Jaw osteonecrosis related to bisphosphonate therapy: a severe secondary disorder.

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Dannemann, C; Grätz, K W; Riener, M O; Zwahlen, R A

2007-04-01

Bisphosphonate-related osteonecrosis of the jaws (BON), first described in 2003, is gaining importance due to the increasing indication spectrum of bisphosphonate therapy [S. Takeyama, M. Ito, H. Shinoda, A novel bisphosphonate, TRK-530, for periodontitis, Bone 38 (2006) 31-31; M. Tagil, A. W-Dahl, J. Astrand, D. Little, S. Toksvig-Larsen, Decreasing the catabolic response by a single bisphosphonate infusion shortens the healing time in hemicallotasis operations, Bone 38 (2006) 84-85; E. Rodriguez, M.C. Duran, L.M. Rodriguez, R. Ros, M.R. Aleman, M. Rodriguez-Gaspar, A.M. Lopez, E. Garcia-Valdecasas, F. Santolaria, Intravenous (IV) bisphosphonates for osteopenic cancer survivor women: an alternative treatment, Bone 38 (2006) 72-73; D.G. Little, K. Ward, P. Kiely, M.C. Bellemore, J. Briody, C.T. Cowell, Bisphosphonate rescue in distraction osteogenesis: a case series, Bone 38 (2006) 80-80; R. Marx, Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic, J. Oral Maxillofac. Surg. 61 (2003) 1115-1118]. BON patients suffering from varying bony defects and symptoms are extremely restricted in their quality of life. Due to a limited knowledge of the aetiology of BON efficient evidence-based treatment strategies are lacking. Until now 23 patients with bisphosphonate-related osteonecrosis have been admitted to the Department of Cranio-Maxillofacial Surgery of the University of Zurich. A complete history has been recorded. All patients underwent clinical and radiographic examination. CT scans and MRI have been performed in selected cases. All patients had in common that, before signs of BON were observed, a local traumatic incidence had occurred. All patients showed signs of infection which could be remarkably reduced by antibacterial treatment. Furthermore, the period of bisphosphonate treatment was found to be one of the significant factors causing bisphosphonate-related osteonecrosis of the jaws. The aetiology of BON

Dental complications and management of patients on bisphosphonate therapy: A review article

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Kalra, Sandeep; Jain, Veena

2012-01-01

Bisphosphonates are group of drugs that inhibit bone resorption and are used to treat a range of pathologies including Paget's disease, osteoporosis, multiple myeloma and metastasis associated with breast or prostate cancer. The most common complication in patients on bisphosphonate therapy is osteonecrosis of jaw (ONJ) which can occur after any surgical dental procedure and the risk for the development of osteonecrosis of jaw is higher in patients receiving intravenous bisphosphonate therapy...

Bisphosphonate-Related Osteonecrosis of the Jaws. A Severe Side Effect of Bisphosphonate Therapy

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Zuzana Janovská

2012-01-01

Full Text Available Bisphosphonates (BP are potent inhibitors of bone resorption used mainly in the treatment of metastatic bone disease and osteoporosis. By inhibiting bone resorption, they prevent complications as pathological fracture, pain, tumor-induced hypercalcemia. Even though patient’s benefit of BP therapy is huge, various side effects may develop. Bisphosphonate-related osteonecrosis of the jaws (BRONJ is among the most serious ones. Oncologic patients receiving high doses of BP intravenously are at high risk of BRONJ development. BPs impair bone turnover leading to compromised bone healing which may result in the exposure of necrotic bone in the oral cavity frequently following tooth extraction or trauma of the oral mucosa. Frank bone exposure may be complicated by secondary infection leading to osteomyelitis development with various symptoms and radiological findings. In the management of BRONJ, conservative therapy aiming to reduce the symptoms plays the main role. In patients with extensive bone involvement resective surgery may lead to complete recovery, provided that the procedure is correctly indicated. Since the treatment of BRONJ is difficult, prevention is the main goal. Therefore in high risk patients dental preventive measures should be taken prior to bisphosphonate administration. This requires adequate communication between the prescribing physician, the patient and the dentist.

