowering efficacy than either monotherapy, and has an excellent safety profile.

  15. A randomized clinical trial comparing long-term clopidogrel vs aspirin monotherapy beyond dual antiplatelet therapy after drug-eluting coronary stent implantation: Design and rationale of the Harmonizing Optimal Strategy for Treatment of coronary artery stenosis-Extended Antiplatelet Monotherapy (HOST-EXAM) trial.

    Science.gov (United States)

    Lee, Heesun; Koo, Bon-Kwon; Park, Kyung Woo; Shin, Eun-Seok; Lim, Sang Wook; Rha, Seung-Woon; Bae, Jang-Whan; Jeon, Dong Woon; Oh, Seok-Kyu; Hur, Seung-Ho; Kim, Bum-Su; Lee, Jung-Hee; Park, Tae-Ho; Lee, Nam Ho; Kim, Hyo-Soo

    2017-03-01

    Percutaneous coronary intervention (PCI) has been developed by drug-eluting stent (DES), but stent implantation has brought the issue of stent thrombosis and optimal antiplatelet therapy. Guidelines recommend at least 6- to 12 months of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor such as clopidogrel. Beyond DAPT after PCI with DES, however, there has been still a debate for antiplatelet regimen. Therefore, we report on the upcoming HOST-EXAM trial (NCT02044250), which will evaluate the efficacy and safety of aspirin and clopidogrel monotherapies beyond DAPT after DES implantation. The HOST-EXAM is a prospective, randomized, open-label, multicenter, comparative effectiveness trial, to compare between clopidogrel (75 mg once daily) and aspirin (100 mg once daily) as long-term antiplatelet agents. A total of 5,530 patients with no clinical events during combined antiplatelet therapy for 12±6 months after index PCI will be screened, enrolled, and randomized to either group (1:1 ratio) receiving antiplatelet monotherapy for 2 years. The primary endpoint will be the rate of clinical events defined as a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, or major bleeding at 24 months after randomization. The HOST-EXAM will be the first large-scale randomized controlled study to directly compare the efficacy and safety of long-term antiplatelet monotherapy beyond DAPT after DES implantation. This study will provide clinical evidence to establish optimal regimen for long-term antiplatelet therapy after DES implantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. A 6-Month, Double-Blind, Maintenance Trial of Lithium Monotherapy Versus the Combination of Lithium and Divalproex for Rapid-Cycling Bipolar Disorder and Co-Occurring Substance Abuse or Dependence

    Science.gov (United States)

    Kemp, David E.; Gao, Keming; Ganocy, Stephen J.; Rapport, Daniel J.; Elhaj, Omar; Bilali, Sarah; Conroy, Carla; Findling, Robert L.; Calabrese, Joseph R.

    2011-01-01

    Objective To assess whether combination treatment with lithium and divalproex is more effective than lithium monotherapy in prolonging the time to mood episode recurrence in patients with rapid-cycling bipolar disorder (RCBD) and comorbid substance abuse and/or dependence. Method A 6-month, double-blind, parallel group comparison was carried out in recently manic/hypomanic/mixed patients who had demonstrated a persistent bimodal response to combined treatment with lithium and divalproex. Subjects were randomly assigned to remain on combination treatment or to discontinue divalproex and remain on lithium monotherapy. Results Of 149 patients enrolled into the open-label acute stabilization phase, 79% discontinued prematurely (poor adherence: 42%; nonresponse: 25%; intolerable side effects: 10%). Of 31 patients (21%) randomly assigned to double-blind maintenance treatment, 55% relapsed (24% into depression and 76% into a manic/hypomanic/mixed episode), 26% completed the study, and 19% were poorly adherent or exited prematurely. The median time to recurrence of a new mood episode was 15.9 weeks for patients receiving lithium monotherapy and 17.8 weeks for patients receiving the combination of lithium and divalproex (p=NS). The rate of relapse into a mood episode for those receiving lithium monotherapy or the combination of lithium and divalproex was 56% and 53%, respectively. The rate of depressive relapse in both arms was 13%, while the rate of relapse into a manic, hypomanic, or mixed episode was 44% for lithium monotherapy and 40% for the combination of lithium and divalproex. Conclusion A small subgroup of patients in this study stabilized after six months of treatment with lithium plus divalproex. Of those who did, the addition of divalproex to lithium conferred no additional prophylactic benefit over lithium alone. Although depression is regarded as the hallmark of RCBD in general, these data suggest that recurrent episodes of mania tend to be more common in

  17. Zonisamide monotherapy for idiopathic epilepsy in dogs.

    Science.gov (United States)

    Chung, J Y; Hwang, C Y; Chae, J S; Ahn, J O; Kim, T H; Seo, K W; Lee, S Y; Youn, H Y

    2012-11-01

    To evaluate the efficacy of zonisamide as a monotherapy in dogs with idiopathic epileptic seizure. The experiment was conducted on 10 dogs with idiopathic epilepsy that were treated at the Seoul National University Hospital for Animals. A diagnosis was conducted based on physical and neurologic examination, complete blood count and chemical analysis, magnetic resonance imaging and cerebrospinal fluid analyses. Idiopathic epilepsy was diagnosed when all of these examinations were normal. Oral zonisamide was administrated to 10 dogs with idiopathic epilepsy at 5-15 mg/kg per os every 12 h to achieve a concentration of zonisamide in serum of 10-40 μg/mL. The frequency of seizures before and after the administration of zonisamide therapy was recorded and the concentrations of zonisamide in serum were measured. Six (60%) of the dogs were favourable responders to treatment, showing a ≥50% reduction in monthly frequency of seizures. Of the remaining four, two dogs did not show a reduction and the other two showed an increase in frequency of seizures. The mean dosage of zonisamide for favourable responders was 7.92 (SD 3.79) mg/kg, which was administered orally twice a day. Only one dog, which was one of the unfavourable responders in the whole study, experienced mild side effects. Among the dogs treated with oral zonisamide, 60% responded favourably. The effect of zonisamide as an anticonvulsant drug was demonstrated in this study. Based on these results, zonisamide monotherapy is effective in some dogs with idiopathic epilepsy.

  18. Retreatment of hepatitis C non-responsive to Interferon. A placebo controlled randomized trial of Ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378

    Directory of Open Access Journals (Sweden)

    Delwaide Jean

    2003-08-01

    Full Text Available Abstract Background Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published untill now. Methods One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%, HCV RNA above 2 × 106 copies/ml (55% and cirrhosis (38%. Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw and ribavirin (1000–1200 mg / day, 6 months ribavirin monotherapy (1000–1200 mg / day or 6 months ribavirin placebo. The study was double blinded for the ribavirin / placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis. Results At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin. During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin

  19. Levamisole Monotherapy for Oral Lichen Planus

    Science.gov (United States)

    Won, Tai Hyok; Park, Se Young; Kim, Bo Suk; Seo, Phil Seung

    2009-01-01

    Background Several different kinds of drugs have been used to treat chronic oral lichen planus (OLP). During the last decade, there have been several reports demonstrating success with levamisole and low dose prednisolone therapy for treating OLP. However, some OLP patients who have underlying diseases such as diabetes, hypertension and malignancy are unable to take steroids. Objective The aim of this study was to evaluate levamisole monotherapy for treating OLP. Methods Eleven patients who had OLP were treated with levamisole between 2005 and 2007. The levamisole was administered at a dose 50 mg thrice daily for three consecutive days, but then it was not administered on the following four days. Results After 2 weeks of treatment, 8 patients reported a partial response, 3 patients reported no response and no patients reported clearance of lesion. After 4 weeks of treatment, 6 patients reported a partial response, 3 patients reported no response and 2 patients reported clearance of lesion. Furthermore, after 3 months of treatment, 3 patients reported a partial response, 3 patients reported no response and 5 patients reported complete clearance of lesion. Clinical improvement was shown in 2 weeks, whilst the mean duration to achieve clearance of lesion was 6.2 weeks. Although 1 patient had mild itching, there were no significant adverse effects. Conclusion Levamisole monotherapy could be a successful and safe treatment option for patients with chronic OLP and who cannot take steroids. PMID:20523798

  20. [Case of MMF monotherapy for membranous nephropathy].

    Science.gov (United States)

    Kobayashi, Mioko; Kojima, Chiari; Sugiura, Hidekazu; Aoki, Asuka; Itabashi, Mitsuyo; Tsukada, Misao; Takei, Takashi; Uchida, Keiko; Nitta, Kosaku

    2010-01-01

    We report the case of a 58-year-old male patient who visited our hospital for the management of edema and proteinuria. He was diagnosed as having nephrotic syndrome, with serum total protein and albumin levels of 4.6 g/dL and 2.1 g/dL, respectively, and a urinary protein excretion level of 6.0 g/day. A percutaneous renal biopsy showed features of membranous glomerulonephritis, with capillary-wall granular deposits of IgG and C3 on immunofluorescence and subepithelial immune complex deposits on electron microscopy. No other secondary cause of membranous glomerulopathy was found even after extensive investigations. The patient was started on mycophenolate mofetil (MMF) monotherapy (1,500 mg/day), and 18 months after the start of this therapy, the proteinuria decreased to 0.5 g/day, with return to a normal serum albumin level. No digestive symptoms, kidney function worsening or increase in blood pressure were noted during treatment. These findings suggest that MMF monotherapy is effective and safe for the treatment of membranous nephropathy.

  1. Duloxetine and pregabalin: high-dose monotherapy or their combination? The "COMBO-DN study"--a multinational, randomized, double-blind, parallel-group study in patients with diabetic peripheral neuropathic pain.

    Science.gov (United States)

    Tesfaye, Solomon; Wilhelm, Stefan; Lledo, Alberto; Schacht, Alexander; Tölle, Thomas; Bouhassira, Didier; Cruccu, Giorgio; Skljarevski, Vladimir; Freynhagen, Rainer

    2013-12-01

    This multicentre, double-blind, parallel-group study in diabetic peripheral neuropathic pain addressed whether, in patients not responding to standard doses of duloxetine or pregabalin, combining both medications is superior to increasing each drug to its maximum recommended dose. For initial 8-week therapy, either 60 mg/day duloxetine (groups 1, 2) or 300 mg/day pregabalin (groups 3, 4) was given. Thereafter, in the 8-week combination/high-dose therapy period, only nonresponders received 120 mg/day duloxetine (group 1), a combination of 60 mg/day duloxetine and 300 mg/day pregabalin (groups 2, 3), or 600 mg/day pregabalin (group 4). Primary outcome (Brief Pain Inventory Modified Short Form [BPI-MSF] 24-hour average pain change after combination/high-dose therapy) was analyzed comparing combination (groups 2, 3 pooled) with high-dose monotherapy (groups 1, 4 pooled). Secondary end points included response rates, BPI-MSF severity items, and comparison of duloxetine and pregabalin in BPI-MSF average pain. Eight hundred four patients were evaluated for initial therapy and 339 for combination/high-dose therapy. There were no significant differences between combination and high-dose monotherapy regarding BPI-MSF average pain (mean change: combination: -2.35; high-dose monotherapy: -2.16; P = 0.370) and most secondary end points, which, however, consistently favoured combination therapy. Fifty-percent response rates were 52.1% for combination and 39.3% for high-dose monotherapy (P = 0.068). In exploratory analyses of the initial 8-week therapy uncorrected for multiple comparisons, 60 mg/day duloxetine was found superior to 300 mg/day pregabalin (P < 0.001). Both drugs and their combination were well tolerated. Although not significantly superior to high-dose monotherapy, combination therapy was considered to be effective, safe, and well tolerated. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  2. Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

    Directory of Open Access Journals (Sweden)

    Fei Zhu

    2015-01-01

    Full Text Available Background: It is important to choose an appropriate antiepileptic drug (AED to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ and valproate (VPA, have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM, oxcarbazepine (OXC, lamotrigine (LTG, or levetiracetam (LEV, were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07. CBZ exhibited the highest 12-month remission rate (85.55%, which was significantly higher than those of TPM (69.38%, P = 0.006, LTG (70.79%, P = 0.001, LEV (72.54%, P = 0.005, and VPA (73.33%, P = 0.002. CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%, rashes (7.76%, abnormal hepatic function (6.24%, and drowsiness (6.24%. Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first

  3. Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

    Institute of Scientific and Technical Information of China (English)

    Fei Zhu; Sen-Yang Lang; Xiang-Qing Wang; Xiao-Bing Shi; Yun-Feng Ma; Xu Zhang; Ya-Nan Chen

    2015-01-01

    Background: It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy.Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects.However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy.As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research.Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy.Methods: This is a retrospective, long-term observational study.Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated.Results: A total of 789 patients were enrolled.The median time of follow-up was 56.95 months.CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07).CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P =0.006), LTG (70.79%, P =0.001), LEV (72.54%,P =0.005), and VPA (73.33%, P =0.002).CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA.Overall,adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%),abnormal hepatic function (6.24%), and drowsiness (6.24%).Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure

  4. Combined versus monotherapy or concurrent therapy for treatment of thalassaemia.

    Science.gov (United States)

    Song, Ta-Shu; Hsieh, Yow-Wen; Peng, Ching-Tien; Chen, Tai-Lin; Lee, Hong-Zin; Chung, Jing-Gung; Hour, Mann-Jen

    2014-01-01

    A combined deferasirox (DFX) and deferiprone (DFP) treatment protocol for relieving thalassemia patients' iron-overload was designed and the pharmacokinetic study was performed by LC-MS/MS. For this open-label, randomized trial, eight patients were recruited and randomly allocated to different treatment regimens: (A) monotherapy with single oral dose of DFX 30 mg/kg, (B) monotherapy with DFP 80 mg/kg/day, twice daily, (C) combined therapy with DFX and DFP (DFX 30 mg/kg for first dose, DFP 40 mg/kg 7 hours later, and DFP 40 mg/kg after another 7 h) and (D) concurrent therapy with DFX 30 mg/kg and DFP 80 mg/kg. Descriptive statistics evaluated pharmacokinetic parameters, AUC0-t, AUC0-inf, Cmax, Tmax, T1/2 and MRT. A positive pharmacokinetic drug interaction was observed in combined therapy. In case of DFX, combined therapy tallied about 2-fold larger than monotherapy in AUC, 1.5-fold larger in Cmax, 1 h longer in Tmax, but 1 h shorter in T1/2. Regarding DFP, most such parameters of combined therapy concurred with monotherapy. Conversely, negative drug interaction was observed in concurrent therapy. With DFX, concurrent therapy attained 1.2- to 2.2-fold lower than monotherapy in AUC0-t and Cmax, 0.6-h shorter in Tmax, and 3-fold longer in T1/2. With DFP, concurrent therapy proved approximately 2-fold larger than monotherapy in AUC and Cmax, 2.5-fold longer in T1/2, and 1.4-fold longer in MRT. Follow-up of subjects' clinical examinations and subjective symptoms showed no adverse events. Our findings showed the combined therapy had advantages, safe, convenient and painless for patients, over the existing concurrent therapy with deferoxamine (DFO) and DFX. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. A phase II trial of erlotinib monotherapy for pretreated elderly patients with advanced EGFR wild-type non-small cell lung cancer.

    Science.gov (United States)

    Minemura, Hiroyuki; Yokouchi, Hiroshi; Azuma, Keisuke; Hirai, Ken-ichiro; Sekine, Satoko; Oshima, Kengo; Kanazawa, Kenya; Tanino, Yoshinori; Inokoshi, Yayoi; Ishii, Taeko; Katsuura, Yutaka; Oishi, Akio; Ishida, Takashi; Munakata, Mitsuru

    2015-06-05

    Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which is an effective treatment for patients with non-small cell lung cancer (NSCLC), especially those harboring activating EGFR mutations. A previous phase III trial suggested that patients with EGFR wild-type (EGFR-wt) NSCLC or elderly patients with disease progression after cytotoxic chemotherapy might benefit from erlotinib monotherapy. However, few studies have prospectively evaluated the efficacy and safety of second- or third-line erlotinib monotherapy for elderly patients with EGFR-wt advanced or recurrent NSCLC. Pretreated patients aged ≥70 years with EGFR-wt stage IIIB/IV NSCLC or those with postoperative recurrence were enrolled and received oral erlotinib at a dose of 150 mg/day until disease progression. Primary outcome was the objective response rate (ORR). Secondary end points included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and toxicity profile. This study was terminated early because of the results from a Japanese phase III trial (DELTA trial). Sixteen patients were enrolled between April 2010 and May 2013. The median age was 78 years (range 70-84 years). Six patients were female. Five patients had an Eastern Cooperative Oncology Group performance status of 0. Eleven (69%) patients had adenocarcinoma. Fifteen (94%) patients were treated with erlotinib as a second-line therapy. The ORR was 0% [95% confidence interval (CI) 0-17.1]. DCR was 56.3% (95% CI 33.2-76.9). The median PFS and OS were 1.7 months (95% CI 1.3-2.2) and 7.2 months (95% CI 5.6-8.7), respectively. The most commonly occurring adverse events included acneiform eruption (31.3%) and skin rash (25.0%). One patient developed grade 3 interstitial lung disease, which improved following steroid therapy. In pretreated elderly patients with advanced or recurrent EGFR-wt NSCLC, daily oral erlotinib was well tolerated; however, administration of the drug should not

  6. Levofloxacin plus metronidazole administered once daily versus moxifloxacin monotherapy against a mixed infection of Escherichia coli and Bacteroides fragilis in an in vitro pharmacodynamic model.

    Science.gov (United States)

    Hermsen, Elizabeth D; Hovde, Laurie B; Sprandel, Kelly A; Rodvold, Keith A; Rotschafer, John C

    2005-02-01

    Moxifloxacin has been suggested as an option for monotherapy of intra-abdominal infections. Recent data support the use of a once-daily metronidazole regimen. The purpose of this study was to investigate the activity of levofloxacin (750 mg every 24 h [q24h]) plus metronidazole (1,500 mg q24h) compared with that of moxifloxacin (400 mg q24h) monotherapy in a mixed-infection model. By using an in vitro pharmacodynamic model in duplicate, Escherichia coli and Bacteroides fragilis were exposed to peak concentrations of 8.5 mg of levofloxacin/liter q24h, 32 mg of metronidazole/liter q24h, and 2 mg for moxifloxacin/liter q24h for 24 h. The activities of levofloxacin, metronidazole, moxifloxacin, and levofloxacin plus metronidazole were evaluated against E. coli, B. fragilis, and E. coli plus B. fragilis. The targeted half-lives of levofloxacin, metronidazole, and moxifloxacin were 8, 8, and 12 h, respectively. Time-kill curves were analyzed for time to 3-log killing, slope, and regrowth. Pre- and postexposure MICs were determined. The preexposure levofloxacin, metronidazole, and moxifloxacin MICs for E. coli and B. fragilis were 0.5 and 1, >64 and 0.5, and 1 and 0.25 mg/liter, respectively. Levofloxacin and moxifloxacin achieved a 3-log killing against E. coli and B. fragilis in all experiments, as did metronidazole against B. fragilis. Metronidazole did not decrease the starting inoculum of E. coli. The area under the concentration-time curve/MIC ratios for E. coli and B. fragilis were 171.7 and 85.9, respectively, for levofloxacin and 26 and 103.9, respectively, for moxifloxacin. Levofloxacin plus metronidazole exhibited the fastest rates of killing. The levofloxacin and moxifloxacin MICs for B. fragilis increased 8- to 16-fold after the organism was exposed to moxifloxacin. No other changes in the postexposure MICs were found. Levofloxacin plus metronidazole administered once daily exhibited activity similar to that of moxifloxacin against the mixed E. coli and B

  7. Volumetric changes in the Basal Ganglia after antipsychotic monotherapy

    DEFF Research Database (Denmark)

    Ebdrup, B H; Nørbak, H; Borgwardt, S

    2013-01-01

    Introduction: Exposure to antipsychotic medication has been extensively associated with structural brain changes in the basal ganglia (BG). Traditionally antipsychotics have been divided into first and second generation antipsychotics (FGAs and SGAs) however, the validity of this classification has...... monotherapy. Material and Methods: We systematically searched PubMed for longitudinal MRI studies of patients with schizophrenia or non-affective psychosis who had undergone a period of antipsychotic monotherapy. We used specific, predefined search terms and extracted studies were hand searched for additional...

  8. Betahistine plus piracetam dual therapy versus betahistine monotherapy for peripheral vestibular vertigo: a confounder-corrected subanalysis of the OSVaLD study.

    Science.gov (United States)

    Melnikov, Oleg A; Lilenko, Sergey V; Nauta, Jos; Ouwens, Mario J N M

    2015-11-01

    This subanalysis compared the efficacy of betahistine plus piracetam dual therapy versus betahistine monotherapy using data from OSVaLD, a 3 month, open-label, observational study conducted in 2272 patients with peripheral vestibular vertigo. Of the 1898 patients included in the original efficacy population, 1076 were from countries where betahistine plus piracetam dual therapy was prescribed to >1 patient; 114 of these 1076 patients (11%) received the dual therapy and 567 (53%) were treated with betahistine monotherapy; these patients were selected for analysis. Efficacy was assessed using the Dizziness Handicap Inventory (DHI) total and subscale scores. Propensity-score matching was used to correct potential differences in patient baseline characteristics between treatment groups. In addition, a subgroup analysis evaluated 103 patients treated with betahistine because of insufficient efficacy with their existing treatment. In the propensity-score matched, total-population evaluation, improvements in the DHI total and subscale scores were numerically greater in the betahistine plus piracetam group (n = 88) versus the betahistine group (n = 89) (DHI total, -42.9 vs. -37.6, respectively; DHI physical, -12.1 vs. -10.4; DHI emotional, -13.5 vs. -13.2) and statistically significant for the DHI functional score (-17.3 vs. -14.0, respectively, p = 0.01). The percentage of patients with no impairment at final visit was 27% with betahistine and 47% with betahistine plus piracetam; odds ratio: 2.3, 95% confidence interval: 1.3-2.4 (p = 0.007). Similar results were obtained in the subgroup analyses for patients whose current vertigo treatment was insufficient. The overall incidence of adverse events was low and similar in both groups, and there were no discontinuations due to drug-related adverse events. By using propensity-score matching, which controls for potential heterogeneity in patient baseline characteristics and small patient numbers, the results of this analysis

  9. Safety and Efficacy of Trifluridine/Tipiracil Monotherapy in Clinical Practice for Patients With Metastatic Colorectal Cancer: Experience at a Single Institution.

    Science.gov (United States)

    Kotani, Daisuke; Shitara, Kohei; Kawazoe, Akihito; Fukuoka, Shota; Kuboki, Yasutoshi; Bando, Hideaki; Okamoto, Wataru; Kojima, Takashi; Doi, Toshihiko; Ohtsu, Atsushi; Yoshino, Takayuki

    2016-09-01

    The combination drug TAS-102 is a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, which prevents the degradation of trifluridine. The global phase III RECOURSE trial (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) demonstrated that TAS-102 prolonged the survival of patients with metastatic colorectal cancer (mCRC) whose disease progressed after standard therapies. TAS-102 was first approved in Japan in March 2014, and little is known about its safety and efficacy in clinical practice, especially for mCRC patients with previous regorafenib treatment. We investigated the safety and efficacy of TAS-102 monotherapy in clinical practice for patients with mCRC refractory to standard therapies who were treated from May 2014 to January 2015. A total of 55 patients received TAS-102. The Eastern Cooperative Oncology Group performance status was 0, 1, and 2 in 41.8%, 47.3%, and 10.9% of patients. Of the 55 patients, 32 (58.2%) had been treated with regorafenib before receiving TAS-102. The median progression-free survival and overall survival was 2.0 months and 5.3 months, respectively. Emergency hospitalization was required for 23.6% of the patients during TAS-102 treatment, although most of the events (76.9%) were disease-related. The most common grade 3 or 4 adverse events were neutropenia (41.8%), leukopenia (27.2%), anemia (23.6%), febrile neutropenia (5.5%), and fatigue (3.6%). The frequency of grade ≥ 3 events was not significantly increased among the patients who had compared with those who had not received regorafenib. The progression-free survival (median 2.1 vs. 2.0 months) and overall survival (median 6.2 vs. 4.7 months) were similar for the 2 subgroups. The safety and efficacy of TAS-102 monotherapy in clinical practice were maintained, irrespective of previous regorafenib treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Rate of relapse in multibacillary patients after cessation of long-course dapsone monotherapy supplemented by a final supervised single dose of 1500 mg of rifampin.

    Science.gov (United States)

    Cartel, J L; Naudin, J C

    1994-06-01

    When multidrug therapy was implemented in Senegal, 406 multibacillary (MB) patients who had been treated for more than 10 years by dapsone alone, and who had become clinically inactive and skin-smear negative, were released from treatment. Of these 406 patients, 298 were given a supervised single dose of 1500 mg of rifampin. Subsequently, 302 of them (229 who had been given rifampin and 73 who had not) were followed up by means of annual clinical and bacteriological examinations. Of the former 229 followed up for a mean period of 4.9 years, 34 patients relapsed (22 males and 12 females), giving a crude relapse rate of 15% and an overall risk of relapse of 3.1 per 100 patient-years. Of the latter 73 followed up for a mean period of 2.4 years, 5 relapsed (4 males and 1 female), giving a crude relapse rate of 6.8% and an overall risk of relapse of 2.9 per 100 patient-years. Such results, which are in agreement with those of a similar study conducted recently in Mali, indicate that the intake of a single dose of 1500 mg of rifampin by MB patients when they are released from long-course dapsone monotherapy does not result in a decrease of the relapse rate. Therefore, MB patients who have been treated with dapsone alone, even for long periods, should be put under multidrug therapy prior to their release from control.

  11. Comparative effectiveness of everolimus-based therapy versus endocrine monotherapy among postmenopausal women with HR+/HER2- metastatic breast cancer: a retrospective chart review in community oncology practices in the US.

    Science.gov (United States)

    Xie, Jipan; Hao, Yanni; Li, Nanxin; Lin, Peggy L; Ohashi, Erika; Koo, Valerie; Signorovitch, James E; Wu, Eric Q; Yardley, Denise A

    2015-06-01

    Everolimus-based therapy and endocrine monotherapy are used among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (mBC) whose disease progressed or recurred on a non-steroidal aromatase inhibitor (NSAI). However, limited evidence exists regarding the real-world comparative effectiveness of these agents. This retrospective chart review examined postmenopausal HR+/HER2- mBC patients in community-based oncology practices who received everolimus-based therapy or endocrine monotherapy (index therapy) as any line of therapy for mBC between 1 July 2012 and 15 April 2013 after NSAI failure. Time on treatment (TOT), progression-free survival (PFS), and time to chemotherapy (TTC) from index therapy initiation were compared using Kaplan-Meier analyses and Cox proportional hazards models adjusting for baseline characteristics. A total of 243 and 270 patients received everolimus-based therapy or endocrine monotherapy in a quota-based sample. Patients treated with everolimus-based therapy had a higher proportion of visceral metastases, high tumor burden, and use of prior chemotherapies for mBC. After adjusting for baseline characteristics, everolimus-based therapy was associated with significantly longer TOT (HR = 0.67, 95% CI: 0.51-0.87) and PFS (HR = 0.75, 95% CI: 0.57-0.98) than endocrine monotherapy. No significant difference was found between everolimus-based therapy and endocrine monotherapy in TTC (HR = 0.81, 95% CI: 0.52-1.27). Results stratified by line of therapy were generally consistent with the overall results. Limitations include recall and information bias with potentially absent or erroneous chart data, unobserved factors due to non-randomization, inability to measure outcome assessments paired with measuring outcomes prior to exposures, and potential patient selection bias associated with chart review. Among a nationwide sample of postmenopausal HR+/HER2- m

  12. Lamivudine monotherapy as a safe option for HIV-infected paediatric clients with adherence challenges: new evidence from a large South African cohort

    Directory of Open Access Journals (Sweden)

    Verena Linder

    2014-11-01

    Full Text Available Introduction: HIV-infected children in resource-poor settings comprise a unique population who require antiretroviral therapy (ART in careful consideration of social and structural barriers to compliance. Given these aggregate challenges and emerging research into “holding” treatment options, we investigated the efficacy of lamivudine monotherapy (LM as an alternative to more complex second and third line therapies. Methods: A retrospective review of all eligible LM events (=6 months from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: >200 cells/L, n=64; Group 2:=200cells/L, n=10. Study endpoints were defined as a decline of absolute CD4=200 cells/L (Group 1, WHO stage 3 or 4 event (Groups 1& 2, or initiation of second or third line (Groups 1 & 2. Results: Seventy-four eligible LM events were identified among 71 HIV-positive children (58% male; median age at LM 9.7 years and median LM duration 11.5 months. CD4 decreases and measured WHO stage 3 or 4 events did not yield overall significance between groups (Table 1. No deaths were recorded. Conclusions: LM offers a promising alternative approach to ART management in young patients with an absolute CD4 >200 cells/L pending availability and/or willingness to adhere to second or third line therapies. In more immunocompromised children, LM may be considered as a last option if either the child or caretaker has concerns about second or third line management, or has defaulted repeatedly.

  13. Virological efficacy of PI monotherapy for HIV-1 in clinical practice

    Science.gov (United States)

    El Bouzidi, Kate; Collier, Dami; Nastouli, Eleni; Copas, Andrew J.; Miller, Robert F.; Gupta, Ravindra K.

    2016-01-01

    Background Clinical trials of PI monotherapy indicate that most participants maintain viral suppression and emergent protease resistance is rare. However, outcomes among patients receiving PI monotherapy for clinical reasons, such as toxicity or adherence issues, are less well studied. Methods An observational study of patients attending an HIV treatment centre in London, UK, who had received PI monotherapy between 2004 and 2013, was conducted using prospectively collected clinical data and genotypic resistance reports. Survival analysis techniques were used to examine the times to virological failure and treatment discontinuation. Results Ninety-five patients had PI monotherapy treatment for a median duration of 126 weeks. Virological failure occurred during 64% of episodes and 8% of patients developed emergent protease mutations. We estimate failure occurs in half of episodes within 2 years following initiation. Where PI monotherapy was continued following virological failure, 68% of patients achieved viral re-suppression. Despite a high incidence of virological failure, many patients continued PI monotherapy and 79% of episodes were ongoing at the end of the study. The type of PI used, the presence of baseline protease mutations and the plasma HIV RNA at initiation did not have a significant impact on treatment outcomes. Conclusions There was a higher incidence of virological failure and emerging resistance in our UK clinical setting than described in PI monotherapy clinical trials and other European observational studies. Despite this, many patients continued PI monotherapy and regained viral suppression, indicating this strategy remains a viable option in certain individuals following careful clinical evaluation. PMID:27402006

  14. Idiopathic generalised epilepsies with 3 Hz and faster spike wave discharges: a population-based study with evaluation and long-term follow-up in 71 patients.

    Science.gov (United States)

    Siren, Auli; Eriksson, Kai; Jalava, Heli; Kilpinen-Loisa, Päivi; Koivikko, Matti

    2002-09-01

    For several years we have been following patients with intractable, childhood-onset idiopathic generalised epilepsies with > or = 3 Hz spike-wave discharges. Our need to find explanations for their intractability was the starting point for this study. We were interested in identifying characteristics, which would predict intractability; evaluating how these patients were treated and whether polytherapy was useful. We identified patients with > or = 3 Hz spike-wave discharges by reviewing EEG reports recorded between 1983 and 1992. Data were collected from medical records and through personal interviews. We identified 82 patients with tentative idiopathic generalised epilepsy. Eleven were excluded. Thirty-eight patients had childhood absence epilepsy, 18 had juvenile absence epilepsy, 13 had juvenile myoclonic epilepsy and two had eyelid myoclonia with absences: 89.5, 78, 38 and 0% of the patients in each group, respectively, had been seizure free for more than 2 years. Twenty percent of the patients had intractable seizures. All intractable patients with juvenile absence epilepsy had rhythmic, random eyelid blinking and generalised tonic-clonic seizures. A history of more than ten generalised tonic-clonic seizures was associated with intractability in juvenile myoclonic patients. Monotherapy with ethosuximide or valproate resulted in seizure control in 65% of patients. Seventeen patients (24%) were treated with polytherapy, six achieved remission. These six patients had childhood absence epilepsy and juvenile absence epilepsy. Positive outcome was found in childhood absence epilepsy and juvenile absence epilepsy. Intractable seizures were more frequent among patients with juvenile myoclonic epilepsy. None of them benefited from polytherapy with conventional anti-epileptic drugs.

  15. Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study.

    Science.gov (United States)

    Thierry, Antoine; Le Meur, Yannick; Ecotière, Laure; Abou-Ayache, Ramzi; Etienne, Isabelle; Laurent, Charlotte; Vuiblet, Vincent; Colosio, Charlotte; Bouvier, Nicolas; Aldigier, Jean-Claude; Rerolle, Jean-Philippe; Javaugue, Vincent; Gand, Elise; Bridoux, Frank; Essig, Marie; Hurault de Ligny, Bruno; Touchard, Guy

    2016-01-01

    Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654). © 2015 Steunstichting ESOT.

  16. Effect of combination therapy with thyroxine (T4) and 3,5,3'-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

    DEFF Research Database (Denmark)

    Nygaard, Birte; Jensen, Ebbe Winther; Kvetny, Jan

    2009-01-01

    the effect of combination therapy with thyroxine (T(4)) and T(3) versus T(4) monotherapy in patients with hypothyroidism on stable T(4) substitution. Study design Double-blind, randomised cross-over. Fifty micrograms of the usual T(4) dose was replaced with either 20 microg T(3) or 50 microg T(4) for 12...... weeks, followed by cross-over for another 12 weeks. The T(4) dose was regulated if needed, intending unaltered serum TSH levels. Evaluation Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods. Inclusion criteria......, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (P=0.002). Serum TSH remained unaltered between the groups as intended. CONCLUSION: In a study design, where morning TSH levels were unaltered between groups combination therapy...

  17. Ongoing HIV replication in cerebrospinal fluid under successful monotherapy

    NARCIS (Netherlands)

    M. Bierhoff (Marieke); C.A. Boucher (Charles); A. Fibriani (Azzania); R.W. ten Kate (Reinier)

    2013-01-01

    textabstractWe report a case of an HIV-infected patient who was successfully treated with ritonavir/lopinavir (r/LPV) monotherapy for several years. He presented with neurological symptoms and high HIV RNA levels in cerebrospinal fluid (CSF). Sequencing of the HIV from the CSF revealed mutations in

  18. Obstetric and birth outcomes in pregnant women with epilepsy: A hospital-based study

    Directory of Open Access Journals (Sweden)

    Noor Haslina Othman

    2013-01-01

    Full Text Available Introduction : In addition to changes in seizure frequency, pregnant women with epilepsy (WWE are at increased risk of complications during pregnancy or delivery. In the absence of a nationwide WWE registry, hospital-based studies may provide important information regarding current management and outcomes in these patients. Objectives: The aims of this study were to determine changes in seizure frequency, and pregnancy and birth outcomes among pregnant WWE. Materials and Methods: We conducted a retrospective review of medical records of pregnant patients with epilepsy, who obtained medical care (from 2006 to 2011 at one of the general hospitals in the North-Eastern State of Malaysia. Data were collected for seizure frequency before and during the pregnancy, concurrent medications, pregnancy complications, and neonatal outcomes. Results: We reviewed records of 25 patients with a total of 33 different pregnancies. All patients were treated with antiepileptic medications during their pregnancies, with 42% monotherapy and 58% polytherapy. Seizure frequency decreased in 5 (15.2%, increased in 18 (54.5% and unchanged in 10 (30.3% cases of pregnancies. Pregnancy complications were anemia, gestational diabetes mellitus, gestational hypertension, intrauterine growth retardation, premature rupture of membrane, and vaginal bleeding. Preterm deliveries were recorded in 11 (33.3% infants. Conclusion: In our setting, many patients were being on polytherapy during their pregnancies. This underscores the need for planned pregnancies so that antiepileptic medications can be optimized prior to pregnancy.

  19. Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

    Science.gov (United States)

    Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

    2016-01-01

    Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435). PMID:27282261

  20. Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy.

    Science.gov (United States)

    Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

    2016-11-15

    The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).

  1. Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution

    Science.gov (United States)

    Jonsson, Vanessa D.; Blakely, Collin M.; Lin, Luping; Asthana, Saurabh; Matni, Nikolai; Olivas, Victor; Pazarentzos, Evangelos; Gubens, Matthew A.; Bastian, Boris C.; Taylor, Barry S.; Doyle, John C.; Bivona, Trever G.

    2017-01-01

    The success of targeted cancer therapy is limited by drug resistance that can result from tumor genetic heterogeneity. The current approach to address resistance typically involves initiating a new treatment after clinical/radiographic disease progression, ultimately resulting in futility in most patients. Towards a potential alternative solution, we developed a novel computational framework that uses human cancer profiling data to systematically identify dynamic, pre-emptive, and sometimes non-intuitive treatment strategies that can better control tumors in real-time. By studying lung adenocarcinoma clinical specimens and preclinical models, our computational analyses revealed that the best anti-cancer strategies addressed existing resistant subpopulations as they emerged dynamically during treatment. In some cases, the best computed treatment strategy used unconventional therapy switching while the bulk tumor was responding, a prediction we confirmed in vitro. The new framework presented here could guide the principled implementation of dynamic molecular monitoring and treatment strategies to improve cancer control. PMID:28287179

  2. Treatment Compliance with Fixed-Dose Combination of Vildagliptin/Metformin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy: A 24-Week Observational Study

    Directory of Open Access Journals (Sweden)

    Grigorios Rombopoulos

    2015-01-01

    Full Text Available Objective. To evaluate the differences in treatment compliance with vildagliptin/metformin fixed-dose versus free-dose combination therapy in patients with type 2 diabetes mellitus (T2DM in Greece. Design. Adult patients with T2DM, inadequately controlled with metformin monotherapy, (850 mg bid, participated in this 24-week, multicenter, observational study. Patients were enrolled in two cohorts: vildagliptin/metformin fixed-dose combination (group A and vildagliptin metformin free-dose combination (group B. Results. 659 patients were enrolled, 360 were male, with mean BMI 30.1, mean T2DM duration 59.6 months, and mean HbA1c at baseline 8%; 366 patients were assigned to group A and 293 to group B; data for 3 patients was missing. In group A, 98.9% of patients were compliant with their treatment compared to 84.6% of group B. The odds ratio for compliance in group A versus B was (OR 18.9 (95% CI: 6.2, 57.7; P<0.001. In group A mean HbA1c decreased from 8.1% at baseline to 6.9% (P<0.001 at the study end and from 7.9% to 6.8% (P<0.001 in group B. Conclusions. Patients in group A were more compliant than patients in group B. These results are in accordance with international literature suggesting that fixed-dose combination therapies lead to increased compliance to treatment.

  3. Efficacy and tolerability of exenatide monotherapy in obese patients with newly diagnosed type 2 diabetes: a randomized, 26weeks metformin-controlled, parallel-group study

    Institute of Scientific and Technical Information of China (English)

    YUAN Ge-heng; SONG Wei-li; HUANG You-yuan; GUO Xiao-hui; GAO Yan

    2012-01-01

    Background Incretin-based therapies provide additional options for treating type 2 diabetes.We aimed to evaluate the efficacy and tolerability of exenatide monotherapy in obese patients with type 2 diabetes.Methods A 26-week,mefformin controlled,parallel-group study was conducted among antidiabetic drug-naive obese patients aged >18 years,and with type 2 diabetes.Participating patients were randomly assigned to receive exenatide or metformin treatments.Results Fifty-nine patients (age (50.5±8.6) years,body mass index (BMI) (30.2±1.6) kg/m2,and hemoglobin A1C (HbA1c (8.2±1.2)%) were enrolled in the study.Glucose control and weight reduction improved in both groups receiving treatment.HbA1c and oral glucose tolerance test (OGTT) 2 hour glycemia reduction with exenatide was superior to that obtained with mefformin ((-2.10±1.79)% vs.(-1.66±1.38)%,(-5.11±2.68) mmol/L vs.(-2.80±2.70) mmol/L,P <0.05).Fast plasma glucose (FPG) reduction was not significantly different between the two groups ((-1.8±2.0) mmol/L vs.(-1.6±1.7) mmol/L,P >0.05).Patients treated with exenatide achieved HbA1c of <7% (97% of patients) and <6.5% (79%)at end-point,vs.93% and 73% with metformin (P >0.05).Greater weight reduction was also achieved with exenatide ((-5.80±3.66) kg) than with metformin ((-3.81±1.38) kg,P <0.01).Homeostasis model assessment of beta-cell function (HOMA-B) was not significantly increased,but the insulinogenic index and HOMA for insulin sensitivity (HOMA-S) were greatly improved in the exenatide group (P <0.05).Nausea was the most common adverse effect in exenatide treatment (30% vs.8%; P <0.05),but most cases were of mild to moderate intensity.One case in the exenatide group was withdrawn earlrly because of severe nausea.Hypoglycemia events were often observed during the first 4 weeks,with 12%of patients in the exenatide and 3.2% in metformin groups,respectively (P <0.05).No incidents of severe hypoglycemia were

  4. Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy: a DBCG study.

    Directory of Open Access Journals (Sweden)

    Maria B Lyng

    Full Text Available PURPOSE: Despite the benefits of estrogen receptor (ER-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. EXPERIMENTAL DESIGN: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40. All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years and half had developed distant recurrence (median time-to-recurrence: 3.5 years. MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables. RESULTS: The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics. CONCLUSIONS: Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics.

  5. Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy: a DBCG study.

    Science.gov (United States)

    Lyng, Maria B; Lænkholm, Anne-Vibeke; Søkilde, Rolf; Gravgaard, Karina H; Litman, Thomas; Ditzel, Henrik J

    2012-01-01

    Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables. The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics. Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics.

  6. Difference in blood pressure response to ACE-Inhibitor monotherapy between black and white adults with arterial hypertension: a meta-analysis of 13 clinical trials.

    Science.gov (United States)

    Peck, Robert N; Smart, Luke R; Beier, Rita; Liwa, Anthony C; Grosskurth, Heiner; Fitzgerald, Daniel W; Schmidt, Bernhard M W

    2013-09-26

    Among African-Americans adults, arterial hypertension is both more prevalent and associated with more complications than among white adults. Hypertension is also epidemic among black adults in sub-Saharan Africa. The treatment of hypertension among black adults may be complicated by lesser response to certain classes of anti-hypertensive agents. We systematically searched literature for clinical trials of ACE-inhibitors among hypertensive adults comparing blood pressure response between whites and blacks. Meta-analysis was performed to determine the difference in systolic and diastolic blood pressure response. Further analysis including meta-regressions, funnel plots, and one-study-removed analyses were performed to investigate possible sources of heterogeneity or bias. In a meta-analysis of 13 trials providing 17 different patient groups for evaluation, black race was associated with a lesser reduction in systolic (mean difference: 4.6 mmHg (95% CI 3.5-5.7)) and diastolic (mean difference: 2.8 mmHg (95% CI 2.2-3.5)) blood pressure response to ACE-inhibitors, with little heterogeneity. Meta-regression revealed only ACE-inhibitor dosage as a significant source of heterogeneity. There was little evidence of publication bias. Black race is consistently associated with a clinically significant lesser reduction in both systolic and diastolic blood pressure to ACE-inhibitor therapy in clinical trials in the USA and Europe. In black adults requiring monotherapy for uncomplicated hypertension, drugs other than ACE-inhibitors may be preferred, though the proven benefits of ACE-inhibitors in some sub-groups and the large overlap of response between blacks and whites must be remembered. These data are particularly important for interpretation of clinical drug trials for hypertensive black adults in sub-Saharan Africa and for the development of treatment recommendations in this population.

  7. A prospective pilot study comparing combined intravitreal ranibizumab and half-fluence photodynamic therapy with ranibizumab monotherapy in the treatment of neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Williams PD

    2012-09-01

    Full Text Available Patrick D Williams,1 David Callanan,1 Wayne Solley,1 Robert L Avery,2 Dante J Pieramici,2 Tom Aaberg31Texas Retina Associates, Dallas, TX, 2California Retina Consultants and Research Foundation, Santa Barbara, CA, 3Retinal Associates, Grand Rapids, MI, USAPurpose: This prospective multi-center pilot study compares the use of half-fluence photodynamic therapy combined with ranibizumab with ranibizumab monotherapy for the treatment of neovascular age-related macular degeneration.Methods: All patients presenting with untreated subfoveal neovascular age-related macular degeneration were considered for inclusion. Patients were randomized to receive either ranibizumab with half-fluence photodynamic therapy or ranibizumab alone. Patients in the ranibizumab alone group were given three consecutive monthly ranibizumab injections and were followed monthly. They were treated with ranibizumab as needed, based on clinical discretion, using vision and optical coherence tomography. Patients in the combined group were given one same-day combined ranibizumab and half-fluence (25 j/cm2 photodynamic therapy treatment and were treated monthly as needed. Outcomes included changes in standardized visual acuity, optical coherence tomography foveal thickness, and percentage of as-needed injections to maintenance examinations.Results: Fifty-six out of 60 enrolled patients completed the twelve month primary outcome visit; this consisted of 27 patients receiving ranibizumab alone and 29 receiving combined treatment. The average age was 79.1 for the ranibizumab alone group and 79.3 for the combined group. The mean visual acuity in the ranibizumab alone group improved from 52.9 Early Treatment of Diabetic Retinopathy letters initially to 62.8 letters at twelve months. The mean visual acuity in the combined group improved from 49.2 letters to 51.8 letters at twelve months. The differences in visual acuity improvements were not statistically significant based on a two

  8. Gemcitabine mono-therapy versus gemcitabine plus targeted therapy in advanced pancreatic cancer: a meta-analysis of randomized phase III trials.

    Science.gov (United States)

    Ottaiano, Alessandro; Capozzi, Monica; De Divitiis, Chiara; De Stefano, Alfonso; Botti, Gerardo; Avallone, Antonio; Tafuto, Salvatore

    2017-03-01

    Prognosis of advanced pancreatic cancer is dismal and the novel targeted therapies, albeit successfully used to treat many advanced tumors, have shown modest results. We performed a meta-analysis in order to quantify the effect size on survival of adding targeted therapy to single agent gemcitabine. Randomized phase III trials comparing gemcitabine mono-therapy versus gemcitabine plus a targeted agent in first-line treatment of advanced pancreatic cancer designed on survival as primary outcome were selected. Search was done through Medline and the registry of the NIH. Keywords used for searching were 'pancreas', 'pancreatic', 'gemcitabine'. Study quality was assessed with MERGE criteria. Findings were depicted in classical Forest plots. Publication bias was evaluated by the construction of funnel plot. Nine studies met the meta-analysis inclusion criteria including 4564 patients. The target therapies were: erlotinib, cetuximab, rigosertib, elpamotide, bevacizumab, aflibercept, axitinib, masitinib and ganitumab. There was no statistically significant heterogeneity among the nine trials (p = 0.77). The hazard ratio (HR) of the pooled analysis was 0.998 (CI 95%: 0.932-1.068). Subgroup meta-analysis was also performed in anti-EGFR and anti-angiogenesis trials: the pooled HR were 0.94 (CI 95%: 0.705-1.175) and 1.055 (CI 95%: 0.913-1.197), respectively. The present meta-analysis does not show significant improvements in survival for targeted drugs in advanced pancreatic cancer. The possible reason of these results could be linked to the biology of pancreatic cancer as well as to the absence of predictive factors.

  9. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI).

    Science.gov (United States)

    Dewint, Pieter; Hansen, Bettina E; Verhey, Elke; Oldenburg, Bas; Hommes, Daniel W; Pierik, Marieke; Ponsioen, Cyriel I J; van Dullemen, Hendrik M; Russel, Maurice; van Bodegraven, Ad A; van der Woude, C Janneke

    2014-02-01

    To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD). Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with active perianal fistulising disease were enrolled. After adalimumab induction therapy (160/80 mg week 0, 2), patients received 40 mg every other week together with ciprofloxacin 500 mg or placebo twice daily for 12 weeks. After 12 weeks, adalimumab was continued. Follow-up was 24 weeks. Primary endpoint (clinical response) was defined as 50% reduction of fistulas from baseline to week 12. Secondary endpoints included remission (closure of all fistulas), Perianal Crohn's Disease Activity Index, Crohn's Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ). Clinical response was observed in 71% of patients treated with adalimumab plus ciprofloxacin and in 47% treated with adalimumab plus placebo (p=0.047). Likewise, remission rate at week 12 was significantly higher (p=0.009) in the combination group (65%) compared with adalimumab plus placebo (33%). Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 (p=0.005 and p=0.009, respectively). At week 24, no difference in clinical response between the two treatment groups was observed (p=0.22). No difference in safety issues was observed. Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD. However, after discontinuation of antibiotic therapy, the beneficial effect of initial coadministration is not maintained. ClinicalTrials.gov Identifier: NCT00736983.