Current state of orthodontic patients under Bisphosphonate therapy

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2013-01-01

Background Bisphosphonates are a common medication for the prevention and therapy of osteoporosis, but are also applied for tumor diseases. They affect bone metabolism, and therefore also orthodontic treatments, but how it does has yet not been definitively clarified. Therefore, the aim of this research was to evaluate and demonstrate the reported effects and the current state of scientific research regarding orthodontic treatment and bisphosphonate medication exclusively in humans. Material and methods A systematic research of the literature for selected keywords in the Medline database (Pubmed) as well as a manual search was conducted. The following search terms were used: ‘Bisphosphonate’ in combination with: orthodontic, orthodontic treatment, tooth movement. Findings To date, only nine reported patients (case reports/series) and one original article (retrospective cohort study) regarding orthodontic treatment under bisphosphonate medication in humans have been published. Decelerated tooth movement with increased side effects (especially in high-risk patients) and longer treatment duration was reported in some articles. Patients with initial spacing or extraction cases had a higher risk of incomplete space closure and poor root parallelism. Conclusions Orthodontic tooth movement under bisphosphonate medication is possible, especially in low-risk patients (low dose and short period of intake). But the treatment is still not predictable, especially in high-risk patients. Therefore, the altered bone metabolism and higher extent of side effects should be considered in treatment planning, especially in extraction cases or high-risk patients. Regardless, longer treatment duration, decelerated tooth movement, and more side effects, e.g., incomplete space closure and poor root parallelism, should be expected, especially in extraction cases or space closure. PMID:23556517

Subtrochanteric stress fractures in patients on oral bisphosphonate therapy: an emerging problem.

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Murphy, Colin G

2012-01-31

The emergence of a new variant of subtrochanteric stress fractures of the femur, affecting patients on oral bisphosphonate therapy, has only recently been described. This fracture is often preceded by pain and distinctive radiographic changes (lateral cortical thickening), and associated with a characteristic fracture pattern (transverse fracture line and medial cortical spike). A retrospective review (2007-2009) was carried out for patients who were taking oral bisphosphonates and who sustained a subtrochanteric fracture after a low velocity injury. Eleven fractures were found in 10 patients matching the inclusion criteria outlined. All were females, and taking bisphosphonates for a mean of 43 years. Five of the 10 patients mentioned prodromal symptoms, for an average of 9.4 months before the fracture. Although all fractures were deemed low velocity, 5 of 11 were even atraumatic. Two patients had previously sustained contralateral subtrochanteric fractures. Plain radiographs of two patients showed lateral cortical thickening on the contralateral unfractured femur; the bisphosphonate therapy was stopped and close surveillance was started. Patients taking oral bisphosphonates may be at risk of a new variant of stress fracture of the proximal femur. Awareness of the symptoms is the key to ensure that appropriate investigations are undertaken.

Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer.

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Stachnik, Agnes; Yuen, Tony; Iqbal, Jameel; Sgobba, Miriam; Gupta, Yogesh; Lu, Ping; Colaianni, Graziana; Ji, Yaoting; Zhu, Ling-Ling; Kim, Se-Min; Li, Jianhua; Liu, Peng; Izadmehr, Sudeh; Sangodkar, Jaya; Scherer, Thomas; Mujtaba, Shiraz; Galsky, Matthew; Gomez, Jorge; Epstein, Solomon; Buettner, Christoph; Bian, Zhuan; Zallone, Alberta; Aggarwal, Aneel K; Haider, Shozeb; New, Maria I; Sun, Li; Narla, Goutham; Zaidi, Mone

2014-12-16

A variety of human cancers, including nonsmall cell lung (NSCLC), breast, and colon cancers, are driven by the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. Having shown that bisphosphonates, a class of drugs used widely for the therapy of osteoporosis and metastatic bone disease, reduce cancer cell viability by targeting HER1, we explored their potential utility in the prevention and therapy of HER-driven cancers. We show that bisphosphonates inhibit colony formation by HER1(ΔE746-A750)-driven HCC827 NSCLCs and HER1(wt)-expressing MB231 triple negative breast cancers, but not by HER(low)-SW620 colon cancers. In parallel, oral gavage with bisphosphonates of mice xenografted with HCC827 or MB231 cells led to a significant reduction in tumor volume in both treatment and prevention protocols. This result was not seen with mice harboring HER(low) SW620 xenografts. We next explored whether bisphosphonates can serve as adjunctive therapies to tyrosine kinase inhibitors (TKIs), namely gefitinib and erlotinib, and whether the drugs can target TKI-resistant NSCLCs. In silico docking, together with molecular dynamics and anisotropic network modeling, showed that bisphosphonates bind to TKIs within the HER1 kinase domain. As predicted from this combinatorial binding, bisphosphonates enhanced the effects of TKIs in reducing cell viability and driving tumor regression in mice. Impressively, the drugs also overcame erlotinib resistance acquired through the gatekeeper mutation T790M, thus offering an option for TKI-resistant NSCLCs. We suggest that bisphosphonates can potentially be repurposed for the prevention and adjunctive therapy of HER1-driven cancers.