  10. Factors influencing the use of tocilizumab as monotherapy in patients with rheumatoid arthritis in a real-life setting: results at 1 year of the ACT-SOLO study

    Science.gov (United States)

    Flipo, René-Marc; Maillefert, Jean-Francis; Chazerain, Pascal; Idier, Isabelle; Coudert, Mathieu; Tebib, Jacques

    2017-01-01

    Introduction Using a biologic disease-modifying antirheumatic drug (bDMARD) as monotherapy in clinical practice for patients with rheumatoid arthritis (RA) is common and recognised by health authorities although current guidelines recommend to combine them with conventional synthetic (cs)DMARDs. This study mainly aimed to search for real-life factors influencing the use of tocilizumab as MONO or in combination (COMBO). Methods In this non-interventional, prospective, national, multicentre study, data were collected every 3 months over a 12-month period in RA patients starting tocilizumab. The proportion of monotherapy patients was described, together with significant explicative factors. Results Among the 577 analysed patients recruited from January 2012 to August 2013 (228 monotherapy patients; 40%), 79% were women, mean RA duration was 11±9 years, previous RA treatments included bDMARDs and csDMARDs in 75% of cases and mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 5.2±1.3 at inclusion. Explicative factors for monotherapy were at least 65 years (OR=1.47, p=0.0485), no methotrexate within the two last years (OR=5.96, p<0.0001), past severe infection (OR=1.99, p=0.0272) and higher baseline DAS28-ESR (OR=1.22, p=0.0086). Regarding clinical results (DAS28-ESR, Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) low disease activity and remission; ACR20/50/70 and European League Against Rheumatism (EULAR) response; Health Assessment Questionnaire Disability Index (HAQ-DI) score), no relevant differences between monotherapy and combination patients were observed at 1 year. A total of 23 tocilizumab-treated patients (4%) experienced serious infections; no new safety signals were noted with no differences between groups. Conclusions ACT-SOLO confirms the high proportion of RA patients receiving tocilizumab as MONO in clinical practice. The study also showed that clinical results at 1 year were

  11. Study to determine the durability of glycaemic control with early treatment with a vildagliptin-metformin combination regimen vs. standard-of-care metformin monotherapy-the VERIFY trial: a randomized double-blind trial.

    Science.gov (United States)

    Del Prato, S; Foley, J E; Kothny, W; Kozlovski, P; Stumvoll, M; Paldánius, P M; Matthews, D R

    2014-10-01

    Durability of good glycaemic control (HbA1c ) is of importance as it can be the foundation for delaying diabetic complications. It has been hypothesized that early initiation of treatment with the combination of oral anti-diabetes agents with complementary mechanisms of action can increase the durability of glycaemic control compared with metformin monotherapy followed by a stepwise addition of oral agents. Dipeptidyl peptidase-4 inhibitors are good candidates for early use as they are efficacious in combination with metformin, show weight neutrality and a low risk of hypoglycaemia. We aimed to test the hypothesis that early combined treatment of metformin and vildagliptin slows β-cell deterioration as measured by HbA1c . Approximately 2000 people with Type 2 diabetes mellitus who were drug-naive or who were treated with metformin for less than 1 month, and who have HbA1c of 48-58 mmol/mol (6.5-7.5%), will be randomized in a 1:1 ratio in VERIFY, a 5-year multinational, double-blind, parallel-group study designed to compare early initiation of a vildagliptin-metformin combination with standard-of-care initiation of metformin monotherapy, followed by the stepwise addition of vildagliptin when glycaemia deteriorates. Further deterioration will be treated with insulin. The primary analysis for treatment failure will be from a Cox proportional hazard regression model and the durability of glycaemic control will be evaluated by assessing treatment failure rate and the rate of loss in glycaemic control over time as co-primary endpoints. VERIFY is the first study to investigate the long-term clinical benefits of early combination treatment vs. the standard-of-care metformin monotherapy with a second agent added by threshold criteria. © 2014 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  12. A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

    DEFF Research Database (Denmark)

    Branco, Jaime C; Zachrisson, Olof; Perrot, Serge

    2010-01-01

    This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.......This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population....

  13. Changes in salivary gland immunohistology and function after rituximab monotherapy in a patient with Sjogren's syndrome and associated MALT lymphoma

    NARCIS (Netherlands)

    Pijpe, J; van Imhoff, GW; Vissink, A; van der Wal, JE; Kluin, PM; Spijkervet, FKL; Kallenberg, CGM; Bootsma, H

    2005-01-01

    Objectives: To report the successful use of rituximab on salivary gland immunohistology and function in a patient with Sjogren's syndrome ( SS) and associated MALT lymphoma. Case report: The patient was a 42 year old woman with primary SS and associated MALT lymphoma located in the parotid gland and

  14. Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    William Insull Jr

    2010-11-01

    Full Text Available William Insull Jr1, Peter P Toth2, H Robert Superko3, Roopal B Thakkar4, Scott Krause4, Ping Jiang4, Rhea A Parreno4, Robert J Padley41Baylor College of Medicine and Methodist Hospital, Houston, Texas; 2University of Illinois College of Medicine, Peoria, Illinois; 3Celera, Alameda, California, Mercer University, Atlanta, Georgia; 4Abbott, Abbott Park, Illinois, USAObjective: To compare the effects of combination niacin extended-release + simvastatin (NER/S versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia.Patients and methods: Patients (n = 137 with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher’s exact test.Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B <80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003. NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022, small LDL (55% versus 45%; P = 0.011, very low-density lipoprotein (VLDL and total chylomicrons (63% versus 39%; P < 0.001, and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007 and VLDL (9.3% versus 0.1%; P < 0.001, compared with atorvastatin.Conclusion: NER/S treatment significantly improved apo A-I levels and the apo

  15. Effect of topical calcineurin inhibitors as monotherapy or combined with phototherapy for vitiligo treatment: a meta-analysis.

    Science.gov (United States)

    Dang, Yu-Ping; Li, Qiang; Shi, Fei; Yuan, Xiao-Ying; Liu, Wei

    2016-01-01

    Vitiligo is a common skin disease for which immunomodulating calcineurin inhibitors have been considered reasonable treatment. We searched the MEDLINE, Embase, and Cochrane central register of controlled trials databases for articles published prior to September 2014. Thirteen studies were included in the meta-analysis. After pooling the trials, we concluded that calcineurin inhibitors showed a better therapeutic effect on vitiligo than placebo, according to lesion report (RR = 2.62, 95%CI, 1.39-4.93, p = 0.003) and patient report (RR = 1.42, 95%, 0.87-2.31, p = 0.157). Subgroup analysis was performed to determine whether the combination with phototherapy was a source of heterogeneity. The trial sequence analysis indicated that the results of combined therapy by lesion report were reliable and conclusive. However, in the patient report trials, the frequency of lesions on the hand and foot was higher, and the effect of combined therapy was still not significant. Calcineurin inhibitors showed a better therapeutic effect than placebo in the treatment of vitiligo with phototherapy. However, the typical UV-resistant sites (i.e., hand and foot) were still difficult to cure even with combined therapy. Because of concerns about photocarcinogenesis, the clinical application of combined therapy should be explored with caution.

  16. Lipoplatin monotherapy: A phase II trial of second-line treatment of metastatic non-small-cell lung cancer.

    Science.gov (United States)

    Ravaioli, A; Papi, M; Pasquini, E; Marangolo, M; Rudnas, B; Fantini, M; Nicoletti, S V L; Drudi, F; Panzini, I; Tamburini, E; Gianni, L; Pasini, G

    2009-02-01

    Lipoplatin is a liposome encapsulated form of cisplatin. phase i studies on lipoplatin have demonstrated that the compound has an excellent toxicity profile. therefore we performed a phase ii trial in heavily pre-treated patients with advanced non-small-cell lung cancer (NSClC), performance status 0-2 in which the primary endpoint was response rate and secondary endpoints were safety and overall survival.Nineteen patients, average age 64 years old, with stage iV NSClC, were treated with lipoplatin 100 mg/m(2) every two weeks, as second line chemotherapy.We observed 1 partial remission (5.2%) and 3 stable diseases (15.9%). Time to progression (ttp) was 16 weeks and median overall survival (OS) was 31 weeks (7.2 months). We observed G1-G2 toxicity during chemotherapy, mainly gastrointestinal with nausea and vomiting (4 patients), asthenia (3 patients), mucositis (2 patients) and anemia (4 patients).Our phase ii study does not support a more extensive use of lipoplatin in phase III studies. An increase of dosage and a better selection of patients are mandatory to understand the real therapeutic activity of lipoplatin.

  17. A multicenter phase II study of TAS-102 monotherapy in patients with pre-treated advanced gastric cancer (EPOC1201).

    Science.gov (United States)

    Bando, Hideaki; Doi, Toshihiko; Muro, Kei; Yasui, Hirofumi; Nishina, Tomohiro; Yamaguchi, Kensei; Takahashi, Shunji; Nomura, Shogo; Kuno, Hirofumi; Shitara, Kohei; Sato, Akihiro; Ohtsu, Atsushi

    2016-07-01

    American phase I studies have reported that the recommended dose of TAS-102 (trifluridine/tipiracil) was 25 mg/m(2) twice a day (b.i.d.), although this schedule did not provide clinically relevant improvements in a phase II study of advanced gastric cancer (AGC). However, a pivotal phase III study revealed that TAS-102 at 35 mg/m(2) b.i.d. provided a clinically relevant improvement in overall survival (OS) among patients with metastatic colorectal cancer. Therefore, we re-evaluated the efficacy, safety, and pharmacokinetic parameters of TAS-102 at 35 mg/m(2) b.i.d among Japanese patients with AGC. All patients had undergone one or two previous chemotherapy regimens that contained fluoropyrimidine, platinum agents, and taxanes or irinotecan. The primary end-point target was a disease control rate (DCR) of ≥50% after 8 weeks of the 35 mg/m(2) b.i.d. schedule. Twenty-nine patients were assessable after completing the 35 mg/m(2) b.i.d. schedule. The investigator-determined DCR was 65.5% (95% confidence interval [CI], 45.7-82.1%) and the independent central review's DCR was 51.9% (95% CI, 31.9-71.3%); both results exceeded the primary end-point target. The median progression-free survival and OS were 2.9 months (95% CI, 1.1-5.3 months) and 8.7 months (95% CI, 5.7-14.9 months), respectively. The grade III/IV adverse events included neutropenia (69.0%), leucopaenia (41.4%), anaemia (20.7%), and anorexia (10.3%). No AGC-specific toxicities were detected. The 35 mg/m(2) b.i.d. dose of TAS-102 provided positive efficacy and an acceptable toxicity profile in patients with AGC. A randomised, double-blind, placebo-controlled, phase III study is ongoing to validate these findings. UMIN000007421. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind,placebo-controlled multicenter trial

    Institute of Scientific and Technical Information of China (English)

    YANG Hai-zhen; LIU Xiao-ming; TU Cai-xia; JI Su-zhen; SHEN Yang; ZHU Xue-jun; WANG Ke; JIN Hong-zhong; GAO Tian-wen; XIAO Sheng-xiang; XU Jin-hua; WANG Bao-xi; ZHANG Fu-ren; LI Chun-yang

    2012-01-01

    Background Tumor necrosis factor-α is a key mediator in the pathogenesis of psoriasis.Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-a.The purpose of this study was to validate the efficacy and safety of 5 mg/kg infiiximab therapy in Chinese patients with moderate to severe plaque psoriasis.Methods In this multicenter,double-blind,placebo-controlled trial,129 patients with moderate-to-severe psoriasis were randomized to the induction therapy (weeks 0,2 and 6) with infliximab 5 mg/kg (n=84) or placebo (n=45),followed with infliximab 5 mg/kg scheduled at week 14 and week 22 in the infliximab group,and infliximab 5 mg/kg scheduled at weeks 10,12 and 16 in the placebo group,The primary end point was the proportion of patients who achieved at least 75%improvement in Psoriasis Area and Severity Index (PASI 75 response rate) from baseline at week 10.Results At week 10,B1.0% of patients treated with infliximab (5 mg/kg) achieved a 75% or greater improvement compared with 2.2% of patients treated with placebo (P <0.001).A significant improvement in PASI,Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI),was seen from week 6 through week 14 in the infliximab group compared with the placebo group.Through week 22,PASI,PGA,DLQI were well maintained.The incidence of adverse events for the infliximab treatment group was slightly higher in comparison to the placebo treatment group during the first 10 weeks without statistical significance.However,there were 3 cases of tuberculosis that developed during the 26 weeks treatment with infliximal.Conclusions Infliximab treatment was effective as induction and maintenance treatments for Chinese patients with moderate to severe plaque psoriasis.Most drug-induced adverse events were mild to moderate,and well tolerated.Screening for tuberculosis is essential and prophylactic treatment should be given if necessary.

  19. Leukotriene receptor antagonists in monotherapy or in combination with antihistamines in the treatment of chronic urticaria: a systematic review

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    Gabriele Di Lorenzo

    2008-12-01

    Full Text Available Gabriele Di Lorenzo1, Alberto D’Alcamo1, Manfredi Rizzo1, Maria Stefania Leto-Barone1, Claudia Lo Bianco1, Vito Ditta1, Donatella Politi1, Francesco Castello1, Ilenia Pepe1, Gaetana Di Fede2, GiovamBattista Rini11Dipartimento di Medicina clinica e delle Patologie Emergenti; 2Dipartimento di Discipline Chirurgiche ed Oncologiche, Università degli Studi di Palermo, ItalyAbstract: In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, ie, leukotriene receptor antagonists and synthesis inhibitors, are a class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma and in rhinitis with asthma. We searched MEDLINE database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin (ASA or food additive hypersensitivity or with autoreactivity to intradermal serum injection (ASST when taken with an antihistamine but not in mild or moderate chronic idiopathic urticaria [urticaria without any possible secondary causes (ie, food additive or ASA and other NSAID hypersensitivity, or ASST]. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angioedema, and exercise-induced anaphylaxis.Keywords: chronic idiopathic urticaria, leukotriene receptor antagonists, montelukast, zafirlukast, antihistamine

  20. Gamma Knife Surgery as Monotherapy with Clinically Relevant Doses Prolongs Survival in a Human GBM Xenograft Model

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    Bente Sandvei Skeie

    2013-01-01

    Full Text Available Object. Gamma knife surgery (GKS may be used for recurring glioblastomas (GBMs. However, patients have then usually undergone multimodal treatment, which makes it difficult to specifically validate GKS independent of established treatments. Thus, we developed an experimental brain tumor model to assess the efficacy and radiotoxicity associated with GKS. Methods. GBM xenografts were implanted intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats were allocated to GKS, with margin doses of 12 Gy or 18 Gy, or to no treatment. Survival time was recorded, tumor sections were examined, and radiotoxicity was evaluated in a behavioral open field test. Results. In the first series, survival from the time of implantation was 96 days in treated rats and 72 days in controls (P<0.001. In a second experiment, survival was 72 days in the treatment group versus 54 days in controls (P<0.006. Polynuclear macrophages and fibrosis was seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed less mobility than GKS-treated animals in the open field test 4 weeks after treatment (P=0.04. Conclusion. GKS administered with clinically relevant doses prolongs survival in rats harboring GBM xenografts, and the associated toxicity is mild.

  1. Intravenous iron monotherapy for the treatment of non-iron-deficiency anemia in cancer patients undergoing chemotherapy: a pilot study

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    Abdel-Razeq H

    2013-08-01

    Full Text Available Hikmat Abdel-Razeq,1 Salah Abbasi,1 Iyad Saadi,1 Rana Jaber,2 Hazem Abdelelah1 1Department of Internal Medicine, 2Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan Background: Anemia in patients with cancer who are undergoing active therapy is commonly encountered and may worsen quality of life in these patients. The effect of blood transfusion is often temporary and may be associated with serious adverse events. Erythropoiesis-stimulating agents are not effective in 30%–50% of patients and may have a negative effect on overall survival. Aims: To assess the efficacy and feasibility of intravenous iron therapy in patients with cancer who have non-iron-deficiency anemia and who are undergoing treatment with chemotherapy without the use of erythropoiesis-stimulating agents. Methods: Adult patients with solid cancers and non-iron-deficiency anemia were included. Ferric sucrose at a dose of 200 mg was given in short intravenous infusions weekly for a total of 12 weeks. Hemoglobin level was measured at baseline, every 3 weeks, and 2 weeks after the last iron infusion (week 14. Adverse events related to intravenous iron were prospectively reported. Results: Of 25 patients included, 19 (76.0% completed at least three iron infusions and 14 (56.0% finished the planned 12 weeks of therapy. The mean hemoglobin level of the 25 patients at baseline was 9.6 g/dL (median, 9.9 g/dL; range, 6.9 g/dL10.9 g/dL. The mean change in hemoglobin level for the 15 patients who completed at least 9 treatments was 1.7 g/dL (median, 1.1 g/dL; range, −1.9 g/dL to 3.2 g/dL; it reached 2.1 g/dL (median, 1.3 g/dL; range, −0.2 g/dL to 4.6 g/dL; P = 0.0007 for the 14 patients who completed all 12 weekly treatments. Five (20.0% patients were transfused and considered as treatment failures. No treatment-related adverse events were reported. Conclusion: Intravenous iron treatment alone is safe and may reduce blood transfusion requirements and improve hemoglobin

  2. Response by sex to statin plus ezetimibe or statin monotherapy: A pooled analysis of 22,231 hyperlipidemic patients

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    Lin Jianxin

    2011-08-01

    Full Text Available Abstract Background Despite documented benefits of lipid-lowering treatment in women, a considerable number are undertreated, and fewer achieve treatment targets vs. men. Methods Data were combined from 27 double-blind, active or placebo-controlled studies that randomized adult hypercholesterolemic patients to statin or statin+ezetimibe. Consistency of treatment effect among men (n = 11,295 and women (n = 10,499 was assessed and percent of men and women was calculated to evaluate the between-treatment ability to achieve specified treatment levels between sexes. Results Baseline lipids and hs-CRP were generally higher in women vs. men. Between-treatment differences were significant for both sexes (all p Conclusions These results suggest that small sex-related differences may exist in response to lipid-lowering treatment and achievement of specified lipid and hs-CRP levels, which may have implications when managing hypercholesterolemia in women.

  3. Zinc mono-therapy in pre-symptomatic Chinese children with Wilson disease: a single center, retrospective study.

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    Kuerbanjiang Abuduxikuer

    Full Text Available BACKGROUND: There is no official consensus regarding zinc therapy in pre-symptomatic children with Wilson Disease (WD; more data is needed. OBJECTIVE: To investigate the safety and efficacy of zinc gluconate therapy for Chinese children with pre-symptomatic WD. METHODS: We retrospectively analyzed pre-symptomatic children receiving zinc gluconate in a single Chinese center specialized in pediatric hepatology. Short-term follow-up data on safety and efficacy were presented, and effects of different zinc dosages were compared. RESULTS: 30 children (21 males aged 2.7 to 16.8 years were followed for up to 4.4 years; 26 (87% children had abnormal ALT at baseline. Most patients (73% received higher than the currently recommended dose of elemental zinc. Zinc gluconate significantly reduced mean ALT (p<0.0001, AST (p<0.0001, GGT (p<0.0001 levels after 1 month, and urinary copper excretion after 6 months (p<0.0054. Mean direct bilirubin levels dropped significantly at 1 month (p = 0.0175, 3 months (p = 0.0010, and 6 months (p = 0.0036. Serum zinc levels gradually increased and reached a significantly higher level after 6 months (p<0.0026, reflecting good compliance with the therapy. Complete blood count parameters did not change throughout the analysis period. 8 children experienced mild and transient gastrointestinal side effects. The higher zinc dose did not affect treatment response and was not associated with different or increased side effects when compared to conventional zinc dose. CONCLUSION: In our cohort, zinc gluconate therapy for Chinese children with pre-symptomatic WD was effective, and higher initial dose of elemental zinc had the same level of efficacy as the conventional dose.

  4. Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis

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    Ismaila AS

    2015-11-01

    Full Text Available Afisi Segun Ismaila,1,2 Eline L Huisman,3 Yogesh Suresh Punekar,4 Andreas Karabis31Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Real World Strategy and Analytics, Mapi Group, Houten, the Netherlands; 4Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UKBackground: Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA efficacy in COPD are limited. This network meta-analysis (NMA assessed the relative efficacy of tiotropium 18 µg once-daily (OD and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD.Methods: A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1, transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use.Results: Twenty-four studies (n=21,311 compared LAMAs with placebo/each other. Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06–125.60]; 117.20 mL [104.50–129.90]; 114.10 mL [103.10–125.20]; 136.70 mL [104.20–169.20]; 24-week trough FEV1 (128.10 mL [84.10–172.00]; 135.80 mL [123.10–148.30]; 106.40 mL [95.45–117.30]; 115.00 mL [74.51–155.30]; 24-week St George’s Respiratory Questionnaire score (-4.60 [-6.76 to -2.54]; -3.14 [-3.83 to -2.45]; -2.43 [-2.92 to -1.93]; -4.69 [-7.05 to -2.31]; 24-week transitional dyspnea index score (1.00 [0.41–1.59]; 1.01 [0.79–1.22]; 0.82 [0.62–1.02]; 1.00 [0.49–1.51]; and 24-week rescue medication use (data not available; -0.41 puffs/day [-0.62 to -0.20]; -0.52 puffs/day [-0

  5. LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis

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    Rodrigo GJ

    2017-03-01

    important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively. LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001, but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively. LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]. Adverse event (AE incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99], including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]. LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87] and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]. Conclusion: The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD. These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. Keywords: LABA/LAMA combinations, COPD, LAMA, LABA/ICS, meta-analysis

  6. Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials

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    Maneeton N

    2016-01-01

    Full Text Available Narong Maneeton,1 Benchalak Maneeton,1 Pakapan Woottiluk,2 Surinporn Likhitsathian,1 Sirijit Suttajit,1 Vudhichai Boonyanaruthee,1 Manit Srisurapanont1 1Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Psychiatric Nursing Division, Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand Background: Some studies have indicated the efficacy of quetiapine in the treatment of generalized anxiety disorder (GAD.Objective: The purpose of this study was to systematically review the efficacy, acceptability, and tolerability of quetiapine in adult patients with GAD.Methods: The SCOPUS, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched in April 2015. All randomized controlled trials (RCTs of GAD were considered to be included in this meta-analysis. All RCTs of quetiapine in GAD patients providing endpoint outcomes relevant to severity of anxiety, response rate, remission rate, overall discontinuation rate, or discontinuation rate due to adverse events were included. The version reports from suitable clinical studies were explored, and the important data were extracted. Measurement for efficacy outcomes consisted of the mean-changed scores of the rating scales for anxiety, and response rate.Results: A total of 2,248 randomized participants in three RCTs were included. The pooled mean-changed score of the quetiapine-treated group was greater than that of the placebo-treated group and comparable to selective serotonin reuptake inhibitors (SSRIs. Unfortunately, the response and the remission rates in only 50 and 150 mg/day of quetiapine-XR (extended-release were better than those of the placebo. Their response and remission rates were comparable to SSRIs. The rates of pooled overall discontinuation and discontinuation due to adverse events of quetiapine-XR were greater than placebo. Only the overall discontinuation rate of quetiapine-XR at 50 and

  7. Complete response to nivolumab monotherapy in a treatment-naive, BRAF wild-type patient with advanced mucosal melanoma and elevated lactate dehydrogenase: a case report from a phase III trial.

    Science.gov (United States)

    Ascierto, Paolo A; Vanella, Vito; Grimaldi, Antonio Maria; Lucia, Festino; Palla, Marco; Simeone, Ester; Mozzillo, Nicola

    2016-11-01

    The anti-PD-1 agent, nivolumab, has been approved both as monotherapy and in combination with ipilimumab for the treatment of unresectable or metastatic melanoma in the USA and European Union. Here we present the case of a patient with treatment-naive, metastatic mucosal melanoma and baseline LDH approximately seven times the upper limit of normal. The patient was enrolled in a clinical trial (CheckMate 066) and achieved a partial response, followed by a durable complete response with nivolumab treatment. The patient's LDH levels were documented in each cycle and dropped markedly within 2 months, when partial response to treatment was already evident. LDH levels remained low for the rest of follow-up, consistent with the ongoing complete response to treatment. The patient experienced only mild immune-related adverse events (grade 1-2), which included vitiligo and rash. This exceptional response suggests that patients with high LDH levels at baseline should be considered for nivolumab treatment. LDH levels, however, should not serve as a predictive marker of response to nivolumab. Moreover, this case suggests the need to identify patients who will achieve the greatest benefit from nivolumab monotherapy.

  8. A Comparison of the Effectiveness of Sodium Stibogluconate Monotherapy to Sodium Stibogluconate and Paromomycin Combination for the Treatment of Severe Post Kala Azar Dermal Leishmaniasis in South Sudan – A Retrospective Cohort Study

    Science.gov (United States)

    Abongomera, Charles; Gatluak, Francis; Buyze, Jozefine; Ritmeijer, Koert

    2016-01-01

    Background Post-kala-azar dermal leishmaniasis (PKDL) is a common dermatological complication following successful treatment of Visceral Leishmaniasis (VL) caused by Leishmania donovani. PKDL presents as macular, papular, nodular or mixed skin rash on sun-exposed body parts. Patients are not ill unless there are complications due to mucosal involvement or ulceration. As PKDL in East Africa is typically self-healing, and treatment is long and with significant adverse events, only severe and complicated cases are treated. Studies to determine optimal treatment of PKDL are rare and based on small cohorts. Since 1989, Médecins Sans Frontières is treating severe PKDL within VL treatment programmes in South Sudan. Treatment was initially with sodium stibogluconate (SSG) monotherapy and since 2002 with a combination of SSG and paromomycin (PM). SSG monotherapy (20 mg/kg/day for a minimum of 30 days) was provided in primary health units, and the combination of PM (15 mg sulphate/kg/day for 17 days) plus SSG (30 mg/kg/day for a minimum of 17 days) was provided in secondary health facilities. Methodology/Principal Findings By retrospective analysis of routinely collected programme data we compared the effectiveness (outcome and treatment duration) of both regimens. Between 2002 and 2008, 422 patients with severe PKDL were treated; 343 received SSG and 79 SSG/PM combination. The cure rate was significantly better with combination treatment when compared to monotherapy (97% vs. 90%; odds ratio [OR], 7.6; p = 0.02), treatment duration was shorter (mean 34 days vs. 42 days; p = 0.005), and defaulter rate was lower (3% vs. 9%; OR, 0.3; p = 0.03). There was no significant difference in death rate (0% vs. 1%; p = 0.5). Conclusions/Significance We found that SSG/PM combination therapy resulted in more favourable outcomes than SSG monotherapy. An additional advantage is the lower cost of the combination therapy, due to the shorter treatment duration. A combination of SSG and PM is

  9. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis.

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    Elizabeth S Mearns

    Full Text Available When first line therapy with metformin is insufficient for patients with type 2 diabetes (T2D, the optimal adjunctive therapy is unclear. We assessed the efficacy and safety of adjunctive antidiabetic agents in patients with inadequately controlled T2D on metformin alone.A search of MEDLINE and CENTRAL, clinicaltrials.gov, regulatory websites was performed. We included randomized controlled trials of 3-12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins in patients experiencing inadequate glycemic control with metformin monotherapy (≥ 1500 mg daily or maximally tolerated dose for ≥ 4 weeks. Random-effects network meta-analyses were used to compare the weighted mean difference for changes from baseline in HbA1c, body weight (BW and systolic blood pressure (SBP, and the risk of developing hypoglycemia, urinary (UTI and genital tract infection (GTI.Sixty-two trials evaluating 25 agents were included. All agents significantly reduced HbA1c vs. placebo; albeit not to the same extent (range, 0.43% for miglitol to 1.29% for glibenclamide. Glargine, sulfonylureas (SUs and nateglinide were associated with increased hypoglycemia risk vs. placebo (range, 4.00-11.67. Sodium glucose cotransporter-2 (SGLT2 inhibitors, glucagon-like peptide-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced BW (range, 1.15-2.26 kg whereas SUs, thiazolindinediones, glargine and alogliptin/pioglitazone caused weight gain (range, 1.19-2.44 kg. SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased SBP (range, 1.88-5.43 mmHg. No therapy increased UTI risk vs. placebo; however, SGLT2 inhibitors were associated with an increased risk of GTI (range, 2.16-8.03.Adding different AHAs to metformin was associated with varying effects on HbA1c, BW, SBP, hypoglycemia, UTI and GTI which should impact clinician choice when selecting adjunctive

  10. A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder

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    Wang G

    2014-01-01

    Full Text Available Gang Wang,1 Alexander McIntyre,2 Willie R Earley,3 Shane R Raines,3 Hans Eriksson4 1Beijing Anding Hospital, Capital Medical University, Beijing, People's Republic of China; 2Department of Psychiatry, Penticton Regional Hospital, Penticton, BC, Canada; 3AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 4AstraZeneca R&D, Södertälje, Sweden Objectives: To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder (MDD. Patients and methods: This was a 10-week (8-week active treatment/2-week post-treatment randomized, double-blind, placebo- and active-controlled study (D1448C00004. Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery–Åsberg Depression Rating Scale [MADRS] total score at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement and remission (score ≤8; Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions – Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI global; and Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form percentage maximum total scores. Tolerability was assessed throughout. Results: A total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346] versus placebo (-15.61. There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37. Mixed-model repeated

  11. A clinical trial to compare the quality of life of HIV+ patients who start monotherapy with LPV/r versus continuing triple therapy with a boosted PI

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    J Pasquau

    2012-11-01

    Full Text Available Purpose of the study: Efficacy, toxicity and complexity of antiretroviral (ARV regimens may impact the quality of life (QoL. Since over the past years the simplification approach of lopinavir/ritonavir (LPV/r as monotherapy (MT has been shown to be non-inferior to triple therapy (TT in virological and immunological efficacy, the objective of this study was to compare several health- and treatment-related outcomes between both ARV strategies with LPV/r. Methods: A phase IV national, multicenter, controlled, randomized (2:1, open label, parallel-group clinical trial to compare the QoL in patients on ARV TT containing any boosted protease inhibitor (PI, undetectable viral load (VL< 50 cop/mL in the past 6 months and a CD4 nadir > 100 cells/µL, versus those who were simplified to LPV/r MT, for 24 weeks. QoL and health outcomes were evaluated by the Medical Outcomes Study HIV Health Survey (MOS-HIV and the five-dimensional EuroQol questionnaire (EQ-5D. Treatment satisfaction was assessed by the Spanish Questionnaire of Satisfaction with ARV Treatment (CESTA. Treatment adherence was assessed by the Spanish Multifactorial Adherence questionnaire (GEEMA and a visual analog scale (VAS. Tolerability, safety and virological and immunological efficacy at week 24 were also analyzed. Summary of results: 225 patients from 29 sites were enrolled (MT: 146, 64.5%; TT: 79, 35.1%. Mean age (years was 44.5 in MT and 45.2 in TT (p=0.745; mean duration (years from HIV infection was 13.4 in MT and 12.8 in TT (p=0.587 and 71% were male in both arms. 87.6% of patients completed correctly the study (MT: 88.4%; TT: 86.1%; p=0.674. Health and treatment outcomes evaluated at final study visit are shown in figure 1 1. At study end, 84.1% in MT and 89.6% in TT had undetectable VL (p=0.313 and mean CD4 count were 742.8 cells/µL in MT and 646.5 cells/µL in TT (p=0.060. There were no significant differences in the percentage of patients with virological failure at week 24 as

  12. Prevalence of Past and Reactivated Viral Infections and Efficacy of Cyclosporine A as Monotherapy or in Combination in Patients with Psoriatic Arthritis—Synergy Study: A Longitudinal Observational Study

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    Delia Colombo

    2014-01-01

    Full Text Available We have prospectively evaluated psoriatic arthritis (PsA patients for (1 seropositivity for former viral infections and seroconversion and (2 efficacy of cyclosporine A (CsA alone or in combination with other immunosuppressants in a time period of 12 months. Screening included HBV antibodies and antigens, HCV antibodies and RNA, HSV 1-2, HZV, EBV, and CMV IgG, and IgM, HHV-6 DNA, and HIV 1-2 antibodies. PsA was evaluated by the Psoriasis Area Severity Index (PASI, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, and the Visual Analogue Scale (VAS. At baseline, 126 (56% out of 225 evaluable patients had 2 or more seropositivities indicative of former infections, and 31 patients (13.8% presented seropositivity for HCV, HBV, HSV-1 and -2, HHV-6, EBV, or parvovirus infection; one of them, positive for HBAg, was treated with lamivudine, while the remaining 30 received no specific treatment. None of the 31 patients developed virus reactivation. A reduction (P<0.001 of PASI, BASDAI, and VAS scores was observed at 6 and 12 months. The treatment of PsA with CsA as monotherapy or in combination was safe and effective. In vitro experiments and clinical findings, including those from our study, suggest that CsA as monotherapy or in combination with biologics might be the treatment of choice in PsA HCV-positive patients.

  13. Potential implications of CYP3A4, CYP3A5 and MDR-1 genetic variants on the efficacy of Lopinavir/Ritonavir (LPV/r monotherapy in HIV-1 patients

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    Giulia Berno

    2014-11-01

    Full Text Available Introduction: Several genetic single nucleotide polymorphisms (SNPs in biotransformation enzymes (CYP3A4, CYP3A5 or transporter proteins (multidrug resistance MDR1 gene product, P-gp are involved in PI metabolism so that PI pharmacokinetics is characterized by a large inter-individual variability. The aim of this study was: (i to develop an in-house PCR/direct sequencing, based on DNA purification of full-length CYP3A4 and CYP3A5 genes (SNPs and MDR1 C3435T variant; (ii to investigate association of CYP3A4 and CYP3A5 reported or unreported genetic polymorphisms and MDR1-C3435T (CC homozygote, CT heterozygote, TT homozygote with clinical outcome of HIV-1 infected subjects treated with PI. Methods: Overall, 39 HIV-1 infected patients receiving boosted Lopinavir (LPV/r monotherapy after virological suppression were genotyped and analyzed through PCR and direct sequencing of full-length CYP3A4 and CYP3A5 gene sequences (1 and MDR1 gene (C3435T. CD4+T-cell counts and plasma viral load were analyzed before and after LPV/r initiation; LPV/r therapeutic drug monitoring (TDM was determined at 12-hours. Results: LPV/r TDM (ng/ml did not show significant differences among CYP3A4 or CYP3A5 SNPs, although a mean lower level of LPV/r was associated with detection of several SNPs: CYP3A5*3 rs776746; CYP3A5 rs28365088, CYP3A5 rs15524, CYP3A4 rs2687116, and a not already described polymorphism CYP3A4 nt20338. In follow-up analysis, <90% adherence was the main factor associated with virological failure of LPV/r monotherapy (83.3% of failure vs 34.4%, p<0.001 at log-rank test. Adjusting for adherence, the detection of a single CYP3A5*3 rs776746 and CYP3A5 rs15524 SNPs was associated with higher probability of LPV/r monotherapy failure (p<0.01, and in general, detection of any CYP3A5 SNP was associated with failure (26.2% vs 58.3%, p=0.067. No-association with detection of any CYP3A4 SNPs was found. MDR1 TT variants showed significant lower frequency of treatment

  14. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients.

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    Damiano Gullo

    Full Text Available CONTEXT: Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients. OBJECTIVE: To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. DESIGN: Retrospective study. SETTING: Academic hospital. PATIENTS: 1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls. MEASUREMENTS: TSH, FT4 and FT3 concentrations by immunoassays. RESULTS: FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients. CONCLUSIONS: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.

  15. Successful monotherapy of pemphigus vegetans with minocycline and nicotinamide.

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    von Köckritz, A; Ständer, S; Zeidler, C; Metze, D; Luger, T; Bonsmann, G

    2017-01-01

    Pemphigus vegetans is a rare variant of pemphigus vulgaris, accounting for 1-2% of all pemphigus diseases. Systemic corticosteroids are the therapy of first choice in combination with immunosuppressants as steroid-sparing agents. To highlight the exceptional but successful use of minocycline/nicotinamide monotherapy in pemphigus vegetans. A review of the literature to date about pemphigus vegetans with special emphasis on therapy was performed. Due to its rarity, multiple anecdotal reports without long-term follow-up are available and prospective controlled trials are lacking. Only one retrospective study from Tunisia includes 17 patients with pemphigus vegetans. We present a 76-year-old woman with pemphigus vegetans achieving complete response to a minocycline/nicotinamide monotherapy at onset and at relapse of the disease. Treatment has been discontinued after repeated direct immunofluorescence (DIF) of previously affected normal skin and anti-desmoglein 3 antibodies had become negative. In addition, DIF of previously involved oral mucosa was negative. During long-term follow-up clinical remission has been maintained for more than 5 years. Up to now, negative results of serial performed indirect immunofluorescence and desmoglein ELISA testing also predict immunological remission. In our patient and in a case with oesophageal involvement, published more than 20 years ago, clearly the benefit of minocycline/nicotinamide monotherapy was demonstrated. We propose to consider minocycline/nicotinamide as first-line monotherapy in pemphigus vegetans, especially in elderly patients with comorbidities and contraindications to standard therapy, as it avoids the toxicities of systemic corticosteroids and immunosuppressants. © 2016 European Academy of Dermatology and Venereology.

  16. A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U;

    2001-01-01

    Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function. Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment, but it is not known how an ACE inhibitor compares to treatment...... with a calcium channel blocker or to treatment with a combination of these drugs. The aim of the study was to evaluate the rate of decline in GFR in patients with chronic renal failure and hypertension treated with isradipine and spirapril as monotherapy and in combination....

  17. Comparative evaluation of glipizide and fenugreek (Trigonella foenum-graecum seeds as monotherapy and combination therapy on glycaemic control and lipid profile in patients with type 2 diabetes mellitus

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    Amandeep Singh

    2016-06-01

    Conclusions: Monotherapy with fenugreek produced significant improvement in glycaemic control and dyslipidaemia. Glipizide monotherapy was more efficacious in controlling FBG and HbA1c levels than fenugreek monotherapy or in combination with fenugreek; glipizide monotherapy had no effect on lipid profile whereas fenugreek monotherapy was more efficacious in controlling dyslipidaemia than in combination with glipizide. Both drugs as monotherapy or in combination were well-tolerated by the patients. [Int J Basic Clin Pharmacol 2016; 5(3.000: 942-950

  18. The burden of chronic obstructive pulmonary disease associated with maintenance monotherapy in the UK

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    Edwards SC

    2016-11-01

    Full Text Available Susan C Edwards,1 Sian E Fairbrother,2 Anna Scowcroft,3 Gavin Chiu,4 Andrew Ternouth,3 Brian J Lipworth5 1Department of Market Access Pricing & Outcomes Research, 2Department of Medical Affairs - Respiratory, 3Department of Market Access, 4Department of Prescription Medicine - Respiratory, Boehringer Ingelheim, Bracknell, UK; 5Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK Background: This study characterized a cohort of chronic obstructive pulmonary disease (COPD patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization.Methods: Data were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting β2-adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013 or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both. A minimum of four consecutive prescriptions and 6 months on continuous monotherapy were required. Patients <50 years old at first COPD diagnosis or with another significant respiratory disease before starting monotherapy were excluded. Disease burden was evaluated by measuring patients’ rate of face-to-face interactions with a health care professional (HCP, COPD-related exacerbations, hospitalizations, and referrals.Results: A cohort of 8,811 COPD patients (95% Global initiative for chronic Obstructive Lung Disease stage A/B on maintenance monotherapy was identified between 2002 and 2013; 45% of these patients were still on monotherapy by the end of the study. Median time from first COPD diagnosis to first monotherapy prescription was 56 days, while the median time on

  19. Long-term levetiracetam monotherapy for partial epilepsy in adults

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    P. N. Vlasov

    2012-01-01

    Full Text Available The paper analyzes the efficiency of 3-year monotherapy with levetiracetam (LTC (keppra in 143 patients aged 16—73 years with partial epilepsy. LTC was used as first-line monotherapy in 71 patients (Group 1; second- or third-line monotherapy in 72 patients (Group 2 when the first-line therapy with antiepileptic drugs was insufficiently effective or poorly tolerated.The percentage of treatment retention is an integral index of the cumulative efficiency of therapy (remission + a >50% reduction in seizure frequency minus the percent of drug discontinuation for various reasons over a given period of time. In Group 1, the retention rate was 90.1, 87.3, and 83.1 in the first, second, and third year and in Group 2, that was 75.0, 70.8, and 69.4%, respectively.LTC was found to be well tolerated. Its discontinuation because of its adverse reactions at one-year follow-up was noted in less than 5.6% (Group 1 and 8.2% (Group of the patients. The findings suggest that the long-term use of keppra is promising in therapy for partial epilepsy.

  20. Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: Results from a pregnancy registry in South India.

    Science.gov (United States)

    Thomas, Sanjeev V; Jose, Manna; Divakaran, Srividya; Sankara Sarma, Prabhakaran

    2017-02-01

    Kerala Registry of Epilepsy and Pregnancy had been prospectively evaluating the reproductive issues of women with epilepsy since April 1998. This analysis aimed to estimate the relative risk of major congenital malformations (MCM) to the registrants. All pregnancies with known outcome in this register until December 2013 were included. Malformation status was evaluated by antenatal ultrasonography, physical examination at birth, echocardiography, and abdomen ultrasonography at 3 months of age and a final review at 1 year of age. There were 1,688 fetuses (singlets 1,643, twins 21, and triplet 1) resulting in 1,622 live births. All were born to women of Asian origin living in South India. The MCM rate for all live births was 6.84% (95% confidence interval [CI] 5.71-8.18) and for all pregnancy outcomes including fetal loss was 7.11% (95% CI 5.98-8.44). The MCM rates (mean with 95% CI) for exposed group were 6.4% (5.03-8.03) for monotherapy and 9.9% (7.37-13.13) for polytherapy; internal control group (women with epilepsy [WWE] not on antiepileptic drugs [AEDs] in first trimester) 5.6% (3.34-9.11), external control group (women without epilepsy or AED exposure in first trimester) 3.45% (1.94-6.07). Valproate monotherapy group had a dose-dependent relative risk for MCM of 2.6 (95% CI 1.30-5.20) compared to the external control group. The preliminary data on MCM rate for the nine total clobazam monotherapy (22.2%; 95% CI 6.2-54.7) signals increased risk that needs further validation on larger sample size. There was no association between MCM rate and maternal socioeconomic status, epilepsy syndrome, or use of folic acid in first trimester. This dataset from South India confirms the increased risk of MCM with exposure to AEDs, particularly polytherapy. A dose-dependent increased risk was observed with valproate. The increased risk associated with clobazam monotherapy is an important signal that needs to be confirmed in a larger sample. Wiley Periodicals, Inc. © 2017

  1. Testing drug additivity based on monotherapies.

    Science.gov (United States)

    Yang, Harry; Novick, Steven J; Zhao, Wei

    2015-01-01

    Under the Loewe additivity, constant relative potency between two drugs is a sufficient condition for the two drugs to be additive. Implicit in this condition is that one drug acts like a dilution of the other. Geometrically, it means that the dose-response curve of one drug is a copy of another that is shifted horizontally by a constant over the log-dose axis. Such phenomenon is often referred to as parallelism. Thus, testing drug additivity is equivalent to the demonstration of parallelism between two dose-response curves. Current methods used for testing parallelism are usually based on significance tests for differences between parameters in the dose-response curves of the monotherapies. A p-value of less than 0.05 is indicative of non-parallelism. The p-value-based methods, however, may be fundamentally flawed because an increase in either sample size or precision of the assay used to measure drug effect may result in more frequent rejection of parallel lines for a trivial difference. Moreover, similarity (difference) between model parameters does not necessarily translate into the similarity (difference) between the two response curves. As a result, a test may conclude that the model parameters are similar (different), yet there is little assurance on the similarity between the two dose-response curves. In this paper, we introduce a Bayesian approach to directly test the hypothesis that the two drugs have a constant relative potency. An important utility of our proposed method is in aiding go/no-go decisions concerning two drug combination studies. It is illustrated with both a simulated example and a real-life example. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Monotherapy for partial epilepsy: focus on levetiracetam

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    Antonio Gambardella

    2008-03-01

    Full Text Available Antonio Gambardella1,2, Angelo Labate1,2, Eleonora Colosimo1, Roberta Ambrosio1, Aldo Quattrone1,21Institute of Neurology, University Magna Græcia, Catanzaro, Italy; 2Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, ItalyAbstract: Levetiracetam (LEV, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is a recently licensed antiepileptic drug (AED for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Five randomized, double-blind, placebo-controlled trials enrolling adult or pediatric patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (≥50% reduction in seizure frequency of 28%–45%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for 6 months of the study and 8% seizure-free for 1 year. More recent studies illustrated successful conversion to monotherapy in patients with refractory epilepsy, and its effectiveness as a single agent in partial epilepsy. LEV has also efficacy in generalized epilepsies. Adverse effects of LEV, including somnolence, lethargy, and dizziness, are generally mild and their occurrence rate seems to be not significantly different from that observed in placebo groups. LEV also has no clinically significant pharmacokinetic interactions with other AEDs, or with commonly prescribed medications. The combination of effective antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive therapy for partial seizures.Keywords: levetiracetam, partial epilepsy, antiepileptic drugs

  3. Effect of a fixed combination of nimodipine and betahistine versus betahistine as monotherapy in the long-term treatment of Ménière's disease: a 10-year experience.

    Science.gov (United States)

    Monzani, D; Barillari, M R; Alicandri Ciufelli, M; Aggazzotti Cavazza, E; Neri, V; Presutti, L; Genovese, E

    2012-12-01

    Despite an abundance of long-term pharmacological treatments for recurrent vertigo attacks due to Ménière's disease, there is no general agreement on the their efficacy. We present the results of a retrospective study based on a 10-year experience with two long-term medical protocols prescribed to patients affected by Ménière's disease (diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines) who completed treatments in the period 1999-2009. A total of 113 medical records were analysed; 53 patients received betahistine-dihydrochloride at on-label dosage (32 mg die) for six months, and 60 patients were treated with the same regimen and nimodipine (40 mg die) as an add-therapy during the same period. Nimodipine, a 1,4-dihydropyridine that selectively blocks L-type voltage-sensitive calcium channels, has previously been tested as a monotherapy for recurrent vertigo of labyrinthine origin in a multinational, double-blind study with positive results. A moderate reduction of the impact of vertigo on quality of life (as assessed by the Dizziness Handicap Inventory) was obtained in patients after therapy with betahistine (p betahistine as monotherapy (p > 0.05), whereas the fixed combination of betahistine and nimodipine was associated with a significant reduction of tinnitus annoyance and improvement of hearing loss (p < 0.005). It was concluded that nimodipine represents not only a valid add-therapy for Ménière's disease, and that it may also exert a specific effect on inner ear disorders. Further studies to investigate this possibility are needed.

  4. Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

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    Correll Christoph

    2005-05-01

    Full Text Available Abstract Background Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. Methods Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796 who were initiated during the study on olanzapine (N = 405, quetiapine (N = 115, or risperidone (N = 276. The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. Results During the 1-year period, only a third (35.7% of the patients were treated predominately with monotherapy (>300 days. Most patients (57.7% had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days. Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043 or quetiapine (p = .002. The number of monotherapy days was significantly greater for olanzapine than quetiapine (p Conclusion Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic

  5. Efficacy and safety of a switch to latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops from latanoprost 0.005% monotherapy

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    Inoue K

    2012-05-01

    Full Text Available Kenji Inoue,1 Takayuki Fujimoto,1 Risako Higa,1 Ryo Moriyama,1 Hiromi Kohmoto,1 Haruka Nagumo,1 Masato Wakakura,1 Goji Tomita21Inouye Eye Hospital, Chiyoda-ku, Tokyo, 2Second Department of Ophthalmology, Toho University School of Medicine, Meguro-ku, Tokyo, JapanBackground: The purpose of this prospective study was to investigate the intraocular pressure (IOP-lowering effect and safety of latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops, now available in Japan.Materials and methods: Thirty-one patients diagnosed with primary open-angle glaucoma who had an insufficient intraocular pressure (IOP decrease with latanoprost 0.005% eyedrop monotherapy were enrolled. The latanoprost 0.005% eyedrops were discontinued, and administration of latanoprost 0.005%/timolol maleate 0.5% fixed combination eyedrops was initiated without any washout period. IOP was compared before and at months 1, 3, and 6 after the switch. The incidence of adverse reactions was investigated at every follow-up visit.Results: Mean IOP was 17.3 ± 2.7 mmHg before the switch, 15.5 ± 2.6 mmHg one month after the switch, 14.9 ± 2.4 mmHg 3 months after the switch, and 15.1 ± 2.2 mmHg 6 months after the switch, indicating that IOP decreased significantly after the change. The IOP reduction rate was 9.9% ± 11.5% after one month, 13.1% ± 10.9% after 3 months, and 11.2% ± 11.8% after 6 months. Two patients (6.5% discontinued therapy due to adverse reactions (one case each of itchiness and bradycardia.Conclusion: When latanoprost 0.005% eyedrop monotherapy was replaced by latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops, IOP decreased significantly without increasing the frequency of administration, and safety was satisfactory.Keywords: latanoprost 0.005%, timolol maleate 0.5%, fixed combination, eyedrops, intraocular pressure, switch

  6. Antiandrogen monotherapy: indications and results

    DEFF Research Database (Denmark)

    Iversen, Peter

    2002-01-01

    Many patients with prostate cancer for whom hormonal therapy is indicated are still physically and sexually active; quality of life is therefore a vital issue when considering treatment options. Traditional castration-based therapies, although effective, have implications with respect to quality...... with castration, in terms of sexual interest and physical capacity, in patients with either M0 and M1 stage disease. Data from a small subgroup of patients with stage M0 disease suggest that bicalutamide may also reduce the risk of osteoporosis compared with castration. Long-term therapy with bicalutamide 150-mg...

  7. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma

    DEFF Research Database (Denmark)

    Lokhorst, Henk M; Plesner, Torben; Laubach, Jacob P

    2015-01-01

    BACKGROUND: Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS: In part 1...... interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen...

  8. Extensive Darier Disease Successfully Treated with Doxycycline Monotherapy

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    Alicia Sfecci

    2015-10-01

    Full Text Available Darier disease (DD is a rare dominantly inherited genodermatosis characterized by loss of intercellular adhesion (acantholysis and abnormal keratinization. DD is often difficult to manage. Numerous treatments have reportedly been used for the treatment of DD, with limited success. Systemic retinoids are considered the drug of choice for treating DD. However, their use is limited by potential deleterious side effects. Considering the recently reported efficacy of doxycycline for Hailey-Hailey disease, an inherited acantholytic skin disorder pathogenetically similar to DD, we report the case of a patient with extensive DD who showed a dramatic response to oral doxycycline monotherapy.

  9. Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

    Science.gov (United States)

    Erlinge, David; Omerovic, Elmir; Fröbert, Ole; Linder, Rikard; Danielewicz, Mikael; Hamid, Mehmet; Swahn, Eva; Henareh, Loghman; Wagner, Henrik; Hårdhammar, Peter; Sjögren, Iwar; Stewart, Jason; Grimfjärd, Per; Jensen, Jens; Aasa, Mikael; Robertsson, Lotta; Lindroos, Pontus; Haupt, Jan; Wikström, Helena; Ulvenstam, Anders; Bhiladvala, Pallonji; Lindvall, Bo; Lundin, Anders; Tödt, Tim; Ioanes, Dan; Råmunddal, Truls; Kellerth, Thomas; Zagozdzon, Leszek; Götberg, Matthias; Andersson, Jonas; Angerås, Oskar; Östlund, Ollie; Lagerqvist, Bo; Held, Claes; Wallentin, Lars; Scherstén, Fredrik; Eriksson, Peter; Koul, Sasha; James, Stefan

    2017-09-21

    The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Among patients undergoing PCI for myocardial

  10. The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.

    Science.gov (United States)

    Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

    2015-01-01

    Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2 h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were also evaluated. At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69-1.14 for the Jinlida group vs. 0.34-0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p changes. No serious adverse events were reported. Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Chinese Clinical Trial Register ChiCTR-TRC-13003159.

  11. A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U;

    2001-01-01

    Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function. Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment, but it is not known how an ACE inhibitor compares to treatment with ...... with a calcium channel blocker or to treatment with a combination of these drugs. The aim of the study was to evaluate the rate of decline in GFR in patients with chronic renal failure and hypertension treated with isradipine and spirapril as monotherapy and in combination.......Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function. Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment, but it is not known how an ACE inhibitor compares to treatment...

  12. Effectiveness of hydrochlorothiazide in combination with telmisartan and olmesartan in adults with moderate hypertension not controlled with monotherapy: a prospective, randomized, open-label, blinded end point (PROBE), parallel-arm study.

    Science.gov (United States)

    Fogari, Roberto; Zoppi, Annalisa; Mugellini, Amedeo; Preti, Paola; Destro, Maurizio; Rinaldi, Andrea; Derosa, Giuseppe

    2008-02-01

    The potential combinations of antihypertensive agents are many, and making rational choices depends on the characteristics of each drug and on their complementary mechanisms of action. The aim of this study was to evaluate the effectiveness of adding hydrochlorothiazide (HCTZ) 12.5 mg to olmesartan 20 mg or telmisartan 80 mg on blood pressure (BP) in patients with moderate hypertension. Consecutive outpatients at the Centro per l'Ipertensione e la Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy, of both sexes aged 39 to 75 years were considered eligible for enrollment if they had a sitting diastolic BP (DBP) ->99 mm Hg and 90 mm Hg) received HCTZ 12.5 mg QD for 8 additional weeks. Clinical and ambulatory BPs were measured at the end of the washout period and at the end of both treatment periods. Adverse events (AEs) were recorded from spontaneous reports and direct inquiry from investigators. One hundred forty-five patients, all of whom were white, were recruited for the study. After the initial washout period, 13 patients did not meet the inclusion criteria and 6 refused to continue. A total of 126 white patients (69 men, 57 women; mean [SD] age, 60.2 [11.6] years) were randomized to receive monotherapy. Of these, 35 patients (56%) in the olmesartan group and 33 (52%) in the telmisartan group had previously received antihypertensive therapy. At the end of monotherapy, the 52 patients in the olmesartan group and the 49 patients in the telmisartan treatment group who were still in the study and had their BP inadequately controlled by treatment had HCTZ 12.5 mg QD added to their treatment regimen. Both combinations induced a greater ambulatory mean (SD) systolic BP (SBP) and DBP reduction than monothera- py (SBP: 145.3 [6.1] in the olmesartan group and 140.1 [6.4] in the telmisartan group, P < 0.05; DBP: 88.1 [5.1] in the olmesartan group and 84.9 [4.9] in the telmisartan group, P < 0.05). The mean (SD) reduction from baseline in the telmisartan

  13. Tenofovir disoproxil fumarate monotherapy is superior to entecavir-adefovir combination therapy in patients with suboptimal response to lamivudine-adefovir therapy for nucleoside-resistant HBV: a 96-week prospective multicenter trial.

    Science.gov (United States)

    Lee, Sae Hwan; Cheon, Gab Jin; Kim, Hong Soo; Kim, Sang Gyune; Kim, Young Seok; Jeong, Soung Won; Jang, Jae Young; Kim, Boo Sung; Jun, Baek Gyu; Don Kim, Young; Jun, Dae Won; Sohn, Joo Hyun; Kim, Tae Yeob; Lee, Byung Seok

    2017-04-24

    A complete virologic response is closely related to the long-term outcome of patients with chronic hepatitis B and prevention of emerging hepatitis B virus (HBV) mutations. We aimed to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy compared to entecavir-adefovir dipivoxil (ETV-ADV) combination therapy in patients with suboptimal responses to long-term lamivudine-adefovir dipivoxil (LAM-ADV) therapy for nucleoside analogue-resistant chronic hepatitis B. Patients (n = 60) were randomized to TDF monotherapy or ETV-ADV combination therapy for 96 weeks. All patients had the rt204I/V mutation and serum HBV DNA was measured (> 60 IU/mL) during LAM-ADV therapy. The primary endpoint was a complete virologic response (HBV DNA < 20 IU/mL) at week 96. The median duration of prior LAM-ADV rescue therapy was 43 (7 - 108) months. A complete virologic response was achieved in 86.6% and 53.3% of patients in the TDF and ETV-ADV groups, respectively, at week 96 (P = 0.005). Reduction in serum HBV DNA was significantly greater in the TDF group than in ETV-ADV group (-3.2 ± 1.2 vs. -2.6 ± 1.2, P = 0.01). HBeAg loss (22.2% vs. 16.6%, P = 0.731) and biochemical responses (76.7% vs. 73.3%, P = 0.766) were not different between the TDF and ETV-ADV groups. No newly emerged mutations were detected. Both therapies demonstrated favorable safety profiles. TDF therapy achieved a better complete virologic response than ETV-ADV therapy in chronic hepatitis B patients with suboptimal response to long-term LAM-ADV rescue therapy. (KCT0000627).

  14. Evaluation of anticonvulsant drugs during pregnancy in a population-based Hungarian study.

    Science.gov (United States)

    Czeizel, A E; Bod, M; Halász, P

    1992-01-01

    The Hungarian Case-Control Surveillance of Congenital Anomalies, from 1980-1987, involved 10,698 malformed cases and 21,546 non-malformed controls. Ninety-five pregnant women were treated by 144 anticonvulsants excluding diazepam and barbiturates. The rate of anticonvulsant use was 2.9 times higher in pregnant women having malformed offspring than in control mothers and this difference was greater in polytherapy than in monotherapy.

  15. Prescription practices and availability of artemisinin monotherapy in India: where do we stand?

    Directory of Open Access Journals (Sweden)

    Mishra Neelima

    2011-12-01

    Full Text Available Abstract Background The World Health Organization has urged all member states to deploy artemisinin-based combination therapy and progressively withdraw oral artemisinin monotherapies from the market due to their high recrudescence rates and to reduce the risk of drug resistance. Prescription practices by physicians and the availability of oral artemisinin monotherapies with pharmacists directly affect the pattern of their use. Thus, treatment practices for malaria, with special reference to artemisinin monotherapy prescription, in selected states of India were evaluated. Methods Structured, tested questionnaires were used to conduct convenience surveys of physicians and pharmacists in eleven purposively selected districts across six states in 2008. In addition, exit interviews of patients with a diagnosis of uncomplicated malaria or a prescription for an anti-malarial drug were also performed. Logistic regression was used to determine patient clinical care, and institutional factors associated with artemisinin monotherapy prescription. Results Five hundred and eleven physicians from 196 health facilities, 530 pharmacists, and 1, 832 patients were interviewed. Artemisinin monotherapy was available in 72.6% of pharmacies and was prescribed by physicians for uncomplicated malaria in all study states. Exit interviews among patients confirmed the high rate of use of artemisinin monotherapy with 14.8% receiving such a prescription. Case management, i.e. method of diagnosis and overall treatment, varied by state and public or private sector. Treatment in the private sector (OR 8.0, 95%CI: 3.8, 17 was the strongest predictor of artemisinin monotherapy prescription when accounting for other factors. Use of the combination therapy recommended by the national drug policy, artesunate + sulphadoxine-pyrimethamine, was minimal (4.9%, with the exception of one state. Conclusions Artemisinin monotherapy use was widespread across India in 2008. The accessible

  16. Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension: A First-in-human, Concept-proven, Prospective, Dose-escalation, Multicenter Study.

    Science.gov (United States)

    Yin, Wei-Hsian; Chen, Pei; Yeh, Hung-I; Wang, Kuo-Yang; Hung, Yi-Jen; Tseng, Wei-Kung; Wen, Ming-Shien; Wu, Tao-Cheng; Wu, Chau-Chung; Cheng, Shu-Meng; Chen, Jaw-Wen

    2016-03-01

    The combination of low rather than high dose of dextromethorphan (DXM) with amlodipine (AM) could improve blood pressure (BP) reduction in hypertensive animals. The study aimed to evaluate the feasibility of different doses of DXM combined with standard AM treatment in clinical hypertension.This was a prospective, 14-week, dose-escalation, multicenter study. After 2-week run-in period with AM 5 mg/day, hypertensive patients who got the BP goal of 140/90 mmHg kept receiving AM monotherapy for another 12 weeks. The nonresponders, while kept on AM 5 mg/day, received additional DXM treatment for 3 sequential dose-titrated periods with initially 2.5 mg/day, followed by 7.5 mg/day, and finally 30 mg/day. Each period was for 4 weeks. The patients at BP goal after each treatment period were defined as the responders and kept on the same combination till the end of the study. The responder rate of each treatment period was recorded. The changes of BP and serum antioxidant/endothelial markers between week 14 and week 2 were evaluated.Of the 103 patients initially enrolled, 89 entered the treatment period. In the 78 patients completing the study, 31 (40%) at BP goal after 2-week AM run-in kept on AM monotherapy (DXM0). The addition of 2.5 (DXM2.5) and 7.5 mg/day (DXM7.5) of DXM enabled BP goal achievement in 22 (47%) nonresponders to AM monotherapy including 16 (29%) with DXM2.5 and 6 (18%) with DXM7.5. Only 4 patients (16%) reached BP goal with the combination of DXM 30 mg/day (DXM30). Overall, 73% of the 78 patients reached BP goal at the end of the 14-week study. Mean systolic BP was reduced by 7.9% ± 7.0% with DXM2.5 (P < 0.001) and by 5.4% ± 2.4% with DXM7.5 (P = 0.003) respectively at week 14 from that at week 2, which was unchanged in either DXM0 or DXM30 group. Besides, the effects of combination treatment were particularly significant in the patients with impaired endothelial function suggested by reduced serum NOx level at baseline

  17. Resistance detected by pyrosequencing following zidovudine-monotherapy for prevention of HIV-1 mother-to-child-transmission

    Science.gov (United States)

    Olson, Scott C.; Ngo-Giang-Huong, Nicole; Beck, Ingrid; Deng, Wenjie; Britto, Paula; Shapiro, David E.; Bumgarner, Roger E.; Mullins, James I.; Van Dyke, Russell B.; Jourdain, Gonzague; Frenkel, Lisa M.

    2015-01-01

    To prevent mother-to-child-transmission-of-HIV-1, the 2010 WHO guidelines recommended prenatal zidovudine monotherapy (Option A). To determine if ZDV-monotherapy selects for HIV-resistance in antiretroviral-naïve women during pregnancy, specimens from 50 were examined using pyrosequencing. ZDV-resistance mutations were detected at delivery in 7 (14%, 95% confidence interval 6.6-26.5%). These data raise the question whether women administered zidovudine monotherapy for PMTCT could have higher risk of virologic failure when later started on combination ARV therapy, as has been demonstrated following single-dose-nevirapine prophylaxis. PMID:26244386

  18. Fluvoxamine monotherapy for psychotic depression: the potential role of sigma-1 receptors

    Directory of Open Access Journals (Sweden)

    Hashimoto Kenji

    2009-12-01

    Full Text Available Abstract Background Psychotic depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI and an atypical antipsychotic or electroconvulsive therapy in treating psychotic depression. In some cases, the clinician or patient may prefer to avoid antipsychotic drugs altogether because of the risk of extrapyramidal side effects (EPS in patients with psychotic depression treated with these drugs. Methods We report five cases where fluvoxamine monotherapy was effective in the patients with psychotic depression. Results The scores on the Hamilton Depression (HAM-D scale and the Brief Psychiatric Rating Scale (BPRS in the five patients with psychotic depression were reduced after fluvoxamine monotherapy. Conclusion Doctors should consider fluvoxamine monotherapy as an alternative approach in treating psychotic depression because it avoids the risk of EPS from antipsychotic drugs.

  19. Immediate virological response predicts the success of shortterm peg-interferon monotherapy for chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Masayoshi; Yada; Akihide; Masumoto; Naoki; Yamashita; Kenta; Motomura; Toshimasa; Koyanagi; Shigeru; Sakamoto

    2010-01-01

    AIM:To investigate the efficacy of short-term peginterferon(PEG-IFN)monotherapy for chronic hepatitis C patients who achieved an immediate virological response.METHODS:Defining an"immediate virological response(IVR)"as the loss of serum hepatitis C virus(HCV) RNA 7 d after the first administration of PEG-IFNα,we conducted a 12-wk course of PEG-IFNα2a monotherapy without the addition of ribavirin for 38 patients who had low pretreatment HCV RNA load and exhibited IVR.The patients included 21 men and 17 women...

  20. Patient persistence with first-line antiglaucomatous monotherapy

    Directory of Open Access Journals (Sweden)

    Alfonso Arias

    2010-04-01

    Full Text Available Alfonso Arias1, Konrad Schargel2, Fernando Ussa3, Maria I Canut4, Amelia y Belén Robles4, Belén Martí Sánchez51Ophthalmology Department, Fundación Hospital Alcorcón, Madrid; 2Ophthalmology Department, Hospital de Torrevieja, Alicante; 3Instituto Universitario de Oftalmobiología Aplicada, Valladolid; 4Centro de Oftalmología Barraquer, Barcelona; 5Autónoma University of Madrid, Madrid, SpainPurpose: To identify the extent of persistence (period of time of continuous therapy with the drug prescribed of glaucoma patients treated with prostaglandins (latanoprost, bimatoprost, or travoprost, or β-blocker (timolol monotherapy.Methods: An observational retrospective study of a 24-month follow-up in 191 patients (from four centers was done to identify the time elapsed until patients discontinued their antiglaucomatous treatment. The relevant information was extracted from patients’ medical charts. A descriptive analysis, a Kaplan–Meier survival analysis, and a Cox regression model were used to determine which drug was associated with greater patient persistence and to detect variables significantly influencing persistence.Results: Descriptive analysis and survival curves showed that after 24 months, latanoprost was associated with a higher persistence in glaucoma treatment than the alternative agents: 81.6% versus 22.9% for bimatoprost, 65.4% for travoprost, and 60.5% for timolol (P < 0.0001. Persistence was significantly influenced by the antiglaucoma agent used as monotherapy (with a six-fold higher risk of treatment discontinuation during the follow-up period due to receiving bimatoprost instead of latanoprost; P < 0.0001 and patient age (P = 0.001. Even though comorbidities could not be directly related to persistence, their occurrence was related to patient age. The main reasons for treatment discontinuation were lack of efficacy, development of intolerance and/or adverse events, which were significant in the bimatoprost group, 28

  1. Six-month results from a Phase III randomized trial of fixed-combination brinzolamide 1% + brimonidine 0.2% versus brinzolamide or brimonidine monotherapy in glaucoma or ocular hypertension

    Directory of Open Access Journals (Sweden)

    Whitson JT

    2013-06-01

    Full Text Available Jess T Whitson,1 Tony Realini,2 Quang H Nguyen,3 Matthew G McMenemy,4 Stephen M Goode5 1University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 2West Virginia University Eye Institute, Morgantown, WV, 3Scripps Clinic, La Jolla, CA, 4Lone Star Eye Care, Sugar Land, TX, 5Alcon Research Ltd, Fort Worth, TX, USA Background: The objective of this study was to examine the safety and intraocular pressure (IOP-lowering efficacy of a fixed combination of brinzolamide 1% + brimonidine 0.2% (BBFC after six months of treatment in patients with open-angle glaucoma or ocular hypertension. Methods: This was a randomized, multicenter, double-masked, three-month, three-arm contribution-of-elements study with a three-month safety extension. Patients were randomly assigned 1:1:1 to treatment with BBFC, brinzolamide 1%, or brimonidine 0.2% after a washout period. Patients dosed their study medications three times daily at 8 am, 3 pm, and 10 pm for six months. Patients returned for visits at two weeks, six weeks, three months, and six months. IOP measurements were used to assess efficacy. Safety assessments were adverse events, corrected distance visual acuity, slit-lamp biomicroscopy, pachymetry, perimetry, fundus parameters, and cardiac parameters. Results: A total of 690 patients were randomized. Six-month mean IOP values were similar to those at three months, when the mean IOP in patients treated with BBFC was significantly lower than that of either monotherapy group. A total of 175 patients experienced at least one treatment-related adverse event (BBFC, 33.0%; brinzolamide, 18.8%; brimonidine, 24.7%, eight of which were severe, and five resulted in discontinuation. Seventy-seven patients discontinued participation due to treatment-related adverse events (BBFC, 17.2%; brinzolamide, 2.1%; brimonidine, 14.5%. There were 21 serious adverse events (n = 7 in each group, none of which was related to treatment. Resting mean pulse and blood pressure with

  2. Lymphocutaneous Sporotrichosis during Treatment with Anti-TNF-Alpha Monotherapy

    Directory of Open Access Journals (Sweden)

    Francesco Ursini

    2015-01-01

    Full Text Available Sporotrichosis is an infectious disease caused by Sporothrix schenckii, a dimorphic fungus isolated for the first time in 1896 by Benjamin Schenck from a 36-year-old male patient presenting lesions on the right hand and arm. The infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Different clinical syndromes are described as a direct consequence of S. schenckii infection, including lymphocutaneous and disseminated forms, although extracutaneous presentations are reported most frequently in AIDS patients. Here we describe the case of a 57-year-old Caucasian male diagnosed in 2004 with ankylosing spondylitis under stable treatment with adalimumab monotherapy (40 mg every other week. During a routine follow-up visit in March 2013, he presented with multiple nodular lesions arranged in a linear fashion along the left hand and forearm. After diagnostic aspiration of the lesions, lymphocutaneous sporotrichosis was diagnosed and appropriate therapy started.

  3. Lymphocutaneous Sporotrichosis during Treatment with Anti-TNF-Alpha Monotherapy

    Science.gov (United States)

    Ursini, Francesco; Calabria, Marilena; Bruno, Caterina; Tripolino, Cesare; Naty, Saverio; Grembiale, Rosa Daniela

    2015-01-01

    Sporotrichosis is an infectious disease caused by Sporothrix schenckii, a dimorphic fungus isolated for the first time in 1896 by Benjamin Schenck from a 36-year-old male patient presenting lesions on the right hand and arm. The infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Different clinical syndromes are described as a direct consequence of S. schenckii infection, including lymphocutaneous and disseminated forms, although extracutaneous presentations are reported most frequently in AIDS patients. Here we describe the case of a 57-year-old Caucasian male diagnosed in 2004 with ankylosing spondylitis under stable treatment with adalimumab monotherapy (40 mg every other week). During a routine follow-up visit in March 2013, he presented with multiple nodular lesions arranged in a linear fashion along the left hand and forearm. After diagnostic aspiration of the lesions, lymphocutaneous sporotrichosis was diagnosed and appropriate therapy started. PMID:25755904

  4. Initial non-compliance with antihypertensive monotherapy is followed by complete discontinuation of antihypertensive therapy

    NARCIS (Netherlands)

    Van Wijk, Boris L G; Klungel, Olaf H; Heerdink, Eibert R; de Boer, Anthonius

    2006-01-01

    PURPOSE: Discontinuation with treatment is a major problem in the treatment of hypertension. The objective of our study was to assess the association between non-compliance and discontinuation in patients who started using antihypertensive monotherapy. METHODS: A nested case-control study within a c

  5. Initial non-compliance with antihypertensive monotherapy is followed by complete discontinuation of antihypertensive therapy

    NARCIS (Netherlands)

    Van Wijk, Boris L G; Klungel, Olaf H; Heerdink, Eibert R; de Boer, Anthonius

    PURPOSE: Discontinuation with treatment is a major problem in the treatment of hypertension. The objective of our study was to assess the association between non-compliance and discontinuation in patients who started using antihypertensive monotherapy. METHODS: A nested case-control study within a

  6. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Tyrrell, C J; Kaisary, A V

    2000-01-01

    Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide mo...

  7. Sulfonylurea versus metformin monotherapy in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Schroll, Jeppe B; Wetterslev, Jørn

    2014-01-01

    BACKGROUND: Guidelines recommend metformin as the first-line oral treatment for type 2 diabetes. We conducted a systematic review to assess whether the use of second- and third-generation sulfonylurea agents is associated with benefits and harms in terms of patient-important outcomes compared...... with metformin. METHODS: We searched several electronic databases and other sources for randomized clinical trials published to August 2011. We included trials that compared sulfonylurea versus metformin monotherapy among patients 18 years or older with type 2 diabetes and that had an intervention period...... of at least 24 weeks. We assessed risk of bias and extracted data related to interventions and outcomes. The risk of random errors was assessed by trial sequential analysis. RESULTS: We included 14 trials (4560 participants). All trials were judged to be at high risk of bias. Data on patient-important...

  8. Comparison of NSAID patch given as monotherapy and NSAID patch in combination with transcutaneous electric nerve stimulation, a heating pad, or topical capsaicin in the treatment of patients with myofascial pain syndrome of the upper trapezius: a pilot study.

    Science.gov (United States)

    Kim, Do-Hyeong; Yoon, Kyung Bong; Park, SangHa; Jin, Tae Eun; An, Yoo Jin; Schepis, Eric A; Yoon, Duck Mi

    2014-12-01

    This study compared the therapeutic effect of monotherapy with a nonsteroidal anti-inflammatory drug (NSAID) patch vs an NSAID patch combined with transcutaneous electric nerve stimulation (TENS), a heating pad, or topical capsaicin in the treatment of patients with myofascial pain syndrome (MPS) of the upper trapezius. A randomized, single-blind, controlled study of combination therapy for patients with MPS was performed. Ninety-nine patients were randomly assigned to one of four different self-management methods for treatment: NSAID patch (N = 25), NSAID patch + TENS (N = 24), NSAID patch + heating pad (N = 25), and NSAID patch + topical capsaicin (N = 25). The NSAID patch used in this study was a ketoprofen patch. All treatment groups were observed for 2 weeks, and the numeric rating scale (NRS) pain score, cervical active range of motion, pressure pain threshold, and Neck Disability Index were assessed. There was no significant difference between the NSAID patch alone group and the three combination therapy groups with respect to decrease in NRS score from baseline (day 0) to each period of observation. In covariate analysis, although there was no difference among the groups in most of the periods, the data at day 14 indicated a trend (P = 0.057). There were no significant differences in the other variables. We did not observe a statistical difference in improvements to the clinical variables among the four different methods. However, further studies regarding the effectiveness of a mixture of topical capsaicin and ketoprofen in patients with MPS should be considered. Wiley Periodicals, Inc.

  9. Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia.

    Science.gov (United States)

    Warsame, Marian; Atta, Hoda; Klena, John D; Waqar, Butt Ahmed; Elmi, Hussein Haji; Jibril, Ali Mohamed; Hassan, Hassan Mohamed; Hassan, Abdullahi Mohamed

    2009-02-01

    In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003-2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS+SP) or AQ (AS+AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS+SP and AS+AQ, proved to be highly efficacious with cure rates of 98-100% supporting the choice of AS+SP combination as first line treatment for uncomplicated malaria for Somalia.

  10. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    Science.gov (United States)

    2016-12-01

    technologies not presented in this SAP may also be explored in this study. The assay results from the most recent tumor biopsy will be used for each...integrity in pre-treatment biopsies with response to a PARPi in a prospective single-agent PARPi phase 2 clinical trial in recurrent ovarian...large number of DNA repair genes on small core biopsy specimens iv) begun accessioning samples from the phase 2 rucaparib trial (Ariel 2, NCT01891344

  11. Antipsychotic patterns of use in patients with schizophrenia: polypharmacy versus monotherapy.

    Science.gov (United States)

    Fisher, Maxine D; Reilly, Kathleen; Isenberg, Keith; Villa, Kathleen F

    2014-11-30

    The objective of this study was to characterize real-world treatment patterns in the prescription of antipsychotic polypharmacy (≥ 2 concurrent antipsychotics) compared with antipsychotic monotherapy for patients with schizophrenia. This study was a retrospective claims-based analysis of patients (aged 13-64 years) with schizophrenia belonging to an employer-based health plan. Duration of therapy was measured as the number of treatment days over one year following the initial date of antipsychotic therapy. Discontinuation was defined as a 90-day gap in antipsychotic treatment (or in at least one antipsychotic for the polypharmacy group). Logistic regression analyses were used to predict discontinuation within one year. Ordinary Least Squares (OLS) regressions were used to predict duration of therapy (by type of therapy) when controlling for gender, region, number of somatic and psychiatric comorbidities, Deyo-Charlson comorbidity score, and number of psychiatric and somatic medications. Of the 4,156 patients, 3,188 received monotherapy and 968 received polypharmacy. Mean age was 40 years (37.8 years for polypharmacy vs 40.3 years for monotherapy, p polypharmacy group and 54% of the monotherapy group discontinued treatment. The average duration of therapy was 163 [SD = 143] days in the polypharmacy group vs 253 [SD = 147] days in the monotherapy group. In both cohorts, patients polypharmacy were independent predictors of treatment duration and discontinuation prior to one year. One quarter of patients with schizophrenia received antipsychotic polypharmacy. Discontinuation was higher in the polypharmacy group. Age and polypharmacy were significant predictors of treatment discontinuation.

  12. Successful long-term monotherapy with rituximab in a patient with chronic lymphocytic leukemia of the B-cell-lineage: a case report

    Directory of Open Access Journals (Sweden)

    Sturm Isrid

    2008-08-01

    Full Text Available Abstract Introduction Treatment of chronic lymphocytic leukemia of the B-cell-lineage is strongly based upon clinical staging because of the heterogeneous clinical course of this disease. Case presentation We describe a 62-year-old patient with newly diagnosed chronic lymphocytic leukemia of the B-cell-lineage who did not respond to several chemotherapy regimens including chlorambucil, fludarabine and cyclophosphamide, developing a marked neutropenia and thrombocytopenia with life-threatening infections. Further chemotherapy appeared not feasible because of bone marrow toxicity. The patient was treated with 600 mg/m2 rituximab weekly followed by eight courses of biweekly therapy and then by long-term maintenance therapy, achieving almost complete remission of the symptoms and disease control. Conclusion After resistance to standard chemotherapy with chlorambucil and fludarabine, a patient with chronic lymphocytic leukemia of the B-cell-lineage was successfully treated with rituximab.

  13. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-­‐13-­‐1-­‐0485 TITLE: Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor...UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Mayo Clinic and Foundation AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...Biomarkers That Predict Response to PARP Inhibitors and Platinum.” Over the past 12 months we have i) completed validation of the immunohistochemical

  14. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    Science.gov (United States)

    2015-10-01

    A pivotal phase II study demonstrated that ola - parib induces responses in BRCA1/2 mutation car- riers with progressive high-grade OC, with efficacy...change that realigns critical residues in the enzyme active site,38-40 producing an up to 500-fold increase in activ- ity.39,41,42 Once activated

  15. A phase I monotherapy study of RG7212, a first-in-class monoclonal antibody targeting TWEAK signaling in patients with advanced cancers

    DEFF Research Database (Denmark)

    Lassen, Ulrik N; Meulendijks, Didier; Siu, Lilian L

    2015-01-01

    TWEAK ligand and reductions in tumor Ki-67 and TRAF1. A patient with BRAF wild-type melanoma who received 36 weeks of RG7212 therapy had tumor regression and pharmacodynamic changes consistent with antitumor effects. Fifteen patients (28%) received 16 or more weeks of RG7212 treatment. CONCLUSION: RG...

  16. A Phase I Monotherapy Study of RG7212, a First-in-Class Monoclonal Antibody Targeting TWEAK Signaling in Patients with Advanced Cancers

    NARCIS (Netherlands)

    Lassen, Ulrik N; Meulendijks, Didier; Siu, Lilian L; Karanikas, Vaios; Mau-Sorensen, Morten; Schellens, Jan H M; Jonker, Derek J; Hansen, Aaron R; Simcox, Mary E; Schostack, Kathleen J; Bottino, Dean; Zhong, Hua; Roessler, Markus; Vega-Harring, Suzana M; Jarutat, Tiantom; Geho, David; Wang, Ka; DeMario, Mark; Goss, Glenwood D

    2015-01-01

    PURPOSE: Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible molecule 14 (Fn14) are a ligand-receptor pair frequently overexpressed in solid tumors. TWEAK: Fn14 signaling regulates multiple oncogenic processes through MAPK, AKT, and NFκB pathway

  17. Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Heloisa Helena Russ

    Full Text Available OBJECTIVES: To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost with 0.5% timolol maleate METHODS: A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer's test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872 RESULTS: All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer's test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression. CONCLUSIONS: All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in the ocular surface

  18. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    Science.gov (United States)

    2014-10-01

    DNA ligase IV, XRCC4 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC...nonhomologous end-joining (NHEJ) pathway (53BP1, Ku70, Ku80, DNA-PKcs, XRCC4, DNA ligase IV) as well as PARP1. This group of proteins was chosen based on our...recombination, nonhomologous end-joining (NHEJ), immunohistochemistry, poly(ADP-ribose) polymerase, Ku70, Ku80, PARP1, 53BP1, DNA-PK, Artemis, DNA ligase IV

  19. Gabapentin monotherapy for the symptomatic treatment of painful neuropathy: a multicenter, double-blind, placebo-controlled trial in patients with diabetes mellitus.

    Science.gov (United States)

    Backonja, M M

    1999-01-01

    Pain is the most disturbing symptom of diabetic neuropathy. Traditionally this type of pain was treated with tricyclic antidepressants which frequently have many side effects. In the study reported here, gabapentin was administered in escalating doses up to 3600 mg per day to eligible patients with moderate to severe diabetic neuropathy pain in a double blind placebo controlled fashion. Gabapentin provided superior and significant pain relief over placebo. In addition, patients taking gabapentin had improvement of sleep scores and a number of items on mood and quality of life questionnaires. Gabapentin was tolerated well with mild and tolerable side effects.

  20. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease : a randomised, double-blind, placebo controlled trial (ADAFI)

    NARCIS (Netherlands)

    Dewint, Pieter; Hansen, Bettina E.; Verhey, Elke; Oldenburg, Bas; Hommes, Daniel W.; Pierik, Marieke; Ponsioen, Cyriel I. J.; van Dullemen, Hendrik M.; Russel, Maurice; van Bodegraven, Ad A.; van der Woude, C. Janneke

    2014-01-01

    Objective To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD). Design Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with active perianal f

  1. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: A randomised, double-blind, placebo controlled trial (ADAFI)

    NARCIS (Netherlands)

    P. Dewint (Pieter); B.E. Hansen (Bettina); E. Verhey (Elke); B. Oldenburg (Bas); D.W.S. Hommes (Daniël); M. Pierik (Marieke); C.Y. Ponsioen (Cyril); H.M. van Dullemen (Hendrik); M. Russel (Maurice); A.A. van Bodegraven (Ad); C.J. van der Woude (Janneke)

    2014-01-01

    textabstractObjective: To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD). Design: Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with act

  2. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease : a randomised, double-blind, placebo controlled trial (ADAFI)

    NARCIS (Netherlands)

    Dewint, Pieter; Hansen, Bettina E.; Verhey, Elke; Oldenburg, Bas; Hommes, Daniel W.; Pierik, Marieke; Ponsioen, Cyriel I. J.; van Dullemen, Hendrik M.; Russel, Maurice; van Bodegraven, Ad A.; van der Woude, C. Janneke

    2014-01-01

    Objective To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD). Design Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with active perianal f

  3. Sequential alternating deferiprone and deferoxamine treatment compared to deferiprone monotherapy: main findings and clinical follow-up of a large multicenter randomized clinical trial in -thalassemia major patients

    DEFF Research Database (Denmark)

    Pantalone, Gaetano Restivo; Maggio, Aurelio; Vitrano, Angela

    2011-01-01

    In β-thalassemia major (β-TM) patients, iron chelation therapy is mandatory to reduce iron overload secondary to transfusions. Recommended first line treatment is deferoxamine (DFO) from the age of 2 and second line treatment after the age of 6 is deferiprone (L1). A multicenter randomized open-l...

  4. Safety and efficacy of fibrate-statin combination therapy compared to fibrate monotherapy in patients with dyslipidemia: a meta-analysis.

    Science.gov (United States)

    Choi, Hye Duck; Shin, Wan Gyoon; Lee, Ju-Yeun; Kang, Byoung Cheol

    2015-01-01

    Dyslipidemia is a major risk factor for the development of cardiovascular disease. Treatment with fibrate, statins, or other lipid-lowering drugs prevents primary or recurrent cardiovascular events. However, all lipid-lowering drugs have side effects, which may become more severe if combination therapy is prescribed. We performed a meta-analysis of published data to compare the safety and efficacy of fibrates alone, compared to fibrate-statin combinations, in patients with dyslipidemia. Six articles were assessed in terms of the efficacy of therapy and nine from the viewpoint of therapeutic safety. In terms of efficacy, fibrate-statin combinations afforded significantly greater reductions in the levels of total cholesterol (SE=-2.248; 95% CI 1.986-2.510), LDL cholesterol (SE=-2.274; 95% CI 2.015-2.533), and triglycerides (SE=-0.465; 95% CI 0.272-0.658) compared to fibrate alone. In terms of safety, treatment with fibrate alone was associated with a significant decrease in the number of kidney-related adverse events (RR=-0.547; 95% CI 0.368-0.812), compared to treatment with fibrate-statin combinations. We suggest that treatment with a fibrate-statin combination affords clinical benefits that are superior to treatment with fibrate alone, but increases the risk of side effects (particularly renal). Therapy should thus be carefully monitored. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. HDR monotherapy for prostate cancer: A simulation study to determine the effect of catheter displacement on target coverage and normal tissue irradiation

    NARCIS (Netherlands)

    I.-K.K. Kolkman-Deurloo (Inger-Karina); M.A. Roos (Martin); S. Aluwini (Shafak)

    2011-01-01

    textabstractPurpose: The aim of this study was to systematically analyse the effect of catheter displacements both on target coverage and normal tissue irradiation in fractionated high dose rate (HDR) prostate brachytherapy, using a simulation study, and to define tolerances for catheter displacemen

  6. EVALUATION OF CYSTICLEAN® CAPSULES, A CRANBERRY EXTRACT WITH HIGH ANTI-ADHESION ACTIVITY, AS MONOTHERAPY IN UNCOMPLICATED CYSTITIS: AN OBSERVATIONAL PILOT STUDY

    Directory of Open Access Journals (Sweden)

    Risco E

    2015-05-01

    Full Text Available Background:Cysticlean® is a cranberry extract product with a high quantity of proanthocyanidins (240 mg/capsule with a significant dose-dependent anti-adhesion activity of Escherichia coli (EC adhered to uroepithelial cells. Previous clinical assays showed that Cysticlean® is a product highly recommended in the prophylaxis and treatment of UTIs. The aim of this study is the evaluation of Cysticlean as an alternative to antibiotics to treat uncomplicated cystitis. Material and Methods This observational study included 30 consecutive ambulatory patients (17 women and 13 men, who were diagnosed of uncomplicated cystitis (UC and agreed to participate in this observational study. Patients were informed to come to visit the doctor again after 15 days after Cysticlean® treatment was started (1 capsule of Cysticlean® every 12 h daily and immediately if signs/symptoms did not disappear. In this case, Cysticlean® was stopped and patients treated with antibiotic. Results: 21 patients were successfully cured with Cysticlean® treatment only (70% and 9 patients needed antibiotic to cure their UC. 82.35% of women and 53.,85% of men did not need antibiotic to be cured. No significant differences at baseline were found regarding signs/symptoms severity between those patients cured with extract alone and those who needed antibiotic. No side effects/adverse reactions were reported. Conclusions: These preliminary data strongly suggest that Cysticlean® could be considered as an alternative to antibiotics for a 1st line treatment of UC. Further clinical studies to confirm whether Cysticlean® could be an alternative to antibiotic treatment for UC and this approach could contribute to reduce world-wide growing antibiotic resistance.

  7. Multiple overlapping stents as monotherapy in the treatment of 'blister' pseudoaneurysms arising from the supraclinoid internal carotid artery: a single institution series and review of the literature.

    Science.gov (United States)

    Walsh, Kevin M; Moskowitz, Shaye I; Hui, Ferdinand K; Spiotta, Alejandro M

    2014-04-01

    The 'blister-type' aneurysm is one of the most devastating cerebrovascular lesions. Flow diversion with stent reconstruction is an emerging treatment and has shown promising initial results. To evaluate the experience of one institution using stent reconstruction for pseudoaneurysms of the supraclinoid internal carotid artery and to compare with a review of the literature. A retrospective review from one institution identified eight patients with 'blister' aneurysms over a 47-month period. The Raymond scale was used to classify the aneurysms. Clinical data were obtained using the modified Rankin Scale (mRS) and the National Institute of Health Stroke Scale. A literature review was performed and compared with our results. Clinical and angiographic data were obtained. After treatment, two aneurysms were Raymond class 1 (25%) and six were class 3 (75%). Of the class 3 aneurysms, two required retreatment, three (50%) progressed to complete occlusion and three (50%) had persistent aneurysm filling. Clinical data revealed two patients with mRS score of 0 (25%), five with mRS score of 1 (62.5%) and one with mRS score of 2 (12.5%). From the literature review, residual filling was evident in nine patients (64.3%) and complete occlusion in four (28.6%). On follow-up angiography, nine (64.3%) were occluded, two (14.3%) had residual neck filling and one (7.1%) had persistent aneurysm filling. Thirteen patients (92.9%) had an mRS score of 2 or better. Combining the available experience, patients demonstrated either improvement (n=9, 41%) or stability (n=11, 50%). Only two (9%) had progression requiring retreatment. Endovascular stent remodeling of 'blister-type' aneurysms is a safe and effective strategy.

  8. Comparison of Different Fractionation Schedules Toward a Single Fraction in High-Dose-Rate Brachytherapy as Monotherapy for Low-Risk Prostate Cancer Using 3-Dimensional Radiobiological Models

    Energy Technology Data Exchange (ETDEWEB)

    Mavroidis, Panayiotis, E-mail: mavroidis@uthscsa.edu [Department of Radiation Oncology, University of Texas Health Sciences Center, San Antonio, Texas (United States); Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm (Sweden); Milickovic, Natasa [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach GmbH, Offenbach (Germany); Cruz, Wilbert F. [Department of Radiation Oncology, University of Texas Health Sciences Center, San Antonio, Texas (United States); Tselis, Nikolaos [Strahlenklinik, Klinikum Offenbach GmbH, Offenbach (Germany); Karabis, Andreas [Pi-Medical Ltd., Athens (Greece); Stathakis, Sotirios; Papanikolaou, Nikos [Department of Radiation Oncology, University of Texas Health Sciences Center, San Antonio, Texas (United States); Zamboglou, Nikolaos [Strahlenklinik, Klinikum Offenbach GmbH, Offenbach (Germany); Baltas, Dimos [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach GmbH, Offenbach (Germany); Nuclear and Particle Physics Section, Physics Department, University of Athens, Athens (Greece)

    2014-01-01

    Purpose: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings. Methods and Materials: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P{sub +}), the biologically effective uniform dose, and the generalized equivalent uniform dose index. Results: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1 × 20 Gy, 98.6% in 2 × 14 Gy, 97.5% in 3 × 11 Gy, and 97.8% in 4 × 9.5 Gy. The corresponding P{sub +} values were 88.8% in 1 × 20 Gy, 83.9% in 2 × 14 Gy, 86.0% in 3 × 11 Gy, and 82.3% in 4 × 9.5 Gy. With use of the fractionation scheme 4 × 9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1 × 19.68 Gy, 2 × 13.75 Gy, and 3 × 11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1 × 19.16 Gy with a P{sub +} of 91.8%, 2 × 13.2 Gy with a P{sub +} of 89.6%, 3 × 10.6 Gy with a P{sub +} of 88.4%, and 4 × 9.02 Gy with a P{sub +} of 86.9%. Conclusions: Among the fractionation schemes 1 × 20 Gy, 2 × 14 Gy, 3 × 11 Gy, and 4 × 9.5 Gy, the first scheme was more effective in terms of P{sub +}. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4 × 9.5 Gy scheme, and it should reduce the expected total complication probability by

  9. Regulation of apoptosis in human melanoma and neuroblastoma cells by statins, sodium arsenite and TRAIL: a role of combined treatment versus monotherapy

    Science.gov (United States)

    Ivanov, Vladimir N.; Hei, Tom K.

    2015-01-01

    Treatment of melanoma cells by sodium arsenite or statins (simvastatin and lovastatin) dramatically modified activities of the main cell signaling pathways resulting in the induction of heme oxygenase-1 (HO-1) and in a downregulation of cyclooxygenase-2 (COX-2) protein levels. Through heme degradation and the production of carbon monoxide and biliverdin, HO-1 plays a protective role in different scenario of oxidative stress followed by mitochondrial apoptosis. Both sodium arsenite and statins could be efficient inducers of apoptosis in some melanoma cell lines, but often exhibited only modest proapoptotic activity in others, due to numerous protective mechanisms. We demonstrated in the present study that treatment by sodium arsenite or statins with an additional inhibition of HO-1 expression (or activation) caused a substantial upregulation of apoptosis in melanoma cells. Sodium arsenite- or statin-induced apoptosis was independent of BRAF status (wild type versus V600E) in melanoma lines. Monotreatment required high doses of statins (20–40 μM) for effective induction of apoptosis. As an alternative approach, pretreatment of melanoma cells with statin at decreased doses (5–20 μM) dramatically enhanced TRAIL-induced apoptosis, due to suppression of the NF-κB and STAT3-transcriptional targets (including COX-2) and downregulation of cFLIP-L (a caspase-8 inhibitor) protein levels. Furthermore, combined treatment with sodium arsenite and TRAIL or simvastatin and TRAIL efficiently induced apoptotic commitment in human neuroblastoma cells. In summary, our findings on enhancing effects of combined treatment of cancer cells using statin and TRAIL provide the rationale for further preclinical evaluation. PMID:21910007

  10. A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus.

    Directory of Open Access Journals (Sweden)

    Stephen D S McCarthy

    2016-01-01

    Full Text Available To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD. While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs, requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs IFN-α and IFN-ß, a panel of viral polymerase inhibitors (lamivudine (3TC, zidovudine (AZT tenofovir (TFV, favipiravir (FPV, the active metabolite of brincidofovir, cidofovir (CDF, and the estrogen receptor modulator, toremifene (TOR, in inhibiting viral replication in dose-response and time course studies. We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-ß inhibited viral replication 24 hours post-infection (IC50 0.038μM and 0.016μM, respectively. 3TC, AZT and TFV inhibited Ebola replication when used alone (50-62% or in combination (87%. They exhibited lower IC50 (0.98-6.2μM compared with FPV (36.8μM, when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25-25μM. When dosed >50μM, CDF treatment enhanced viral infection. IFN-ß exhibited strong synergy with 3TC (97.3% inhibition or in triple combination with 3TC and AZT (95.8% inhibition. This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug

  11. Safety and efficacy of dual therapy with GSK233705 and salmeterol versus monotherapy with salmeterol, tiotropium, or placebo in a crossover pilot study in partially reversible COPD patients

    Directory of Open Access Journals (Sweden)

    Brooks J

    2012-03-01

    Full Text Available Jutta Beier1, Jan van Noord2, Amanda Deans3, Jean Brooks3, Claire Maden3, Suus Baggen4, Rashmi Mehta5, Anthony Cahn31INSAF Respiratory Research Institute, Germany; 2Atrium Medisch Centrum, The Netherlands; 3GlaxoSmithKline, Stockley Park, UK; 4GlaxoSmithKline, Zeist, The Netherlands; 5GlaxoSmithKline, RTP, NC, USABackground: GSK233705 is an inhaled, long-acting muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD. This study was performed to see if the addition of GSK233705 to salmeterol would provide greater bronchodilation than salmeterol or tiotropium alone in COPD.Methods: In an incomplete-block, three-period, crossover design, dually responsive patients received three of the following five treatments: GSK233705 20 µg plus salmeterol 50 µg twice-daily; GSK233705 50 µg plus salmeterol 50 µg twice-daily; salmeterol 50 µg or placebo, each twice-daily; and tiotropium 18 µg or placebo once-daily for 7 days. Each treatment period was separated by a 14-day washout. The primary efficacy endpoint was morning (trough forced expiratory volume in 1 second (FEV1 on Day 8, following 7 days of treatment. Secondary endpoints included pulmonary function, plethysmography, pharmacokinetics of GSK233705 and salmeterol, adverse events (AEs, electrocardiograms (ECGs, vital signs, and laboratory parameters.Results: A total of 47 patients were randomized. The mean % predicted normal postbronchodilator FEV1 was 55% at screening. Compared with placebo (n = 24, the adjusted mean change from baseline in trough FEV1 on Day 8 was 215 mL higher with GSK233705 20 µg + salmeterol (n = 23 and 203 mL higher with GSK233705 50 µg + salmeterol (n = 27, whereas with salmeterol (n = 27 and tiotropium (n = 28 the changes were 101 mL and 118 mL higher, respectively. The primary efficacy results were supported by the results from the other secondary lung function assessments. AEs were reported by similar proportions of patients

  12. Defining the optimal biological monotherapy in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Tarp, Simon; Furst, Daniel E; Dossing, Anna;

    2017-01-01

    OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for rando......OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources...

  13. Hormone-dependent abnormality of the female sexual sphere during monotherapy with valproate, carbamazepine, and lamotrigine

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2012-01-01

    Full Text Available Hormonal function of the ovary was analyzed in 95 childbearing-age (18—30-year-old epileptic patients receiving monotherapy with antiepileptic drugs (AEDs for at least a year. Of them, 40, 40, and 15 patients had monotherapy with valproic acid, carbamazepine, or lamotrigine, respectively. Fifty-two (54.7% patients with epilepsy were observed to have ovarian hormonal dysfunctions characterized by lower progesterone levels and higher luteinizing hormone and testosterone concentrations in both the follicular and luteinic phase of a menstrual cycle. The magnitude of hormonal changes depended on the specific features of epilepsy: duration, form, site of an epileptogenic focus. The use of various AEDs had an insignificant impact on the rate and pattern of hormonal abnormalities.

  14. Augmentation Strategies for Patients with Major Depressive Disorder with an Inadequate Response to Antidepressant Monotherapy

    Directory of Open Access Journals (Sweden)

    Moica Th

    2014-04-01

    Full Text Available Introduction: Major depressive disorder is a chronic and debilitating disease characterized by a wide range of emotional and physical symptoms that coexist during a depressive episode and may reoccur at some point during the progression of the disease for the majority of patients. The purpose of the study was to investigate psychiatrists’ experience regarding the response to antidepressive treatment and their options regarding augmentation strategies in depression with incomplete response to antidepressant monotherapy.

  15. Cost-effectiveness of dipeptidyl peptidase-4 inhibitor monotherapy in elderly type 2 diabetes patients in Thailand

    Science.gov (United States)

    Permsuwan, Unchalee; Dilokthornsakul, Piyameth; Saokaew, Surasak; Thavorn, Kednapa; Chaiyakunapruk, Nathorn

    2016-01-01

    Background The management of type 2 diabetes mellitus (T2DM) in elderly population poses many challenges. Dipeptidyl peptidase-4 (DPP-4) inhibitors show particular promise due to excellent tolerability profiles, low risk of hypoglycemia, and little effect on body weight. This study evaluated, from the health care system’s perspective, the long-term cost-effectiveness of DPP-4 inhibitor monotherapy vs metformin and sulfonylurea (SFU) monotherapy in Thai elderly T2DM patients. Methods The clinical efficacy was estimated from a systematic review and meta-analysis. Baseline cohort characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. A validated IMS CORE Diabetes Model version 8.5 was used to project clinical and economic outcomes over a lifetime horizon using a 3% annual discount rate. Costs were expressed in 2014 Thai Baht (THB) (US dollar value). Incremental cost-effectiveness ratios were calculated. Base-case assumptions were assessed through several sensitivity analyses. Results For treating elderly T2DM patients, DPP-4 inhibitors were more expensive and less effective, ie, a dominated strategy, than the metformin monotherapy. Compared with SFU, treatment with DPP-4 inhibitors gained 0.031 more quality-adjusted life years (QALYs) at a total cost incurred over THB113,701 or US$3,449.67, resulting in an incremental cost-effectiveness ratio of THB3.63 million or US$110,133.50 per QALY. At the acceptable Thai ceiling threshold of THB160,000/QALY (US$4,854.37/QALY), DPP-4 inhibitors were not a cost-effective treatment. Conclusion DPP-4 inhibitor monotherapy is not a cost-effective treatment for elderly T2DM patients compared with metformin monotherapy and SFU monotherapy, given current resource constraints in Thailand. PMID:27703387

  16. QTc interval in patients with schizophrenia receiving antipsychotic treatment as monotherapy or polypharmacy

    DEFF Research Database (Denmark)

    Elliott, Anja Friis; Johan Mørk, Thibault; Højlund, Mikkel

    2017-01-01

    Objective: Antipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolong...... on monitoring the QTc interval in women with schizophrenia receiving antipsychotics as polypharmacy....... by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia......, and measured the frequency of QTc prolongation among patients. Methods: We carried out an observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the region of Central Jutland, Denmark. Patients were enrolled from January of 2013 to June of 2015, with follow...