Hyperparathyroidism Associated with Long-Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults.

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Hinson, Andrew M; Wilkerson, Bekka M; Rothman-Fitts, Ivy; Riggs, Ann T; Stack, Brendan C; Bodenner, Donald L

2015-10-01

To measure the effect of proton pump inhibitors (PPIs), with and without concurrent bisphosphonates, on parathyroid hormone (PTH), vitamin D, and calcium. Retrospective chart review of individuals 60 years and older. Subjects with reduced renal function (creatinine >1.3 mg/dL) and low vitamin D (hyperparathyroidism regardless of concurrent oral BP administration. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Tooth alterations in areas of bisphosphonate-induced osteonecrosis.

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de Camargo Moraes, Paulo; Silva, Carolina Amália Barcellos; Soares, Andresa Borges; Passador-Santos, Fabrício; Corrêa, Maria Elvira Pizzigatti; de Araújo, Ney Soares; de Araújo, Vera Cavalcanti

2015-03-01

Osteonecrosis of the jaw is a potential side effect when using bisphosphonates. Most studies on the effects of bisphosphonates on teeth have been conducted in vitro or in animal models of tooth development. Therefore, the aim of this study was to describe alterations found in human teeth extracted from areas of bisphosphonate-induced osteonecrosis. Using a retrospective study design, 16 teeth from 13 patients were extracted from areas of bisphosphonate-induced osteonecrosis during surgical debridement. The specimens were decalcified and embedded in paraffin. A series of 5-μm sections were prepared, stained with hematoxylin and eosin (H&E) and observed under a light microscope. The majority of the patients were female (53.85 %), with a mean age of 60.23 ± 13.18 years. Zoledronate (IV) was the most common bisphosphonate used (92.3 %), over a mean period of 2 years. The commonest alteration observed was hypercementosis (87.5 %), followed by pulpar necrosis (81.25 %), pulp stones attached to the dentine and loose pulp stones in the pulp chamber and root canals in addition to linear calcifications (68.75 %), dentinoid/osteoid material formation (18.75 %), and dental ankylosis (6.25 %). Patients undergoing bisphosphonate therapy present diverse tooth alterations, which should be closely monitored by clinicians to prevent complications. It is paramount that the teeth involved in oral lesions are always examined. Attention should be drawn to the need to establish preventive measures, in terms of dental treatment, for patients prior to starting bisphosphonate therapy.

Clinical strategies to address patients' concerns in osteoporosis management with bisphosphonates.

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Cole, Raymond E

2011-03-01

Approximately 44 million Americans either have, or are at risk of developing, osteoporosis, a disease associated with an increased risk of fracture and, consequently, morbidity and mortality. Osteoporosis affects 20% to 30% of postmenopausal women, and resulting fractures pose a major economic burden, with estimated annual direct costs ranging from $17 billion to $19 billion. Hip fractures account for the majority of costs (~60%) because they often require costly long-term follow-up care in addition to the direct costs of initial treatment. Screening, diagnosis, and disease management are of paramount importance when treating patients at risk for osteoporosis. The National Osteoporosis Foundation recommends that all postmenopausal women be evaluated for osteoporosis risk factors and that all women aged ≥ 65 years undergo bone mineral density testing. Once the primary care physician has identified a patient at risk for osteoporosis-related fracture, the physician must decide whether and how to treat the patient (ie, nonpharmacologic or pharmacologic options). Bisphosphonates are the first-line pharmacologic treatment for women aged ≥ 50 years with postmenopausal osteoporosis. Bisphosphonates-which have a favorable safety and tolerability profile in clinical trials-have shown efficacy in reducing fractures. However, achieved real world effectiveness is very much dependent on good treatment adherence by the patient. Media attention to rare adverse events has motivated some patients to deliberate nonadherence. Physicians should screen patients for contraindications and adverse event risk factors, educate them on the risks of fracture and benefits and risks of treatment, and monitor them during therapy. To assist primary care physicians in clinical decision making for women at risk for or with confirmed osteoporosis, this article presents a review of the guidelines for the diagnosis and treatment of postmenopausal osteoporosis, recent long-term efficacy data for

Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday.

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Villa, Jordan C; Gianakos, Arianna; Lane, Joseph M

2016-02-01

Bisphosphonates are the most widely used treatment for osteoporosis. They accumulate in the bone for years, and therefore, their inhibitory effects on osteoclasts may persist after drug discontinuation. The ideal duration of therapy remains controversial. The purpose of this study is to review the literature to determine the (1) indications for drug holiday, (2) the duration of drug holiday, (3) the evaluation during drug holiday, and (4) the proper treatment and maintenance after drug holiday. A review of two electronic databases (PubMed/MEDLINE and EMBASE) was conducted using the term "(Drug holiday)," in January 29, 2015. Inclusion criteria were as follows: (1) clinical trials and case control, (2) human studies, (3) published in a peer-review journal, and (4) written in English. Exclusion criteria were as follows: (1) case reports, (2) case series, and (3) in vitro studies. The literature supports a therapeutic pause after 3-5 years of bisphosphonate treatment in patients with minor bone deficiencies and no recent fragility fracture (low risk) and in patients with moderate bone deficiencies and/or recent fragility fracture (moderate risk). In these patients, a bone health reevaluation is recommended every 1-3 years. Patients with high fracture risk should be maintained on bisphosphonate therapy without drug holiday. The duration and length of drug holiday should be individualized for each patient. Evaluation should be based on serial bone mass measurements, bone turnover rates, and fracture history evaluation. If after drug therapy, assessments show an increased risk of fracture, the patient may benefit from initiating another treatment. Raloxifene, teriparatide, or denosumab are available options.

New Dimensional Staging of Bisphosphonate-Related Osteonecrosis of the Jaw Allowing a Guided Surgical Treatment Protocol: Long-Term Follow-Up of 266 Lesions in Neoplastic and Osteoporotic Patients from the University of Bari

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Simonetta Franco

2014-01-01

Full Text Available Bisphosphonate-related osteonecrosis of the jaw (BRONJ is the most serious side effect in patients receiving bisphosphonates (BPs for neoplastic disease and osteoporosis. The aim of this study is to propose a new dimensional stage classification, guiding the surgical treatment of BRONJ patients, and to evaluate the success rate of this new management. From 2004 to 2013, 203 neoplastic and osteoporotic patients with 266 BRONJ lesions were referred to the Odontostomatology Unit of the University of Bari. All patients underwent surgery after suspension of BPs therapy and antibiotic treatment. The surgical procedure was complemented by piezosurgery and followed by the application of hyaluronate and amino acids. The new dimensional staging suggests the choice of the surgical approach, and allows the prediction of postoperative complications and soft and hard tissues healing time, guiding the surgical treatment protocol. This protocol could be a successful management strategy for BRONJ, considering the low recurrences rate and the good stabilisation of the surgical sites observed after a long-term follow-up.

Recurrent Proximal Femur Fractures in a Teenager With Osteogenesis Imperfecta on Continuous Bisphosphonate Therapy: Are We Overtreating?

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Vasanwala, Rashida F; Sanghrajka, Anish; Bishop, Nicholas J; Högler, Wolfgang

2016-07-01

Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment

Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

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Holt, Abby; Khan, Muhammad A; Gujja, Swetha; Govindarajan, Rangaswmy

2014-01-01

Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer

Cost-effectiveness of combined oral bisphosphonate therapy and falls prevention exercise for fracture prevention in the USA.