  17. Switching patients from preserved prostaglandin-analog monotherapy to preservative-free tafluprost

    Directory of Open Access Journals (Sweden)

    Hommer A

    2011-05-01

    Full Text Available Anton Hommer¹, Friedemann Kimmich²¹Sanatorium Hera, Vienna, Austria; ²eyecons, Pfinztal, GermanyPurpose: Efficacy, tolerability and safety of the novel preservative-free prostaglandin tafluprost 0.0015% were investigated for the treatment of patients with glaucoma or ocular hypertension in a clinical setting.Patients and methods: Data were collected in a non-interventional, prospective, multi-center, observational, open label study. 118 patients were treated with a prostaglandin analog (PGA monotherapy (preserved formulations of latanoprost, travoprost or bimatoprost prior to baseline. Intraocular pressure (IOP readings were recorded for each eye at baseline (previous therapy, 4–6 weeks, and 12 weeks after changing medical treatment to preservative-free tafluprost once-daily. We analyzed the change in IOP over the study period for all patients as well as for a subgroup of patients with prior PGA monotherapy. Subjective symptoms and objective ocular signs were determined. Comfort was measured using a 4 step scale. All adverse events were recorded. Paired t-tests were conducted to compare IOP values at baseline to IOP values after treatment with tafluprost 0.0015%. Bowker’s test of symmetry was used for statistical evaluation of changes of clinical signs (hyperemia.Results: In total 118 patients were eligible for evaluation. In these patients with prior PGA monotherapy (n = 118 IOP decreased significantly from 16.2 ± 4.3 mm Hg (95% CI: 0.55 at treated baseline to 14.8 ± 3.2 mm Hg (95% CI: 0.43; P < 0.001 at final visit on tafluprost. In a subset of patients with prior latanoprost monotherapy (n = 68 mean IOP at baseline (±SD was reduced from 16.2 ± 4.6 mm Hg (95% CI: 0.77 14.8 ± 3.1 mm Hg at final visit (95% CI: 0.54, P < 0.001, in patients with prior travoprost monotherapy (n = 32 from 16.2 ± 4.3 mm Hg (95% CI: 1.05 to 14.9 ± 3.3 mm Hg (95% CI: 0.91; P < 0.05 and in patients with prior bimatoprost monotherapy (n = 18 from 16.4 ± 3

  18. Nelfinavir monotherapy increases naïve T-cell numbers in HIV-negative healthy young adults.

    Science.gov (United States)

    Rizza, Stacey R; Tangalos, Eric G; McClees, Mark D; Strausbauch, Michael A; Targonski, Paul V; McKean, David J; Wettstein, Peter J; Badley, Andrew D

    2008-01-01

    Although patients treated with HIV protease inhibitor (PI) containing regimens manifest increases in naïve T cell number, it is unclear whether this is due to reduction in viral replication or a direct drug effect. We questioned whether Nelfinavir monotherapy directly impacted naïve T-cell number in HIV-negative individuals. HIV-negative volunteers received Nelfinavir, 1250 mg orally, BID for 3 weeks, and T-cell receptor recombination excision circles (TREC) content in peripheral blood were assessed. Whereas TREC copies did not change over 3 weeks in untreated controls, TREC copies/copies CCR5 increased following Nelfinavir monotherapy in 8 patients (p negative patients, monotherapy with the HIV PI Nelfinavir for 21 days increases TREC-positive naïve T cell number, particularly in individuals who are healthy and young.

  19. The Effects of Enzalutamide Monotherapy on Multiparametric 3T MR Imaging in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Rosanne CV. Van der Roest

    2016-07-01

    Full Text Available The effects of enzalutamide monotherapy on prostate tumor downsizing and multiparametric MRI are currently unknown. Here we present the first case in literature of a patient with high-grade prostate cancer who underwent 3 months of neoadjuvant enzalutamide, for which the effects on mpMRI and histology were determined. Tumor size reduction and downstaging were noted. Neoadjuvant enzalutamide resulted in an increase in ADC value on the DWI-MRI sequences. Histological changes were also observed.

  20. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Demanes, D. Jeffrey, E-mail: jdemanes@mednet.ucla.edu [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, CA (United States); Martinez, Alvaro A.; Ghilezan, Michel [William Beaumont Hospital, Royal Oak, MI (United States); Hill, Dennis R.; Schour, Lionel; Brandt, David [California Endocurietherapy, Oakland, CA (United States); Gustafson, Gary [William Beaumont Hospital, Royal Oak, MI (United States)

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  1. Enzalutamide monotherapy in hormone-naive prostate cancer

    DEFF Research Database (Denmark)

    Tombal, Bertrand; Borre, Michael; Rathenborg, Per

    2014-01-01

    BACKGROUND: The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. METHODS:...

  2. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis

    Science.gov (United States)

    Emery, Paul; Sebba, Anthony; Huizinga, Tom W J

    2013-01-01

    Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX. PMID:23918035

  3. Plasma total thiol pool in children with asthma: Modulation during montelukast monotherapy.

    Science.gov (United States)

    Dilek, Fatih; Ozkaya, Emin; Kocyigit, Abdurrahim; Yazici, Mebrure; Guler, Eray Metin; Dundaroz, Mehmet Rusen

    2016-03-01

    Inflammation, which is a hallmark of asthma, is one of the main sources of oxidative stress in the human body. Thiols are powerful antioxidants that protect cells against the consequences of oxidative stress. We aimed to investigate whether asthma and montelukast monotherapy affect the total plasma thiol pool in children. A total of 60 children with asthma and 35 healthy controls participated in the study. Group I consisted of newly diagnosed asthmatics who did not have regular anti-asthmatic therapy previously. Group II consisted of patients who had been undertaking montelukast monotherapy regularly for at least 4 months. Plasma total antioxidant status (TAS) and plasma total thiol (PTT) were measured using spectrophotometric methods. Bronchial asthma patients in both groups I and II had decreased median TAS levels compared with the control group (1.59 [interquartile range, 1.04-1.70] and 1.67 [1.50-1.75] vs. 2.98 [2.76-3.16] Trolox equiv./L, respectively; P0.05). In addition, the median TAS and PTT levels for groups I and II were not statistically different (P>0.05). There was a positive correlation between TAS and PTT levels (rho=0.38, Pchildren with asthma. Montelukast monotherapy can limit oxidative stress and thus restore PTT levels but not TAS levels in asthmatic children. © The Author(s) 2015.

  4. Parameters of metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy

    Directory of Open Access Journals (Sweden)

    Aditi Dhir

    2015-01-01

    Full Text Available Objectives: The prevalence of obesity is rapidly increasing among Indian children, who, in general, are more prone to develop metabolic complications at an early age. Valproate and phenytoin are commonly used antiepileptic drugs in children. This study aimed to assess the parameters of the metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy. Methods: This cross-sectional study recruited children from the Pediatric Epilepsy Clinic, Department of Pediatrics, Kalawati Saran Children Hospital, New Delhi from March 2012 to September 2012. All consecutive children diagnosed with epilepsy as per International League Against Epilepsy definition aged 3-18 years on valproate or phenytoin monotherapy for at least 6 months were enrolled at a tertiary care children′s hospital in Northern India. After clinical and anthropometric evaluation (including body mass index [BMI] and waist circumference, the blood samples were analyzed for fasting serum glucose, total cholesterol, high-density lipoprotein-cholesterol, and serum triglyceride. Results: Children with BMI >95 th centile and waist circumference >90 th centile were not significantly different among children on valproate and phenytoin monotherapy. Children on valproate had significantly higher mean serum triglyceride (96.9 mg/dL vs. 77.6 mg/dL; P < 0.001 and total cholesterol (148.3 mg/dL vs. 132.8 mg/dL; P = 0.002 levels as compared to children on phenytoin monotherapy. Conclusions: The lipid abnormalities may be observed in children on valproate or phenytoin therapy and may warrant periodic screening.

  5. Quetiapine monotherapy in adolescents with bipolar disorder comorbid with conduct disorder.

    Science.gov (United States)

    Masi, Gabriele; Pisano, Simone; Pfanner, Chiara; Milone, Annarita; Manfredi, Azzurra

    2013-10-01

    Bipolar Disorders (BD) are often comorbid with disruptive behaviour disorders (DBDs) (oppositional-defiant disorder or conduct disorder), with negative implications on treatment strategy and outcome. The aim of this study was to assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid with conduct disorder (CD). A consecutive series of 40 adolescents (24 males and 16 females, age range 12-18 years, mean age 14.9 ± 2.0 years), diagnosed with a clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]) according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria were included. All the patients were treated with quetiapine monotherapy (mean final dose 258 ± 124 mg/day, range 100-600 mg/day). At the end-point (3 months), 22 patients (55.0%) were responders (Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2 and CGI-Severity [CGI-S] ≤ 3 and improvement of at least 30% Children's Global Assessment Scale [C-GAS] during 3 consecutive months). Both CGI-S and C-GAS significantly improved (pdisorder (ADHD) comorbidity. Eight patients (20.0%) experienced moderate to severe sedation and eight (20.0%) experienced increased appetite and weight gain. In these severely impaired adolescents, quetiapine monotherapy was well tolerated and effective in>50% of the patients.

  6. Effects of switching to PI monotherapy on measures of lipoatrophy: meta-analysis of six randomized HIV clinical trials

    Directory of Open Access Journals (Sweden)

    J Arribas

    2012-11-01

    Full Text Available Background: Switching from triple combination treatment to protease inhibitor (PI monotherapy may prevent or reverse adverse events related to long-term nucleoside analogues. Lipoatrophy is associated with long-term use of thymidine analogues (zidovudine and stavudine. Methods: A detailed MEDLINE search was conducted to identify randomised clinical trials of triple combination treatment versus PI monotherapy. Summary results from analysis of changes in body composition (DEXA analysis were collected: the mean change in limb fat and trunk fat to Week 48 or 96, and the percentage of patients with lipoatrophy (20% reduction from baseline in limb fat or lipohypertrophy (20% rise from baseline in trunk fat. Results: Six randomised trials of PI monotherapy versus triple therapy with data on body composition changes, measured by DEXA scanning at baseline and Week 48 or 96, were identified: Abbott-613 (LPV/r vs ZDV/3TC/EFV, induction-maintenance trial, n=105, Monark (LPV/r vs ZDV/3TC/LPV/r, first-line trial, n=63, Kalesolo (LPV/r vs LPV/r +2NRTIs, switch trial, n=42, MONOI (DRV/r vs DRV/r + 2NRTIs, switch trial, n=156, MONARCH (DRV/r vs DRV/r + 2NRTIs, switch trial, n=30 and KRETA (LPV/r vs LPV/r + ABC/3TC, switch trial, n=74. In the meta-analysis, there were greater rises in limb fat in the PI monotherapy arms than the triple therapy arms (mean difference =277g, 95% CI=+36 to+517g, p=0.024. The percentage of patients with lipoatrophy was significantly lower in the PI monotherapy arms (4% than the triple therapy arms (20%, (p=0.0005. There was no difference between PI monotherapy and triple therapy for mean change in trunk fat (mean difference=−73g, 95% CI = −621 to +475g, p=ns. There was also no significant difference in the risk of lipohypertrophy between the PI monotherapy arms (32% and the triple therapy arms (27% (p=ns. In each of the four analyses, there was no evidence for heterogeneity of treatment effects between the trials (Cochran's Q

  7. A randomized, double-blind, parallel-group, phase III study of shortening the dosing interval of subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis and an inadequate response to subcutaneous tocilizumab every other week: Results of the 12-week double-blind period.

    Science.gov (United States)

    Ogata, Atsushi; Tanaka, Yoshiya; Ishii, Tomonori; Kaneko, Motohide; Miwa, Hiroko; Ohsawa, Shino

    2017-06-16

    To determine the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) monotherapy every week (qw) versus every other week (q2w) in patients with rheumatoid arthritis who had an inadequate response to TCZ-SC q2w. Adult patients in Japan with inadequate response to TCZ-SC q2w were randomized to either TCZ-SC 162 mg qw monotherapy or TCZ-SC 162 mg q2w monotherapy for 12 weeks (double-blind). The primary endpoint was the change from baseline in adjusted Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) at week 12. Efficacy, safety and pharmacokinetics were assessed. TCZ-SC qw was superior to TCZ-SC q2w for adjusted mean change in DAS28-ESR from baseline to week 12. The difference in the change in DAS28-ESR between TCZ-SC qw and q2w was -1.21 (95%CI: -2.13, -0.30, p = .0108). A higher proportion of patients receiving TCZ-SC qw achieved DAS28-ESR remission/low disease activity than TCZ-SC q2w. Adverse events were 71.4% and 66.7% for TCZ-SC qw and q2w, respectively; infection was the most common event with one fatal case with TCZ-SC qw. In patients with inadequate response to TCZ-SC q2w, shortening the dosing interval to qw improved efficacy with acceptable tolerability. Occurrence of infection for both TCZ q2w and qw is important and needs careful attention.

  8. CyberKnife stereotactic radiotherapy as monotherapy for low- to intermediate-stage prostate cancer: Early experience, feasibility, and tolerance

    NARCIS (Netherlands)

    S. Aluwini (Shafak); P.H. van Rooij (Peter); M.S. Hoogeman (Mischa); C.H. Bangma (Chris); W.J. Kirkels (Wim); L. Incrocci (Luca); I.-K.K. Kolkman-Deurloo (Inger-Karina)

    2010-01-01

    textabstractPurpose: The CyberKnife (CK), a linear accelerator mounted on a robotic device, enables excellent dose conformation to the target and minimizes dose to surrounding normal tissue. It is a very suitable device for performing hypofractionated stereotactic body radiotherapy as monotherapy fo

  9. Efficacy and tolerability of a switch to fixed-dose combination therapy with amlodipine besylate/benazepril hydrochloride after monotherapy with amlodipine besylate: Data from the African-American subpopulation of a practice-based, open-label study (the LOGIC study)☆

    OpenAIRE

    Gatlin, Marjorie; Jarrett, Wentworth G.; Nwose, Oliseyenum M.; LOGIC (LOtrel: Gauging Improved Control) Study Investigators

    2004-01-01

    Background: The LOGIC (LOtrel: Gauging Improved Control) study assessed the efficacy and tolerability of switching from amlodipine besylate monotherapy to fixed-dose combination therapy with amlodipine besylate/benazepril hydrochloride (HCI) in patients who were experiencing uncontrolled blood pressure (BP) or edema with monotherapy.

  10. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

    LENUS (Irish Health Repository)

    Campbell, E

    2014-09-01

    Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.

  11. The comparison between monotherapy and combination therapy in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Khalvat A

    2007-05-01

    Full Text Available Background: Rheumatoid arthritis (RA is a chronic inflammatory condition. The condition can affected many tissues throught out the body, but the joints are usually most severely affected. The high incidence of RA, the conventional treatments and the experimental observation have shown by combination therapy, the disease symptoms of the patients reduce. To compare the efficacy and tolerability of single-agent Hydroxychloroquin (HCQ with combination therapies composed of (HCQ and Methotrexate (MTX and (HCQ, (MTX and Sulfasalazin (SSZ in active rheumatoid arthritis patients with additive arthritis. Methods: One hundred and twenty RA patients with active arthritis (male/female: 30/90 who were treated in rheumatology clinic between 2003 and 2005 were enrolled in this trial. Patients treated with (HCQ alone(200 mg/daywere include in group (I, patients treated with combination of (HCQ (200 mg/dayand (MTX (7.5mg/weekin group (II,and patents treated with combination of (HCQ (200mg/day,(MTX (7.5mg/weekand (SSZ(1 gr/dayin group (III, Forty patients (male/female:10/30 in group (I,(II and (IIIwere eligible for statistical analysis at the end of study. Changes in variable were compared by the T-test. Results: The combination of (MTX, (HCQand (SSZ and the combination of (MTX and (HCQ were more effective regarding the clinical and laboratory parameters than (HCQ alone (P<0.05. Moreover the combination of (MTX, (HCQ and (SSZ was more effective than the combination of (MTX and (HCQ (P<0.05. Combination therapies seem to be more effective and no more toxic than monotherapy in RA patients with additive arthritis. Conclusion: Combination therapy with methotrexate, hydroxychloroquin and sulfasalazin is more effective than hydroxychloroquin alone or a combination of methotrexate and hydroxychloroquin in RA. We suggest starting combination therapy for the patients with early RA, when the diagnosis has been established.

  12. Risk of infection in monotherapy with tumor necrosis factor alpha inhibitor: a Meta-analysis%肿瘤坏死因子α抑制剂单药疗法致感染风险的Meta分析

    Institute of Scientific and Technical Information of China (English)

    李文思; 吕迁洲; 陈璋璋

    2015-01-01

    Objective To evaluate the risk of infection in monotherapy of tumor necrosis factor alpha (TNF-α) inhibitor.Methods The database of Pubed, Embase, Cochrane library, and Web with Science were searched from the inception to November, 2014.The literatures of randomized controlled trials in English which included reports that only used TNF-α inhibitor (the test group) and placebo or positive controlled drug (the control group) were selected.The methodological quality of the literatures which enrolled into the study were assessed by Jadad scale (inferior quality: < 3 points, high quality: 3-5 points).The software RevMan 5.2 was used for Meta-analysis.The infection rate and the severe infection rate were expressed by relative risk (RR), Peto odds ratio (Peto OR)and 95 % confidence interval (CI).Results A total of 33 trials presented by 32 reports, and 11 819 patients (7 408 cases in the test group using adalimumab or golimumab or infliximab or etanercept, respectively, and 4 411 cases in the control group using placebo, positive control drug such as methotrexate or salazosulfapyridine, respectively) were enrolled into the Meta-analysis.The Jadad scores of the 33 trials were all ≥ 3 points.The results of the Meta-analysis showed that the overall total incidence of infection in patients who used TNF-α inhibitors only was higher than that in the patients who used placebo [33.03% (1 702/5 153) vs.29.53% (873/2 956), RR =1.17, 95% CI: 1.09-1.25, P <0.000 01].There was no significant difference in the overall incidence of infection between the test group and the positive controlled drug group [50.1% (362/723)vs.48.3% (320/662), RR =1.10, 95% CI: 0.90-1.34, P =0.36].There were no significant differences in the incidence of severe infection between the test group and the placebo control group, the positive controlled drug group [1.4% (73/5 067)vs.1.7% (48/2 902), Peto OR =0.90, 95% CI: 0.61-1.32, P =0.46;2.4% (34/1 410) vs.2.8% (28/976), RR =1

  13. Antiretroviral simplification with darunavir/ritonavir monotherapy in routine clinical practice: safety, effectiveness, and impact on lipid profile.

    Directory of Open Access Journals (Sweden)

    José R Santos

    Full Text Available BACKGROUND: Simplification of antiretroviral treatment (ART with darunavir/ritonavir (DRV/r monotherapy has achieved sustained suppression of plasma viral load (pVL in clinical trials; however, its effectiveness and safety profile has not been evaluated in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective cohort analysis of HIV-1-infected patients who initiated DRV/r monotherapy once daily with a pVL 50 copies/mL at week 48, and time to VF. Other causes of treatment discontinuation and changes in lipid profile were evaluated up to week 48. Ninety-two patients were followed for a median (IQR of 73 (57-92 weeks. The median baseline and nadir CD4+ T-cell counts were 604 (433-837 and 238 (150-376 cells/mm3, respectively. Patients had previously received a median of 5 (3-9 ART lines and maintained a pVL<50 copies/mL for a median of 76 (32-176 weeks before initiating DRV/r monotherapy. Nine (9.8% patients developed VF at week 48; time to VF was 47.1 (IQR: 36.1-47.8 weeks among patients with VF. Other reasons for changing ART were gastrointestinal disturbances (n = 3, rash (n = 1, and impaired CD4 recovery (n = 2. Median low-density lipoprotein cholesterol levels increased from 116.1 mg/dL at baseline to 137.3 mg/dL at 48 weeks (p = 0.001. CONCLUSIONS/SIGNIFICANCE: Treatment simplification with DRV/r monotherapy seems safe and effective in routine clinical practice. Further research is needed to elucidate the effect of DRV/r monotherapy on cholesterol levels.

  14. A comparison between S-1 based combination chemotherapy and S-1 monotherapy in patients with advanced gastric cancer:a Meta-analysis%S-1为基础的联合化疗与S-1单独治疗晚期胃癌患者比较的Meta分析

    Institute of Scientific and Technical Information of China (English)

    贺湘萍; 李荣辉; 李正斌

    2015-01-01

    Objective To compare the efficacy and safety of S‐1‐based combination chemotherapy with S‐1 monotherapy in patients with advanced gastric cancer (AGC) .Methods We performed a Meta‐analysis to com‐pare the efficacy and safety of S‐1‐based combination chemotherapy with S‐1 monotherapy in AGC patients .Stud‐ies stratifying overall survival (OS) ,progression‐free survival (PFS) ,objective response rate (ORR) ,and grade 3 or 4 adverse events (AEs) in AGC patients in an S‐1‐based therapy versus an S‐1 monotherapy setting were eligi‐ble for analysis by systematic computerized PubMed ,EMBASE ,Cochrane Library ,MEDLINE and CNKI sear‐ches .Data from these studies were pooled using Stata package version 12 .0 .Results Six studies involved 913 AGC patients were ultimately identified ,of which 443 (48 .5% ) received S‐1‐based combination chemotherapy and 470 (51 .5% ) received S‐1 monotherapy .Median OS and median PFS were significantly prolonged in AGC patients receiving S‐1‐based combination chemotherapy compared with those receiving S‐1 monotherapy (HR=0.775 ;95%CI:0.652 ,0.899 ;P<0.01 ;HR=0.656 ;95% CI:0 .556 ,0 .756 ;P<0.01 ,respectively) .The ORR favored pa‐tients with S‐1‐based combination chemotherapy (OR=1.535 ;95% CI:1.189 ,1.880 ;P< 0.01) .Higher inci‐dence of grade 3/4 AEs was found in patients with S‐1‐based combination chemotherapy (P<0.01) .Conclusion For the Asian population ,S‐1‐based combination chemotherapy significantly improved OS and PFS and enhanced ORR in comparison to S‐1 monotherapy .The incidence of grade 3/4 AEs was higher in patients with S‐1‐based combination chemotherapy ,compared with S‐1 monotherapy group .%目的:比较S‐1为基础的联合化疗与S‐1单独治疗晚期胃癌患者的疗效与安全性。方法通过检索PubMed、EMBASE、Cochrane Library、MEDLINE和CNKI等数据库,全面收集S‐1为基础的联合化疗与S‐1单独治疗晚期胃癌患

  15. Tardive oculogyric crisis associated with amisulpride monotherapy

    Directory of Open Access Journals (Sweden)

    Mendhekar D

    2010-01-01

    Full Text Available Oculogyric crisis (OGC is a dystonic and distressing side- effect which occurs immediately after the administration of high-potency antipsychotic drugs and is usually reported as a subtype of dystonia. We report a case of a young woman with schizophrenia who presented with tardive OGC related to amisulpride.

  16. Original Research Monotherapy with amlodipine or ...

    African Journals Online (AJOL)

    Department of Obstetrics and Gynaecology, University of Nigeria Teaching Hospital, Enugu, Nigeria. 6. Department of ... anti-hypertensive drugs.4 However, a trial that evaluated this guideline found that a combination therapy with amlodipine.

  17. Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Niraj H., E-mail: nmehta@mednet.ucla.edu [University of California, Los Angeles, Los Angeles, California (United States); Kamrava, Mitchell; Wang, Pin-Chieh; Steinberg, Michael; Demanes, Jeffrey [University of California, Los Angeles, Los Angeles, California (United States)

    2013-07-15

    Purpose: To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. Methods and Materials: Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). Results: A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). Conclusions: A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

  18. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis.

    Science.gov (United States)

    Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F

    2016-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA. NCT01039688; Results.

  19. Dexamethasone intravitreal implants for diabetic macular edema refractory to ranibizumab monotherapy or combination therapy.

    Science.gov (United States)

    Gutiérrez-Benítez, L; Millan, E; Arias, L; Garcia, P; Cobos, E; Caminal, M

    2015-10-01

    To determine the effectiveness and local safety of dexamethasone intravitreal implants as a treatment in diabetic macular edema (DME) refractory to intravitreal injections of ranibizumab monotherapy or combination therapy. A retrospective study conducted on patients with DME refractory to ranibizumab monotherapy or combined with other treatments treated with dexamethasone intravitreal implants. The parameters analyzed were visual acuity (VA) by ETDRS (Early Treatment Diabetic Retinopathy Study) charts and foveal thickness by spectral-domain optical coherence tomography (SD-OCT) before the treatment, 2 months after treatment, and at the end of the follow-up. A total of 14 eyes of 14 patients were included, with a mean age of 64 years (SD: 9.5; range 41-78) and a mean follow-up of 7.6 months. The mean VA improved from 53 letters to 59 letters at 2 months (P=.03), and 57 at the end of the follow-up period (P=.3). The mean foveal thickness decreased from 502 μ to 304 μ at 2 months (P=.001), and 376 μ at the end of the follow-up period (P=.009). Further treatment with intravitreal dexamethasone was required in 43% of the patients, and 21% had increased intraocular pressure, which was controlled with topical medication. Intravitreal dexamethasone implant is an effective and locally safe treatment for the management of DME refractory to ranibizumab monotherapy or combined with other treatments. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Efficiency of Ibandronate in Monotherapy and in Combination with Alfacalcidol in Women with Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    S.I. Ismailov

    2016-09-01

    Full Text Available The aim of this study was to carry out a comparative analysis of the efficiency of ibandronate monotherapy and combined therapies with ibandronate and alfacalcidol in PMO women. Materials and Methods: A total of 53 women (mean age 60.7 years with postmenopausal osteoporosis (PMO were randomized to monotherapy with ibandronate 150 mg/month (Group Ib (n=25 and therapy with ibandronate 150mg/month plus alpha-D3(AD31μg (alfacalcidol daily (Group Ib+AD3 (n=28. All women received calcium and vitamin D3 supplements. Patients were recruited in one center and were followed up for 6 months on a monthly basis. To assess the efficacy of therapy, BMD was measured at LS (L1–L4 and PF at the beginning and end of therapy by DEXA. Biochemical markers of bone turnover were also assessed. Results: Statistically significant increases in BMD compared with baseline values and the control group were observed in both ibandronate treatment groups. Growth of BMD was significantly higher in Group Ib+AD3 compared to Group Ib. An assessment of CTX dynamics showed a notable decrease in CTX level in patients of both groups compared with levels before treatment. Generally, PTH level decreased insignificantly, but a more pronounced reduction was seen in Group Ib+AD3. TP1NP level significantly increased in Group Ib and was more pronounced in Group Ib+AD3. Conclusion: Combined therapy with ibandronate sodium and the D-hormone analog alfacalcidol augments the effectiveness of treatment observed in ibandronate sodium monotherapy in PMO women.

  1. Veränderungen kognitiver Funktionen unter LH-RH-Therapie bzw. unter Bicalutamid-Monotherapie

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    Brössner C

    2009-01-01

    Full Text Available Einleitung: Androgendeprivationstherapie mit LH-RH-Agonisten bzw. Androgenrezeptorblockade mit Bicalutamid wurde zur Standardtherapie beim fortgeschrittenen Prostatakarzinom. Der Großteil der existierenden Literatur beschreibt unter LH-RH-Gabe und damit verbundener Senkung des Testosteronspiegels eine Verschlechterung bestimmter kognitiver Gedächtnisleistungen. Ziel unserer prospektiven, konsekutiven Studie ist es, kognitive und emotionale Funktionen sowie die Lebensqualität bei Männern unter LH-RH bzw. unter Bicalutamid-Monotherapie zu untersuchen. Methoden: In Gruppe A wurden 15 Männer (mean 70,5 a; 57–81 inkludiert, die ein LH-RHAnalogon für 1 Jahr erhielten. In Gruppe B wurden 12 Männer (mean 69,3 a; 56–80 unter Bicalutamid-Monotherapie (150 mg/d für 1 Jahr inkludiert. Zum Zeitpunkt der kognitiven Testung waren alle Patienten frei von klinischer Metastasierung und die PSA-Werte waren 0,5 ng/ml. Für die Untersuchung der kognitiven Leistungen wurde eine umfangreiche neuropsychologische alters-, geschlechts- und bildungskorrigierte Testbatterie eingesetzt: Tests für Aufmerksamkeit (ZVT, Stroop-Test, Gedächtnis (NAI, WMS-R, Demenz (MMSE, Lebensqualität (WHOQOL-BREF, Wahrnehmung (Mosaik-Test, Sprache (LPS 50 Depression (BDI sowie für Angst (STAI wurden durchgeführt. Ergebnisse: In Gruppe A (unter LH-RH fanden wir signifikante Defizite im topografischen (T = 39,3 und visuellen Langzeitgedächtnis (T = 35,6. Das visuelle und verbale Arbeitsgedächtnis zeigte in dieser Gruppe grenzwertige Defizite (T = 40,67 und T = 41,67. In Gruppe B (Bicalutamid konnten wir dagegen bei keinem der Patienten ein kognitives Defizit feststellen. Schlussfolgerung: Unsere Daten suggerieren einen signifikanten negativen Einfluss der LH-RHLangzeittherapie auf bestimmte kognitive Funktionen. Im Gegensatz dazu fanden wir keine Veränderungen unter Bicalutamid-Monotherapie.

  2. Clinical resistance of Staphylococcus keratitis to ciprofloxacin monotherapy.

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    Sharma Vijay

    2004-01-01

    , showed no response and required PK. CONCLUSIONS: This study shows a significant resistance of S. aureus to many antibiotics including ciprofloxacin and highlights the need for an alternative to ciprofloxacin monotherapy for the treatment of staphylococcal keratitis.

  3. A prospective randomized trial: a comparison of the analgesic effect and toxicity of 153Sm radioisotope treatment in monotherapy and combined therapy including local external beam radiotherapy (EBRT) among metastatic castrate resistance prostate cancer (mCRPC) patients with painful bone metastases.

    Science.gov (United States)

    Baczyk, M; Milecki, P; Pisarek, M; Gut, P; Antczak, A; Hrab, M

    2013-01-01

    Bone metastases in prostate cancer constitute the most frequent cause of systemic failure in treatment, which results in numerous complications and finally leads to patient's death. Pain is one of the first and most important clinical symptoms of bone metastases and can be found among more than 80% of patients. Therefore, the most analgetic effective and simultaneously the least toxic treatment is an important point of therapeutic management in this group of patients. The aim of this prospective clinical trial was a comparison of analgetic effectiveness and toxicity of monotherapy with 153Sm isotope to combined therapy (153Sm + EBRT) among patients diagnosed with multiple painful bone metastases due to CRPC (mCRPC). 177 patients with mCRPC were included into the prospective randomised clinical trial in which 89 patients were assigned to the 153Sm isotope monotherapy, while 88 patients were assigned to the combined therapy including 153Sm isotope therapy and EBRT. All patients were diagnosed (bone scan and X-ray or/and CT or/and MRI) with painful bone metastases (bone pain intensity >= 6 according to VAS classification). The following additional inclusion criteria were established: histologically confirmed adenocarcinoma of prostate, multifocal bone metastases, no prior chemotherapy or palliative radiotherapy to bone. All patients signed informed consent.The combination of the isotope therapy with EBRT was more effective analgetic treatment than isotope therapy alone. The highest pain decline was noticed in the first weeks after treatment termination. In the whole group, a total or partial analgesic effect was observed among 154 (87%) patients while among 23 (13%) patients there was a lack of analgesic effect or even pain intensification. The results of this clinical trial demonstrated that for patients with multiple mCRPC it is recommended to combine the 153Sm isotope therapy with local EBRT because of a greater analgetic effect. It is important to note that

  4. A comparison of efficacy and tolerance of nateglinide and acarbose monotherapy in type 2 diabetes mellitns%那格列奈与阿卡波糖有效性及耐受性比较研究

    Institute of Scientific and Technical Information of China (English)

    潘长玉; 高妍; 李光伟; 朱禧星; 高鑫; 刘昕

    2009-01-01

    目的 比较那格列奈与阿卡波糖在2型糖尿病(T2DM)患者中的有效性及耐受性.方法 随机、双盲、双模拟、平行组、多中心临床研究.237例单纯饮食治疗血糖控制不佳[糖化血红蛋白(HbA1c)6.5%~11.0%]的T2DM患者,随机给予那格列奈(120 mg,3次/d,119例)或阿卡波糖(100 mg,3次/d,118例)治疗12周.结果 与基线相比,治疗后两组患者HbA1c、空腹血糖(FPG)、餐后2 h血糖(PG2h)及体重均显著降低(P0.05);FPG与基线相比的变化,两组差异亦无统计学意义(P>0.05),PG2h与基线相比的变化,那格列条组与阿卡波糖组分别为(-1.45±2.74)mmol/L、(-2.20±2.21)mmol/L(P=0.0017),体重与基线相比,那格列奈组与阿卡波糖组分别为(-0.66±1.79)kg、(-2.06±2.00)kg,P=0.0000.两组可能与研究药物相关的不良反应例数及比例差异无统计学意义.结论 那格列奈(120 mg,3次/d)在单纯饮食治疗血糖控制不佳的T2DM患者中疗效肯定,与阿卡波糖(100 mg,3次/d)降低HbA1c疗效相当,且耐受性良好.%Objective To compare the efficacy and tolerability of nateglinide with those of acarbose in Chinese type 2 diabetes mellitus (T2DM) patients.Methods This multi-center,randomized,double-blind,parallel-arm study compared the efficacy and tolerability of nateglinide( 120 mg,3/d,n = 119) and those of acarbose( 100 mg,3/d,n = 118) during a 12-week treatment in T2DM patients uncontrolled by diet with glycosylated haemoglobin (HbA1c) 6.5% - 11.0% .Results Monotherapy with nateglinide (120 mg,3/d)or acarbose (100 mg,3/d)decreased HbA1c to a similar extent during 12-week treatment.The mean change from baseline to end-point in HbAlc was ( -0.90±0.98)% and ( -0.83±0.81 )% in patients receiving nateglinide and acarbose,respectively,with no significant difference between the two groups (P>0.05).The decrease in fasting plasma glucose (FPG)was similar between nateglinide and acarbose (P > 0.05).The mean change in 2-hour postprandial plasma glucose ( PG

  5. Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy

    Science.gov (United States)

    Sunkaraneni, Soujanya; Passarell, Julie A; Ludwig, Elizabeth A; Fiedler-Kelly, Jill; Pitner, Janet K; Grinnell, Todd A; Blum, David

    2017-01-01

    Purpose Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS. Patients and methods A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (Cmin) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted Cmin as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure–response model was used to relate time-varying eslicarbazepine exposure to the time to study exit. Results For virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold. Conclusion This model-based assessment supports conversion to ESL 800 mg QD monotherapy

  6. Assessing parasite clearance during uncomplicated Plasmodium falciparum infection treated with artesunate monotherapy in Suriname

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    Vreden SGS

    2016-11-01

    Full Text Available Stephen GS Vreden,1 Rakesh D Bansie,2 Jeetendra K Jitan,3 Malti R Adhin4 1Foundation for Scientific Research Suriname (SWOS, 2Department of Internal Medicine, Academic Hospital Paramaribo, 3Department of Public Health, Ministry of Health, 4Department of Biochemistry, Anton de Kom University of Suriname, Paramaribo, Suriname Background: Artemisinin resistance in Plasmodium falciparum is suspected when the day 3 parasitemia is >10% when treated with artemisinin-based combination therapy or if >10% of patients treated with artemisinin-based combination therapy or artesunate monotherapy harbored parasites with half-lives ≥5 hours. Hence, a single-arm prospective efficacy trial was conducted in Suriname for uncomplicated P. falciparum infection treated with artesunate-based monotherapy for 3 days assessing day 3 parasitemia, treatment outcome after 28 days, and parasite half-life. Methods: The study was conducted in Paramaribo, the capital of Suriname, from July 2013 until July 2014. Patients with uncomplicated Plasmodium falciparum infection were included and received artesunate mono-therapy for three days. Day 3 parasitaemia, treatment outcome after 28 days and parasite half-life were determined. The latter was assessed with the parasite clearance estimator from the WorldWide Antimalarial Resistance Network (WWARN. Results: Thirty-nine patients were included from July 2013 until July 2014. The day 3 parasitemia was 10%. Eight patients (20.5% could be followed up until day 28 and showed adequate clinical and parasitological response. Parasite half-life could only be determined from ten data series (25.7%. The median parasite half-life was 5.16 hours, and seven of these data series had a half-life ≥5 hours, still comprising 17.9% of the total data series. Conclusion: The low follow-up rate and the limited analyzable data series preclude clear conclusions about the efficacy of artesunate monotherapy in Suriname and the parasite half

  7. Cost-effectiveness of dipeptidyl peptidase-4 inhibitor monotherapy in elderly type 2 diabetes patients in Thailand

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    Permsuwan U

    2016-09-01

    Full Text Available Unchalee Permsuwan,1 Piyameth Dilokthornsakul,2 Surasak Saokaew,2–4 Kednapa Thavorn,5–7 Nathorn Chaiyakunapruk2,4,8,9 1Faculty of Pharmacy Chiang Mai University, Chiang Mai, 2Center of Pharmaceutical Outcomes Research, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 3Center of Health Outcomes Research and Therapeutic Safety, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand; 4School of Pharmacy, Monash University Malaysia, Sunway, Malaysia; 5Ottawa Hospital Research Institute, The Ottawa Hospital, 6School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, Ottawa, 7Institute for Clinical and Evaluative Sciences, Toronto, ON, Canada; 8School of Population Health, The University of Queensland, Brisbane, QLD, Australia; 9School of Pharmacy, University of Wisconsin–Madison, Madison, WI, USA Background: The management of type 2 diabetes mellitus (T2DM in elderly population poses many challenges. Dipeptidyl peptidase-4 (DPP-4 inhibitors show particular promise due to excellent tolerability profiles, low risk of hypoglycemia, and little effect on body weight. This study evaluated, from the health care system’s perspective, the long-term cost-effectiveness of DPP-4 inhibitor monotherapy vs metformin and sulfonylurea (SFU monotherapy in Thai elderly T2DM patients. Methods: The clinical efficacy was estimated from a systematic review and meta-analysis. Baseline cohort characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. A validated IMS CORE Diabetes Model version 8.5 was used to project clinical and economic outcomes over a lifetime horizon using a 3% annual discount rate. Costs were expressed in 2014 Thai Baht (THB (US dollar value. Incremental cost-effectiveness ratios were calculated. Base-case assumptions were assessed through several sensitivity analyses. Results: For treating elderly T2DM

  8. Mutations in carboxy-terminal part of E2 including PKR/eIF2αphosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b:Their correlation with response to interferon monotherapy and viral load

    Institute of Scientific and Technical Information of China (English)

    Koji Ukai; Masatoshi Ishigami; Kentaro Yoshioka; Naoto Kawabe; Yoshiaki Katano; Kazuhiko Hayashi; Takashi Honda; Motoyoshi Yano; Hidemi Goto

    2006-01-01

    AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR)and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-1b-infected patients treated with IFN.METHODS: The C-terminal part of E2 (codons 617-711)including PKR/eIF2α phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy.RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2was significantly correlated with both small viral load (33.9% vs 13.8%, P=0.0394) and sustained response to IFN (25.0% vs 6.9%,P=0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P<0.0001) and sustained response to IFN (85.7% vs 2.9%, P<0.0001).In multivariate analysis, ISDR in nonstructural (NS) 5A (OR=0.39, P<0.0001) and N-terminal variable region (OR=0.51, P=0.039) was selected as the independent predictors for small viral load, and ISDR (OR=39.0, P<0.0001) was selected as the only independent predictor for sustained response.CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.

  9. Successful Treatment of Mild Pediatric Kasabach-Merritt Phenomenon with Propranolol Monotherapy

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    Worawut Choeyprasert

    2014-01-01

    Full Text Available Kasabach-Merritt phenomenon (KMP is relatively rare in childhood and adolescents with high mortality rate because of its hemorrhagic complications and unresponsiveness to treatments such as corticosteroids, vincristine, intravascular embolization, and/or surgery. Propranolol, a β-adrenergic receptor blocker, has a promising efficacy against vascular tumors such as infantile hemangiomas. But limited and variable data has been reported regarding the role of propranolol in treatment of KMP. We herein reported the successful treatment of mild pediatric KMP with propranolol monotherapy in a case of a five-week-old child with kaposiform hemangioendothelioma with successful treatment of both clinical and hematologic responses. After eight months of follow-up, patient still had stable cutaneous lesion while receiving propranolol monotherapy. Regular hematologic monitoring was done in order to detect any late relapse of the disease. Six months after discontinuation of propranolol, patient has still remained free of hematologic relapse, and primary cutaneous lesion has become a pale pink, 1 cm sized skin lesion.

  10. Combining bosentan and sildenafil in pulmonary arterial hypertension patients failing monotherapy: real-world insights.

    Science.gov (United States)

    Dardi, Fabio; Manes, Alessandra; Palazzini, Massimiliano; Bachetti, Cristina; Mazzanti, Gaia; Rinaldi, Andrea; Albini, Alessandra; Gotti, Enrico; Monti, Enrico; Bacchi Reggiani, Maria Letizia; Galiè, Nazzareno

    2015-08-01

    Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3-4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (p<0.003).The favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.

  11. Efficacy and Safety of Levetiracetam and Carbamazepine as Monotherapy in Partial Seizures

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    Swaroop Hassan Suresh

    2015-01-01

    Full Text Available Introduction. Levetiracetam (LEV is a newer antiepileptic drug with better pharmacokinetic profile. Currently, it is frequently used for the treatment of partial seizures. The present study was undertaken to compare the efficacy and safety of LEV and Carbamazepine (CBZ in partial epilepsy. Methods. This was a prospective, open labeled, randomized study. It was conducted in participants suffering from partial seizures after the approval of ethics committee and written informed consent. The first group received Tab LEV (500 to 3000 mg/day and the second group received Tab CBZ (300 to 600 mg/day. The primary outcomes were efficacy and safety. The secondary outcome was the Quality of Life (QOL. Efficacy was assessed by comparing the seizure freedom rates at the end of 6 months. Safety profile was evaluated by comparing the adverse effects. QOL was assessed by QOLIE-10 scale. Results. The overall seizure freedom rate at the end of 6 months was 71.42% in CBZ group compared to 78.57% in LEV group (p=0.2529. Both LEV and CBZ reported a similar incidence of adverse reactions. LEV group reported more behavioral changes like increased aggression and anxiety. Also, it showed better QOL compared to the CBZ group. Conclusion. LEV monotherapy and CBZ monotherapy demonstrated similar efficacy for treatment of partial epilepsy and were found to be well tolerated.

  12. 光动力学疗法联合雷珠单抗对比雷珠单抗治疗湿性AMD有效性和安全性的Meta分析%A comparison of the efficacy and safety of ranibizumab combined with photodynamic therapy (PDT) versus ranibizumab monotherapy for the treatment of wet age-related macular degeneration: a meta analysis

    Institute of Scientific and Technical Information of China (English)

    蒋璐; 陶继伟; 洪明胜; 余心洁; 沈丽君

    2014-01-01

    Objective To evaluate the efficacy and safety of ranibizumab combined with photodynamic therapy versus ranibizumab monotherapy for the treatment of wet age-related macular degeneration (AMD).Methods In this meta analysis,searches were conducted in Pubmed,EMbase,Cochrane Library,CNKI,and Wanfang databases.Six randomized control trials (RCT) in the literature were selected for meta-analysis,a total of 626 eyes:a monotherapy group (323 eyes) and a combined treatment group (303 eyes).The methodological quality was conducted according to evidence-based medicine (EBM).The qualities of the RTCs were evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions,Version 5.0.The Cochrane Collaboration's software RevMan 5.0 was used for meta-analysis.Results The results of the meta-analysis showed the following:①Best corrected visual acuity(BCVA):the monotherapy group showed greater improvement in BCVA compared with the combined treatment group [WMD=-2.84,95%CI(0.25-5.43),P<0.05].The incidence of people who gained ≥ 15 letters in the monotherapy group was higher than the combined treatment group [WMD=0.66,95%CI(0.45-0.96),P<0.05].However,there was no significant difference between the two groups in the incidence of people who lost ≥15 letters [WMD=1.37,95%CI(0.78-2.41),P>0.05].②Central retinal thickness (CRT):There was no significant difference between the two groups [WMD=-3.17,95%CI(-25.64-31.97),P>0.05].③Lesion size (LZ):There was no significant difference between the two groups [WMD=0.24,95%CI(-0.38-0.86),P>0.05].④Injection times:There was no significant difference between the two groups [WMD=-1.00,95%CI(-2.56~0.56),P>0.05].⑤Complications:The combined treatment group had a higher probability of retinal hemorrhage than the monotherapy group [RR=2.65,95%CI(1.04-6.71),P<0.05].Conclusion Meta-analysis shows that ranibizumab monotherapy is effective in achieving a BCVA gain comparable to the combined treatment

  13. The efficacy and safety of fixed-dose combination of amlodipine/benazepril in Chinese essential hypertensive patients not adequately controlled with benazepril monotherapy: a multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial.

    Science.gov (United States)

    Yan, Pingping; Fan, Weihu

    2014-01-01

    This double-blind, double-dummy clinical trial evaluated the efficacy and safety of two strengths of fixed-dose combination of amlodipine/benazepril in Chinese hypertensive patients not adequately controlled with benazepril. Of 442 patients who received treatment with benazepril 10 mg for 4 weeks, 341 patients failed to achieve to diastolic blood pressure (DBP) amlodipine/benazepril 2.5/10 mg, or amlodipine/benazepril 5/10 mg, or benazepril 10 mg for 8 weeks. BP reductions with amodipinel/benazepril 2.5/10 mg (15.2/11.8 mmHg) or amlodipine/benazepril 5/10 mg (15.4/12.4 mmHg) were significantly greater than that with benazepril 10 mg (9.88/9.46 mmHg) at study end (p benazepril). BP control rate was 83.8% with amlodipine/benazepril 2.5/10 mg, 80.2% with amlodipine/benazepril 5/10 mg, 64.9% with benazepril 10 mg at study end (p benazepril). Three groups were generally well tolerated. Our study indicated that amlodipine/benazepril fixed-dose combination offered significant additional BP reductions and BP control rate compared with the continuation of benazepril monotherapy. No significant differences were observed in both BP reductions and BP control rate between amlodipine/benazepril 2.5/10 mg and amlodipine/benazepril 5/10 mg.

  14. Clinical observation of capecitabine monotherapy in elderly patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Miao Zhang; Zhaozhe Liu Co-first author; Zhendong Zheng; Tao Han; Yaling Han; Min Song; Xiaodong Xie

    2015-01-01

    Objective The aim of the study was to evaluate the safety and ef icacy of capecitabine mono-chemo-therapy in elderly patients with advanced breast cancer. Methods The data from 36 cases of capecitabine monotherapy in elderly patients with advanced breast cancer were retrospectively analyzed. Oral administration of capecitabine 2000 mg/m2 twice daily (D1–14) for 21 days constituted a cycle. The ef ect of the disease and main adverse reactions were evaluated every 2 cycles. Results The data from 36 elderly patients were studied. The median number of chemotherapy cycles was 4. The total ef ective rate was 30.6% (11/36) and the disease control rate was 72.2% (26/36). The number of patients with clinical complete remission was 2, clinical partial response was 9, stable disease was 15, and progressive disease was 10. Where treatment was ef ective, the median time to progression was 6 months and the median overal survival was 9.5 months. The main adverse events were gastroin-testinal reactions, bone marrow suppression, and oral mucositis; most of the reactions were grade 1 to 2. Grade 3 to 4 adverse reactions included granulocytopenia in 2 patients (12.5%) and hand-foot syndrome in 1 patient (6.7%). Conclusion Capecitabine monotherapy was ef ective in control ing disease progression, and adverse reactions were tolerated by elderly patients with advanced breast cancer.

  15. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study

    DEFF Research Database (Denmark)

    Savonitto, S; Ardissiono, D; Egstrup, K

    1996-01-01

    10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p ...OBJECTIVES: This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotherapy in individual patients with stable angina pectoris. BACKGROUND: Combination therapy with a beta-adrenergic blocking agent...... (which reduces myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the treatment of stable angina pectoris. However, it is not clear whether, in individual patients, this combined therapy is more effective than monotherapy...

  16. Effects of an olmesartan/amlodipine fixed dose on blood pressure control, some adipocytokines and interleukins levels compared with olmesartan or amlodipine monotherapies.

    Science.gov (United States)

    Derosa, G; Cicero, A F G; Carbone, A; Querci, F; Fogari, E; D'Angelo, A; Maffioli, P

    2013-02-01

    To evaluate the effects of an olmesartan/amlodipine single pill combination compared with olmesartan or amlodipine monotherapies on blood pressure control, lipid profile, insulin sensitivity and some adipocytokines levels. Two hundred and seventy-six patients were enroled in the study and were randomly assigned to take olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20 mg/5 mg for 12 months. We evaluated at the baseline, and after 6 and 12 months: body weight, body mass index, systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), resistin (r), interleukin-1β (IL-1β) and interleukin-5 (IL-5). At the baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp to assess insulin sensitivity (M value). There was a similar decrease in SBP and DBP after 6 and 12 months in all groups, even if olmesartan/amlodipine combination gave a major decrease in SBP and DPB compared with amlodipine and olmesartan monotherapies. Olmesartan/amlodipine combination decreased FPG after 12 months compared with amlodipine monotherapy. Olmesartan/amlodipine combination decreased FPI and HOMA index and increased M value both compared with baseline and compared with olmesartan and amlodipine monotherapies. Both olmesartan and olmesartan/amlodipine increased ADN and reduced r, without significant differences between the two groups. Regarding interleukins, no differences emerged in group to group comparison. Olmesartan/amlodipine combination resulted more effective than olmesartan and amlodipine monotherapies in reducing blood pressure, and in increasing insulin sensitivity parameters, but not resulted more effective in improving adipocytokines and interleukins levels analysed, compared with amlodipine or olmesartan monotherapy in hypertensive patients in this double-blind, randomized clinical trial. © 2012 Blackwell

  17. Effects of antiepileptic drug monotherapy on one-carbon metabolism and DNA methylation in patients with epilepsy.

    Directory of Open Access Journals (Sweden)

    Guanzhong Ni

    Full Text Available The aim of this study was to compare the serum levels of one-carbon metabolism (OCM nutrients (e.g., folate, homocysteine and vitamin B12 and peripheral blood DNA methylation in epileptic patients under treatment with antiepileptic drugs (AEDs and in healthy controls.In this cross-sectional study, 60 patients with epilepsy who were receiving valproate (VPA (n = 30 or lamotrigine (LTG (n = 30 monotherapy were enrolled. Thirty age and sex matched healthy subjects served as the controls. Serum concentrations of OCM nutrients and peripheral blood DNA methylation status were measured.Compared to the control group, the VPA group had higher serum levels of homocysteine (p<0.05. No difference in homocysteine concentration was observed in the LTG group. Patients receiving VPA or LTG had significantly lower serum folate levels in comparison with controls (p<0.001. The level of methylation of long interspersed nucleotide element-1 (LINE-1 in peripheral blood was not significantly different between the AED monotherapy group and healthy controls. A difference in the methylation levels of methylenetetrahydrofolate reductase (MTHFR amplicon was observed between AED-treated patients with epilepsy and controls (p<0.01. A positive correlation between serum folate levels and peripheral blood MTHFR amplicon methylation status was also observed (r = 0.25, p = 0.023.Our findings suggest that the effects of AED monotherapy on OCM may induce specific regions of DNA hypomethylation.

  18. Long-term, maintenance MMF monotherapy improves the fibrosis progression in liver transplant recipients with recurrent hepatitis C.

    Science.gov (United States)

    Manzia, Tommaso Maria; Angelico, Roberta; Toti, Luca; Bellini, Maria Irene; Sforza, Daniele; Palmieri, Giampiero; Orlando, Giuseppe; Tariciotti, Laura; Angelico, Mario; Tisone, Giuseppe

    2011-05-01

    Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well-matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.

  19. Rational choice of monotherapy for the treatment of type 2 diabetes mellitus based on the pharmacoeconomical analysis

    Directory of Open Access Journals (Sweden)

    Tatyana Ivko

    2014-12-01

    Full Text Available Research was conducted to scientific justification of rational choice of monotherapy diabetes mellitus (DM type 2 based on the pharmacoeconomical analysis. It has been found that the unit of efficiency was the cheapest in the scheme of the monotherapy with gliclazide and most expensive – in the scheme of the monotherapy with metformin.

  20. Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation.

    Science.gov (United States)

    Johnston, Rhona; Uthman, Olalekan; Cummins, Ewen; Clar, Christine; Royle, Pamela; Colquitt, Jill; Tan, Bee Kang; Clegg, Andrew; Shantikumar, Saran; Court, Rachel; O'Hare, J Paul; McGrane, David; Holt, Tim; Waugh, Norman

    2017-01-01

    BACKGROUND Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. OBJECTIVE To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. SOURCES MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. METHODS Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. RESULTS We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). LIMITATIONS There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated

  1. [Efficacy of lamivudine monotherapy and combination therapy with adefovir dipivoxil for patients with hepatitis B virus-related decompensated cirrhosis].

    Science.gov (United States)

    Jia, Hong-Yu; Lu, Wei; Zheng, Lin; Ying, Ling-Jun; Yang, Yi-da

    2011-02-01

    To compare the efficacy of Lamivudine (LAM) monotherapy and combination therapy with Adefovir Dipivoxil (ADV) for patients with hepatitis B virus (HBV) -related decompensated cirrhosis for 2 years. A total of 115 patients with HBV-related decompensated cirrhosis were erolled in this study, among 60 patients were treated with LAM combined with ADV and 55 were treated with LAM. The liver and kidney functions, HBV DNA, HBV-M, AFP, Ultrasond or CT scan of liver were tested every 1-3months. the treatment efficacy was evaluated by month 12 and 24. By month 12, the HBV DNA negative rates of combination therapy group and LAM monotherapy group were 51.1% (45 cases) and 47.5% (40 cases) respectively, by month 24 the rates were 86.7% and 60.0% respectively. By month 24 the HBeAg negative rates of combination therapy group and LAM monotherapy group were 43.5% and 30.0% respectively, with significant difference existed between the two therapy groups (P values is less than 0.05). By month 24, the ALT normalization rates of the two groups were 88.9% and 72.5% respectively. Viral breakthrough happened in 2 cases (4.4%) by month 12 and 3 cases (6.7%) by month 24 in LAM and ADV combination group, but no viral resistance observed. Viral breakthrough happened in 9 cases (22.5%) by month 12 and 15 cases (37.5%) by month 24 in LAM monotherapy group with viral resistance observed in 7 cases (17.5%) by month 12 and 13 cases (32.5) by month 24. Significant difference existed between the two groups (P is less than 0.05). Improvement of liver function was more obviously in the combination group. The accumulative total mortality or liver transplantation rate were 16.7% and 20.0% respectively in combination therapy group and LAM monotheapy group. No renal dysfunction observed in both groups. LAM combined with ADV is better choice for patients with HBV-related decompensated cirrhosis as compared to LAM monotherapy.

  2. Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia.

    Science.gov (United States)

    Benes, Lane B; Bassi, Nikhil S; Davidson, Michael H

    2016-01-01

    The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin.

  3. Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of metastatic prostate cancer. The Scandinavian Casodex Cooperative Group

    DEFF Research Database (Denmark)

    Iversen, P; Tveter, K; Varenhorst, E

    1996-01-01

    The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen, given as 50 mg monotherapy, was compared with orchidectomy in a randomised, multicentre, open study in 376 patients with metastatic prostate cancer. At 3 months, PSA was reduced by 86% in the Casodex group and by 96% ...

  4. Prostate-specific antigen kinetics after stereotactic body radiotherapy as monotherapy or boost after whole pelvic radiotherapy for localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Hun Jung Kim

    2015-12-01

    Conclusions: In this report of low- and intermediate-risk prostate cancer patients, an initial period of rapid PSA decline was followed by a slow decline, which resulted in a lower PSA nadir. The PSA kinetics of SBRT monotherapy appears to be comparable to those achieved with SBRT boost with WPRT.

  5. Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of metastatic prostate cancer. The Scandinavian Casodex Cooperative Group

    DEFF Research Database (Denmark)

    Iversen, P; Tveter, K; Varenhorst, E

    1996-01-01

    The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen, given as 50 mg monotherapy, was compared with orchidectomy in a randomised, multicentre, open study in 376 patients with metastatic prostate cancer. At 3 months, PSA was reduced by 86% in the Casodex group and by 96% ...

  6. Cost-efficacy analysis of darunavir/r monotherapy in clinical practice

    Directory of Open Access Journals (Sweden)

    M Pérez Elías

    2012-11-01

    Full Text Available Purpose of the study: To evaluate the economic impact of a swiching strategy to DRV/r mx in clinical practice using Spanish prices. Methods: Multicenter retrospective study of four tertiary hospitals in Spain. The analysis includes 147 patients switching to DRV/r mx mainly due to toxicity or simplification from March 2009 to June 2011. The Spanish costs (ex-factory price+VAT per patient with HIV RNA<50 copies/ml were calculated, accounting for additional/ switch antiretroviral taken after initial treatment failure and management of adverse events. Cost of adverse events were based on a Spanish publication [1] (updated by the inflation rate until april 2012 The horizon of the analysis was of 48 weeks. Summary of results: Baseline characteristics were: women (30.6%, median age (49 yr, IDU (45%, AIDS stage (32%, HCV coinfected (48%, 40% with advanced fibrosis, length of HIV-RNA<1.7 before DRV/rtv mtx 67.6. Most frequent reasons for switching to DRVr mx were toxicity (62.6% and simplification (23.8%. If a hospital with 600 patients in ART treatment, switched from 10% to 20% of its patients to DRV/r mx, there is a potential to save up to 448,000€/year. Conclusions: Switching to DRV/r mx is a cost-effective strategy that allows more patients to be treated for a fixed budget. Higher cost saving is expected when toxicity is the reason for switching. 48 Weeks Cost-Efficacy analysis: Simplification strategy to DRV/r monotherapy Hospital Budget Impact Analysis: assuming that 10%–20% of 600 patients in ARV treatment simplifies to DRV/r monotherapy

  7. Seasonal variations in TSH serum levels in athyreotic patients under L-thyroxine replacement monotherapy.

    Science.gov (United States)

    Gullo, Damiano; Latina, Adele; Frasca, Francesco; Squatrito, Sebastiano; Belfiore, Antonino; Vigneri, Riccardo

    2017-08-01

    Whether serum TSH undergoes seasonal fluctuations in euthyroid and hypothyroid residents of temperate climates is controversial. Monthly TSH and thyroid hormone levels were cross-sectionally analysed in a large cohort of euthyroid subjects (n=11 806) and L-thyroxine (L-T4)-treated athyreotic patients (n=3 934). Moreover, in a small group (n=119) of athyreotic patients treated with an unchanged dosage of L-T4 monotherapy, hormones were measured both in the coldest and in the hottest seasons of the same year (longitudinal study). No seasonal hormone change was observed in the euthyroid subjects except for a small FT3 increase in winter (+2.9%, PL-T4-treated athyreotic patients had significantly higher serum TSH values in the cold season when the FT4 values were significantly lower. The differences were more notable in the longitudinal series (TSH, 0.80 vs. 0.20 mU/L and FT4, 16.3 vs. 17.8 pmol/L in December-March vs. June-September, respectively). In these patients also serum FT3 values significantly decreased in winter (in the longitudinal series, 3.80 in winter vs 4.07 pmol/L in summer). Regression analysis showed that in athyreotic subjects, a greater FT4 change is required to obtain a TSH change similar to that of euthyroid controls and that this effect is more pronounced in the summer. Athyreotic patients undergoing L-T4 monotherapy have abnormal seasonal variations in TSH. These changes are secondary to the FT4 and FT3 serum decreases in winter, which occur in spite of the constant treatment. The underlying mechanisms are unclear, but in some cases, these changes may be clinically relevant. © 2017 John Wiley & Sons Ltd.

  8. Variation of some inflammatory markers in hypertensive patients after 1 year of olmesartan/amlodipine single-pill combination compared with olmesartan or amlodipine monotherapies.

    Science.gov (United States)

    Derosa, Giuseppe; Cicero, Arrigo F G; Carbone, Anna; Querci, Fabrizio; Fogari, Elena; D'Angelo, Angela; Maffioli, Pamela

    2013-01-01

    The purpose of this study was to evaluate a fixed olmesartan/amlodipine combination on blood pressure control, lipid profile, insulin sensitivity, and some inflammatory markers compared with single-drug monotherapy. A total of 276 hypertensive patients were randomly assigned to olmesartan 20 mg, amlodipine 10 mg, or a single pill containing olmesartan/amlodipine combination 20/5 mg for 12 months. We evaluated the following at baseline and after 6 and 12 months: body weight, body mass index, systolic (SBP) and diastolic blood pressures (DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, tumor necrosis factor-α (TNF-α), retinol binding protein-4 (RBP-4), and interleukins 6 and 7 (IL-6 and IL-7). At baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp. The olmesartan/amlodipine combination provided a greater decrease of SBP and DPB compared with amlodipine and olmesartan monotherapies. The olmesartan/amlodipine combination decreased FPG after 12 months compared with amlodipine monotherapy. The combination decreased FPI and homeostasis model assessment index and increased M value both compared with baseline and with olmesartan and amlodipine monotherapies. Olmesartan/amlodipine decreased IL-7, but not IL-6, compared with single drug components. The olmesartan/amlodipine combination is effective and safe in reducing blood pressure and has some additive effects not shown by single drugs, such as an improvement of IL-7. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  9. Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues

    DEFF Research Database (Denmark)

    Antinori, Andrea; Clarke, Amanda; Svedhem-Johansson, Veronika

    2015-01-01

    BACKGROUND: In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance. METHODS: A total of 273 patients with HIV-1 RNA less than ...

  10. Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases IGF-I bioactivity similarly

    NARCIS (Netherlands)

    A.J. Varewijck (Aimee); J.A.M.J.L. Janssen (Joseph); M. Vähätalo (M.); L.J. Hofland (Leo); S.W.J. Lamberts (Steven); H. Yki-Jarvinen (Hannele)

    2012-01-01

    textabstractAims/hypothesis The aim of this study was to compare IGFI bioactivity 36 weeks after the addition of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) or NPH insulin to metformin therapy in type 2 diabetic patients who had poor glucose control under metformin monotherapy. Methods In

  11. Fractional CO 2 laser resurfacing as monotherapy in the treatment of atrophic facial acne scars

    Directory of Open Access Journals (Sweden)

    Imran Majid

    2014-01-01

    Full Text Available Background: While laser resurfacing remains the most effective treatment option for atrophic acne scars, the high incidence of post-treatment adverse effects limits its use. Fractional laser photothermolysis attempts to overcome these limitations of laser resurfacing by creating microscopic zones of injury to the dermis with skip areas in between. Aim: The aim of the present study is to assess the efficacy and safety of fractional CO 2 laser resurfacing in atrophic facial acne scars. Materials and Methods: Sixty patients with moderate to severe atrophic facial acne scars were treated with 3-4 sessions of fractional CO 2 laser resurfacing at 6-week intervals. The therapeutic response to treatment was assessed at each follow up visit and then finally 6 months after the last laser session using a quartile grading scale. Response to treatment was labelled as ′excellent′ if there was >50% improvement in scar appearance and texture of skin on the grading scale while 25-50% response and <25% improvement were labelled as ′good′ and ′poor′ response, respectively. The overall satisfaction of the patients and any adverse reactions to the treatment were also noted. Results: Most of the patients showed a combination of different morphological types of acne scars. At the time of final assessment 6 months after the last laser session, an excellent response was observed in 26 patients (43.3% while 15 (25% and 19 patients (31.7% demonstrated a good and poor response respectively. Rolling and superficial boxcar scars responded the best while pitted scars responded the least to fractional laser monotherapy. The commonest reported adverse effect was transient erythema and crusting lasting for an average of 3-4 and 4-6 days, respectively while three patients developed post-inflammatory pigmentation lasting for 8-12 weeks. Conclusions: Fractional laser resurfacing as monotherapy is effective in treating acne scars especially rolling and superficial boxcar

  12. Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy

    Directory of Open Access Journals (Sweden)

    Sunkaraneni S

    2017-06-01

    Full Text Available Soujanya Sunkaraneni,1 Julie A Passarell,2 Elizabeth A Ludwig,2 Jill Fiedler-Kelly,2 Janet K Pitner,1 Todd A Grinnell,1 David Blum1 1Sunovion Pharmaceuticals Inc., Marlborough, MA, USA; 2Cognigen Corporation (a SimulationsPlus company, Buffalo, NY, USA Purpose: Eslicarbazepine acetate (ESL is a once-daily (QD oral antiepileptic drug (AED indicated for partial-onset seizures (POS. Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS. Patients and methods: A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (Cmin in 1,500 virtual patients taking 1 (n=1,000 or 2 (n=500 AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose. Model-predicted Cmin as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure–response model was used to relate time-varying eslicarbazepine exposure to the time to study exit. Results: For virtual patients receiving ESL monotherapy (800 mg QD, the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1

  13. Combination therapy or monotherapy for the depressed type of schizoaffective disorder

    Directory of Open Access Journals (Sweden)

    Lubomira Izáková

    2009-02-01

    Full Text Available Lubomira Izáková1, Ivan Andre1, Angelos Halaris21Psychiatric Clinic, Faculty of Medicine Comenius University and Faculty Hospital, Bratislava, Slovakia; 2Department of Psychiatry and Behavioral Neurosciences, Loyola University Medical Center, Maywood, IL, USAAbstract: Several studies have demonstrated the effectiveness of adjunctive antidepressant drug therapy to improve the depressive or negative symptoms of schizoaffective disorder, however, monotherapy with atypical antipsychotics may be advantageous. We compared the efficacy and safety of risperidone monotherapy versus combination therapy of haloperidol with sertaline for the acute treatment of schizoaffective disorder, depressed type. This is an open label study of 52 female inpatients randomly assigned to risperidone alone (N = 26 or haloperidol in combination with sertraline (N = 26 for 12 weeks. The mean daily doses of medications were: risperidone: 3.75–3.29 mg/day, haloperidol: 5.35–4.15 mg/day, sertraline: 65.39–133.82 mg/day. Efficacy was measured using clinical rating scales of treatment, safety, and tolerability. Risperidone patients showed statistically significant greater improvement than haloperidol-sertraline patients on efficacy measures including Positive and Negative Syndrome Scale and Clinical Global Impressions rating. A higher number of risperidone patients dropped out of the study early. Fewer adverse events and lesser need for concomitant medications occurred in patients on risperidone. The risperidone group showed better psychological, social and occupational functioning (Global Assessment of Functioning and higher quality of life (Heinrich’s Quality of Life Scale. Risperidone has higher antipsychotic efficacy and tolerability compared with haloperidol-sertraline combination for the acute treatment of schizoaffective disorder, depressed type. Both treatments were comparable in terms of antidepressant efficacy.Keywords: schizoaffective disorder, depressed type

  14. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukemia groups (AML-19)

    Science.gov (United States)

    Amadori, Sergio; Suciu, Stefan; Selleslag, Dominik; Stasi, Roberto; Alimena, Giuliana; Baila, Liliana; Rizzoli, Vittorio; Borlenghi, Erika; Gaidano, Gianluca; Magro, Domenico; Torelli, Giuseppe; Muus, Petra; Venditti, Adriano; Cacciola, Emma; Lauria, Francesco; Vignetti, Marco; de Witte, Theo

    2010-01-01

    Summary This study compared two schedules of low-dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best supportive care or a course of GO according to one of two schedules: 3 mg/m2 on days 1, 3 and 5 (arm A), or GO 6 mg/m2 on day 1 and 3 mg/m2 on day 8 (arm B). Primary endpoint was the rate of disease non-progression (DnP), defined as the proportion of patients either achieving a response or maintaining a stable disease following GO induction in each arm. Fifty-six patients were randomized in the two GO arms (A, n=29; B, n=27). The rate of DnP was 38% (90% confidence interval [CI], 23%–55%) in arm A, and 63% (90% CI, 45%–78%) in arm B. Peripheral cytopenias were the most common adverse events for both regimens. The all-cause early mortality rate was 14% in arm A and 11% in arm B. The day 1+8 schedule, which was associated with the highest rate of DnP, met the statistical criteria to be selected as the preferred regimen for phase III comparison with best supportive care. PMID:20230405

  15. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML-19).

    Science.gov (United States)

    Amadori, Sergio; Suciu, Stefan; Selleslag, Dominik; Stasi, Roberto; Alimena, Giuliana; Baila, Liliana; Rizzoli, Vittorio; Borlenghi, Erika; Gaidano, Gianluca; Magro, Domenico; Torelli, Giuseppe; Muus, Petra; Venditti, Adriano; Cacciola, Emma; Lauria, Francesco; Vignetti, Marco; de Witte, Theo

    2010-05-01

    This study compared two schedules of low-dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukaemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best supportive care or a course of GO according to one of two schedules: 3 mg/m(2) on days 1, 3 and 5 (arm A), or GO 6 mg/m(2) on day 1 and 3 mg/m(2) on day 8 (arm B). Primary endpoint was the rate of disease non-progression (DnP), defined as the proportion of patients either achieving a response or maintaining a stable disease following GO induction in each arm. Fifty-six patients were randomized in the two GO arms (A, n = 29; B, n = 27). The rate of DnP was 38% [90% confidence interval (CI), 23-55] in arm A, and 63% (90% CI, 45-78) in arm B. Peripheral cytopenias were the most common adverse events for both regimens. The all-cause early mortality rate was 14% in arm A and 11% in arm B. The day 1 + 8 schedule, which was associated with the highest rate of DnP, met the statistical criteria to be selected as the preferred regimen for phase III comparison with best supportive care.

  16. Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Tyrrell, C J; Kaisary, A V

    1998-01-01

    To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer....

  17. Decision Analysis Modelling of Costs and Outcomes following Cefepime Monotherapy in Canada

    Directory of Open Access Journals (Sweden)

    Michael T Halpern

    1997-01-01

    Full Text Available OBJECTIVE: To evaluate the comparative cost of treatment and intermediate outcomes (percentage resistant organisms, days in hospital, etc among cefepime and alternative parenteral antibiotics used for empiric monotherapy.

  18. Effect on Intraocular Pressure of Switching from Latanoprost and Travoprost Monotherapy to Timolol Fixed Combinations in Patients with Normal-Tension Glaucoma

    Directory of Open Access Journals (Sweden)

    Ryoko Igarashi

    2014-01-01

    Full Text Available Purpose. To evaluate the effect on intraocular pressure (IOP of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in Japanese patients with normal-tension glaucoma (NTG. Methods. 27 NTG patients (54 eyes were compared IOP, superficial punctuate keratitis (SPK scores, and conjunctival injection scores in eyes treated with prostaglandin (PG or PG analog/beta-blocker (PG/b fixed-combination 6 months after the change in therapy. Results. The mean baseline intraocular pressure was 17.4±1.59 mmHg in eyes receiving PG therapy only and 17.4±1.69 mmHg in eyes switched to PG/b. Switching to fixed combination therapy from PG monotherapy, the mean IOP was 13.1±1.79 mmHg (P<0.001  (-24.71% reduction from baseline at 6 months. The mean conjunctival injection score was 0.69 for eyes on PG monotherapy and 0.56 for eyes on fixed combination therapy (P=0.028. The mean SPK scores were 0.46 and 0.53. This difference was not statistically significant (P=0.463. Conclusions. Switching from PG monotherapy to PG/b fixed combination therapy for NTG resulted in a greater intraocular pressure reduction than PG alone without increasing the number of instillations.

  19. Effect on intraocular pressure of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in patients with normal-tension glaucoma.

    Science.gov (United States)

    Igarashi, Ryoko; Togano, Tetsuya; Sakaue, Yuta; Yoshino, Takaiko; Ueda, Jun; Fukuchi, Takeo

    2014-01-01

    Purpose. To evaluate the effect on intraocular pressure (IOP) of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in Japanese patients with normal-tension glaucoma (NTG). Methods. 27 NTG patients (54 eyes) were compared IOP, superficial punctuate keratitis (SPK) scores, and conjunctival injection scores in eyes treated with prostaglandin (PG) or PG analog/beta-blocker (PG/b) fixed-combination 6 months after the change in therapy. Results. The mean baseline intraocular pressure was 17.4 ± 1.59 mmHg in eyes receiving PG therapy only and 17.4 ± 1.69 mmHg in eyes switched to PG/b. Switching to fixed combination therapy from PG monotherapy, the mean IOP was 13.1 ± 1.79 mmHg (P < 0.001)  (-24.71% reduction from baseline) at 6 months. The mean conjunctival injection score was 0.69 for eyes on PG monotherapy and 0.56 for eyes on fixed combination therapy (P = 0.028). The mean SPK scores were 0.46 and 0.53. This difference was not statistically significant (P = 0.463). Conclusions. Switching from PG monotherapy to PG/b fixed combination therapy for NTG resulted in a greater intraocular pressure reduction than PG alone without increasing the number of instillations.

  20. Effectiveness and drug adherence of biologic monotherapy in routine care of patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jørgensen, Tanja Schjødt; Kristensen, Lars Erik; Christensen, Robin;

    2015-01-01

    DMARD) treatment as monotherapy without concomitant conventional synthetic DMARDs (csDMARDs) during the study period 1 May, 2011 through 30 April 2013 were eligible for inclusion. All patient files were checked to ensure that they were in accordance with the treatment registration in DANBIO. Descriptive statistics......DMARDs, with the exception of infliximab, which had significantly poorer drug adherence (P treatments for RA was prescribed in Denmark as monotherapy, of which 70% were...

  1. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML-19).

    NARCIS (Netherlands)

    Amadori, S.; Suciu, S.; Selleslag, D.; Stasi, R.; Alimena, G.; Baila, L.; Rizzoli, V.; Borlenghi, E.; Gaidano, G.; Magro, D.; Torelli, G.; Muus, P.; Venditti, A.; Cacciola, E.; Lauria, F.; Vignetti, M.; Witte, T.J.M. de

    2010-01-01

    This study compared two schedules of low-dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukaemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best

  2. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML-19).

    NARCIS (Netherlands)

    Amadori, S.; Suciu, S.; Selleslag, D.; Stasi, R.; Alimena, G.; Baila, L.; Rizzoli, V.; Borlenghi, E.; Gaidano, G.; Magro, D.; Torelli, G.; Muus, P.; Venditti, A.; Cacciola, E.; Lauria, F.; Vignetti, M.; Witte, T.J.M. de

    2010-01-01

    This study compared two schedules of low-dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukaemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best suppor

  3. A comparative trial of a combined therapy (Yangyin-Qinggan decoction combined with paroxetine)versus mono-therapy on depressive patients with somatic symptoms%养阴清肝汤联合帕罗西汀治疗抑郁症躯体化症状研究

    Institute of Scientific and Technical Information of China (English)

    毛稚霞; 杨媛; 李根起; 马静; 王勇

    2013-01-01

    目的 探讨中西医结合治疗抑郁症患者躯体化症状的有效方法.方法 以简单随机法将入选患者分为两组,对照组35例、治疗组34组.治疗组给予中药养阴清肝汤联合盐酸帕罗西汀治疗,对照组单纯采用盐酸帕罗西汀治疗.比较两组患者治疗前后的抑郁症状及躯体化症状.结果 ①治疗组、对照组均可缓解抑郁症状:治疗组治疗前及治疗后2周、4周、8周的汉密尔顿抑郁量表(HAMD)评分分别为(19.29±2.38)分、(17.38±2.37)分、(15.27±2.15)分、(13.35±2.09)分;治疗后4周与治疗后2周比较、治疗后8周与治疗后4周比较,差异均有统计学意义(P均<0.05).对照组治疗前及治疗后2周、4周、8周的HAMD评分分别为(18.69±3.03)分、(16.63±3.09)分、(15.20±2.95)分、(14.60±2.72)分,治疗后4周与治疗后2周比较、治疗后8周与治疗后4周比较,差异均有统计学意义(P均<0.05).治疗结束时,两组HAMD比较治疗组优于对照组(P<0.05).②在改善躯体化症状方面,治疗组治疗前及治疗后2周、4周、8周的躯体化症状自评量表(SSS)评分分别为(48.74±4.07)分、(46.74±4.16)分、(43.74±3.77)分、(41.18±3.50)分;治疗后4周与治疗后2周比较、治疗后8周与治疗后4周比较,差异均有统计学意义(P均<0.05).对照组治疗前及治疗后2周、4周、8周的躯体化症状自评量表(SSS)评分分别为(47.71±4.72)分、(46.20±4.64)分、(44.80±4.52)分、(43.91±4.31)分,治疗后4周与治疗后2周比较、治疗后8周与治疗后4周比较,差异无统计学意义(P均>0.05).结论 养阴清肝汤联合盐酸帕罗西汀可有效缓解抑郁症状,改善躯体化症状.%Objective To evaluate the effectiveness of treating depressive patients with somatic symptoms with combined TCM and western medicine.Methods 69 patients were randomly divided into 2 groups:a combined therapy group (treated with Yangyin-Qinggan decoction and paroxetine) and mono-therapy

  4. Women with epilepsy initiating a progestin IUD: A prospective pilot study of safety and acceptability.

    Science.gov (United States)

    Davis, Anne R; Saadatmand, Heva J; Pack, Alison

    2016-11-01

    Effective contraception enables women with epilepsy (WWE) to plan their pregnancies and improve outcomes for themselves and their children. Although popular among all women, complex drug interactions limit the efficacy and safety of oral contraceptives (OCs) for WWE. We sought to explore the safety, acceptability, and pharmacokinetic impact of a progestin-containing intrauterine device (IUD) in WWE. We enrolled 20 women with well-controlled epilepsy and a stable antiepileptic drug (AED) regimen and who were initiating a progestin-containing IUD (levonorgestrel 52 mg) in a prospective, observational study. For each AED, we compared the trough concentration before IUD insertion to the trough concentration 3 weeks, and 3 and 6 months later. Participants recorded seizures in a daily paper diary. We compared seizures that occurred during the month before IUD insertion to those occurring in the 6 months thereafter. Participants completed an acceptability questionnaire at 3 and 6 months. Participants' average age was 28 years; 60% were nulligravid. They reported a history of multiple seizure types. During the baseline month, 75% were seizure-free and the remainder reported between one and three seizures. Fourteen received monotherapy and six received polytherapy. Lamotrigine use was most common (n = 12). AED trough concentrations remained stable during the 6 months after IUD insertion, without clinically meaningful deviations from baseline. Diary data showed that seizure frequency worsened in 3, and remained unchanged in 13 and improved in 4 after IUD insertion. Subjectively, no participant believed the IUD worsened her seizure control. All participants were either somewhat or very satisfied with the IUD throughout the study. All participants continued the IUD use at 6 months. No pregnancies occurred. This pilot study suggests that the progestin-containing IUD is a safe and acceptable long-acting contraceptive for WWE. Wiley Periodicals, Inc. © 2016 International League

  5. Effect of a fixed combination of nimodipine and betahistine versus betahistine as monotherapy in the long-term treatment of Ménière's disease: a 10-year experience

    OpenAIRE

    Monzani, D; Barillari, M.R.; Alicandri Ciufelli, M; Aggazzotti Cavazza, E; Neri, V.; Presutti, L.; Genovese, E

    2012-01-01

    SUMMARY Despite an abundance of long-term pharmacological treatments for recurrent vertigo attacks due to Ménière's disease, there is no general agreement on the their efficacy. We present the results of a retrospective study based on a 10-year experience with two long-term medical protocols prescribed to patients affected by Ménière's disease (diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines) who completed tre...

  6. Efficacy of Monotherapy with Either Bimatoprost or Travoprost in Patients with Primary Open-Angle Glaucoma Resistant to Latanoprost Therapy

    Directory of Open Access Journals (Sweden)

    Yusuf Koçluk

    2011-10-01

    Full Text Available Pur po se: This prospective study aimed to evaluate the efficacy of monotherapy with either bimatoprost or travoprost in patients with primary open-angle glaucoma (POAG resistant to latanoprost therapy. Patients and Methods: Forty patients with POAG who received therapy with topical latanoprost at Gaziantep University Hospital, Department of Ophthalmology between March 2009 and March 2010 were chosen to participate in this study. The decision to stop latanoprost therapy in these patients was made either due to the fact that they were resistant to therapy or due to the necessity to further decrease the intraocular pressure (IOP; 20 subjects were chosen to receive monotherapy with bimatoprost and 20 were chosen to receive monotherapy with travoprost. The patients were observed for 6 months with follow-up visits at 1 week, 1 month, 3 months and 6 months. Results: For the group of patients receiving therapy with bimatoprost, the average decrease in IOP was measured to be 2.05 mmHg at 1 week, 2.25 mmHg at 1 month, 1.90 mmHg at 3 months and 2.40 mmHg at 6 months. For the group of patients receiving therapy with travoprost, the average decrease in IOP was measured to be 1.47 mmHg at 1 week, 1.75 mmHg at 1 month, 1.42 mmHg at 3 months and 1.27 mmHg at 6 months. At the end of 6 months, there were no significant changes observed in the mean deviation and central corneal thickness in both therapy groups. Conjunctival hyperemia and ocular irritation were the most common side effects observed in both groups, with the bimatoprost therapy group showing higher values than the travoprost group. Discussion: For patients resistant to latanoprost therapy, prior to any adjuvant therapy, monotherapy with either bimatoprost, which is a prostamide, or travoprost, a prostaglandin analogue, has been shown to be effective at lowering IOP. (Turk J Ophthalmol 2011; 41: 295-8

  7. Long-term results of interventional treatment of large unresectable hepatocellular carcinoma (HCC): significant survival benefit from combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) compared to TACE monotherapy; Langzeitergebnisse der interventionellen Therapie von grossen, inoperablen hepatozellulaeren Karzinomen (HCC): signifikanter Ueberlebensvorteil von transarterieller Chemoembolisation (TACE) und perkutaner Ethanolinjektion (PEI) gegenueber der TACE-Monotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Lubienski, A.; Bitsch, R.G.; Grenacher, L.; Kauffmann, G.W. [Radiologische Universitaetsklinik Heidelberg, Abt. Radiodiagnostik, Heidelberg (Germany); Schemmer, P. [Chirurgische Universitaetsklinik Heidelberg (Germany); Duex, M. [Radiologisches Zentralinstitut Krankenhaus Nordwest Frankfurt (Germany)

    2004-12-01

    Purpose: A retrospective analysis of long-term efficacy of combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) and TACE monotherapy was conducted in patients with large, non-resectable hepatocellular carcinoma (HCC). Methods and Materials: Fifty patients with large, unresectable HCC lesions underwent selective TACE. Liver cirrhosis was present in 42 patients, due to alcohol abuse (n = 22) and viral infection (n = 17). In three patients, the underlying cause for liver cirrhosis remained unclear. Child A cirrhosis was found in 22 and Child B cirrhosis in 20 patients. Repeated and combined TACE and PEI were performed in 22 patients and repeated TACE monotherapy was performed in 28 patients. Survival and complication rates were determined and compared. Results: The 6-, 12-, 24- and 36-month survival rates were 61%, 21%, 4%, and 4% for TACE monotherapy and 77%, 55%, 39% and 22% for combined TACE and PEI (Kaplan-Meier method). The kind of treatment significantly affected the survival rate (p=0.002 log-rank test). Severe side effects were present in two patients of the monotherapy group and in three patients of the combination therapy group. (orig.)

  8. Safety and efficacy of moxifloxacin monotherapy for treatment of orthopedic implant-related staphylococcal infections.

    Science.gov (United States)

    San Juan, Rafael; Garcia-Reyne, Ana; Caba, Pedro; Chaves, Fernando; Resines, Carlos; Llanos, Fernando; López-Medrano, Francisco; Lizasoain, Manuel; Aguado, Jose Maria

    2010-12-01

    The rifampin-ciprofloxacin combination is recommended for treatment of orthopedic implant-related staphylococcal infections to avoid the emergence of ciprofloxacin resistance; however, the efficacy of this combination is limited by the tolerability problems associated with the use of rifampin. Moxifloxacin is a quinolone up to 10 times more active against staphylococci than ciprofloxacin and the risk of resistance development during monotherapy against staphylococci is theoretically lower for moxifloxacin, but information regarding its use in bone infections is lacking. The aim of the present study was to evaluate the safety and clinical efficacy of moxifloxacin monotherapy in patients with orthopedic implant-related staphylococcal infections. From June 2006 to April 2009, all patients with culture-proven infection by quinolone-sensitive staphylococcal strains associated with orthopedic implants at our institution were included in a management protocol that mostly included specific surgery, 1 to 2 weeks of an intravenous course of cloxacillin-cefazolin or vancomycin, and long-term therapy with moxifloxacin (400 mg/day for 3 months). Cure was defined as (i) a lack of clinical signs and symptoms of infection, (ii) a C-reactive protein level less than 5 mg/liter, and (iii) absence of radiological signs of loosening or infection at the latest follow-up visit. Failure was defined as (i) persisting clinical and/or laboratory signs of infection or (ii) persisting or new isolation of the initial microorganism. A total of 48 patients with a median follow-up of 716 days (range, 102 to 1,613 days) were included in the study. Complete drug compliance was achieved in all but two patients (4.2%), who required drug discontinuation because of side effects (diarrhea and dizziness). No moxifloxacin-induced arrhythmia was reported. Twenty patients had joint prosthesis infections (5 acute-onset infections and 15 chronic infections), and 28 patients had osteosynthesis material

  9. Safety and Efficacy of Moxifloxacin Monotherapy for Treatment of Orthopedic Implant-Related Staphylococcal Infections ▿

    Science.gov (United States)

    San Juan, Rafael; Garcia-Reyne, Ana; Caba, Pedro; Chaves, Fernando; Resines, Carlos; Llanos, Fernando; López-Medrano, Francisco; Lizasoain, Manuel; Aguado, Jose Maria

    2010-01-01

    The rifampin-ciprofloxacin combination is recommended for treatment of orthopedic implant-related staphylococcal infections to avoid the emergence of ciprofloxacin resistance; however, the efficacy of this combination is limited by the tolerability problems associated with the use of rifampin. Moxifloxacin is a quinolone up to 10 times more active against staphylococci than ciprofloxacin and the risk of resistance development during monotherapy against staphylococci is theoretically lower for moxifloxacin, but information regarding its use in bone infections is lacking. The aim of the present study was to evaluate the safety and clinical efficacy of moxifloxacin monotherapy in patients with orthopedic implant-related staphylococcal infections. From June 2006 to April 2009, all patients with culture-proven infection by quinolone-sensitive staphylococcal strains associated with orthopedic implants at our institution were included in a management protocol that mostly included specific surgery, 1 to 2 weeks of an intravenous course of cloxacillin-cefazolin or vancomycin, and long-term therapy with moxifloxacin (400 mg/day for 3 months). Cure was defined as (i) a lack of clinical signs and symptoms of infection, (ii) a C-reactive protein level less than 5 mg/liter, and (iii) absence of radiological signs of loosening or infection at the latest follow-up visit. Failure was defined as (i) persisting clinical and/or laboratory signs of infection or (ii) persisting or new isolation of the initial microorganism. A total of 48 patients with a median follow-up of 716 days (range, 102 to 1,613 days) were included in the study. Complete drug compliance was achieved in all but two patients (4.2%), who required drug discontinuation because of side effects (diarrhea and dizziness). No moxifloxacin-induced arrhythmia was reported. Twenty patients had joint prosthesis infections (5 acute-onset infections and 15 chronic infections), and 28 patients had osteosynthesis material

  10. Long-term safety and efficacy of linagliptin as monotherapy or in combination with other oral glucose-lowering agents in 2121 subjects with type 2 diabetes: up to 2 years exposure in 24-week phase III trials followed by a 78-week open-label extension.

    Science.gov (United States)

    Gomis, R; Owens, D R; Taskinen, M-R; Del Prato, S; Patel, S; Pivovarova, A; Schlosser, A; Woerle, H-J

    2012-08-01

    Aim:  The aim of this study was to evaluate the long-term safety, tolerability and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin given either alone or in combination with other oral glucose-lowering agents in persons with type 2 diabetes. Methods:  A 78-week open-label extension study evaluated subjects who participated in one of four preceding 24-week, randomised, double-blind, placebo-controlled parent trials and who received linagliptin, linagliptin + metformin, linagliptin + metformin + a sulphonylurea or linagliptin + pioglitazone (all with linagliptin administered orally once daily). Individuals receiving one of these treatments during a previous trial continued the same treatment (n = 1532) for up to a total of 102 weeks, whereas those previously receiving placebo were switched to linagliptin (n = 589). All 2121 participants received at least one dose of the trial medication and were included in the primary safety analysis. Results:  In subjects previously receiving active treatment, the glycosylated haemoglobin A(1c) reduction achieved during the 24-week parent trials was sustained through the 78-week extension period (change from baseline to week 102: -0.8%). Drug-related adverse events were experienced by 14.3% of participants. Hypoglycaemia occurred in 13.9% of participants and was similar between those previously receiving treatment (13.6%) and those switching from placebo to linagliptin (14.6%). Hypoglycaemia occurred most frequently with the use of metformin + a sulphonylurea background therapy (11%). Overall, no clinically relevant changes in body weight were observed. Conclusion:  Long-term treatment with linagliptin was well tolerated with no change in the safety profile observed during the extension study. Sustained long-term glycaemic control was maintained for up to 102 weeks with either linagliptin monotherapy or linagliptin in combination with other oral glucose-lowering agents. © 2012

  11. Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study

    Directory of Open Access Journals (Sweden)

    Kun Ho Yoon

    2011-02-01

    Full Text Available BackgroundAlthough many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.MethodsWe evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.ResultsHbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001, from 7.9% to 7.0% in the metformin group (P<0.001, and from 7.8% to 7.0% (P<0.001 in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.ConclusionThe efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

  12. Resistance mutations in protease gene at baseline are not related to virological failure in patients treated with darunavir/ritonavir monotherapy

    Directory of Open Access Journals (Sweden)

    Angela Gutierrez-Liarte

    2014-11-01

    Full Text Available Introduction: Monotherapy with darunavir plus ritonavir (DRV/r is a good maintenance strategy for suppressed HIV-infected patients. The clinical trials designed to prove the efficacy of PI/r do not include patients with resistance mutation in protease gene [1,2]. Sometimes in routine practice, basically to avoid NRTIs toxicity, monotherapy with DRV/r is used despite PI resistance mutations. The aim of this study is to know the effect of previous protease resistance mutation on DRV/r monotherapy efficacy. Materials and Methods: We designed an observational cohort study of adults in treatment with DRV/r monotherapy in a tertiary Spanish hospital since 2011 to 2014. Demographic data and clinical outcomes were described. The analysis of efficacy was done according to the snapshot algorithm (defining virological failure as viral load >50 copies/mL, ITTe, at 48 and 96 weeks. We analyzed the difference of efficacy between patients with and without baseline resistance mutations at 48 and 96 weeks by using the χ2 test; and during the follow-up by using the Kaplan–Meier test. The statistical analysis was done with SPSS 17.0. Results: Eighty-nine patients were included in the cohort but 14 were excluded because they had not reached more than six months with monotherapy. The cohort was composed mainly by men (78%, the medium age was 51 years (SD±10, 35% were MSM and 19% were former IDU. Twenty-four patients (35% had a previous diagnosis of AIDS. The mean time taking NRTIs was 10.5 years (SD±5.4. Sixty-four patients (85% had been treated with PI in the past. Previous failure with PI had been reported in 15 (20%. A resistance mutation test had been done at baseline in 45 patients (51%. Twenty-two patients (29% had some mutations in protease gene, 10 patients (13% had major mutations and 1 patient had some mutations of resistance for darunavir (I64V. At 48 weeks, 93% (CI 95% 86–98% had VL<50 copies/mL, and 79% (CI 95% 67–89% at 96 weeks. There were

  13. Ranibizumab in monotherapy and combined with photodynamic therapy for retinal angiomatous proliferation

    Directory of Open Access Journals (Sweden)

    Arias L

    2016-05-01

    Full Text Available Luis Arias,1–3 Francisco Gómez-Ulla,2–4 José M Ruiz-Moreno2,3,51Ophthalmology Department, Bellvitge University Hospital, C/Feixa Llarga, L’Hospitalet de Llobregat, Barcelona, 2Spanish Vitreoretinal Society (SERV, C/Xosé Chao Rego, Santiago de Compostela, 3RETICS OFTARED, Institute of Health Carlos III, C/Sinesio Delgado, Madrid, 4Gómez-Ulla Eye Institute, Santiago de Compostela, 5Department of Ophthalmology, Albacete University Hospital, Avenida de Almansa s/n, Albacete, Spain Purpose: To compare the effects of intravitreal ranibizumab in monotherapy (group A and combined with photodynamic therapy (PDT with verteporfin (group B in retinal angiomatous proliferation (RAP treatment.Methods: This was a multicentric, prospective, randomized clinical study conducted with parallel groups. The study eye in both groups received ranibizumab on days 1, 30, and 60 (loading dose; group B received PDT additionally on day 1. Early Treatment Diabetic Retinopathy Study (ETDRS visual acuity (VA testing and optical coherence tomography were performed monthly, and fluorescein angiography and indocyanine green angiography were performed quarterly. Retreatment criteria were leakage in fluorescein angiography or indocyanine green angiography, mean foveal thickness increase ≥100 µm, or VA decrease ≥5 letters.Results: Twenty patients were recruited (ten patients in each group. Six eyes had previous treatment (three eyes in group A and three eyes in group B, so only 14 eyes were naïve. At 12-month follow-up, mean VA improved +1.5 letters in group A and +5.6 letters in group B (analysis of variance test; P>0.05. Two patients (20% in both groups gained ≥15 letters (chi-square test; P>0.05. Mean changes in greatest linear dimension and in foveal thickness were not statistically significant between groups of treatment (analysis of variance test; P>0.05. Mean retreatments per patient were 1.8 (group A and 0.9 (group B (Mann–Whitney U-test; P>0.05. One

  14. Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching

    Directory of Open Access Journals (Sweden)

    Hayasaka M

    2013-02-01

    Full Text Available Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai41Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, JapanBackground: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters.Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130 of clopidogrel (75 mg/day plus aspirin (100 mg/day and a propensity score matched sample of new users (n = 130 of aspirin alone (100 mg/day. We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs.Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and

  15. Effectiveness and safety of high-dose valsartan monotherapy in hypertension treatment: the ValTop study.

    Science.gov (United States)

    Parati, Gianfranco; Asmar, Roland; Bilo, Grzegorz; Kandra, Albert; Di Giovanni, Robert; Mengden, Thomas

    2010-10-01

    Early combination therapy is increasingly recommended in hypertension management because of increased risk of adverse effects with high-dose monotherapy. However, this risk is not necessarily increased for high doses of angiotensin receptor blockers (ARB). ValTop study compared efficacy and safety of high vs. conventional dose of valsartan in hypertensive patients. ValTop was a controlled, randomized, double-blind trial. Of 6035 screened subjects, 4004 mild-to-moderate hypertensive patients (mean seated diastolic blood pressure (MSDBP) 90-109 mm Hg) started 4-week open-label treatment with valsartan 160 mg. Of them, 3776 were randomized to receive valsartan 160 mg (N=1900) or 320 mg (N=1876) o.d. for 4 weeks. In 28-week open-label extension study, all participating patients (N=642) received valsartan 320 mg. Valsartan 160 mg reduced MSDBP by 10.0 mm Hg in the initial open-label phase. Further BP reductions in the double-blind phase were significantly (PHigh-dose valsartan is safe and effective in uncomplicated mild-to-moderate hypertension independently of the initial response to a moderate dose. High-dose ARB monotherapy may thus be a viable option in hypertension management.

  16. Ecological Assessment of Clinicians’ Antipsychotic Prescription Habits in Psychiatric Inpatients: A Novel Web- and Mobile Phone–Based Prototype for a Dynamic Clinical Decision Support System

    Science.gov (United States)

    Barrigón, Maria Luisa; Brandt, Sara A; Nitzburg, George C; Ovejero, Santiago; Alvarez-Garcia, Raquel; Carballo, Juan; Walter, Michel; Billot, Romain; Lenca, Philippe; Delgado-Gomez, David; Ropars, Juliette; de la Calle Gonzalez, Ivan; Courtet, Philippe; Baca-García, Enrique

    2017-01-01

    Background Electronic prescribing devices with clinical decision support systems (CDSSs) hold the potential to significantly improve pharmacological treatment management. Objective The aim of our study was to develop a novel Web- and mobile phone–based application to provide a dynamic CDSS by monitoring and analyzing practitioners’ antipsychotic prescription habits and simultaneously linking these data to inpatients’ symptom changes. Methods We recruited 353 psychiatric inpatients whose symptom levels and prescribed medications were inputted into the MEmind application. We standardized all medications in the MEmind database using the Anatomical Therapeutic Chemical (ATC) classification system and the defined daily dose (DDD). For each patient, MEmind calculated an average for the daily dose prescribed for antipsychotics (using the N05A ATC code), prescribed daily dose (PDD), and the PDD to DDD ratio. Results MEmind results found that antipsychotics were used by 61.5% (217/353) of inpatients, with the largest proportion being patients with schizophrenia spectrum disorders (33.4%, 118/353). Of the 217 patients, 137 (63.2%, 137/217) were administered pharmacological monotherapy and 80 (36.8%, 80/217) were administered polytherapy. Antipsychotics were used mostly in schizophrenia spectrum and related psychotic disorders, but they were also prescribed in other nonpsychotic diagnoses. Notably, we observed polypharmacy going against current antipsychotics guidelines. Conclusions MEmind data indicated that antipsychotic polypharmacy and off-label use in inpatient units is commonly practiced. MEmind holds the potential to create a dynamic CDSS that provides real-time tracking of prescription practices and symptom change. Such feedback can help practitioners determine a maximally therapeutic drug treatment while avoiding unproductive overprescription and off-label use. PMID:28126703

  17. Is narrowband ultraviolet B monotherapy effective in the treatment of pityriasis lichenoides?

    Science.gov (United States)

    Park, Jung-Min; Jwa, Seung-Wook; Song, Margaret; Kim, Hoon-Soo; Chin, Hyun-Woo; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Byung-Soo

    2013-08-01

    Pityriasis lichenoides (PL) is a self-limiting papulosquamous disease that may persist for years and is associated with a high relapse rate. To date, few comparative studies have investigated the efficacy of narrowband ultraviolet B (NB-UVB) phototherapy and other therapies in the treatment of PL. The present study retrospectively compared the clinical efficacies of NB-UVB phototherapy, systemic therapy, and a combination of NB-UVB and systemic medication in the treatment of PL. Seventy patients diagnosed with PL were enrolled in this study. They were divided into three subgroups: the NB-UVB treatment group; the systemic treatment group; and the combination treatment group. Therapeutic efficacy was evaluated according to whether the subjects demonstrated a complete response (> 90% improvement in skin lesions), partial response (50-90% improvement), or no response (< 50% improvement) to treatment. A 91.9% complete response rate was achieved in the NB-UVB group, whereas only 69.2 and 80.0% of patients achieved a complete response in the systemic and combination treatment groups, respectively; these differences were not statistically significant. The mean treatment periods were 8.3, 5.3, and 7.9 weeks in the NB-UVB, systemic, and combination treatment groups, respectively; these differences were also not significant. Monotherapy using NB-UVB is effective in achieving a complete response in the treatment of PL and thus eliminates the need for concurrent systemic medication. © 2013 The International Society of Dermatology.

  18. Clinical evidence for caspofungin monotherapy in the first-line and salvage therapy of invasive Aspergillus infections.

    Science.gov (United States)

    Heinz, Werner J; Buchheidt, Dieter; Ullmann, Andrew J

    2016-08-01

    In 2001, caspofungin received market authorisation by the FDA and EMA and is globally licensed for several indications, including candidiasis, empirical antifungal therapy in patients with neutropenic fever of unknown origin and treatment of invasive aspergillosis in patients refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B or itraconazole. Despite the lack of phase III data in first-line treatment of invasive aspergillosis, increasing evidence supports the use of first-line therapy. Here, we analyse the evidence of therapeutic activity, represented by favourable response rates, of caspofungin for invasive aspergillosis. A systematic literature search was conducted to identify international presentations and papers reporting monotherapy with caspofungin. Efficacy data are summarised separately for first-line and salvage therapy. Thirty-one papers and published abstracts reported caspofungin therapy for aspergillosis. Fifteen full papers and two abstracts fulfilled the criteria of reporting significant outcome data for caspofungin monotherapy for invasive aspergillosis. Consistent with other analyses and the known safety profile, few adverse events and associated terminations of caspofungin medication have been reported. Although a randomised, comparative, prospective study using caspofungin in this indication is still lacking, growing evidence supports the efficacy of this echinocandin not only for salvage but also for first-line therapy.

  19. Visual outcomes of age-related macular degeneration patients undergoing intravitreal ranibizumab monotherapy in an urban population

    Directory of Open Access Journals (Sweden)

    Basheer K

    2015-05-01

    Full Text Available Khadijah Basheer, Evelyn Mensah, Tina Khanam, Neda Minakaran Ophthalmology Department, Central Middlesex Hospital, London, UK Aim: To compare the visual outcomes of an urban population with age-related macular degeneration (AMD undergoing ranibizumab monotherapy to the results from major clinical trials.Procedures: Prospective data was collected from 164 wet AMD patients receiving intravitreal ranibizumab. Visual acuities were obtained with the Early Treatment Diabetic Retinopathy Study chart. All patients underwent a loading phase of three monthly treatments of ranibizumab. Patients were monitored monthly using a retreatment criterion. Treatment was further individualized by sequentially lengthening follow-up intervals when stable.Results: At 12 and 24 months, respectively, the percentage of eyes that maintained vision was 91% and 88.6%. We found that 20.3% of eyes had improved vision at 12 months and 20% at 24 months. At 12 months, 8.3% of eyes’ vision worsened and 12% worsened at 24 months.Conclusion: Individualized ranibizumab monotherapy is effective in preserving vision in wet AMD and follows the same trends as the pivotal trials. Keywords: visual acuity, comparison of age-related macular degeneration treatment trials, choroidal neovascular membrane

  20. Treatment of corneal squamous cell carcinoma using topical 1% 5-fluorouracil as monotherapy.

    Science.gov (United States)

    Dorbandt, Daniel M; Driskell, Elizabeth A; Hamor, Ralph E

    2016-05-01

    The purpose of this report is to discuss the use of topical 1% 5-fluorouracil as a sole therapy for canine corneal squamous cell carcinoma (SCC). A 12-year-old castrated male pug was evaluated for a well-demarcated, central, 3 mm in diameter, pale pink, raised, right corneal mass. An incisional biopsy was obtained using a #64 beaver blade after topical anesthesia and without sedation. A definitive diagnosis of corneal SCC was obtained after histopathologic evaluation of the biopsy. Topical 1% 5-fluorouracil ointment was applied to the right eye four times daily for 2 weeks followed by no treatment for 2 weeks, then treatment again twice daily for 2 weeks. The cornea remained free of recurrence 10 months after cessation of treatment. In dogs affected with corneal SCC, topical 1% 5-fluorouracil monotherapy may be a viable and cost-effective treatment option with minimal side effects. This chemotherapy agent may also have an effect on corneal pigmentation. Chronic cyclosporine therapy did not contribute to the pathogenesis of corneal SCC in the case described.

  1. Polymorphisms and pharmacogenomics for the toxicity of methotrexate monotherapy in patients with rheumatoid arthritis

    Science.gov (United States)

    Qiu, Qi; Huang, Jing; Lin, Yang; Shu, Xiaoming; Fan, Huizheng; Tu, Zhihua; Zhou, Youwen; Xiao, Cheng

    2017-01-01

    Abstract Background: Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10% to 30% of patients discontinue therapy within a year of starting the treatment, usually because of undesirable side effects. Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX toxicity in RA patients, although inconsistent results have been reported. Methods: We searched EMBASE and PubMed in February 2016 for polymorphisms and pharmacogenomics study of the toxicity of MTX monotherapy in RA patients. The meta-analysis was stratified by whether genetic variants associated with MTX toxicity. Results: A total of 42 publications that included 28 genes with 88 gene SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the SR, and 31 studies were included in 7 meta-analyses. The meta-analysis showed a significant association between the toxicity of MTX and the RFC-1 80G > A (rs1051266) polymorphism in the European RA patients. Conclusion: RFC-1 80G > A (rs1051266) polymorphism was associated with MTX toxicity, and larger and more stringent study designs may provide more accurate results for the effect of these SNPs on the MTX toxicity. PMID:28296761

  2. Pharmacokinetics and safety of olmesartan medoxomil in combination with either amlodipine or atenolol compared to respective monotherapies in healthy subjects.

    Science.gov (United States)

    Bolbrinker, Juliane; Huber, Matthias; Scholze, Jürgen; Kreutz, Reinhold

    2009-12-01

    The aim of this study was to investigate any influence on olmesartan plasma pharmacokinetics from amlodipine or atenolol. We analysed pharmacokinetics and safety of olmesartan medoxomil in combination with either amlodipine or atenolol compared to respective monotherapies in two separate studies. In one study, 18 subjects received once daily treatment for 7 days with olmesartan medoxomil 20 mg alone or with amlodipine 5 mg or amlodipine 5 mg alone. In the other study, atenolol 50 mg once daily replaced amlodipine. Concentration vs. time profiles for olmesartan monotherapy were similar to combination therapy. Mean olmesartan AUC(ss,tau) for olmesartan alone and with amlodipine were 2439 and 2388 ng h/mL and for olmesartan alone and with atenolol were 2340 and 2247 ng h/mL. Corresponding olmesartan C(ss,max) values were 465.7 and 439.5 ng/mL for amlodipine, and 447.4 and 423.8 ng/mL for atenolol. Median t(max) values for olmesartan were 1.5 h for each group in each study. Bioequivalence was established for all pharmacokinetic parameters. Lack of significant pharmacokinetic interactions between olmesartan and amlodipine or atenolol provides a basis for combination therapy.

  3. Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia

    Directory of Open Access Journals (Sweden)

    Benes LB

    2016-12-01

    Full Text Available Lane B Benes1, Nikhil S Bassi2, Michael H Davidson1 1Department of Medicine, Section of Cardiology, 2Department of Medicine, University of Chicago, Chicago, IL, USA Abstract: The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin. Keywords: omega-3 carboxylic acids, non-HDL-C, hypertriglyceridemia, residual risk, statin

  4. 贝那普利/氨氯地平复方制剂与贝那普利单药治疗轻中度高血压的多中心随机双盲平行对照研究%Comparison of benazepril monotherapy to amlodipine plus benazepril in the treatment of patients with mild and moderate hypertension: a multicentre, randomized, double-blind , parallel-controlled study

    Institute of Scientific and Technical Information of China (English)

    樊朝美; 卢晓雷; 庞会敏; 李一石; 闫丽荣; 陶永康; 王莉; 刘玉清; 高明明; 王燕妮; 李成祥; 王效浣

    2011-01-01

    目的 评价贝那普利/氨氯地平复方片剂与贝那普利片单药治疗轻、中度高血压患者的有效性和安全性.方法 本研究为多中心、随机、双盲、平行对照研究.356例原发性高血压患者经2周洗脱期后,再给予4周贝那普利片10 mg单药治疗,220例平均坐位舒张压(SeDBP)仍≥90 mm Hg(1 mm Hg=0.133 kPa)的患者随机分为贝那普利(10 mg)/氨氯地平(5 mg)固定剂量复方片剂组(复方制剂组,1片/d,n=113)和贝那普利片单药组(单药治疗组,20 mg/d,n=107),治疗4周末两组诊室SeDBP≥90 mmHg者剂量加倍.SeDBP<90 mm Hg者续服原剂量,共随机双盲治疗8周.以总有效率和SeDBP下降差值作为主要疗效指标.其中74例患者(复方片剂组38例,单药组36例)完成了24 h动态血压监测,并作为降压疗效的评价指标.结果 随机、双盲治疗8周末,复方片剂组SeDBP下降值为(11.7±6.8)mm Hg、达目的 血压占65.7%、总有效率为88.5%;单药治疗组SeDBP下降值为(7.7±6.9)mm Hg、达目的 血压占35.5%、总有效率为65.5%.两组组间比较差异均有统计学意义(P<0.001).24 h动态血压监测结果,复方制剂组和单药组的舒张压/收缩压(DBP/SBP)的谷/峰比率(T/P)分别为83.1%/76.0%和85.8%/79.5%(P<0.05).复方制剂组与单药治疗组的不良反应发生率分别为16.8%和35.5%(P<0.01).结论 贝那普利/氨氯地平复方制剂治疗原发性高血压患者的降压疗效明显优于贝那普利单药治疗,且有良好的耐受性.%Objective To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring Methods In a multicenter, randomized,double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash

  5. A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections

    NARCIS (Netherlands)

    Gyssens, I.C.J.; Dryden, M.; Kujath, P.; Nathwani, D.; Schaper, N.; Hampel, B.; Reimnitz, P.; Alder, J.; Arvis, P.

    2011-01-01

    OBJECTIVES: The primary aim of the RELIEF study was to evaluate the efficacy and safety of two sequential intravenous (iv)/oral regimens: moxifloxacin iv/oral versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate (AMC). PATIENTS AND METHODS: The study had a prospective, ra

  6. Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: Final results of a randomized, double-blind, placebo-controlled, phase 3 study

    NARCIS (Netherlands)

    Urba, S.; Herpen, C.M. van; Sahoo, T.P.; Shin, D.M.; Licitra, L.; Mezei, K.; Reuter, C.; Hitt, R.; Russo, F.; Chang, S.C.; Hossain, A.M.; Frimodt-Moller, B.; Koustenis, A.; Hong, R.L.

    2012-01-01

    BACKGROUND: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial e

  7. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial.

    Science.gov (United States)

    Rosenstock, Julio; Diamant, Michaela; Aroda, Vanita R; Silvestre, Louise; Souhami, Elisabeth; Zhou, Tianyue; Perfetti, Riccardo; Fonseca, Vivian

    2016-09-01

    This study assessed the efficacy and safety of LixiLan, a fixed-ratio, titratable, combination of 2 units insulin glargine (Gla-100) and 1 μg lixisenatide administered once daily via a single pen, versus Gla-100 in insulin-naïve type 2 diabetes on metformin. Participants were randomized to once-daily LixiLan (n = 161) or Gla-100 (n = 162) for 24 weeks, while continuing metformin. LixiLan and Gla-100 were started at 10 units/5 μg and 10 units, respectively, and titrated based on the Gla-100 requirement according to fasting plasma glucose levels. The primary objective was to test noninferiority (upper bound of the 95% CI ≤0.4%) of LixiLan in reducing HbA1c; if met, statistical superiority was tested. Secondary objectives included body weight changes, hypoglycemia, and safety. Baseline characteristics (mean age 57 years, diabetes duration 6-7 years, BMI 32 kg/m(2)) were similar between groups. At week 24, mean HbA1c was reduced from 8.0% (64 mmol/mol) at baseline to 6.3% (45 mmol/mol) and 6.5% (48 mmol/mol) with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan (least-squared mean [95% CI] difference: -0.17% [-0.31, -0.04] {-1.9 mmol/mol [-3.4, -0.4]}; P = 0.01). HbA1c <7.0% (<53 mmol/mol) was achieved in 84% and 78% of participants (nonsignificant), respectively. LixiLan improved 2-h postmeal plasma glucose versus Gla-100 (least-squared mean difference: -3.17 mmol/L [-57 mg/dL]; P < 0.0001). Body weight was reduced with LixiLan (-1 kg) and increased with Gla-100 (+0.5 kg; P < 0.0001), with no increase in hypoglycemic events (∼25% in each group). The incidence of nausea (7.5%) and vomiting (2.5%) was low with LixiLan. LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin. © 2016 by

  8. Risperidone long-acting injectable monotherapy in the maintenance treatment of bipolar I disorder.

    Science.gov (United States)

    Quiroz, Jorge A; Yatham, Lakshmi N; Palumbo, Joseph M; Karcher, Keith; Kushner, Stuart; Kusumakar, Vivek

    2010-07-15

    Treatment adherence is a significant problem in patients with bipolar disorder. This study was designed to determine the efficacy of risperidone long-acting injectable (LAI) in the maintenance treatment of bipolar I disorder. Eligible patients with current or recent manic or mixed episodes (n = 559, aged 18-65 years) were treated with open-label oral risperidone for 3 weeks (period II) and open-label risperidone LAI for 26 weeks (n = 501; period III). Patients who maintained response (n = 303) were randomly allocated 1:1 to placebo injections (n = 149) or to continue risperidone LAI (n = 154) for up to 24 months (period IV). Most (77%) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV. Time to recurrence for any mood episode (primary outcome variable) was significantly longer in the risperidone LAI group versus placebo (p or = 7% (compared with the period's baseline) occurred in 15% of patients in period III; in 12% of patients on risperidone LAI and 3% of patients on placebo in period IV. Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes, versus placebo, in this controlled, randomized study in patients with bipolar I disorder. Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Cost-effectiveness of glaucoma management with monotherapy medications in Egypt

    Directory of Open Access Journals (Sweden)

    Amal Abd-Elaal El-Khamery

    2017-01-01

    Full Text Available Glaucoma is a serious chronic ophthalmic disease since it causes irreversible visual disability if untreated can lead to blindness. Treatment options include medications (classified into five major classes of drugs which are muscarinic cholinergic agonists, alpha-2 adrenergic agonists, beta-1 adrenergic antagonists, prostaglandins [PGs], and carbonic anhydrase inhibitors; use of laser therapy or conventional surgery. Pharmacoeconomic analysis helps in choosing among this variety of treatments. There is a great need for such analysis in Egypt since undergoing of it in different countries or societies may produce different results. This work aimed to compare cost-effectiveness of bimatoprost 0.03% once daily versus brimonidine 0.2% twice daily and timolol 0.5% twice daily as monotherapy treatment in Egyptian patients with open-angle glaucoma or ocular hypertension. Clinical data revealed that all treatments decreased intraocular pressure (IOP significantly but bimatoprost 0.03% showed the highest efficacy (27.7% decrease in IOP from baseline, while timolol 0.5% reduced IOP by 22.5% then brimonidine 0.2% which decreased IOP by 20.8%. From the cost-effectiveness view, it would be preferable to initiate treatment with timolol in case of absence of any contraindications. PG analog can be used as add-on therapy in low responder patients or as alternative treatment in case of presence of contraindication to use of beta blockers.

  10. Candesartan cilexetil/hydrochlorothiazide combination treatment versus high-dose candesartan cilexetil monotherapy in patients with mild to moderate cardiovascular risk (CHILI Triple T

    Directory of Open Access Journals (Sweden)

    Bramlage P

    2011-02-01

    Full Text Available Gerd Bönner1, Bernhard Landers2, Peter Bramlage31Park-Klinikum Bad Krozingen, Germany; 2Internal Medicine Practice, Diabetes Center, Mayen, Germany; 3Institute for Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyBackground: Candesartan cilexetil has been shown to effectively reduce blood pressure and cardiovascular risk. Whether it is advantageous to combine candesartan cilexetil with low-dose hydrochlorothiazide (HCTZ or uptitrate it in cases of insufficient blood pressure control has not been fully investigated under routine clinical conditions.Methods: CHILI Triple T is a prospective, noninterventional, observational study. Patients with uncontrolled hypertension and added cardiovascular risk received a fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg (combination therapy group or high-dose monotherapy with candesartan cilexetil 32 mg (high-dose monotherapy group.Results: A total of 4600 patients with a mean age of 63.1 ± 11.0 years, of which 44.7% were female, was included. The combination therapy group had 3337 patients, and the high-dose monotherapy group 1263 patients. Patients in both treatment groups were comparable with respect to age and gender, but patients receiving high-dose monotherapy had a slightly higher mean systolic blood pressure, more prior revascularizations, renal insufficiency, diabetic nephropathy, peripheral artery disease, and a lower ankle brachial index. The use of combination therapy resulted in a blood pressure reduction of -28.5 ± 13.8/-14.2 ± 9.4 mm Hg (P < 0.001 vs 160.2 ± 13.3/94.5 ± 8.2 mm Hg at baseline. The use of high-dose monotherapy reduced blood pressure by -29.73 ± 15.3/-14.1 ± 9.6 mm Hg (P < 0.001 vs 162.4 ± 14.7/94.7 ± 8.7 mm Hg at baseline. Differences in subgroups of patients defined by age, gender, body mass index, dyslipidemia, waist circumference, smoking, prior cardiovascular event, glomerular filtration rate, and microalbuminuria were minor

  11. Physician adherence to hypertension treatment guidelines and drug acquisition costs of antihypertensive drugs at the cardiac clinic: a pilot study.

    Science.gov (United States)

    Abdulameer, Shaymaa Abdalwahed; Sahib, Mohanad Naji; Aziz, Noorizan Abd; Hassan, Yahaya; Alrazzaq, Hadeer Akram Abdul; Ismail, Omar

    2012-01-01

    Prescribing pattern surveys are one of the pharmacoepidemiological techniques that provide an unbiased picture of prescribing habits. Prescription surveys permit the identification of suboptimal prescribing patterns for further evaluation. The aims of this study were to determine the prescribing trend, adherence of the prescribers to the guideline, and the impact of drug expenditure on drug utilization at the cardiac clinic of Penang Hospital, Malaysia. This was a cross-sectional study. Demographic data of the patients, diagnoses and the drugs prescribed were recorded. The average drug acquisition costs (ADAC) were calculated for each antihypertensive drug class on a daily and annual basis. Adherence to the guideline was calculated as a percentage of the total number of patients. A total of 313 individuals fulfilled the inclusion criteria. The average age of the study population was 59.30 ± 10.35 years. The mean number of drugs per prescription in the study was 2.09 ± 0.78. There were no significant differences in the demographic data. Antihypertensive drugs were used in monotherapy and polytherapy in 20.8% and 79.2% of the patients, respectively. Adherence to the guideline regarding prescription occurred in 85.30% of the patients. The lowest priced drug class was diuretics and the highest was angiotensin-receptor blockers. In conclusion, the total adherence to the guideline was good; the adherence percentage only slightly decreased with a co-existing comorbidity (such as diabetes mellitus). The use of thiazide diuretics was encouraged because they are well tolerated and inexpensive, and perindopril was still prescribed for diabetic patients since it is relatively cheap (generic drug) and its daily dosage is beneficial.

  12. DRUG PRESCRIBED TO DIABETIC PATIENTS AND EFFECTIVENESS OF COMBINATION AND MONOTHERAPY

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    Safila Naveed

    2014-02-01

    Full Text Available To study the pattern of drug prescribed to diabetic patients & the effectiveness of combination & mono therapy. Method: We took a survey of primary & tertiary care hospitals to gather the data for this study randomized diabetic patients of type 1 & type 2 diabetes of different age, gender & conditions. Results: We included 110 patients for this study to check the effectiveness of combination & mono therapy in diabetic patients. Out of 110 patients we found 37 patients on mono therapy of metformin & the % effectiveness was 32%, 30 patients on insulin monotherapy, 13 patients taking combination therapy of insulin plus metformin & the % effectiveness was 54%, combination therapy of metformin plus sulphonyl urea were taken by 22 patients among which only 3 patients were on effective therapy & % effectiveness was found to be 14%. The result shows that combination of insulin plus metformin is more effective than the combination of metformin plus sulphonyl lurea & mono therapy of insulin & metformin. Conclusion: Combined therapy with insulin plus oral agents is widely used and has been shown to be effective in improving glycemic control in many short-term studies. When oral therapy is continued during insulin therapy, enhancing effectiveness of endogenous insulin control with similar hypoglycemic risk, or equal glycemic control with less hypoglycemia.

  13. Prostate-specific antigen kinetics after stereotactic body radiotherapy as monotherapy or boost after whole pelvic radiotherapy for localized prostate cancer

    OpenAIRE

    Kim, Hun Jung; Phak, Jung Hoon; Kim, Woo Chul

    2015-01-01

    Purpose Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate-specific antigen (PSA) kinetics after SBRT has not been well characterized. The purpose of the current study is to assess the kinetics of PSA for low- and intermediate-risk prostate cancer patients treated with SBRT using Cyberknife as both monotherapy and boost after whole pelvic radiotherapy (WPRT) in the absence of androgen deprivation therapy. Methods A tota...

  14. Medicinal Plants with Multiple Effects on Cardiovascular Diseases: A Systematic Review.

    Science.gov (United States)

    Rouhi-Boroujeni, Hojjat; Heidarian, Esfandiar; Rouhi-Boroujeni, Hamid; Deris, Fatemeh; Rafieian-Kopaei, Mahmoud

    2017-01-01

    Hyperlipidemia, obesity, hypertension, and diabetes are the most important risk factors for cardiovascular diseases. The aim of this systematic review article is to introduce the medicinal plants that exert significant clinical effects on hypertension, hyperlipidemia, obesity, and diabetes. In this review article, the international research databases including MEDLINE, Google scholar, EBSCO, Academic Search, Web of Science, SciVerse, Scopus (SCOPUS), EBSCO, Academic Search, Cochrane, Central Register of Controlled Trials (CENTRAL) and a Chinese database (China Network Knowledge Infrastructure [CNKI]) were searched using the key words hyperlipidemia, hypertension, diabetes, herbal, obesity, and phytomedicine, matched by MESH, from their respective inceptions up to March, 2016. The plants that were effective on one, two, three, or all of four diseases were determined. The doses, side effects, the most important pharmaceutically effective compounds, the used organs, and important points regarding usage were separately recorded. Also known clinically significant interactions were presented. 1023 articles were found to be about medicinal plants and hypertension, 1912 articles about medicinal plants and hyperlipidemia, 810 articles about medicinal plants and obesity, 1174 articles about medicinal plants and diabetes. Of 144 plants included in the analysis, 83 were found to be effective on hyperlipidemia, 100 on hypertension, 66 on obesity, and 72 on diabetes. 43 plants were found to be effective on two diseases, 14 on three diseases, and 34 on all four diseases. Three plants (Tomato, Cranberry and Pomegranate), in food and therapeutic doses, were found to be used to treat cardiovascular diseases especially in pre-eclampsia and hyperlipidemia in pregnancy. Regarding the findings of this study, we can argue that the medicinal plants, other than monotherapy, can be used as poly-therapy, to treat cardiovascular diseases. Copyright© Bentham Science Publishers; For any

  15. Effect of fixed-dose ACE-inhibitor/calcium channel blocker combination therapy vs. ACE-inhibitor monotherapy on arterial compliance in hypertensive patients with type 2 diabetes.

    Science.gov (United States)

    Winer, Nathaniel; Folker, Amy; Murphy, Julie A; Hung, Elena; Bard, Mara; Perkelvald, Alexander; Sowers, James R; Bakris, George L

    2005-01-01

    Assessment of vascular compliance may be a useful measurement of the clinical effects of antihypertensive treatment. Both angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are known to improve vascular elasticity. A study was performed to test the hypothesis that combined therapy with an ACE inhibitor and a calcium channel blocker would have additive benefits on vascular compliance at similar levels of blood pressure (BP), as compared with monotherapy with an ACE inhibitor. This 12-week, double-blind study was a substudy of a larger clinical hypertension study conducted in patients with hypertension and type 2 diabetes. Subjects (N = 20) were randomized to either a fixed-dose combination of amlodipine besylate/benazepril HCl or to enalapril monotherapy. BP, heart rate, large- and small-vessel compliance, systemic vascular resistance, and urinary microalbumin excretion were assessed at baseline and after treatment. Both treatments were similarly effective in lowering BP, reducing systemic vascular resistance, and decreasing urinary microalbumin excretion. Improvement in large-vessel compliance was significantly greater among subjects who received ACE-inhibitor/calcium channel blocker combination therapy (52%) as compared with those who received ACE-inhibitor monotherapy (32%; p < 0.05). No significant change in small-vessel compliance was observed with either treatment. Greater improvement in large-vessel compliance with combination therapy was independent of BP lowering.

  16. Switch to 1.5 grams MMF monotherapy for CNI-related toxicity in liver transplantation is safe and improves renal function, dyslipidemia, and hypertension.

    Science.gov (United States)

    Orlando, Giuseppe; Baiocchi, Leonardo; Cardillo, Andrea; Iaria, Giuseppe; De Liguori Carino, Nicola; De Liguori, Nicola; De Luca, Linda; Ielpo, Benedetto; Tariciotti, Laura; Angelico, Mario; Tisone, Giuseppe

    2007-01-01

    Although mycophenolate mofetil (MMF) monotherapy has been successfully used in liver transplant recipients suffering from calcineurin-inhibitor (CNI)-related chronic toxicity, still no consensus has been reached on its safety, efficacy and tolerability. We attempted the complete weaning off CNI in 42 individuals presenting chronic renal dysfunction and/or dyslipidemia and/or arterial hypertension and simultaneously introduced 1.5 gm/day MMF. CNI could be completely withdrawn in 41 cases. A total of 32 (75%) patients are currently on MMF. Mean follow-up from the introduction of MMF is 31.5 months and mean length of follow-up from the beginning of MMF monotherapy is 27.3 months. Renal function improved in 31/36 (89%) cases. Blood levels of cholesterol and triglycerides decreased in 13 of 17 (76%) and 15 of 17 (89%) patients, respectively. Arterial hypertension improved in 4 of 5 (80%) cases. A total of 8 patients showed a single episode of fluctuation of liver function tests during tapering off CNI. This feature was interpreted as an acute rejection (AR), based on the resolution of the clinical setting after escalation of MMF daily dose to 2 gm. A further patient developed a biopsy-proven AR insensitive to MMF adjustment, requiring reinstitution of the CNI dose. No deaths or major toxicity requiring MMF discontinuation occurred. In conclusion, low dose MMF monotherapy is safe, effective, and well tolerated.

  17. Differential Effects in Cardiovascular Markers between High-Dose Angiotensin II Receptor Blocker Monotherapy and Combination Therapy of ARB with Calcium Channel Blocker in Hypertension (DEAR Trial

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    Kenichiro Kinouchi

    2011-01-01

    Full Text Available Background/Aims. Arterial stiffness is an independent risk factor for cardiovascular morbidity and mortality. This study was conducted to determine the effect of olmesartan (OLM and azelnidipine (AZL on arterial stiffness using the cardio-ankle vascular index (CAVI, which is a novel blood pressure (BP-independent marker for arterial stiffness in hypertensive patients. Methods. Fifty-two consecutive hypertensive patients were randomly assigned either to a group treated with OLM monotherapy or to a group treated with OLM and AZL combination therapy. Clinical and biological parameters were measured before and 12 months after the start of this study. Results. Both therapies significantly and similarly reduced BP, augmentation index, and plasma aldosterone levels. The combination therapy significantly decreased CAVI and serum low-density lipoprotein (LDL-C levels and these reductions were significantly greater than those produced with monotherapy. No significant differences in metabolic parameters were observed between the two therapies. Conclusion. The combination therapy with OLM and AZL had beneficial effects on arterial stiffness assessed by CAVI, LDL-C, and metabolism, despite the similar BP reduction, compared with OLM monotherapy. Since these markers are known to influence the future risk of cardiovascular events, combination therapy with OLM and AZL could be a useful choice for treating hypertensive patients.

  18. [Expediency of switching from combined therapy with prostamol Uno and alpha-1-adrenoblockers to monotherapy with prostamol Uno in patients with prostatic adenoma].

    Science.gov (United States)

    Razumov, S V; Egorov, A A

    2007-01-01

    A 9-month randomized open comparative trial was performed of efficacy and safety of combined treatment with prostamol Uno and tamsulosin followed by monotherapy with prostamol Uno. A total of 58 patients with prostatic adenoma (PA) treated with prostamol Uno in combination with tamsulosin were divided into two groups: 28 patients continued the above combined therapy, 30 patients were switched to monotherapy with prostamol Uno. All the patients were examined in the course of 4 visits according to standard protocol requesting information on the disease history, complaints, digital rectal examination, IPSS questionnaire, QOL, uroflowmetry with test for residual urine, transrectal ultrasonography of the prostate, blood test for PSA. The results of the trial show reduction of IPSS and QOL indices in 87% patients. QOL improved both in group 1 after 3 months of combined treatment and in group 2 who continued on monotherapy with prostamol Uno to the end of month 9 (p 0.05). Prostamol Uno was especially safe for hypotensive patients and those on antihypertensive therapy. After discontinuation of tamsulosin 100% patients of group 2 stopped exhibiting symptoms of retrograde ejaculation. None cases of a hypotonic reaction to the drug were registered. Mean cost of a course of therapy in group 1 to that of group 2 was 1:3.16. Thus, pharmacotherapy with prostamol Uno in moderate symptoms of PA is comparable in efficacy with combination prostamol Uno + tamsulosin, is safe and cost-effective.

  19. Pergolide versus levodopa monotherapy in early Parkinson's disease patients : The PELMOPET study

    NARCIS (Netherlands)

    Oertel, WH; Wolters, E; Sampaio, C; Gimenez-Roldan, S; Bergamasco, B; Dujardin, M; Grosset, DG; Arnold, G; Leenders, KL; Hundemer, HP; Lledo, A; Wood, A; Frewer, P; Schwarz, J

    2006-01-01

    Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complcations. This paradigm is based on longterm studies, allowing "rescue" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the p

  20. Long-Term Exclusive Zinc Monotherapy in Symptomatic Wilson Disease : Experience in 17 Patients

    NARCIS (Netherlands)

    Linn, Francisca H. H.; Houwen, Roderick H. J.; van Hattum, Jan; van der Kleij, Stefan; van Erpecum, Karel J.

    2009-01-01

    Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13-26) with approximately half presenting as adolescents. Presentation

  1. Initial monotherapy and combination therapy and hypertension control the first year.

    Science.gov (United States)

    Egan, Brent M; Bandyopadhyay, Dipankar; Shaftman, Stephanie R; Wagner, C Shaun; Zhao, Yumin; Yu-Isenberg, Kristina S

    2012-06-01

    Initial antihypertensive therapy with single-pill combinations produced more rapid blood pressure control than initial monotherapy in clinical trials. Other studies reported better cardiovascular outcomes in patients achieving lower blood pressure during the first treatment year. We assessed the effectiveness of initial antihypertensive monotherapy, free combinations, and single-pill combinations in controlling untreated, uncontrolled hypertensives during their first treatment year. Electronic record data were obtained from 180 practice sites; 106 621 hypertensive patients seen from January 2004 to June 2009 had uncontrolled blood pressure, were untreated for ≥ 6 months before therapy, and had ≥ 1 one-year follow-up blood pressure data. Control was determined by the first follow-up visit with blood pressure blood pressure, body mass index, diabetes mellitus, chronic kidney disease, cardiovascular disease, initial therapy, final blood pressure medication number, and therapeutic inertia. Patients on initial single-pill combinations (N = 9194) were more likely to have stage 2 hypertension than those on free combinations (N = 18 328) or monotherapy (N = 79 099; all Phypertension control in the first year than free combinations (HR, 1.34; [95% CI, 1.31-1.37]) or monotherapy (reference) with benefits in black and white patients. Greater use of single-pill combinations as initial therapy may improve hypertension control and cardiovascular outcomes in the first treatment year.

  2. Oxidative stress is increased in women with epilepsy: Is it a potential mechanism of anti-epileptic drug-induced teratogenesis?

    Directory of Open Access Journals (Sweden)

    Damayanthi Deepa

    2012-01-01

    Full Text Available Context: Oxidative stress can be a final common pathway for AED-induced teratogenesis. Aims: To compare the oxidative stress of women with epilepsy (WWE and unfavorable pregnancy outcome (fetal malformation or spontaneous abortion - group EM with that of WWE with normal pregnancy outcome (group ENM and healthy women with normal pregnancy outcome (group C. Materials and Methods: We identified WWE under group EM (n = 43 and group ENM (n = 22 from the Kerala Registry of Epilepsy and Pregnancy (KREP. Group C was constituted of healthy volunteers (N = 20. Oxidative stress was assessed by estimating serum levels of malondialdehyde (MDA and isoprostane (ISP. The antioxidant profile was evaluated as activity of superoxide dismutase (SOD, glutathione reductase (GR, catalase (CAT, total antioxidant status (TAO, and glutathione (GSH content. Results: The MDA and ISP levels for group EM (3.46 + 0.82 and 17.77 + 3.0 were higher than that of group ENM (3.07 + 1.02 and 14.0 + 5.3, and both were significantly higher than that of group C (2.42 + 0.51 and 10.77 + 4.1. Their levels of SOD (146.82 + 42.64 vs. 175.81 + 42.61 and GSH (0.98 + 0.98 vs. 1.55 + 1.3 were significantly lower than those of controls. No significant changes were seen in TAO and GR. WWE on polytherapy showed significant increase in MDA when compared to monotherapy group. Conclusion: WWE (group EM and ENM had higher oxidative stress and reduced antioxidant activity. The subgroup of WWE with unfavorable pregnancy outcome (group EM had higher oxidative stress. Excess oxidative stress can be a final common pathway, by which AEDs exert teratogenic effects.

  3. COMPARATIVE EFFECTS OF MONOTHERAPY WITH MAGNESIUM AND COMBINED THERAPY WITH MAGNESIUM AND Β-BLOCKER ON PRIMARY MITRAL VALVE PROLAPSE WITH HEART RHYTHM DISORDERS

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    E. G. Nurtdinova

    2007-01-01

    Full Text Available Aim. To compare effects of monotherapy with magnesium and combined therapy with magnesium and β-blocker on primary mitral valve prolapse (MVP with heart rhythm disorders.Material and methods. 71 patients with primary MVP 1-2 degree and heart rhythm disorders were involved in the study. The patients were split into three groups. Group I (25 persons received monotherapy with magnesium orotate at a dose of 1-3 g per day; group II (28 persons received combined therapy with magnesium orotate and betaxolol. The control group (18 persons received no therapy. Initially and after 12 weeks of observation all the patients underwent electrocardiography (ECG, ECG-Holter monitoring, echocardiography and autonomic balance assessment by A.M. Vein’s questionnaire.Results. In 12 weeks of treatment groups I and II showed positive dynamics in the MVP manifestations, including significant reduction in severity of the autonomic dysfunction syndrome, ECG positive dynamics, antiarrhythmic effect, decrease in the degree of prolapse, diminution of mitral regurgitation and left auricle volumes. More substantial hemodynamic effects were found in the group of patients who received combination therapy.Conclusion. Combined therapy has proven advantages in comparison with magnesium monotherapy in terms of daily quantity of extrasystoles, reduction in heart rate, decrease in autonomic disfunction and normalization of intracardiac hemodynamics.

  4. Gengnianchun recipe inhibits apoptosis of pheochromocytoma cells from beta-amyloid 25-35 insult, better than monotherapies and their compounds

    Institute of Scientific and Technical Information of China (English)

    Jun Li; Wenjun Wang; Dajin Li; Wenjiang Zhou

    2011-01-01

    This study aims to determine and compare the protective effects of Gengnianchun recipe drug serum and compounds of its representative drug monotherapies against sympathetic nerve pheochromocytoma cell line PC12 cells damaged by beta-amyloid 25-35 at the cellular apoptosis and related signal pathway levels. PC12 cells cultured with medicated rat serum showed enhanced cell viability and reduced cellular apoptosis rates compared with those of monotherapies and their compounds. Furthermore, Gengnianchun recipe up-regulated expressions of anti-apoptotic protein Bcl-2, estrogen receptor-beta and phosphorylated extracellular-signal-regulated kinase 1/2; and down-regulated expressions of pro-apoptotic proteins Bax and caspase-3. Gengnianchun recipe was superior to representative drug monotherapies, such as paeoniflorin, berberine, timosaponin A-III, icariine and their compounds in protecting PC12 cells. Mitogen-activated protein kinase blocker and estrogen receptor antagonist were found to reverse the above effects of Gengnianchun recipe. The experimental findings indicate that, Gengnianchun recipe protects PC12 cells from beta-amyloid 25-35 insult; its inhibitory effect on apoptosis may be achieved through the mitogen-activated protein kinase and estrogen receptor pathways.

  5. Impact of time to treatment intensification on glycemic goal attainment among patients with type 2 diabetes failing metformin monotherapy.

    Science.gov (United States)

    Rajpathak, Swapnil N; Rajgopalan, Srini; Engel, Samuel S

    2014-01-01

    Patients with type 2 diabetes on metformin monotherapy frequently require treatment intensification with another anti-hyperglycemic medication over time. Previous studies have indicated that a high proportion of patients with diabetes have a significant delay in the initiation of oral add-on therapy after metformin alone fails to achieve targeted glycemic control. In this study, we evaluated the impact of the timing of treatment intensification with oral add-on drug on glycemic goal attainment among diabetic patients failing metformin monotherapy. Using the General Electric (GE) Centricity Electronic Medical Record database (January 2004 through December 2009), we identified 5,870 patients with type 2 diabetes with treatment failure on metformin monotherapy - defined by a glycosylated hemoglobin (HbA1c) of ≥7.5% (index date). This cut-off of ≥7.5% (trigger HbA1c) was chosen rather than that of >7.0% to ensure that selected patients were more likely to be indicated for treatment intensification with add-on drug. Continuous enrollment of one year prior and two years after index date was required to be included in the study. Add-on treatment was defined as prescription of second oral agent from any available therapeutic classes while continuing metformin. Early treatment intensification was defined as initiation of oral add-on therapy within 3 months (n=1,012) of index date while late intensification was defined as add-on initiation between 10 and 15 months after index date (n=461). The study outcome was defined as glycemic goal attainment (HbA1cgender, trigger HbA1c level, Charlson comorbidity index, anti-hypertensive and anti-hyperlipidemic drug use and history of cardiovascular disease, the adjusted odds ratio (OR) for glycemic goal attainment was 1.36 (95% confidence intervals [CI]: 1.09-1.72) comparing early add-on to late add-on treatment. This association was stronger among patients with higher trigger HbA1c at baseline; ORs of 1.53 (95% CI: 1.08-2.19) for

  6. Stereotactic Body Radiotherapy as Monotherapy or Post-External Beam Radiotherapy Boost for Prostate Cancer: Technique, Early Toxicity, and PSA Response

    Energy Technology Data Exchange (ETDEWEB)

    Jabbari, Siavash [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Weinberg, Vivian K. [Biostatistics and Computational Biology Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California (United States); Kaprealian, Tania; Hsu, I-Chow; Ma Lijun; Chuang, Cynthia; Descovich, Martina; Shiao, Stephen [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Shinohara, Katsuto [Department of Urology, University of California San Francisco, San Francisco, California (United States); Roach, Mack [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Department of Urology, University of California San Francisco, San Francisco, California (United States); Gottschalk, Alexander R., E-mail: AGottschalk@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States)

    2012-01-01

    Purpose: High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. Patients and Methods: To date, 38 patients have been treated with SBRT at University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy Multiplication-Sign 4 fractions), and 18 were treated with SBRT boost (9.5 Gy Multiplication-Sign 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. Results: SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). Conclusions: Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost

  7. Outcome of shock wave lithotripsy as monotherapy for large solitary renal stones (>2 cm in size without stenting

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    Shanmugasundaram Rajaian

    2010-01-01

    Full Text Available Purpose : To evaluate the outcome of shock wave lithotripsy (SWL as monotherapy for solitary renal stones larger than 2 cm without ureteral stenting. Materials and Methods : Our retrospective study included patients with solitary renal radio opaque stones larger than 2 cm treated with SWL using electromagnetic Dornier Compact S lithotripter device (Wessling, Germany for a period of 3 years (September 2002-2005. Stone clearance was assessed at 1 week, 1 month, and 3 months with plain X-rays of kidney, ureter, and bladder region, ultrasonography, and tomograms. Stone-free status, morbidity of the procedure, and fate of clinically insignificant residual fragments (CIRF were studied. A stone-free state was defined as no radiologic evidence of stone. Success was defined as complete clearance + CIRF. Results : Fifty-five patients, aged 11-65 years (mean 49.8 underwent SWL. Of them, only two were children. Male-to-female ratio was 3:1. The stone size was 21-28 mm (average 24 mm. The mean number of shocks were 3732 (range 724-12,100 and average energy level was 14 kV (range 11-16 kV. The mean follow-up was 18 months (range 3-22 months. Over all, stone-free status was achieved in 50% and success in 81% at 3 months. Stone clearance was not affected by stone location. Stones 26 mm (P = -0.10. Of 54 patients, 39 developed steinstrasse with mean length of 3.2 cm (range 1.4-6.2 cm and only four required intervention. Effectiveness quotient (EQ for SWL monotherapy for solitary renal stones more than 2 cm was 25.3%. The EQ for stones <25 mm and those more than 25 mm were 28.4% and 10% (P = -0.12, respectively. There was a lesser trend of difference between stones with size <25 and more than 25 mm. During the last review, the overall stone-free rate was 67.2%. Conclusions : SWL monotherapy was safe but significantly less effective for solitary renal stones larger than 2 cm. It can only be suggested to those who refuse surgical intervention. Pretreatment DJ

  8. NI-60RECURRENT PATTERNS OF BEVACIZUMAB MONOTHERAPY FOR RECURRENT PRIMARY GLIOBLASTOMA AND PERSPECTIVES ON BEVACIZUMAB-BASED THERAPIES

    Science.gov (United States)

    Nagane, Motoo; Kobayashi, Keiichi; Saito, Kuniaki; Shiokawa, Yoshiaki

    2014-01-01

    BACKGROUND. Prognosis of patients with recurrent glioblastoma (GBM) remains dismal, their median overall survival (mOS) ranging from 7 to 10 months. Currently, bevacizumab (BEV), a monoclonal antibody against VEGF, has been widely used since it prolonged progression-free survival (PFS) accompanied with symptom relief in BEV trials. However, improvement of OS seems modest at most, and issues regarding short survival after BEV failure, invasive relapse, and difficulty in determining true progression remain unsolved. Here we examined the patterns of radiological BEV failure in relationship with survival of several post-treatment periods. METHODS. Twenty-five patients with primary GBM who were treated with BEV monotherapy at recurrence in Kyorin University hospital since August 2009 were included in this study. Mean age was 53 yo, 13 males/12 females, median KPS was 60 (30-100), and mOS from the initial surgery was 23.2 months. MRI patterns at BEV progression were determined using modified classification by Nowosielsky et al. (Neurology 2014) as follows: 1) T2-diffuse, 2) cT1-flare up, 3) Primary non-responders, 4) T2-circumscribed, and 5) Remote metastasis. RESULTS. mPFS and mOS of BEV monotherapy were 3.4 and 7.6 months, respectively, and post-BEV mOS was 4.7 months. Frequency and BEV-PFS/post-BEV OS were 1) 20%, 3.8/0.8 months; 2) 40%, 3.4/7.1 months, 3) 24%, 0.9/3.3 months, 4) 8%, 3.7/3.9 months, 5) 8%, 2.0/4.2 months. The cT1-flare up recurrent pattern was found most frequently with relatively better survivals, whereas the T2-diffuse recurrence included fatal brain stem invasion in two cases, resulting in poorer prognosis. CONCLUSIONS. BEV monotherapy showed limited survival benefit and the clinical course after BEV failure may differ by patterns of relapse. Although RANO criteria have been a standard method to determine progression, measurement of T2/FLAIR hyperintensity remains critically controversial. Efforts to improve BEV-based therapy for recurrent GBM

  9. Efficacy and safety of travoprost 0.004%/timolol 0.5% fixed combination as transition therapy in patients previously on prostaglandin analog monotherapy

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    Costa VP

    2012-05-01

    Full Text Available Vital Paulino Costa1, Hamilton Moreira2, Mauricio Della Paolera3, Maria Rosa Bet de Moraes Silva41Universidade Estadual de Campinas – UNICAMP, São Paulo, 2Universidade Federal do Paraná, Curitiba, 3Santa Casa de Misericórdia de São Paulo, São Paulo, 4Faculdade de Medicina de Botucatu, UNESP, BrazilPurpose: To assess the safety and efficacy of transitioning patients whose intraocular pressure (IOP had been insufficiently controlled on prostaglandin analog (PGA monotherapy to treatment with travoprost 0.004%/timolol 0.5% fixed combination with benzalkonium chloride (TTFC.Methods: This prospective, multicenter, open-label, historical controlled, single-arm study transitioned patients who had primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension and who required further IOP reduction from PGA monotherapy to once-daily treatment with TTFC for 12 weeks. IOP and safety (adverse events, corrected distance visual acuity, and slit-lamp biomicroscopy were assessed at baseline, week 4, and week 12. A solicited ocular symptom survey was administered at baseline and at week 12. Patients and investigators reported their medication preference at week 12.Results: Of 65 patients enrolled, 43 had received prior travoprost therapy and 22 had received prior nontravoprost therapy (n = 18, bimatoprost; n = 4, latanoprost. In the total population, mean IOP was significantly reduced from baseline (P = 0.000009, showing a 16.8% reduction after 12 weeks of TTFC therapy. In the study subgroups, mean IOP was significantly reduced from baseline to week 12 (P = 0.0001 in the prior travoprost cohort (19.0% reduction and in the prior nontravoprost cohort (13.1% reduction. Seven mild, ocular, treatment-related adverse events were reported. Of the ten ocular symptom questions, eight had numerically lower percentages with TTFC compared with prior PGA monotherapy and two had numerically higher percentages with TTFC (dry eye symptoms and ocular

  10. Efficacy of generic levetiracetam (epiterra in monotherapy for epilepsy in adult patients: preliminary results

    Directory of Open Access Journals (Sweden)

    V. A. Karlov

    2015-01-01

    Full Text Available Objective: to evaluate the efficacy and tolerability of levetiracetam (LEV (epiterra, TEVA in adult patients with focal epilepsy (FE or juvenile myoclonic epilepsy (JME who took the drug for і6 months as of December 15, 2014. Patients and methods. The efficacy of LEV as a generic (epiterra used in monotherapy was analyzed in 23 patients with FE and in 4 female patients with JME who had taken the drug for ≥6 months. In FE, LEV was switched to epiterra because of the high cost of the former and inadequate efficacy/poor tolerability of initial antiepileptic drugs (AEDs in 17 and 6 cases, respectively. In JMA, epiterra was prescribed as initial therapy in 2 cases and, with the diagnosis being changed, in 2 more patients. Results and discussion. When LEV was switched to its generic, the indicators of efficacy, tolerability, quality of life, and a plain electroencephalogram (EEG were significantly unchanged. When epiterra was substituted for other AEDs, the efficiency of its therapy was also significantly unchanged and tolerance, quality of life, and EEG characteristics were improved. Epiterra’s adverse reactions as sleepiness (n = 1 and a higher rate of mental processes (n=1 were observed exclusively when it was switched from another AED. However, they were transient (for 2–3 weeks and seen during either dose adjustment or at the stage of transitional combined therapy. Dual therapy (valproate + epiterra had to be used in only 1 female patient. Thus, the 6-month use of epiterra in adult patients with FE as an alternative to brand LEV did not deteriorate the clinical picture of the disease (remission rates and injury frequency and severity were significantly unchanged baseline tolerability, quality of life, or plain EEG values. The findings suggest that the use of epiterra is highly promising in epileptology, particularly in FE and JME in adult patients. 

  11. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Byrd, John C; Flynn, Joseph M; Kipps, Thomas J; Boxer, Michael; Kolibaba, Kathryn S; Carlile, David J; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P

    2016-01-07

    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205.

  12. Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Ju Andrew W

    2013-01-01

    Full Text Available Abstract Background Hypofractionated stereotactic body radiation therapy (SBRT has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Methods Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL measures were assessed at baseline and follow-up. Results All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. Conclusions In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. Trial registration The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510.

  13. Treatment of peritoneal dialysis-related peritonitis with ciprofloxacin monotherapy: clinical outcomes and bacterial susceptibility over two decades.

    Science.gov (United States)

    Fontán, Miguel Pérez; Cambre, Helena Díaz; Rodríguez-Carmona, Ana; Muñiz, Andrés López; Falcón, Teresa García

    2009-01-01

    There is controversy about the preferred initial antibiotic therapy for peritoneal dialysis (PD)-related peritonitis. Quinolones have been used extensively in this setting, yet their long-term effectiveness is unknown. To analyze the results of a protocol of treatment of PD-related peritonitis with ciprofloxacin, maintained over two decades. We analyzed the clinical outcome of 682 episodes of bacterial peritonitis treated with intraperitoneal ciprofloxacin monotherapy, and the time course of bacterial susceptibility to this antimicrobial, in a historical cohort of 641 PD patients (1988-2007). Main outcome variables included changes to initial therapy and rates of hospital admission, catheter removal, relapse, reinfection, PD dropout, and mortality. For comparisons we divided the study period into phases A (1988-1994), B (1995-2000), and C (2001-2007). The incidence of Staphylococcus aureus peritonitis decreased, while the incidences of polymicrobial and negative-culture peritonitis increased after phase A. In vitro susceptibility to ciprofloxacin decreased significantly only among coagulase-negative staphylococci (87.0% susceptible strains in phase A vs 70.0% in B and 70.1% in C, p = 0.006). Overall success rates (catheter not removed and ongoing PD after the episode) remained stable, at over 85%. However, the proportion of patients treated solely with ciprofloxacin declined from 75.7% (A) to 47.3% (B) to 32.4% (C) (p ciprofloxacin was a marker of multiresistance and correlated strongly with clinical outcome of peritonitis. Among isolates susceptible to ciprofloxacin, changing initial therapy for any reason also predicted a poor outcome. Following satisfactory early results, the effectiveness of ciprofloxacin as monotherapy for PD-related peritonitis has declined markedly in the long term. This decline cannot be explained solely by a decrease of in vitro susceptibility to this antimicrobial, which was significant only among coagulase-negative staphylococci

  14. Monotherapy With Major Antihypertensive Drug Classes and Risk of Hospital Admissions for Mood Disorders

    Science.gov (United States)

    Boal, Angela H.; Smith, Daniel J.; McCallum, Linsay; Muir, Scott; Touyz, Rhian M.; Dominiczak, Anna F.

    2016-01-01

    Major depressive and bipolar disorders predispose to atherosclerosis, and there is accruing data from animal model, epidemiological, and genomic studies that commonly used antihypertensive drugs may have a role in the pathogenesis or course of mood disorders. In this study, we propose to determine whether antihypertensive drugs have an impact on mood disorders through the analysis of patients on monotherapy with different classes of antihypertensive drugs from a large hospital database of 525 046 patients with follow-up for 5 years. There were 144 066 eligible patients fulfilling the inclusion criteria: age 40 to 80 years old at time of antihypertensive prescription and medication exposure >90 days. The burden of comorbidity assessed by Charlson and Elixhauser scores showed an independent linear association with mood disorder diagnosis. The median time to hospital admission with mood disorder was 847 days for the 299 admissions (641 685 person-years of follow-up). Patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had the lowest risk for mood disorder admissions, and compared with this group, those on β-blockers (hazard ratio=2.11; [95% confidence interval, 1.12–3.98]; P=0.02) and calcium antagonists (2.28 [95% confidence interval, 1.13–4.58]; P=0.02) showed higher risk, whereas those on no antihypertensives (1.63 [95% confidence interval, 0.94–2.82]; P=0.08) and thiazide diuretics (1.56 [95% confidence interval, 0.65–3.73]; P=0.32) showed no significant difference. Overall, our exploratory findings suggest possible differential effects of antihypertensive medications on mood that merits further study: calcium antagonists and β-blockers may be associated with increased risk, whereas angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be associated with a decreased risk of mood disorders. PMID:27733585

  15. CSF LPV concentrations and viral load in viral suppressed patients on LPV/r monotherapy given once daily

    Directory of Open Access Journals (Sweden)

    Juan Tiraboschi

    2014-11-01

    Full Text Available Introduction: Plasma trough concentrations of lopinavir (LPV given as LPV/r 800/200 mg once daily (OD are reduced in comparison with 400/100 mg twice daily (BID. While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV-1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD. Material and Methods: This is a cross-sectional sub-study within a prospective, open-label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID, the “Kmon study” (NCT01581853. To assess LPV concentrations and HIV-1 RNA in CSF, a lumbar puncture (LP was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma-paired samples of all patients were also obtained. HIV-1 RNA was determined by real-time PCR (limit of detection 40 copies/mL. Liquid chromatography-tandem mass spectrometry (Tandem labs, NJ was used to determine CSF and blood plasma LPV concentrations. Results: Nine patients were included. Median (range age was 48 (34–56 years, median CD4 cell count 672 (252–1,408 cells/mL, median nadir CD4 count 125 (35–537 cells/mL and 40% of subjects were HCV-positive. Before starting LPV/rMOD median time on a LPV/r-containing regimen and on LPV/rMBID were 9 (4–11 years and 15 (7–24 months respectively, median time with undetectable HIV viral load was 5 (3–12 years and 2 patients had a previous documented blip. LP was performed a median of 24 (8–36 weeks after starting LPV/rMOD and 24 (11–28 hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93–78.3 ng

  16. Empiric penicillin monotherapy of CAP is not associated with increased mortality; experiences from the retrospective CAP-North cohort

    DEFF Research Database (Denmark)

    Baunbæk-Knudsen, Getrud; Vestergaard Jensen, Andreas; Andersen, Stine

    2016-01-01

    Background: Community-acquired pneumonia (CAP) is a severe infection, with high morbidity and mortality. The antibiotic strategies for CAP differ across Europe. Objective: To assess the usage of Penicillin monotherapy in a real-life cohort and to evaluate predictors of treatment duration...... and the prognosis of patients with CAP. Methods: Adult patients with CAP, verified by an infiltrate on chest X-ray, hospitalized in three Danish hospitals during January 2011 to July 2012 were identified. We calculated the population-based incidence, reviewed types and duration of antibiotic treatment......, and evaluated predictors of treatment duration by linear regression. Mortality of patients receiving empiric penicillin-G/V was compared to others by logistic regression analysis. The CAPNETZ database technology was used for data-capture. Results: We included 1320 patients. The incidence of hospitalized CAP...

  17. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy

    Science.gov (United States)

    Veldt, B J; Saracco, G; Boyer, N; Cammà, C; Bellobuono, A; Hopf, U; Castillo, I; Weiland, O; Nevens, F; Hansen, B E; Schalm, S W

    2004-01-01

    Background: The key end point for treatment efficacy in chronic hepatitis C is absence of detectable virus at six months after treatment. However, the incidence of clinical events during long term follow up of patients with sustained virological response is still poorly documented and may differ between the Eastern and Western world. Aims: To assess clinical end points during long term follow up of European patients with a sustained virological response to interferon monotherapy. Methods: Meta-analysis of individual patient data from eight European protocolled follow up studies of interferon treatment for chronic hepatitis C. Results: A total of 286 sustained virological responders and 50 biochemical responders (detectable virus but normal alanine aminotransferase levels) were followed up for 59 months. Fifteen sustained virological responders (5.2%) had cirrhosis before treatment and 112 (39%) had genotype 1. The late virological relapse rate after five years of follow up was 4.7% (95% confidence interval (CI) 2.0–7.4) among sustained virological responders; all late relapses occurred within four years after treatment. Among sustained virological responders, the rate of decompensation after five years of follow up was 1.0% (95% CI 0.0–2.3) and none developed hepatocellular carcinoma (HCC). Survival was comparable with the general population, matched for age and sex, the standard mortality ratio being 1.4 (95% CI 0.3–2.5). Clinical outcome of patients with cirrhosis was similar to other sustained virological responders. For biochemical responders, the rates of development of decompensation and HCC during long term follow up were 9.1% (95% CI 0.5–17.7) and 7.1% (95% CI 0–15.0), respectively. Conclusions: Five year survival of European sustained virological responders was similar to the overall population, matched for age and sex. No HCCs were detected during long term follow up. PMID:15361504

  18. QTc interval in young Gujarati hypertensives: Effect of disease, antihypertensive monotherapy, and coexisting risk factors.

    Science.gov (United States)

    Solanki, Jayesh Dalpatbhai; Gadhavi, Bhakti P; Makwana, Amit H; Mehta, Hemant B; Shah, Chinmay J; Gokhale, Pradnya A

    2016-01-01

    To study the effect of disease duration, treatment and risk factors on QTc interval among young hypertensives. A case-control study was conducted on 142 hypertensives (60 males, 82 females) taking calcium channel blocker (CCB) or angiotensin-converting enzyme inhibitor (ACEI) as monotherapy. After blood pressure measurement, we recorded lead II electrocardiograph with minimum ten waveforms. QTc was derived from average of ten values using Bazett's formula. QTc interval >0.43 s in male and >0.45 s in female was considered abnormal. Cases had mean duration of hypertension 5 years, mean age of 40 years, and poor blood pressure control (systolic blood pressure >140 and diastolic blood pressure >90 mm of Hg). Newly diagnosed hypertensives had significantly higher QTc values than the matched known cases (0.44 vs. 0.42 s, P < 0.05). Known hypertensives did not differ significantly in QTc values by the duration of disease. CCB users showed small, insignificant disadvantage for abnormally prolonged QTc values than ACEI users. With coexisting diabetes, smoking, and positive family history of hypertension, there was odds risk of 7.69, 2.75, and 2.54, respectively for prolonged QTc. Our study showed prolonged QTc in hypertensives more so in newly diagnosed, unaffected by duration or use of ACEI, or CCB but associated with modifiable risk factors. This underscores high risk of repolarization abnormality-induced future events, suggesting early screening of hypertension, strict blood pressure control, optimum use of QTc measurement, and preventive pharmacotherapy to reduce this aftermath.

  19. Blood serum levels of CART peptide in patients with schizophrenia on clozapine monotherapy.

    Science.gov (United States)

    Wysokiński, Adam; Kłoszewska, Iwona

    2014-12-15

    CART (cocaine- and amphetamine-regulated transcript) is an endogenous inhibitor of food intake. We compared fasting serum CART levels in subjects with schizophrenia on clozapine monotherapy (n=24) with sex- and age-matched healthy controls (n=24). CART levels were higher in the clozapine group (262.76±359.91 vs. 90.40±169.90 pg/mL). CART levels were higher in subjects with metabolic syndrome compared to subjects without metabolic syndrome in the clozapine group (415.63±416.93 vs. 122.62±237.17 pg/mL, n=12 and 12, respectively) and in the whole study group (377.73±401.09 vs. 88.58±172.35 pg/mL, n=16 and 32, respectively). In the control group CART levels were higher in subjects with total body fat lower than the target maximum compared to subjects with total body fat below the target maximum (121.71±154.91 vs. 66.32±182.96 pg/mL, n=14 and 10, respectively). CART levels did not correlate with age, weight, BMI, abdominal, waist and hip circumferences, WHR, blood pressure, laboratory tests, clozapine dose, antipsychotic or clozapine treatment duration, body composition, and markers of insulin resistance in the study group. Further studies are required to confirm whether increased levels of circulating CART are compensatory in response to treatment-induced weight gain and abdominal obesity or a primary feature of schizophrenia.

  20. Parameters of metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy

    OpenAIRE

    Aditi Dhir; Suvasini Sharma; Puneet Jain; Bhanu K Bhakhri; Satinder Aneja

    2015-01-01

    Objectives: The prevalence of obesity is rapidly increasing among Indian children, who, in general, are more prone to develop metabolic complications at an early age. Valproate and phenytoin are commonly used antiepileptic drugs in children. This study aimed to assess the parameters of the metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy. Methods: This cross-sectional study recruited children from the Pediatric Epilepsy Clinic, Department of Pediatrics...

  1. Long-term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: Results up to 8 years.

    Science.gov (United States)

    Fung, James; Wong, Tiffany; Chok, Kenneth; Chan, Albert; Cheung, Tan-To; Dai, Jeff Wing-Chiu; Sin, Sui-Ling; Ma, Ka-Wing; Ng, Kelvin; Ng, Kevin Tak-Pan; Seto, Wai-Kay; Lai, Ching-Lung; Yuen, Man-Fung; Lo, Chung-Mau

    2017-10-01

    Long-term antiviral prophylaxis is required to prevent hepatitis B recurrence for patients with chronic hepatitis B after liver transplantation. We determined the long-term outcome of 265 consecutive chronic hepatitis B liver transplant recipients treated with entecavir monotherapy without hepatitis B immune globulin. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. The median duration of follow-up was 59 months. The cumulative rates of hepatitis B surface antigen (HBsAg) seroclearance were 90% and 95% at 1 and 5 years, respectively. At 1, 3, 5, and 8 years, 85%, 88%, 87.0%, and 92% were negative for HBsAg, respectively, and 95%, 99%, 100%, and 100% had undetectable hepatitis B virus (HBV) DNA, respectively. Fourteen patients remained persistently positive for HBsAg, all of whom had undetectable HBV DNA. There was no significant difference in liver stiffness for those who remained HBsAg-positive compared to those who achieved HBsAg seroclearance (5.5 versus 5.2 kPa, respectively; P = 0.52). The overall 9-year survival was 85%. There were 37 deaths during the follow-up period, of which none were due to hepatitis B recurrence. Long-term entecavir monotherapy is highly effective at preventing HBV reactivation after liver transplantation for chronic hepatitis B, with a durable HBsAg seroclearance rate of 92%, an undetectable HBV DNA rate of 100% at 8 years, and excellent long-term survival of 85% at 9 years. (Hepatology 2017;66:1036-1044). © 2017 by the American Association for the Study of Liver Diseases.

  2. Quality of Life and Functioning in Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder After Treatment With Citalopram Monotherapy.

    Science.gov (United States)

    Steiner, Alexander J; Boulos, Nathalie; Mirocha, James; Wright, Stephanie M; Collison, Katherine L; IsHak, Waguih W

    Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) often have high comorbidity, consequently influencing patient-reported outcomes of depressive symptom severity, quality of life (QOL), and functioning. We hypothesized that the combined effects of concurrent PTSD and MDD would result in worse treatment outcomes, whereas individuals who achieved MDD remission would have better treatment outcomes. We analyzed 2280 adult participants who received level 1 treatment (citalopram monotherapy) in the Sequenced Treatment Alternatives to Relieve Depression study, including 2158 participants with MDD without comorbid PTSD and 122 participants with MDD with comorbid PTSD (MDD + PTSD). Post hoc analysis examined the proportion of participants whose scores were within normal or severely impaired for functioning and QOL. Remission status at exit from MDD was also determined. At entry, participants with MDD + PTSD experienced significantly worse QOL, functioning, and depressive symptom severity compared with participants with MDD without comorbid PTSD. Although both groups had significant improvements in functioning and QOL posttreatment, the participants with MDD + PTSD were less likely to achieve remission from MDD. Findings suggested that participants with MDD + PTSD are at a greater risk for severe impairment across all domains and less likely to achieve remission from MDD after treatment with citalopram monotherapy. As such, the use of patient-reported measures of QOL and functioning may inform practicing clinicians' and clinical trial researchers' abilities to develop appropriate interventions and monitor treatment efficacy. More importantly, we encourage clinicians and health care providers to routinely screen for PTSD in patients with MDD because this at-risk group requires tailored and specific pharmacotherapy and psychotherapy interventions beyond traditionally standard treatments for depression.

  3. Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics

    NARCIS (Netherlands)

    Selle, V.; Schalkwijk, S.J.; Vazquez, G.H.; Baldessarini, R.J.

    2014-01-01

    BACKGROUND: Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. METHODS: We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants,

  4. Monotherapy with boosted protease inhibitors as antiretroviral treatment simplification strategy in the clinical setting

    Directory of Open Access Journals (Sweden)

    J Santos

    2012-11-01

    Full Text Available Antiretroviral treatment simplification with darunavir/ritonavir or lopinavir/ritonavir monotherapy maintains sustained HIV viremia suppression in clinical trials. However, data about the efficacy of this strategy in routine clinical practice is still limited, and no direct comparison between darunavir/ritonavir and lopinavir/ritonavir has been performed to date. We retrospectively studied all HIV-1-infected subjects who initiated monotherapy with darunavir/ritonavir or lopinavir/ritonavir while having plasma VL<50 c/mL, and had at least 1 subsequent follow-up visit in our clinic. When two consecutive PI-monotherapy regimens were used, each regimen was considered separately. The primary endpoint was the percentage of patients who maintained virological suppression (HIV-1 VL <50 c/mL through follow-up. Virological failure was defined as at least two consecutive HIV-1 VL >50 c/mL. We also evaluated other reasons for treatment discontinuation. Analyses were performed considering all regimens (full dataset analysis either as “on treatment” or as “treatment switch equals failure”. Five hundred and seventy-three PI-monotherapy regimens corresponding to 520 subjects were included, 262 with darunavir/ritonavir and 311 with lopinavir/ritonavir. Medians (IQR follow-up were 50 (26.3–107.6 and 85.6 (36.9–179.1 weeks for subjects on darunavir/ritonavir and lopinavir/ritonavir, respectively (p<0.001. Overall, 67 (11.7% subjects experienced virological failure, 23 (8.7% were on darunavir/ritonavir and 42 (13.5% were on lopinavir/ritonavir (p=0.796. Two hundred and three (77.5% patients on darunavir/ritonavir and 154 (49.5% on lopinavir/ritonavir maintained virological suppression in the “treatment switch equals failure” (p=0.002. Other reasons for treatment discontinuation were gastrointestinal toxicity and dyslipidemia in 7.2% and 5.9% of cases, respectively. Gastrointestinal toxicities and dyslipidemia leading to treatment discontinuation

  5. 恩替卡韦与阿德福韦酯单药治疗慢性乙型肝炎相关性肝病患者240周的随机对照研究%A randomized controlled trial on 240-week monotherapy with entecavir or adefovir in patients with chronic hepatitis B and cirrhosis

    Institute of Scientific and Technical Information of China (English)

    连佳; 韩涛; 向慧玲; 刘芳; 吕洪敏; 高艳颖; 王凤梅

    2015-01-01

    目的 评估恩替卡韦及阿德福韦酯片单药治疗慢性乙型肝炎相关性肝病患者240周的疗效. 方法 90例确诊为慢性乙型肝炎肝硬化(代偿期和失代偿期)患者,随机分成两组,分别接受恩替卡韦0.5 mg/d(38例)或阿德福韦酯片10 mg/d(52例),于治疗前及治疗24、48、96、144、192周和240周,检测HBV DNA、生物化学指标、腹部B型超声、乙型肝炎病毒血清学标志物,同时观察并发症及药物相关不良反应.治疗48周未获得完全病毒学应答或治疗期间出现病毒学突破的患者,均可改变原治疗方案加用一种更强且无交叉耐药的药物继续治疗并观察.两组间均数比较采用t检验,计数资料比较采用x2检验,多因素分析采用COX回归. 结果 恩替卡韦组脱落1例,阿德福韦酯组脱落7例;治疗240周后,恩替卡韦组与阿德福韦酯组HBV DNA转阴率分别为91.9%和57.8%(x2=10.362,P=0.001);HBeAg转阴率分别为46.2%和24.0% (x2=5.055,P=0.025);HBeAg血清转换率分别为23.1%和8.0%(P=0.047),差异均有统计学意义,两组进行符合方案集分析与意向性分析结论相一致.恩替卡韦组与阿德福韦酯组原发性肝癌发生率分别为8.1%和6.7%(x2=0.000,P=1.000),病死率分别为8.1%和4.4%(x2=0.051,P=0.821),差异均无统计学意义.进行COX回归分析,恩替卡韦组HBV DNA转阴的可能性为阿德福韦酯组的2.761倍(95%可信区间为1.630 ~ 4.679);男性HBeAg血清转换的可能性为女性的0.192倍(95%可信区间为0.046 ~0.806). 结论 恩替卡韦在抗乙型肝炎病毒治疗过程中,具有高效、迅速抑制病毒的作用,是理想的一线抗病毒药物.%Objective To compare the efficacies ofentecavir and adefovir in patients with chronic hepatitis B (CHB) and cirrhosis when administered as monotherapies using a 240-week course.Methods Ninety patients diagnosed with CHB and cirrhosis (compensated or decompensated) were randomly divided into two

  6. Botulinum Toxin as Monotherapy in Symptomatic Trigeminal Neuralgia.

    Science.gov (United States)

    Lunde, Hanne Marie Bøe; Torkildsen, Øivind; Bø, Lars; Bertelsen, Anne Kjørsvik

    2016-06-01

    Trigeminal neuralgia (TN) is one of the most agonizing facial pain disorders that humans endure. Studies on onabotulinum toxin A (BTX-A) treatment for TN are limited, but promising with respect to TN of no identifiable cause. We aimed to investigate the efficiency and safety of BTX-A treatment in a 60-year-old male with diabetes mellitus who in March 2013 presented with TN caused by an exostosis in Meckel's cave. The patient was medically treatment refractory due to insufficient pain relief and adverse events of hyperglycemia, and surgery was declined due to complex anatomy. As a last resort, BTX-A was injected into the pain trigger zones of the trigeminal nerve (V5). Complete analgesia was reported 2 weeks after BTX-A injection. Pain medications were discontinued and laboratory values returned to acceptable levels. Regular BTX-A treatment during the next 28 months showed sustained analgesic effect. BTX-A has an excellent safety profile and may be efficient for patients with symptomatic TN not suited for conventional therapies. © 2016 American Headache Society.

  7. Targeting CD38 with daratumumab monotherapy in multiple myeloma

    NARCIS (Netherlands)

    Lokhorst, H. M.; Plesner, T.; Laubach, J. P.; Nahi, H.; Gimsing, P.; Hansson, M.; Minnema, M. C.; Lassen, U.; Krejcik, J.; Palumbo, A.; Van De Donk, N. W C J; Ahmadi, T.; Khan, I.; Uhlar, C. M.; Wang, J.; Sasser, A. K.; Losic, N.; Lisby, S.; Basse, L.; Brun, N.; Richardson, P. G.

    2015-01-01

    Background: Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. Methods: In part 1, t

  8. Seizure frequency in pregnant women treated with lamotrigine monotherapy

    DEFF Research Database (Denmark)

    Sabers, Anne; Petrenaite, Vaiva

    2009-01-01

    Previous studies have demonstrated that the pharmacokinetics of the new antiepileptic drug (AED) lamotrigine (LTG) are substantially influenced by pregnancy and are more likely to be associated with seizure deterioration in pregnancy compared to other AEDs. This is of great concern, as LTG has de...

  9. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne;

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE To i...

  10. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures

    NARCIS (Netherlands)

    Koch, Marcus W.; Polman, Susanne K. L.

    2009-01-01

    Background Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. Objectives To compare efficacy and tolerability of carbamazepine and oxcarbazepine mono

  11. Cognitive and Behavioral Effects of Topiramate Versus Carbamazepine Monotherapy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-09-01

    Full Text Available The cognitive and behavioral effects of topiramate (TPM versus carbamazepine (CBZ were evaluated in a multicenter, randomized, open-label, parallel-group trial at Sanggye Paik Hospital, Seoul, and other university centers in Korea.

  12. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures

    NARCIS (Netherlands)

    Koch, Marcus W.; Polman, Susanne K. L.

    2009-01-01

    Background Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. Objectives To compare efficacy and tolerability of carbamazepine and oxcarbazepine mono

  13. Sulphonylurea monotherapy for patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Schroll, Jeppe B; Lund, Søren

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. Whether sulphonylureas show better, equal or worse therapeutic effects in comparison with other antidiabetic interventions for patients with T2DM remains controversial.......Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. Whether sulphonylureas show better, equal or worse therapeutic effects in comparison with other antidiabetic interventions for patients with T2DM remains controversial....

  14. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

    DEFF Research Database (Denmark)

    Larkin, James; Chiarion-Sileni, Vanna; Gonzalez, Rene

    2015-01-01

    BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab...... alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression...... melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; Check...

  15. Short‑term Effect of Tamsulosin and Finasteride Monotherapy and ...

    African Journals Online (AJOL)

    2017-05-18

    May 18, 2017 ... least effective. Bothersome, side effects were more in patients taking finasteride .... chronic prostatitis, or two or more episodes of acute urinary retention ... greatest reduction in quality of life score was in the. Group A while the ...

  16. Durability of lopinavir/r monotherapy in people with viral load ≤50 copies/Ml

    Directory of Open Access Journals (Sweden)

    A d'Arminio Monforte

    2012-11-01

    Full Text Available There is debate about whether lopinavir/r mono-therapy (LPV/r-MT is a valid treatment option for HIV-infected patients who have shown perfect adherence to therapy. The objective was to evaluate the durability of LPV/r-MT in terms of time to virological rebound (VR, time to discontinuation/intensification or a composite endpoint considering both (=treatment failure. We also identified factors associated with faster progression to treatment failure and estimated the median CD4 count over time while people were still on LPV/r-MT. Patients enrolled in 10 clinical sites in Italy who ever started LPV/r-MT with a viral load ≤50 copies/mL (baseline are included. Patients’ follow-up accrued from baseline to the date of the event of interest (VR, defined using the thresholds of 50 and 200 copies/mL, or discontinuation/intensification or at the date of last available visit/VL measurement. Standard survival analysis employing Kaplan-Meier curves was used. We studied 139 patients starting LPV/r-MT on average in 2010 (IQR: 2009–2011 with a VL≤50 copies/mL already for a median of 1 month (range: 1–17. Median age 45 years (IQR: 39–50, 35% females, 32% IDU. Median time from first initiation of ART was 33 months (16–58 with no history of virological failure. Median (IQR marker values at baseline were 611 (432–741 CD4 count cells/mm3, 937 (655–1254 CD8 count and 28 (19–47 IU/L of ALT. Median CD4 count were 519 cells/mm3 at 3 months, 660 at 6 months, 603 at 9 months and 467 at 12 months. The table shows the Kaplan-Meier estimates by 1 year and 2 years for a number of endpoints examined. There was a wide range of estimates depending on the endpoint used. Of those stopping/intensifying, 6 people (4% added Truvada (n=4, Kivexa (n=1 and darunavir (n=1, the remaining 8 restarted cART.In our ‘real-life’ setting, by 2 years of starting LPV/r-MT, 70% of patients remained persistently suppressed ≤50 copies/mL. This percentage was >80% when

  17. Safety and efficacy of fixed-combination travoprost/timolol in patients with open-angle glaucoma or ocular hypertension not controlled with timolol monotherapy.

    Science.gov (United States)

    Jordão, Marcelo Lopes da Silva; Hatanaka, Marcelo; Ogundele, Abayomi; de Moraes Silva, Maria Rosa Bet; Vessani, Roberto Murad

    2014-01-01

    To assess the intraocular pressure (IOP)-lowering effect of travoprost 0.004%/timolol 0.5% fixed-dose combination (TRAV/TIM-FC) in patients not achieving the target IOP of ≤18 mmHg while on timolol 0.5% (TIM) monotherapy. A multicenter, prospective, open-label study (NCT01336569) was conducted in patients with open-angle glaucoma or ocular hypertension. Eligible patients were receiving TIM monotherapy with a screening/baseline IOP of 19-35 mmHg in ≥1 eye. TIM was discontinued on the baseline visit day (no washout period) and TRAV/TIM-FC was initiated and administered once daily at 8 pm for 4-6 weeks. The primary efficacy variable was mean change in IOP from TIM-treated baseline to study end, measured by Goldmann applanation tonometry. Results were analyzed by analysis of variance and paired samples t-test (5% significance). A total of 49 patients were enrolled (mean age, 63 [range, 42-82] years; 55.1% White; 73.5% women), and 45 were included in the intent-to-treat (ITT) population. Mean duration of treatment with TRAV/TIM-FC was 31 days. Mean ± standard deviation IOP reduction from baseline (TIM) to the follow-up visit (TRAV/TIM-FC) was -5.0±3.6 mmHg. IOP decreased significantly (PTRAV/TIM-FC lowered IOP in patients who were not at target IOP while receiving TIM monotherapy, with most patients achieving an IOP ≤18 mmHg with TRAV/TIM-FC. TRAV/TIM-FC was well tolerated in this population.

  18. Extent of use of immediate-release formulations of calcium channel blockers as antihypertensive monotherapy by primary care physicians: multicentric study from Bahrain.

    Directory of Open Access Journals (Sweden)

    Sequeira R

    2002-07-01

    Full Text Available BACKGROUND: The issue of cardiovascular safety of calcium channel blockers (CCBs has been widely debated in view of reflex increase in sympathetic activity induced by immediate release (IR / short acting formulations. It is generally agreed that such CCBs should not be used alone in the management of hypertension. AIMS: We have determined the extent to which primary care physicians prescribe CCBs as monotherapy, especially the immediate release formulations, in the management of uncomplicated hypertension and diabetic hypertension - with an emphasis upon the age of the patients. SETTING, DESIGN AND METHODS: A retrospective prescription-based study was carried out in seven out of 18 Health Centres in Bahrain. The study involved a registered population of 229,300 representing 46% of registered individuals, and 35 physicians representing 43% of all primary care physicians. The data was collected between November 1998 and January 1999 using chronic dispensing cards. RESULTS: In all categories CCBs were the third commonly prescribed antihypertensive as monotherapy, with a prescription rate of 11.1% in uncomplicated hypertension, 18% in diabetic hypertension and 20.1% in elderly patients above 65 years of age. Nifedipine formulations were the most extensively prescribed CCBs. Almost half of the CCB-treated patients were on IR-nifedipine, whereas IR-diltiazem and IR-verapamil, and amlodipine were infrequently prescribed. CONCLUSION: Prescription of IR-formulations of CCBs as monotherapy by primary care physicians does not conform with recommended guidelines. In view of concerns about the safety of such practice, measures to change the prescribing pattern are required.

  19. Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain

    Science.gov (United States)

    Grau, Santiago; Azanza, Jose Ramon; Ruiz, Isabel; Vallejo, Carlos; Mensa, Josep; Maertens, Johan; Heinz, Werner J; Barrueta, Jon Andoni; Peral, Carmen; Mesa, Francisco Jesús; Barrado, Miguel; Charbonneau, Claudie; Rubio-Rodríguez, Darío; Rubio-Terrés, Carlos

    2017-01-01

    Objective According to a recent randomized, double-blind clinical trial comparing the combination of voriconazole and anidulafungin (VOR+ANI) with VOR monotherapy for invasive aspergillosis (IA) in patients with hematologic disease or with hematopoietic stem cell transplant, mortality was lower after 6 weeks with VOR+ANI than with VOR monotherapy in a post hoc analysis of patients with galactomannan-based IA. The objective of this study was to compare the cost-effectiveness of VOR+ANI with VOR, from the perspective of hospitals in the Spanish National Health System. Methods An economic model with deterministic and probabilistic analyses was used to determine costs per life-year gained (LYG) for VOR+ANI versus VOR in patients with galactomannan-based IA. Mortality, adverse event rates, and life expectancy were obtained from clinical trial data. The costs (in 2015 euros [€]) of the drugs and the adverse event-related costs were obtained from Spanish sources. A Tornado plot and a Monte Carlo simulation (1,000 iterations) were used to assess uncertainty of all model variables. Results According to the deterministic analysis, for each patient treated with VOR+ANI compared with VOR monotherapy, there would be a total of 0.348 LYG (2.529 vs 2.181 years, respectively) at an incremental cost of €5,493 (€17,902 vs €12,409, respectively). Consequently, the additional cost per LYG with VOR+ANI compared with VOR would be €15,785. Deterministic sensitivity analyses confirmed the robustness of these findings. In the probabilistic analysis, the cost per LYG with VOR+ANI was €15,774 (95% confidence interval: €15,763–16,692). The probability of VOR+ANI being cost-effective compared with VOR was estimated at 82.5% and 91.9%, based on local cost-effectiveness thresholds of €30,000 and €45,000, respectively. Conclusion According to the present economic study, combination therapy with VOR+ANI is cost-effective as primary therapy of IA in galactomannan

  20. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy

    DEFF Research Database (Denmark)

    Magnussen, Line V; Glintborg, Dorte; Hermann, Pernille;

    2016-01-01

    AIMS: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy....... MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM...

  1. Long-Term Efficacy and Toxicity of Low-Dose-Rate {sup 125}I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kittel, Jeffrey A.; Reddy, Chandana A.; Smith, Kristin L.; Stephans, Kevin L.; Tendulkar, Rahul D. [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States); Ulchaker, James; Angermeier, Kenneth; Campbell, Steven; Stephenson, Andrew; Klein, Eric A. [Department of Urology, Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio (United States); Wilkinson, D. Allan [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States); Ciezki, Jay P., E-mail: ciezkij@ccf.org [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States)

    2015-07-15

    Purpose/Objectives: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. Methods and Materials: From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with {sup 125}I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer–specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. Results: The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Conclusions: Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.

  2. Clinical efficacy and safety of lamotrigine monotherapy in newly diagnosed pediatric patients with epilepsy

    Directory of Open Access Journals (Sweden)

    Ji Hye Han

    2010-04-01

    Full Text Available Purpose : To verify the efficacy and safety of lamotrigine (LTG monotherapy in newly diagnosed children with epilepsy. Methods : We prospectively enrolled 148 children who had undergone LTG monotherapy at our institution between September 2002 and June 2009. Twenty-nine patients were excluded: 19 due to incomplete data and 10 were lost to follow up. The data of the remaining 119 patients was analyzed. Results : We enrolled 119 pediatric epilepsy patients (aged 2.8-19.3 years; 66 males and 53 females in this study. Out of 119 patients, 29 (25.2% had generalized epilepsy and 90 (74.8% had partial epilepsy. The responses of seizure reduction were as follows: Seizure freedom (no seizure attack for at least 6 months in 87/111 (78.4%, n=111 patients; partial response (reduced seizure frequency compared to baseline in 13 (11.7% patients; and persistent seizure in 11 (9.9% patients. The seizure freedom rate was in 81.6% in patients with partial seizure (75.9% for complex partial seizure and 90.9% for benign rolandic epilepsy and 44.8% in patients with generalized epilepsy (30.0% for absence seizure, 35.7% for juvenile myoclonic epilepsy patients, and 100.0% for idiopathic generalized epilepsy patients. Adverse reactions were reported in 17 (14.3% patients, and 8 patients (6.7% discontinued LTG because of rash and tic. No patient experienced severe adverse reaction such as Stevens-Johnson syndrome. Conclusion : LTG showed excellent therapeutic response and had few significant adverse effects. Our findings report may contribute in promoting the use of LTG monotherapy in epileptic children.

  3. Additive intraocular pressure-lowering effect of dorzolamide 1%/timolol 0.5% fixed combination on prostaglandin monotherapy in patients with normal tension glaucoma

    Directory of Open Access Journals (Sweden)

    Mizoguchi T

    2011-10-01

    Full Text Available Takanori Mizoguchi1, Mineo Ozaki2, Harumi Wakiyama1,3, Nobuchika Ogino11Mizoguchi Eye Clinic, Sasebo, 2Ozaki Eye Clinic and Dept of Opthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, 3The Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, JapanPurpose: To evaluate the intraocular pressure (IOP-lowering effect of adding dorzolamide 1.0%/timolol 0.5% fixed combination (DTFC to prostaglandin analogs (PGAs as monotherapy in patients with normal tension glaucoma.Methods: A prospective, clinical, case-controlled study of patients with normal tension glaucoma. Patients had been on a once-daily night dose of prostaglandins (PGs as monotherapy and then received DTFC added to PGs for 8 weeks. The IOP was measured at 9 am, week 0 (baseline, week 4, and week 8.Results: The baseline IOP of 40 patients who had previously been treated by prostaglandin monotherapy was 15.6 ± 2.0 mmHg at baseline. The IOPs at 4 and 8 weeks after adding DTFC to PGs were 13.5 ± 2.1 mmHg and 13.7 ± 2.2 mmHg, respectively. Significant decrease of the IOP was observed at each time point of measurement as compared with the baseline IOP before adding DTFC (P = 0.01. The percent IOP reduction from the baseline IOP at week 4 and week 8 was 13.5% ± 12.3% and 11.7% ± 13.1%, respectively. The percentage of patients who achieved 10% or more IOP reduction from the baseline IOP at week 8 was 62.5%. The baseline IOP was significantly correlated with the percent IOP reduction at week 8 (P = 0.03, r = 0.34.Conclusion: DTFC therapy added to PGAs as glaucoma monotherapy is effective in patients with normal tension glaucoma.Keywords: IOP-lowering effect, prostaglandin, dorzolamide 1%/timolol 0.5% fixed combination, fixed combination, normal tension glaucoma

  4. KRAS-mutated plasma DNA as predictor of outcome from irinotecan monotherapy in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, K G; Appelt, A L; Pallisgaard, N

    2013-01-01

    Background:We investigated the clinical implications of KRAS and BRAF mutations detected in both archival tumor tissue and plasma cell-free DNA in metastatic colorectal cancer patients treated with irinotecan monotherapy.Methods:Two hundred and eleven patients receiving second-line irinotecan (350...... with mutations detectable in plasma responded to therapy. Response rate and disease control rate in plasma KRAS wt patients were 19 and 66% compared with 0 and 37%, in patients with pKRAS mutations, (P=0.04 and 0.01). Tumor KRAS status was not associated with PFS but with OS in the validation cohort. Plasma BRAF...

  5. Long-term effects with ambrisentan monotherapy in patients with pulmonary arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    文莉

    2014-01-01

    Objective To investigate long-term efficacy and safety of ambrisentan monotherapy in patients with pulmonary arterial hypertension(PAH).Methods Patients with PAH who received 2.5 mg or 5 mg of ambrisentan once daily between July 10,2011 and August 30,2012for at least 6 months were enrolled.The efficacy endpoints were changes in exercise capacity,World Health Organization(WHO)functional class and N-terminal probrain natriuretic peptide(NT-pro BNP)level,echocardiographic parameters.The safety endpoint was the safety of long-term ambrisentan administration,as defined by

  6. Efficacy of intravenous immunoglobulin monotherapy in patients with cutaneous lupus erythematosus: results of proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Christa Ky

    2015-03-01

    Full Text Available Cutaneous lupus erythematosus (CLE is a chronic inflammatory autoimmune skin disease. Evidence-based therapy for CLE is lacking in the most part. Intravenous immunoglobulin (IVIg is being increasingly utilized as off-label therapy for a variety of autoimmune and inflammatory conditions, especially in dermatology. The usefulness of IVIg in CLE is not well established. The goal of the present study was to obtain the proof-of-concept evidence that IVIg can control acute CLE and thus replace current systemic immunosuppressive therapy that causes severe side effects and adverse reactions. Sixteen patients who tried and failed various systemic treatments for CLE were screened and consented to use IVIg as a monotherapy. The IVIg was administered at 500 mg/kg/day on 4 consecutive days up to a total of 2 g/kg/month for 3 months, and the subjects were monitored for additional 6 months off any drug for a possible relapse. The cumulative results revealed an overall improvement, as evinced by a decrease of both objective and subjective measures of disease activity. The most sensitive and specific objective and subjective instruments for assessment of the therapeutic effect of IVIg were CLASI-A (Cutaneous Lupus Erythematosus Disease Area and Severity Index measuring disease activity and Skindex-29 scores, respectively. The CLASI-A score dropped down from the initial value taken as 100%, and remained in the range of approximately 70% until the last visit. Three patients (18.8% had a temporary flare of CLE symptoms but recovered within a month from the relapse. No serious side effects and adverse reactions occurred. Thus, IVIg monotherapy in CLE allowed to achieve: i rapid and persistent decreased in disease activity; ii steady improvement of patients’ quality of life assessed by Skindex-29; iii low relapse rate; and iv mild nature and short duration of relapses. Since healing was maintained for months after IVIg treatment, it is possible that the IVIg

  7. Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy

    Directory of Open Access Journals (Sweden)

    Rhee MY

    2015-06-01

    -daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg.Results: Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 (6.88±8.10 mmHg vs 3.38±7.33, P=0.0008, and the effect persisted at Week 8 (8.67±9.39 mmHg vs 5.02±8.27 mmHg, P=0.0023. Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week 4, 10.50±13.76 mmHg vs 5.75±12.18 mmHg, P=0.0069 and, at Week 8, 13.45±15.15 mmHg vs 6.84±13.57 mmHg, P=0.0007. The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP <90 mmHg after 4 weeks of treatment was higher in the fimasartan/HCTZ treatment group than in the fimasartan treatment group (53.6% vs 39.8%, P=0.0359. The overall incidence of adverse drug reaction was 11.79% with no significant difference between the treatment groups.Conclusion: The combination treatment of fimasartan and HCTZ achieved better BP control than fimasartan monotherapy, and had comparable safety and tolerance to fimasartan monotherapy. Keywords: blood pressure, antihypertensive, angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, angiotensin II type 1 receptor, renin–angiotensin–aldosterone system inhibitor

  8. Intra-individual variability of mycophenolic acid concentration according to renal function in liver transplant recipients receiving mycophenolate monotherapy

    Science.gov (United States)

    Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Ahn, Chul-Soo; Moon, Deok-Bog; Ha, Tae-Yong; Kim, Ki-Hun; Lee, Sung-Gyu

    2017-01-01

    Backgrounds/Aims Mycophenolate mofetil (MMF) has wide inter- and intra-individual variability of mycophenolic acid (MPA) after liver transplantation (LT). On this study, we aimed to analyse the intra-individual variability of MPA concentration in stable adult LT recipients receiving MMF monotherapy and develop a method to determine the target level in the situation of wide intra-individual variability. Methods This retrospective cross-sectional study included 30 LT recipients. All patients received MMF monotherapy at a dose of 500 mg twice daily for ≥2 years and were divided into two groups based on renal function. MPA concentration-associated values were presented as mean with standard deviation and coefficient of variation (CV). Results The normal renal function group (n=15) showed a mean 12-hour MPA concentration of 2.5±0.5 µg/ml (range, 1.8±0.5 to 3.6±0.7 µg/ml) and a mean CV of 20.4±7.7% (range, 8.7% to 39.4%). In the renal dysfunction group (n=15), the 12-hour MPA concentration fluctuated more widely with a mean value of 3.7±0.9 µg/ml (range, 2.8±0.8 to 5.1±1.2 µg/ml) and a mean CV of 24.5±4.9% (range, 17.1% to 37.5%). The 12-hour MPA concentration was significantly higher in the renal dysfunction group, as compared to the normal renal function group (p=0.001); whereas, the CV was not significantly different between the two groups (p=0.093). Conclusions We determined the inter- and intra-individual variability of 12-hour MPA concentration after LT. The results suggested that therapeutic drug monitoring of MPA is necessary due to the inter-individual and intra-individual variability of MMF pharmacokinetics, especially in LT recipients with renal dysfunction. PMID:28317040

  9. Monotherapy of androgen deprivation therapy versus radical prostatectomy among veterans with localized prostate cancer: comparative effectiveness analysis of retrospective cohorts

    Directory of Open Access Journals (Sweden)

    Liu J

    2012-05-01

    Full Text Available Jinan Liu1,2, Lizheng Shi1,2,3, Oliver Sartor31Tulane University, School of Public Health and Tropical Medicine, 2Southeast Louisiana Veterans Health Care System, Tulane University, 3School of Medicine and Tulane Cancer Center, New Orleans, LA, USABackground: This retrospective cohort study aimed to examine the comparative effectiveness of monotherapy of primary androgen deprivation therapy or radical prostatectomy.Methods: Male patients with localized prostate cancer (T1-T2, N0, M0 were identified in the Veterans Affairs Veterans Integrated Service Network 16 data warehouse (January 2003 to June 2006, with one-year baseline and at least three-year follow-up data (until June 2009. Patients were required to be 18–75 years old and without other recorded cancer history. The initiation of primary androgen deprivation therapy or monotherapy of radical prostatectomy within six months after the first diagnosis of prostate cancer was used as the index date. Primary androgen deprivation therapy patients were matched to the radical prostatectomy patients via propensity score, which was predicted from a logistic regression of treatment selection (primary androgen deprivation therapy versus radical prostatectomy on age, race, marital status, insurance type, cancer stage, Charlson comorbidity index, and alcohol and tobacco use. The overall survival from initiation of index treatment was then analyzed using the Kaplan–Meier and Cox proportional hazards model.Results: The two cohorts were well matched at baseline (all P > 0.05. During a median follow-up of 4.3 years, the cumulative incidence of death was 13 (10.57% among 123 primary androgen deprivation therapy patients and four (3.25% among 123 radical prostatectomy patients (P < 0.05. The overall three-year survival rate was 92.68% for primary androgen deprivation therapy and 98.37% for radical prostatectomy (P < 0.05. Patients who received primary androgen deprivation therapy had almost three times as

  10. Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance

    Directory of Open Access Journals (Sweden)

    Kline JA

    2016-04-01

    Full Text Available Jeffrey A Kline,1,2 Zachary P Kahler,1,3 Daren M Beam1,2 1Department of Emergency Medicine, 2Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, 3Department of Emergency Medicine, University of South Carolina Greenville School of Medicine, Greenville, SC, USA Background: Oral monotherapy anticoagulation has facilitated home treatment of venous thromboembolism (VTE in outpatients. Objectives: The aim of this study was to measure efficacy, safety, as well as patient and physician perceptions produced by a protocol that selected VTE patients as low-risk patients by the Hestia criteria, and initiated home anticoagulation with an oral factor Xa antagonist. Methods: Patients were administered the Venous Insufficiency Epidemiological and Economic Study Quality of life/Symptoms ques­tionnaire [VEINEs QoL/Sym] and the physical component summary [PCS] from the Rand 36-Item Short Form Health Survey [SF36]. The primary outcomes were VTE recurrence and hemorrhage at 30 days. Secondary outcomes compared psychometric test scores between patients with deep vein thrombosis (DVT to those with pulmonary embolism (PE. Patient perceptions were abstracted from written comments and physician perceptions specific to PE outpatient treatment obtained from structured survey. Results: From April 2013 to September 2015, 253 patients were treated, including 67 with PE. Within 30 days, 2/ 253 patients had recurrent DVT and 2/253 had major hemor­rhage; all four had DVT at enrollment. The initial PCS scores did not differ between DVT and PE patients (37.2±13.9 and 38.0±12.1, respectively and both DVT and PE patients had similar improvement over the treatment period (42.2±12.9 and 43.4±12.7, respectively, consistent with prior literature. The most common adverse event was menorrhagia, present in 15% of women. Themes from patient-written responses reflected satisfaction with increased autonomy. Physicians’ (N=116

  11. Benazepril combined with either amlodipine or hydrochlorothiazide is more effective than monotherapy for blood pressure control and prevention of end-organ injury in hypertensive Dahl rats.

    Science.gov (United States)

    Zhou, Ming-Sheng; Jaimes, Edgar A; Raij, Leopoldo

    2006-07-01

    We studied the effect of hydrochlorothiazide (HCTZ), the angiotensin-converting enzyme inhibitor benazepril, the calcium channel blocker amlodipine, or a combination of benazepril/amlodipine or benazepril/HCTZ on systolic blood pressure (BP) and end-organ injury (left ventricular hypertrophy, proteinuria, and endothelium-dependent relaxation to acetylcholine) in hypertensive Dahl salt-sensitive rats fed either a normal-salt (0.5% NaCl) or high-salt (4% NaCl) diet for 6 weeks. Rats fed a high-salt diet developed hypertension and significant end-organ injury. Monotherapy with HCTZ (75 mg/L in drinking water) or amlodipine (10 mg/kg/day by gavage) reduced systolic BP and proteinuria; benazepril (40 mg/kg/day by gavage) decreased proteinuria without significantly lowering systolic BP. In rats receiving a high-salt diet, only HCTZ reduced left ventricular hypertrophy, whereas endothelium-dependent relaxation was improved by amlodipine and benazepril but not by HCTZ. Combining benazepril with either amlodipine or HCTZ dramatically reduced systolic BP and end-organ injury. These data clearly support clinical studies suggesting that combination therapy is more effective than monotherapy for systolic BP control and prevention of end-organ injury. Complementary mechanisms of action of agents from different antihypertensive classes appear to facilitate the greater benefit on BP and end-organ injury.

  12. An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    William Eardley

    2010-04-01

    Full Text Available William Eardley, Cory TothDepartment of Clinical Neurosciences and the University of Calgary, Calgary, AB, CanadaAbstract: Although many therapies are used in the management of neuropathic pain (NeP due to polyneuropathy (PN, few comparison studies exist. We performed a prospective, non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain Inventory [BPI], quality of life and health status measures [EuroQol 5 Domains, EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and Depression Scale [HADS] and Short Form 36 Health Survey [SF-36] after 6 months of therapy. Significant improvements in VAS pain scores occurred for all treatment groups after 6 months. Improvements in aspects of daily life and anxiety were identified in all treatment groups. Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management. We advocate for head-to-head, randomized, double-blinded studies of current NeP therapies.Keywords: peripheral neuropathy, neuropathic pain, pharmacotherapy, venlafaxine, gabapentin

  13. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection.

    Directory of Open Access Journals (Sweden)

    Jesper Waldenström

    Full Text Available In this pilot study (RibaC, 58 hepatitis C virus (HCV genotype 1 infected treatment-naïve patients were randomized to (i 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α, (ii 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii standard-of-care (SOC ribavirin dosing concurrent with pegIFN-α. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10 IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10 IU/mL for CC and CT/TT respectively; P = 0.006, increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-α and thus shortened treatment duration (P<0.05, and decreased median IP-10 concentration from 550 to 345 pg/mL (P<0.001. Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03. Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes.

  14. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Berlant Jeffrey L

    2004-08-01

    Full Text Available Abstract Background In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. Methods Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5 or augmentation (n = 28. The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. Results For those taking the PCL-C at both baseline and week 4 (n = 30, total symptoms declined by 49% at week 4 (paired t-test, P Conclusions Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

  15. Combined Iron Chelator and Antioxidant Exerted Greater Efficacy on Cardioprotection Than Monotherapy in Iron-Overloaded Rats.

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    Suwakon Wongjaikam

    Full Text Available Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO, deferiprone (DFP and deferasirox (DFX or an antioxidant (N-acetyl cysteine (NAC with a combined DFP and NAC treatments on left ventricular (LV function with iron overload has not been investigated.Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group for 4 months. After 2 months, the HFe-fed rats were divided into 6 groups to receive either: a vehicle, DFO (25 mg/kg/day, DFP (75 mg/kg/day, DFX (20 mg/kg/day, NAC (100 mg/kg/day or the combined DFP and NAC for 2 months. Our results demonstrated that HFe rats had increased plasma non-transferrin bound iron (NTBI, malondialdehyde (MDA, cardiac iron and MDA levels and cardiac mitochondrial dysfunction, leading to LV dysfunction. Although DFO, DFP, DFX or NAC improved these parameters, leading to improved LV function, the combined DFP and NAC therapy caused greater improvement, leading to more extensively improved LV function.The combined DFP and NAC treatment had greater efficacy than monotherapy in cardioprotection through the reduction of cardiac iron deposition and improved cardiac mitochondrial function in iron-overloaded rats.

  16. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Westin, Johan; Nyström, Kristina;

    2016-01-01

    In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (......In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard......, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes....

  17. Preclinical and clinical studies on afatinib in monotherapy and in combination regimens: Potential impact in colorectal cancer.

    Science.gov (United States)

    De Pauw, I; Wouters, A; Van den Bossche, J; Peeters, M; Pauwels, P; Deschoolmeester, V; Vermorken, J B; Lardon, F

    2016-10-01

    Targeting the epidermal growth factor receptor (EGFR) with monoclonal antibodies (mAbs) or tyrosine kinase inhibitors (TKI) has been an interesting therapeutic strategy because aberrant activation of this receptor plays an important role in the tumorgenesis of many cancer types, including colorectal cancer (CRC). After the initial promising results of EGFR-targeted therapies, therapeutic resistance is a major clinical problem. In order to overcome resistance to these EGFR-targeted therapies, new treatment options are necessary. In contrast to first generation EGFR inhibitors, afatinib (BIBW2992) is a second-generation irreversible ErbB family blocker that inhibits EGFR as well as HER2 and HER4. Consequently, treatment with afatinib may result in a distinct and more pronounced therapeutic benefit. Preclinical studies have reported promising results for afatinib in monotherapy as well as in combination with other drugs in CRC model systems. Furthermore, clinical studies examining afatinib as single agent and in combination therapy demonstrated manageable safety profile. Nevertheless, only limited antitumor activity has been observed in CRC patients. Although several combination treatments with afatinib have already been investigated, no optimal combination has been identified for CRC patients yet. As molecular tumor characteristics have gained increased importance in the choice of treatment, additional studies with biomarker-driven patient recruitment are required to further explore afatinib efficacy in CRC.

  18. The real-world dose-relativity of sevelamer hydrochloride and lanthanum carbonate monotherapy in patients with end-stage renal disease.

    Science.gov (United States)

    Wilson, Rosamund J; Keith, Michael S; Preston, Peter; Copley, J Brian

    2013-12-01

    Sevelamer hydrochloride (SH) and lanthanum carbonate (LC) are calcium-free phosphate binders used for the management of hyperphosphatemia in patients with end-stage renal disease (ESRD). The objective of this analysis was to evaluate the real-world dose-relativity between SH and LC monotherapy in US patients with ESRD. This was a post hoc analysis of a 16-week, real-world study (Vemuri et al. in BMC Nephrol 12:49, 2011) of the efficacy of conversion to LC monotherapy from other phosphate binders. The SH:LC dose-relativity ratio, based on the mean daily dose, was calculated in the subset of patients from the Vemuri study who converted from SH to LC monotherapy and had available SH and LC dose data. A total of 950 patients converted from SH to LC monotherapy and had recorded dose data. The post hoc analysis population comprised 691 patients with available dose data for both SH at baseline and LC at week 16. The mean (SD) serum phosphate level at baseline was 5.91 (1.66) mg/dL. After conversion to LC monotherapy for 16 weeks, the mean (SD) serum phosphate level was 5.93 (1.85) mg/dL. The mean (SD) daily baseline SH dose was 7,703 (3,642) mg and the mean (SD) daily LC dose at week 16 was 2,800 (939) mg (9.6 versus 2.8 tablets, respectively; P relativity ratio of 2.8. The median individual patient SH:LC dose-relativity ratio was 2.6 (95% CI 2.6-2.8). Across baseline SH dose subgroups (2,400-4,800, >4,800-7,200, >7,200-9,600, and >9,600 mg/day), the mean daily SH dose was 4,051, 7,047, 9,253, and 13,150 mg, respectively. In comparison, the mean daily LC dose was 2,445-3,156 mg. Thus, patients requiring baseline SH doses >7,200 mg/day (41% of the analysis population) had higher SH:LC dose-relativity ratios of 3.1-4.2 (median individual patient ratios 3.1-4.0). In this post hoc analysis of real-world dose-relativity, the overall SH:LC dose-relativity ratio was 2.8 (median individual patient ratio 2.6 (95% CI 2.6-2.8). These findings are consistent with the World Health

  19. Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Platinum-based chemotherapy can improve the survival and quality of life of patients with locally advanced and metastatic lung cancer. Second-line docetaxel monotherapy can improve overall survival following the failure of first line chemotherapy. However, many limiting factors such as poor performance status, advanced age, adverse effects of chemotherapy and reluctance to receive cytotoxic chemotherapeutic agents render patients unable to accept chemotherapy. Furthermore, for patients who have failed second-line chemotherapy treatment options are often limited to best support care or palliative radiotherapy. 1 Gefitinib (Iressa) is a HER1/EGFR (epidermal growth factor receptor)- tyrosine kinase inhibitor approved in a number of countries including the US, Japan and recently China for the treatment of patients with non-small cell lung cancer (NSCLC), who have failed platinum/docetaxel-based first line and second line chemotherapy. 2,3 Current data show heterogeneity in response to gefitinib among people of different ethnic origin, but there is very little data concerning the safety and efficacy of gefitinib in Chinese patients. This paper aims to summarize the safety and efficacy data for gefitinib 250 mg treatment in Chinese NSCLC patients at Peking Union Medical College Hospital who received gefitinib as part of an Expanded Access Programme.

  20. Combination and monotherapy of Leishmania major infection in BALB/c mice using plant extracts and herbicides

    Directory of Open Access Journals (Sweden)

    Judith A. Makwali , Frederick M.E. Wanjala , Josyline C. Kaburi , Johnstone Ingonga , Wabwoba W. Byrum & Christopher O. Anjili

    2012-09-01

    Full Text Available Background & objectives: Leishmaniasis is a growing health problem in many parts of the world. Efforts to findnew chemotherapeutics for leishmaniasis remain a priority. This study was carried out to determine the effect ofcombination and monotherapies using plant extracts and herbicides on Leishmania major infection in BALB/cmice.Methods: The herbicides and saponin extract were purchased from Sigma. Roots of Plumbago capensis werecollected from Karura forest, Nairobi, Kenya. Plant extractions were done in KEMRI at Center for TraditionalMedicines and Drugs Research.Results: Lesion sizes after infection of BALB/c mice were similar in all the experimental groups till the onset oftherapeutic treatments (p >0.05. At 15 days post-treatment, significant differences (p < 0.05 were discerned inthe lesion sizes of the BALB/c mice in all the mono- and combined-treated groups. However, the combinedtherapies caused total elimination of the parasites from the lesions and significantly reduced parasite burden inliver and spleen compared to the untreated controls at the end of the experiment.Interpretation & conclusion: The results of this study demonstrate that combination therapy using alternativeadministration of saponin, acriflavine, trifluralin and plumbagin is effective in treating L. major infection inmice. In this regard, an investigation into the efficacy of these combined therapies against other Leishmaniastrains should be explored further. Furthermore, studies with these combination therapies should be done onnon-human primates such as the vervet monkey (Cercopithecus aethiops.

  1. All-cause mortality and cardiovascular effects associated with the DPP-IV inhibitor sitagliptin compared with metformin, a retrospective cohort study on the Danish population

    DEFF Research Database (Denmark)

    Scheller, N M; Mogensen, U M; Andersson, Charlotte;

    2014-01-01

    AIM: We performed a retrospective cohort study, investigating the clinical outcomes including mortality and cardiovascular disease of sitagliptin compared with metformin monotherapies. METHODS: All patients receiving monotherapy with the dipeptidyl peptidase-IV inhibitors (DPP-IV) inhibitor sitag...

  2. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

    NARCIS (Netherlands)

    Vos, Rimke C; van Avendonk, Mariëlle JP; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy EHM

    2016-01-01

    BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of insu

  3. Comparison of efficacy and side effects of combination therapy of angiotensin-converting enzyme inhibitor (benazepril) with calcium antagonist (either nifedipine or amlodipine) versus high-dose calcium antagonist monotherapy for systemic hypertension.

    Science.gov (United States)

    Messerli, F H; Oparil, S; Feng, Z

    2000-12-01

    The present 2 multicenter studies were designed to evaluate whether patients with essential hypertension derived equal benefits from use of combination therapy with a calcium antagonist and angiotensin-converting enzyme (ACE) inhibitor as from doubling the dose of the calcium antagonist. After a 2-week washout and a 2-week single-blind placebo run-in period, a total of 1,390 patients were treated with either nifedipine 30 mg (study 1) or amlodipine 5 mg (study 2) once daily for 4 weeks. The 1,079 patients whose diastolic blood pressure remained between 95 and 115 mm Hg were randomized to 8 weeks of double-blind therapy with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/ benazepril 20 mg, nifedipine 30 mg or nifedipine 60 mg (study 1), and amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg or amlodipine 10 mg (study 2). Both doses of the calcium antagonist/ACE inhibitor combination therapy lowered diastolic pressure as much as the high dose and significantly better than the lower dose of calcium antagonist monotherapy (with either nifedipine or amlodipine). However, 15% of patients in the nifedipine high-dose monotherapy group and 24% in the amlodipine high-dose monotherapy group presented with some form of edema. In contrast, the incidence of edema was similar for patients treated with both combination therapy and low-dose calcium antagonists. Thus, combination therapy with a calcium antagonist and an ACE inhibitor provides blood pressure control equal to that of high-dose calcium antagonist monotherapy but with significantly fewer dose-dependent adverse experiences such as vasodilatory edema. Inc.

  4. Fluoxetine Monotherapy in Attention-Deficit/Hyperactivity Disorder and Comorbid Non-Bipolar Mood Disorders in Children and Adolescents

    Science.gov (United States)

    Quintana, Humberto; Butterbaugh, Grant J.; Purnell, William; Layman, Ann K.

    2007-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing comorbid non-bipolar mood disorders. Fluoxetine monotherapy is an established treatment for pediatric mood disorders; however its efficacy in ADHD and comorbid mood disorder is unknown. Therefore, we evaluated 30 children who met DSM-IV criteria for…

  5. Fluoxetine Monotherapy in Attention-Deficit/Hyperactivity Disorder and Comorbid Non-Bipolar Mood Disorders in Children and Adolescents

    Science.gov (United States)

    Quintana, Humberto; Butterbaugh, Grant J.; Purnell, William; Layman, Ann K.

    2007-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing comorbid non-bipolar mood disorders. Fluoxetine monotherapy is an established treatment for pediatric mood disorders; however its efficacy in ADHD and comorbid mood disorder is unknown. Therefore, we evaluated 30 children who met DSM-IV criteria for…

  6. Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics

    NARCIS (Netherlands)

    Selle, V.; Schalkwijk, S.J.; Vazquez, G.H.; Baldessarini, R.J.

    2014-01-01

    BACKGROUND: Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. METHODS: We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-gene

  7. JUVENILE MYOCLONIC EPILEPSY: A FOCUS ON THE EFFICACY OF THERAPY AND THE RATE OF RELAPSES ACCORDING TO LONG-TERM FOLLOW-UP DATA

    Directory of Open Access Journals (Sweden)

    K. Yu. Mukhin

    2015-01-01

    the Saint Luka’s Institute of Pediatric Neurology and Epilepsy for 3 to 28 years (mean 8.6 years. The authors detailed the clinical characteristics of the disease and the results of the investigation in the observed patients. The investigation showed that JME was the second common type (next to rolandic epilepsy among all idiopathic epilepsies. Clinical remission lasting 3 years or longer was achieved in the vast majority of cases (89.6 %; however, clinical and electroencephalographic remission was in only 22 % of the patients. Treatment was not absolutely ineffective in any of the cases. Monotherapy for JME was used in most patients (79 %, duotherapy in 17 % and polytherapy (3 AEDs in 4 %. Valproate was most commonly used as monotherapy for JME (56 %; levetiracetam and topiramate were more rarely in 13 and 8 %, respectively.Unfortunately, despite the high effect of treatment, the recurrence rate during or after discontinuation of AED therapy (which was gradually done under guidance of video-assisted electroencephalographic monitoring at least 3–4 years after remission was very high (92 %. The recurrence risk was highest when the dose was reduced by more than 50 % and within the first year after therapy discontinuation. Multiple attempts to discontinue the treatment were made at an interval of an average of 4.3-years of remission in a number of patients. The authors identified a number of factors increasing the recurrence risk after withdrawal of an AED.

  8. Safety and Efficacy of Nucleic Acid Polymers in Monotherapy and Combined with Immunotherapy in Treatment-Naive Bangladeshi Patients with HBeAg+ Chronic Hepatitis B Infection.

    Directory of Open Access Journals (Sweden)

    Mamun Al-Mahtab

    Full Text Available Previous in vivo studies have suggested that nucleic acid polymers (NAPs may reduce circulating levels of HBsAg in the blood by blocking its release from infected hepatocytes and that this effect may have clinical benefit. NAP treatment, was evaluated in two clinical studies in patients with HBeAg positive chronic HBV infection. The REP 101 study examined REP 2055 monotherapy in 8 patients and the REP 102 study examined REP 2139-Ca, in monotherapy in 12 patients, 9 of which transitioned to short term combined treatment with pegylated interferon alpha 2a or thymosin alpha 1. In both studies NAP monotherapy was accompanied by 2-7 log reductions of serum HBsAg, 3-9 log reductions in serum HBV DNA and the appearance of serum anti-HBsAg antibodies (10-1712 mIU / ml. Eight of the 9 patients transitioning to combined treatment with immunotherapy (pegylated interferon or thymosin alpha 1 in the REP 102 study experienced HBsAg loss and all 9 patients experienced substantial increases in serum anti-HBsAg antibody titers before withdrawal of therapy. For 52 weeks after removal of REP 2055 therapy, rebound of serum viremia (HBV DNA > 1000 copies / ml, HBsAg > 1IU / ml was not observed in 3 / 8 patients. Suppression of serum virema was further maintained for 290 and 231 weeks in 2 of these patients. After withdrawal of all therapy in the 9 patients that transitioned to combination therapy in the REP 102 study, 8 patients achieved HBV DNA < 116 copies / ml after treatment withdrawal. Viral rebound occurred over a period of 12 to 123 weeks in 7 patients but was still absent in two patients at 135 and 137 weeks of follow-up. Administration tolerability issues observed with REP 2055 were rare with REP 2139-Ca but REP 2139-Ca therapy was accompanied by hair loss, dysphagia and dysgeusia which were considered related to heavy metal exposure endemic at the trial site. These preliminary studies suggest that NAP can elicit important antiviral responses during

  9. Application of calcineurin inhibitor monotherapy in renal transplantation after alemtuzumab induction:a Meta-analysis%阿仑单抗诱导后钙神经蛋白抑制剂单药治疗方案在肾移植中的应用:一项系统评价研究

    Institute of Scientific and Technical Information of China (English)

    谢礼波; 王应强; 王显丁; 林涛; 卢一平

    2016-01-01

    Objective To evaluate the clinical efficacy and safety of immunosuppression of calcineurin inhibitor monotherapy (AiCNIm)after alemtuzumab induction following renal transplantation.Methods Randomized control clinical trials related to application of AiCNIm (AiCNIm group ) and conventional triple regimes (Triple group ) for immunosupression after renal transplantation,published from 1 980 to December 31 201 4,were searched online from PubMed,Embase,Web of Science,Cochrance library and China National Knowledge Infrastructure (CNKI) databases.Meta-analysis was performed by Rev Man 5.2 software.Results Five randomized control studies consisting of 421 renal transplant recipients were included.The results of follow up for 6-1 2 months revealed that compared with the Triple group, the incidence of rejection response confirmed by acute rejection or aspiration biopsy in the AiCNIm group was significantly lower [relative risk (RR) =0.59,95% confidence interval (CI):0.40-0.89 ].However,there was no significant difference in the risk of renal allograft dysfunction (RR =0.85,95%CI:0.38-1 .87),death of recipient (RR =0.89,95%CI:0.30-2.67),infection (RR =1 .03,95%CI:0.91 -1 .1 7)and new-onset diabetes after transplantation (RR =0.62, 95%CI:0.29-1 .30)between two groups (all in P >0.05).Conclusions According to the existing evidence,application of calcineurin inhibitor monotherapy after renal transplantation exerts short-term immunosuppressive effect and high safety after alemtuzumab induction.%目的:探讨阿仑单抗诱导后钙神经蛋白抑制剂单药治疗(AiCNIm)方案应用于肾移植术后免疫抑制的有效性和安全性。方法应用计算机检索 Pubmed、Embase、Web of science、Cochrance library 及中国知网(CNKI)等数据库,查找1980年至2014年12月31日发表的有关 AiCNIm 方案(AiCNIm 组)和常规三联方案(Triple 组)进行肾移植术后免疫抑制的随机对照临床研究。采用 Rev Man 5.2软件进行 Meta

  10. Effect of Psychopharmacotherapy on Body Mass Index Among Children and Adolescents with Bipolar Disorders.

    Science.gov (United States)

    Patel, Ayush; Chan, Wenyaw; Aparasu, Rajender R; Ochoa-Perez, Melissa; Sherer, Jeff T; Medhekar, Rohan; Chen, Hua

    2017-05-01

    To assess the long-term effect of all treatment options for pediatric bipolar disorders on body mass index (BMI) and to explore individual characteristics associated with less BMI increase during psychotropic medication exposures. A retrospective cohort study was conducted by using the 1995 to 2010 General Electric Electronic Medical Record database. Individuals aged 18 years or younger who had a new bipolar disorder episode were identified. Treatment exposure was defined based on the medication regimens patients received, which include atypical antipsychotic (AT) monotherapy, mood stabilizer (MS) monotherapy, antidepressant (AD) monotherapy, AT+MS polytherapy, AT+AD polytherapy, MS+AD polytherapy, and no treatment. Both treatment exposure and BMI were coded as time varying, which could change from month to month. According to the duration of treatment and the availability of BMI measures, individuals were followed for up to 3, 6, 9, and 12 months since the treatment initiation. Repeated-measures mixed models were applied to compare the impact of different medication regimens and the length of drug exposure on BMI after adjusting for the baseline BMI, sociodemographic factors, comorbidities, and psychotherapy. A total of 2299 treated and 4544 untreated children and adolescents who met the inclusion criteria were identified. Analysis using repeated-measures mixed models showed that those on AT monotherapy (the reference group) had a gradually diminished, but statistically significant, monthly increase in BMI during all durations of drug exposure (3 months: 0.36 kg/m(2), 6 months: 0.20 kg/m(2), 9 months: 0.17 kg/m(2), and 12 months: 0.16 kg/m(2)). As compared with AT monotherapy, the magnitude of increase in BMI associated with MS, AD monotherapy, and no treatment was significantly less at all time points, indicating less steep slopes of BMI change over time compared with AT monotherapy, especially during the short-term exposure. The combinations of AT with

  11. Degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH) agonists plus anti-androgen flare protection in advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; Damber, Jan-Erik; Malmberg, Anders

    2016-01-01

    hazards regression model and a conditional logistic regression model was used for a case-control analysis of odds ratios (ORs). RESULTS: Patients received degarelix monotherapy (n = 972) or LHRH agonist (n = 483) of whom 57 also received AA. Overall, prostate-specific antigen progression-free survival....../ml in the LHRH agonist + AA group, a case-control analysis using a conditional logistic regression model was utilized. This resulted in an OR for PSA PFS of 0.42 (95% CI 0.20-0.89; p = 0.023) in the overall population, and 0.35 (95% CI 0.13-0.96; p = 0.042) in patients with PSA >50 ng/ml at baseline, when...... protection therapy in patients with prostate cancer when a case-control analysis was used to compensate for differences between treatment groups....

  12. Dynamic MRI of the bone marrow for monitoring multiple myeloma during treatment with thalidomide as monotherapy or in combination with CED chemotherapy; Dynamische MRT des Knochenmarks zum Monitoring des Multiplen Myeloms unter Thalidomid-Monotherapie oder Kombination mit CED-Chemotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Wasser, K. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Onkologische Diagnostik und Therapie; Universitaetsklinikum Mannheim (Germany). Inst. fuer Klinische Radiologie; Moehler, T.; Neben, K.; Goldschmidt, H.; Hillengass, J. [Universitaetsklinikum Heidelberg (Germany). Medizinische Klinik und Poliklinik V; Nosas, S.; Heiss, J.; Kauczor, H.U.; Delorme, S. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Onkologische Diagnostik und Therapie; Dueber, C. [Universitaetsklinikum Mannheim (Germany). Inst. fuer Klinische Radiologie

    2004-09-01

    Purpose: To quantify changes of bone marrow microcirculation in multiple myeloma (MM) using contrast enhanced dynamic MRI (dMRI) during thalidomide as antiangiogenic monotherapy or in combination with chemotherapy (cyclophosphamide, etoposide, dexamethasone). Materials and Methods: The study includes 63 patients with refractory or relapsed MM, who underwent dMRI with high temporal resolution (T1w-turboFLASH) of the lumbar spine before and following treatment. The contrast uptake was quantified using a two compartment model with the output parameters amplitude and k{sub ep} (exchange rate constant). The evaluation considered the initial dMRI finding (pathological or non-pathological) and the clinical therapeutic response (response or no response). Results: During monotherapy with thalidomide (n=38), no significant changes of the dMRI parameters were found, even when considering the initial dMRI finding (positive n=22) and the therapeutic response (responder n=14). The combination with chemotherapy (n=25) had a significant reduction of k{sub ep} (p=0.01) in 18 patients with positive initial dMRI finding and therapeutic response. Reduction of the amplitude was seen in most cases, but in the end without any significance (p=0.09). (orig.)

  13. [The prevalence of obesity and metabolic syndrome in paediatric patients with epilepsy treated in monotherapy with valproic acid].

    Science.gov (United States)

    Carmona-Vazquez, C R; Ruiz-Garcia, M; Pena-Landin, D M; Diaz-Garcia, L; Greenawalt, S R

    2015-09-01

    Valproic acid (VPA) is a useful antiepileptic drug for controlling different types of epilepsy. It has several side effects and is associated to increased body weight, as well as metabolic and endocrine disorders, including metabolic syndrome. To determine the prevalence of obesity and metabolic syndrome among paediatric patients with epilepsy treated in monotherapy with VPA. The study was cross-sectional, observational and analytical. A sample of patients treated with VPA between 2010-2014 were studied and the body mass index (BMI), abdominal perimeter, arterial blood pressure, glucose, triglycerides and high density lipoproteins (HDL) were studied in search of obesity and metabolic syndrome. Obesity was defined as a BMI above the 95th percentile, and metabolic syndrome was considered if at least three of the following criteria were fulfilled: abdominal perimeter above the 90th percentile, systolic arterial pressure above the 90th percentile, triglycerides above 110 mg/dL and HDL below 40 mg/dL. A total of 47 patients with a mean age of 10.1 ± 4 years were studied; 51.06% were males. Eight (17%) of them developed obesity and, of those, two (25%) had metabolic syndrome. Three patients went on to become overweight (6%). Statistically significant differences were observed in the mean age in comparison to the BMI groups, where the obese patients were adolescents (ANOVA, p = 0.0001) and those who took more VPA per day were the obese (ANOVA, p = 0.024). Patients treated with VPA who become obese may go on to develop metabolic syndrome. They require careful monitoring and, if they are seen to put on weight, withdrawal of the drug should be considered.

  14. Analysis of monotherapy prostate brachytherapy in patients with prostate cancer. Initial PSA and Gleason are important for recurrence?

    Directory of Open Access Journals (Sweden)

    Pedro Galego

    2015-04-01

    Full Text Available Purpose To evaluate the clinical outcome of a cohort of localized prostate cancer patients treate with 125-I permanent brachytherapy at the São José Hospital – CHLC, Lisbon. Materials and Methods A retrospective analysis was carried out on 429 patients with low and intermediate-risk of prostate adenocarcinoma, according to the recommendations of the EORTC, who underwent 125I brachytherapies in intraoperative dosimetry “real-time” system between September 2003 and September 2013. Results The mean follow-up was 71.98 months. Biochemical relapse of disease by rising PSA (Phoenix criterion was observed in 18 patients (4.2%. Through the application of Kaplan-Meier survival curves in this sample, the rate of survival at 6 years without biochemical relapse was higher than 95%. By Iog rank test comparing biochemical relapse with initial PSA (15-10 and <10 and Gleason values (7 and <7, there was no statistical difference (P=0.830 of the initial PSA in the probability of developing biochemical relapse. In relation to Gleason score, it was noted a statistical difference (P<0.05, demonstrating that patients with Gleason 7 are more likely to develop biochemical relapse. Conclusions Brachytherapy as monotherapy is at present an effective choice in the treatment of localized prostate adenocarcinoma. Biochemical relapses are minimal. The initial PSA showed no statistically difference in the rate of relapses, unlike the value Gleason, where it was demonstrated that patients with Gleason 7 have a higher probability of biochemical relapse. Cases with PSA bounce should be controlled before starting a salvage treatment.

  15. Effect of Monotherapy with Darunavir/Ritonavir on Viral Load in Seminal Fluid, and Quality Parameters of Semen in HIV-1-Positive Patients

    Science.gov (United States)

    Lopez-Ruz, Miguel A.; Navas, Purificación; López-Zúñiga, Miguel A.; Gonzalvo, María Carmen; Sampedro, Antonio; Pasquau, Juan; Hidalgo-Tenorio, Carmen; Javier, Rosario; Castilla, José A.

    2016-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load 20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality. PMID:27442068

  16. Weight change after initiation of oral hypoglycemic monotherapy for diabetes predicts 5-year mortality: An observational study.

    Science.gov (United States)

    Kocarnik, Beverly M; Moore, Kathryn P; Smith, Nicholas L; Boyko, Edward J

    2017-01-01

    To investigate whether weight change in the first year after initiating an oral hypoglycemic agent (OHA) for type 2 diabetes treatment is associated with mortality in a national cohort. We prospectively followed Veterans Health Administration patients with type 2 diabetes initiating treatment with an OHA and not receiving any other diabetes pharmacotherapy for at least one year. Information on OHAs, weight, co-morbidities, other medications, demographics, and laboratory measurements was obtained from electronic medical records. Logistic regression was used to estimate 5-year mortality odds by weight change during the first year after OHA treatment initiation. Patients (mean age 65years, 97% male, mean BMI 32.3kg/m(2)) initiating OHA monotherapy between 2003 and 2008 totaled 145,198 (metformin n=89,111, glipizide n=27,100, glyburide n=25,226, rosiglitazone n=3,761). Most patients (65%) maintained a stable weight (change ⩽5% from baseline) during the first year after OHA initiation. Those losing >5% of baseline weight had a significantly higher odds of death over the subsequent 5-years ranging from 1.64 to 2.13 depending on OHA type. In the metformin group, weight gain >5% of baseline was also associated with higher odds of 5-year mortality. The same results were obtained after conducting three sensitivity analyses that excluded patients for the following reasons: weight loss in the one year prior to OHA initiation, weight change >100lbs, or weight change >50lbs. Weight loss was associated with higher odds of 5-year mortality among patients initiating an OHA, as was weight gain for metformin only. Published by Elsevier B.V.

  17. Antiepileptic drug regimens and major congenital abnormalities in the offspring.

    Science.gov (United States)

    Samrén, E B; van Duijn, C M; Christiaens, G C; Hofman, A; Lindhout, D

    1999-11-01

    To assess the risk of major congenital abnormalities associated with specific antiepileptic drug regimens, a large retrospective cohort study was performed. The study comprised 1,411 children born between 1972 and 1992 in four provinces in The Netherlands who were born to mothers with epilepsy and using antiepileptic drugs during the first trimester of pregnancy, and 2,000 nonepileptic matched controls. We found significantly increased risks of major congenital abnormalities for carbamazepine and valproate monotherapy, with evidence for a significant dose-response relationship for valproate. The risk of major congenital abnormalities was nonsignificantly increased for phenobarbital monotherapy when caffeine comedication was excluded, but a significant increase in risk was found when caffeine was included. Phenytoin monotherapy was not associated with an increased risk of major congenital abnormalities. Regarding polytherapy regimens, increased risks were found for several antiepileptic drug combinations. Clonazepam, in combination with other antiepileptic drugs, showed a significantly increased relative risk. Furthermore, there were significantly increased relative risks for the combination of carbamazepine and valproate and the combination of phenobarbital and caffeine with other antiepileptic drugs. This study shows that most antiepileptic drug regimens were associated with an increased risk of major congenital abnormalities in the offspring, in particular valproate (dose-response relationship) and carbamazepine monotherapy, benzodiazepines in polytherapy, and caffeine comedication in combinations with phenobarbital.

  18. Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain

    Directory of Open Access Journals (Sweden)

    Grau S

    2016-12-01

    Full Text Available Santiago Grau,1 Jose Ramon Azanza,2 Isabel Ruiz,3 Carlos Vallejo,4 Josep Mensa,5 Johan Maertens,6 Werner J Heinz,7 Jon Andoni Barrueta,8 Carmen Peral,9 Francisco Jesús Mesa,8 Miguel Barrado,10 Claudie Charbonneau,11 Darío Rubio-Rodríguez,12 Carlos Rubio-Terrés12 1Pharmacy Department, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, 2Clinical Pharmacology Department, Clínica Universidad de Navarra, Pamplona, 3Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Barcelona, 4Hematology Department, Hospital Universitario Donostia, San Sebastián, 5Infectious Diseases Department, Hospital Clínic de Barcelona, Barcelona, Spain; 6Hematology Department, University Hospital Gasthuisberg, Leuven, Belgium; 7Hematology/Oncology Department, Medizinische Klinik und Poliklinik II, Universitätsklinikum, Würzburg, Germany; 8Medical Department, 9Economics and Outcomes Research Department, Pfizer S.L.U, Alcobendas, 10Clinical Trials Department, Trial Form Support, Madrid, Spain; 11Pharmacoeconomics Department, Pfizer International Operations, Paris, France; 12Pharmacoeconomics Department, Health Value, Madrid, Spain Objective: According to a recent randomized, double-blind clinical trial comparing the combination of voriconazole and anidulafungin (VOR+ANI with VOR monotherapy for invasive aspergillosis (IA in patients with hematologic disease or with hematopoietic stem cell transplant, mortality was lower after 6 weeks with VOR+ANI than with VOR monotherapy in a post hoc analysis of patients with galactomannan-based IA. The objective of this study was to compare the cost-effectiveness of VOR+ANI with VOR, from the perspective of hospitals in the Spanish National Health System.Methods: An economic model with deterministic and probabilistic analyses was used to determine costs per life-year gained (LYG for VOR+ANI versus VOR in patients with galactomannan-based IA. Mortality, adverse event rates, and life expectancy were

  19. Real-world dose-relativity, tablet burden, and cost comparison of conversion between sevelamer hydrochloride/carbonate and lanthanum carbonate monotherapies.

    Science.gov (United States)

    Keith, Michael S; Sibbel, Scott; Copley, J Brian; Wilson, Rosamund J; Brunelli, Steven M

    2014-10-01

    Sevelamer hydrochloride/carbonate (SH/C) and lanthanum carbonate (LC) are noncalcium-based phosphate binders used for the management of hyperphosphatemia in patients with end-stage renal disease (ESRD). The objectives of this study were to examine the dose-relativity, tablet burden, and cost difference of bidirectional conversion between SH/C and LC monotherapy in a large cohort of real-world patients with ESRD. This retrospective cohort study included three 30-day preconversion periods (days -90 to -61, -60 to -31, and -30 to -1) followed by three 30-day postconversion periods (days 1 to 30, 31 to 60, and 61 to 90); day 0 was the index date of conversion. The full analysis population (FAP) comprised two cohorts: SH/C to LC (S-L) converters and LC to SH/C (L-S) converters. The SH/C:LC dose-relativity ratio was assessed in the dose-relativity subset, defined as patients whose serum phosphate levels fell within a caliper range of ± 0.5 mg/dL in the final preconversion (days -30 to -1) and postconversion (days 61 to 90) periods. Tablet burden and phosphate binder costs were assessed in the FAP. Phosphate binder costs were based on average wholesale prices. The FAP contained a total of 303 patients, comprising the S-L (128 patients) and L-S (175 patients) converter cohorts. The dose-relativity subset contained 159 patients, 72 from the S-L cohort and 87 from the L-S cohort. The overall mean SH/C:LC dose-relativity ratio was 2.27 (95% CI, 2.04 to 2.52). In SH/C dose strata >800 to 2400, >2400 to 4800, >4800 to 7200, and >7200 mg/d, overall mean dose-relativity ratios were 0.79 (95% CI, 0.57 to 1.10), 1.45 (95% CI, 1.20 to 1.75), 2.05 (95% CI, 1.75 to 2.39), and 3.24 (95% CI, 2.89 to 3.66), respectively. The overall mean tablet burden was 6.6 tablets per day lower with LC monotherapy than with SH/C monotherapy (95% CI, -7.1 to -6.0; P 7800 mg/d was the inflection point at which conversion to LC resulted in mean cost savings. Patients requiring SH/C >7800 mg/d comprised

  20. Efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in castration-resistant prostate cancer patients: report of 102 cases and review of literature.

    Science.gov (United States)

    Matsumoto, Kazuhiro; Tanaka, Nobuyuki; Hayakawa, Nozomi; Ezaki, Taisuke; Suzuki, Kenjiro; Maeda, Takahiro; Ninomiya, Akiharu; Nakamura, So

    2013-12-01

    This retrospective chart review study was conducted to evaluate the efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in patients with castration-resistant prostate cancer (CRPC) and to determine who would benefit from EMP therapy. EMP was administered at a daily dose of 560 mg to 102 patients as a third-line therapy, who had already received combined androgen blockade (CAB) and subsequent alternative antiandrogen therapy. The responses to EMP after its induction and its toxicity were evaluated. We also analyzed the association between the clinicopathological factors of the patients and their responses to EMP therapy. A reduction in the serum prostate-specific antigen (PSA) 4 weeks after induction was observed in 70 patients (68.6%), while 30 cases (29.4%) achieved more than 50% reduction of PSA. Long-term reduction of PSA from baseline for more than 6 months was observed in 31 patients (30.4%). EMP treatment was discontinued in 11 patients (10.8%) because of side effects (nausea in six patients, gynecomastia in three patients, eruption in one patient, and liver dysfunction in one patient). Multivariate analysis demonstrated that long duration of prior hormonal therapy was an independent favorable factor for reduced PSA levels, long responses, and overall survival. The data suggest that oral EMP administration as a third-line monotherapy is well tolerated and effective to some degree in patients with CRPC who have already received CAB and subsequent alternative antiandrogen therapy. Thus, EMP can be regarded as one treatment option, especially for patients whose prior duration of hormonal therapy was long.

  1. Comparative effectiveness of monotherapy with mood stabilizers versus second generation (atypical) antipsychotics for the treatment of bipolar disorder in children and adolescents.

    Science.gov (United States)

    Chen, Hua; Mehta, Sonam; Aparasu, Rajender; Patel, Ayush; Ochoa-Perez, Melissa

    2014-03-01

    This study compared the effectiveness and safety of second generation (atypical) antipsychotic (SGA) versus traditional mood stabilizers (MS) in children and adolescents with bipolar disorder. The study was a retrospective cohort study on 5 years (2003-2007) of Medicaid claims data from four geographically diversified states. Children and adolescents aged 6-18 years who initiated a new treatment episode for bipolar disorder on either an SGA or an MS were followed for 12 months to compare the effectiveness and safety between the two therapeutic categories for pediatric bipolar disorder (PBD). The outcome measures were psychiatric hospital admission, all cause medication discontinuation and treatment augmentation. Potential selection bias caused by unobserved confounding was addressed with instrumental variable methods, using physician prescribing preference and year of cohort entry as the instruments. Sensitivity analysis was conducted to test the robustness of findings against the uncertainties on PBD diagnosis. Of the 7423 bipolar children and adolescents identified, 66.60% started treatment on SGA, whereas 33.40% initiated on MS. Patients who initiated on MS and SGA had comparable risk of psychiatric hospital admission (HR=1.172, 95%CI: 0.827-1.660). However, as compared with those who initiated on MS, patients who initiated on SGA were less likely to discontinue the treatment (HR=0.634, 95%CI: 0.419-0.961) and less likely to receive treatment augmentation (HR=0.223, 95%CI: 0.103-0.484). As compared with MS monotherapy, SGA monotherapy could be a more effective and safer treatment option for PBD. Copyright © 2014 John Wiley & Sons, Ltd.

  2. Virological efficacy in cerebrospinal fluid and neurocognitive status in patients with long-term monotherapy based on lopinavir/ritonavir: an exploratory study.

    Directory of Open Access Journals (Sweden)

    José R Santos

    Full Text Available BACKGROUND: Data on suppression of HIV replication in the CNS and on the subsequent risk of neurocognitive impairment using monotherapy with boosted protease inhibitors are limited. METHODS: Ours was an exploratory cross-sectional study in patients on lopinavir/ritonavir-based monotherapy (LPV/r-MT or standard triple therapy (LPV/r-ART for at least 96 weeks who maintained a plasma viral load <50 copies/mL. HIV-1 RNA in CSF was determined by HIV-1 SuperLow assay (lower limit of detection, 1 copy/mL. Neurocognitive functioning was assessed using a recommended battery of neuropsychological tests covering 7 areas. Neurocognitive impairment (NCI was determined and also a global deficit score (GDS for study comparisons. RESULTS: Seventeen patients on LPV/r-MT and 17 on LPV/r-ART were included. Fourteen (82.4% patients on LPV/r-MT and 16 (94.1% on LPV/r-ART had HIV-1 RNA <1 copy/mL in CSF (p = 0.601. NCI was observed in 7 patients on LPV/r-MT and in 10 on LPV/r-ART (41% vs 59%; p = 0.494. Mean (SD GDS was 0.22 (0.20 in patients on LPV/r-MT and 0.47 (0.34 in those on LPV/r-ART (p = 0.012. CONCLUSIONS: Suppression of HIV in CSF is similar in individuals with durable plasma HIV-1 RNA suppression who are receiving LPV/r-MT or LPV/r-ART for at least 96 weeks. Findings for HIV-1 replication in CSF and neurocognitive status indicate that this strategy seems to be safe for CNS functioning.

  3. Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

    Science.gov (United States)

    Zhang, Chi; Ke, Weixia; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

    2016-01-01

    Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

  4. Medical care costs of newly diagnosed children with structural-metabolic epilepsy: a one year prevalence-based approached.

    Science.gov (United States)

    Salih, Muhannad R M; Bahari, Mohd Baidi; Shafie, Asrul Akmal; Hassali, Mohamed Azmi Ahmad; Al-lela, Omer Qutaiba B; Abd, Arwa Y; Ganesan, Vigneswari M

    2012-12-01

    Aims of this study were to estimate the first-year medical care costs of newly diagnosed children with structural-metabolic epilepsy and to determine the cost-driving factors in the selected population. This was a prevalence-based retrospective chart review that included patients who attended a pediatric neurology clinic in a tertiary referral center in Malaysia. The total first-year medical care costs were estimated from the provider (i.e., hospital) perspective, using a bottom-up, microcosting analysis. Medical chart/billing data (i.e., case reports) obtained from the hospital (i.e., provider) were collected to determine the resources used. Prices or cost data were standardized for the year 2010 (One Malaysian Ringgit MYR is equivalent to 0.26 Euro or 0.32 USD). The most expensive item in the costs list was antiepileptic drugs, whereas ultrasound examination represented the cheapest item. Hospitalization and the use of non-antiepileptic drugs were the second and third most costly items, respectively. The cost of therapeutic drug monitoring comprised only a small proportion of the total annual expenditure. None of the demographic variables (i.e., gender, race, and age) significantly impacted the first-year medical care costs. Similarly, child development, seizure type, therapy type (i.e., polytherapy versus monotherapy), and therapeutic drug monitoring utilization were also not associated with the cost of management. The first-year medical care costs positively correlated with seizure frequency (r(s)=0.294, p=0.001). However, the only variable that significantly predict the first-year medical care costs was the type of antiepileptic drugs (R(2)=0.292, F=7.772, pMalaysia. The total first-year medical care costs for 120 patients with structural-metabolic epilepsy were MYR 202,816 (i.e., MYR 1690.13 per patient per year). The study findings highlight the importance of optimizing seizure control in reducing the cost of management. Copyright © 2012 British Epilepsy

  5. Physician adherence to hypertension treatment guidelines and drug acquisition costs of antihypertensive drugs at the cardiac clinic: a pilot study

    Directory of Open Access Journals (Sweden)

    Abdulameer SA

    2012-01-01

    Full Text Available Shaymaa Abdalwahed Abdulameer1, Mohanad Naji Sahib1, Noorizan Abd Aziz1,2, Yahaya Hassan1,2, Hadeer Akram Abdul AlRazzaq1, Omar Ismail31School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia; 2Faculty of Pharmacy, Universiti Teknologi MARA (UiTM, 42300 Puncak Alam, Selangor, Malaysia; 3Hospital Pulau Pinang, 10900, Penang, MalaysiaAbstract: Prescribing pattern surveys are one of the pharmacoepidemiological techniques that provide an unbiased picture of prescribing habits. Prescription surveys permit the identification of suboptimal prescribing patterns for further evaluation. The aims of this study were to determine the prescribing trend, adherence of the prescribers to the guideline, and the impact of drug expenditure on drug utilization at the cardiac clinic of Penang Hospital, Malaysia. This was a cross-sectional study. Demographic data of the patients, diagnoses and the drugs prescribed were recorded. The average drug acquisition costs (ADAC were calculated for each antihypertensive drug class on a daily and annual basis. Adherence to the guideline was calculated as a percentage of the total number of patients. A total of 313 individuals fulfilled the inclusion criteria. The average age of the study population was 59.30 ± 10.35 years. The mean number of drugs per prescription in the study was 2.09 ± 0.78. There were no significant differences in the demographic data. Antihypertensive drugs were used in monotherapy and polytherapy in 20.8% and 79.2% of the patients, respectively. Adherence to the guideline regarding prescription occurred in 85.30% of the patients. The lowest priced drug class was diuretics and the highest was angiotensin-receptor blockers. In conclusion, the total adherence to the guideline was good; the adherence percentage only slightly decreased with a co-existing comorbidity (such as diabetes mellitus. The use of thiazide diuretics was encouraged because they are well tolerated and

  6. Blood Pressure Effects of High-Dose Amlodipine-Benazepril Combination in Black and White Hypertensive Patients Not Controlled on Monotherapy

    OpenAIRE

    Chrysant, Steven G

    2012-01-01

    Background Black hypertensive patients are more resistant to angiotensin-converting enzyme (ACE) inhibitor monotherapy than White patients. This resistance can be overcome with the combination of ACE inhibitors with diuretics or calcium-channel blockers (CCBs). Objectives The objective of this clinical investigation was to evaluate the antihypertensive effectiveness of monotherapy with the ACE inhibitor benazepril or the CCB amlodipine and their combination in Black and White hypertensive pat...

  7. An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia

    DEFF Research Database (Denmark)

    Pauer, Lynne; Winkelmann, Andreas; Arsenault, Pierre

    2011-01-01

    To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States.......To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States....

  8. Humanized anti-interleukin-6-receptor antibody (tocilizumab) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography, and BMI: data from the SAMURAI study.

    Science.gov (United States)

    Hashimoto, Jun; Garnero, Patrick; van der Heijde, Désirée; Miyasaka, Nobuyuki; Yamamoto, Kazuhiko; Kawai, Shinichi; Takeuchi, Tsutomu; Yoshikawa, Hideki; Nishimoto, Norihiro

    2011-02-01

    Our aim was to assess the ability of tocilizumab monotherapy to reduce progressive structural joint damage in rheumatoid arthritis patients at high risk of progression. This study was a subanalysis from a prospective 1-year, multicenter, X-ray-reader-blinded, randomized controlled trial of tocilizumab [Study of Active Controlled Monotherapy Used for Rheumatoid Arthritis, an IL-6 Inhibitor (SAMURAI) trial]. All patients were categorized into two or three groups according to four independent predictive markers for progressive joint damage [urinary C-terminal crosslinking telopeptide (uCTX-II), urinary pyridinoline/deoxypyridinoline (uPYD/DPD) ratio, body mass index (BMI), and joint-space narrowing (JSN) score at baseline]. One-year progression of joint destruction was assessed in high-risk versus low-risk groups receiving tocilizumab monotherapy and compared with patients receiving conventional disease-modifying antirheumatic drugs (DMARDs) (n = 157 and 145, respectively). In patients at high risk of progression of erosion as estimated by high uCTX-II, uPYD/DPD, or low BMI, and at high risk of progression of JSN as estimated by low BMI or high JSN score, the 52-week changes in radiological erosion and JSN, respectively, were significantly less in patients treated with tocilizumab monotherapy compared with those receiving DMARDs for each type of risk factor. In patients at low risk, those receiving tocilizumab also progressed less than those on DMARDs, although the difference did not reach statistical significance. Tocilizumab monotherapy is more effective in reducing radiological progression in patients presenting with risk factors for rapid progression than in low-risk patients. Patients at high risk for progression may benefit more from tocilizumab treatment.

  9. EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

    Science.gov (United States)

    Kitamura, Tadaichi; Nishimatsu, Hiroaki; Hamamoto, Toshiaki; Tomita, Kyoichi; Takeuchi, Takumi; Ohta, Nobutaka

    2002-02-01

    Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

  10. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Ragonesi, Pietro D; Querci, Fabrizio; Franzetti, Ivano G; Gadaleta, Gennaro; Ciccarelli, Leonardina; Piccinni, Mario N; D'Angelo, Angela; Cicero, Arrigo F G

    2010-06-01

    The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >7.5%) in therapy with pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day, or pioglitazone 15 mg plus metformin 850 mg twice a day. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index, fasting plasma proinsulin (Pr), Pr/FPI ratio, adiponectin, resistin (R), tumor necrosis factor-alpha (TNF-alpha), and high-sensitivity C-reactive protein. A decrease of body weight and body mass index was observed with metformin, but not with sitagliptin, at the end of the study. We observed a comparable significant decrease of HbA(1c), FPG, and PPG and a significant increase of homeostasis model assessment beta-cell function index compared with baseline in both groups without any significant differences between the 2 groups. Fasting plasma insulin, fasting plasma Pr, Pr/FPI ratio, and HOMA-IR values were decreased in both groups even if the values obtained with metformin were significantly lower than the values obtained with sitagliptin. There were no significant variations of ADN, R, or TNF-alpha with sitagliptin, whereas a significant increase of ADN and a significant decrease of R and TNF-alpha values were recorded with metformin. A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any

  11. Atazanavir/ritonavir monotherapy as maintenance strategy in HIV-1 treated subjects with viral suppression: 96-week analysis results of the MODAT study

    Directory of Open Access Journals (Sweden)

    Vincenzo Spagnuolo

    2014-11-01

    Full Text Available Introduction: The 48-week interim analysis of the MODAT study showed that confirmed virologic failure (CVF was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r-based triple therapy. The DSMB recommended stopping study enrollment but continuing follow-up of enrolled patients. We present the 96-week efficacy analysis. Material and Methods: Multicentre, randomized, open-label, non-inferiority trial (non-inferiority margin −10%. Treatment failure (TF was defined as CVF (two consecutive HIV-RNA >50 cp/mL or discontinuation for any cause. In the monotherapy arm, patients with CVF re-introduced their previous NRTIs and remained in the study if HIV-RNA <50 copies/mL within 12 weeks of re-intensification. Results: 101 patients evaluated (Figure 1: 85% males, 21% HCV-positive, median (IQR age of 42 (36–48 years, baseline CD4+ 576 (447–743 cells/µL. In the 96-week analysis (ITT; TF=failure, efficacy was 64% (32/50 in the monotherapy arm and 63% (32/51 in the triple-therapy arm (difference +1.3%, 95% CI −17.5–20.1. Fourteen patients in monotherapy and two in triple-therapy arm had CVF; median HIV-RNA was 136 (72–376 copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations were observed at CVF. All patients who re-intensified re-suppressed. In monotherapy arm, TF was more frequent in HCV-co-infected patients (64% vs 28%; p=0.041. In the secondary analysis (ITT; re-intensification=success, 82% (41/50 in monotherapy arm and 63% (32/51 in triple-therapy arm were on study at week 96 (difference +19.3%, 95% CI 2.2–36.3. SAEs occurred in four (8% patients in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis, one traumatic lesion, one nephrolithiasis and two (4% in the triple therapy arm (one sepsis, one renal failure. Drug-related adverse events (AEs leading to discontinuation were three (6% in the monotherapy arm (two AEs occurred in patients after successful re

  12. FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical Outcome in Gemcitabine-Monotherapy Treated Patients.

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    Cindy Serdjebi

    Full Text Available Because cytidine deaminase (CDA is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships.One hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine.Five patients out of 120 (i.e., 4.6% were found to be CDA deficient (i.e., CDA activity <1.3 U/mg, and only one among them experienced early severe hematological toxicity. There was no statistically significant difference in CDA activity between patients experiencing hematological severe toxicities (28.44% and patients who tolerated the treatment (71.56%. CDA genetic analysis failed in evidencing an impact in terms of toxicities or in CDA activity. Regarding pharmacokinetics, a wide inter-individual variability has been observed

  13. Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy

    Science.gov (United States)

    Park, Ki Ho; Hubatsch, Douglas A.; Er