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Mori, T; Crandall, C J; Ganz, D A

2017-02-01

We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone. The purpose of this study was to examine the cost-effectiveness of the combined strategy of oral bisphosphonate therapy for 5 years and falls prevention exercise for 1 year compared with either strategy in isolation. We calculated incremental cost-effectiveness ratios [ICERs] (2014 US dollars per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women with different starting ages (65, 70, 75, and 80) without prior history of hip, vertebral, or wrist fractures over a lifetime horizon from the societal perspective. At ages 65, 70, 75, and 80, the combined strategy had ICERs of $202,020, $118,460, $46,870, and $17,640 per QALY, respectively, compared with oral bisphosphonate therapy alone. The combined strategy provided better health at lower cost than falls prevention exercise alone at ages 70, 75, and 80. In deterministic sensitivity analyses, results were particularly sensitive to the change in the opportunity cost of participants' time spent exercising. In probabilistic sensitivity analyses, the probabilities of the combined strategy being cost-effective compared with the next best alternative increased with age, ranging from 35 % at age 65 to 48 % at age 80 at a willingness-to-pay of $100,000 per QALY. Among community-dwelling US white women ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a willingness-to-pay of $100,000 per QALY, compared with oral bisphosphonate therapy only. This analysis will help clinicians and policymakers make better decisions about treatment

Osteonecrosis of the jaw: a rare and devastating side effect of bisphosphonates.

LENUS (Irish Health Repository)

Ryan, P

2009-12-01

Evidence has emerged that bisphosphonate use in cancer patients is associated with osteonecrosis of the jaw. This form of osteonecrosis has been termed bisphosphonate induced osteonecrosis of the jaw (BIONJ). BIONJ is commonly precipitated by a tooth extraction in patients treated with long term, potent, high dose intravenous bisphosphonates for the management of myeloma, breast or prostate cancer. The overall prevalence of BIONJ is about 5% in patients with these malignancies. Current evidence shows that the risk of BIONJ in non-cancerous patients, such as those with osteoporosis, is very low and appears to be comparable with that of the general population. Prescribing physicians need to encourage cancer patients to see their dentists before the initiation of bisphosphonate treatment, and regularly thereafter.

BISPHOSPHONATE INDUCED STRESS FRACTURE OF BILATERAL FEMUR: A CASE REPORT

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Saidapur

2015-08-01

Full Text Available Osteoporosis is a common problem affecting people after 4 - 5 decade of life. There are various treatment options available for Osteoporosis and Bisphosphonates are widely used. Bisphosphonates work by blocking osteoclast mediated bone resorption and can be given in oral and injectable forms. R ecent studies have brought to light the risk of sub trochanteric stress fracture secondary to bisphosphonate therapy. Here we are presenting a case with bilateral sub trochanteric fracture following prolonged bisphosphonate therapy

Established role of bisphosphonate therapy for prevention of skeletal complications from myeloma bone disease.

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Terpos, Evangelos; Dimopoulos, Meletios A; Berenson, James

2011-02-01

Patients with advanced multiple myeloma (MM) often have increased osteolytic activity of osteoclasts and impaired osteogenesis by osteoblasts, resulting in osteolytic bone lesions that increase the risk of skeletal-related events (SREs) including pathologic fracture, the need for radiotherapy or surgery to bone, and spinal cord compression. Such SREs are potentially life-limiting, and can reduce patients' functional independence and quality of life. Bisphosphonates (e.g., oral clodronate and intravenous pamidronate and zoledronic acid) can inhibit osteoclast-mediated osteolysis, thereby reducing the risk of SREs, ameliorating bone pain, and potentially prolonging survival in patients with MM. Extensive clinical experience demonstrates that bisphosphonates are generally well tolerated, and common adverse events are typically mild and manageable. Studies are ongoing to optimize the timing and duration of bisphosphonate therapy in patients with bone lesions from MM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Long-term use of Bonviva for the treatment of postmenopausal osteoporosis: new evidence

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Olga Borisovna Yershova

2012-01-01

Full Text Available Osteoporosis is a disease of great social importance. Its treatment is a complicated problem and it is associated with low compliance and a risk for adverse reactions. Ibandronate belongs to a group of bisphosphonates. The performed trials have proven the efficacy of its two formulations (a tablet once monthly and intravenous injection once every 3 months in reducing the risk of bone fractures. At present there are data of trials of long-term therapy with this drug, which demonstrate its positive effect on bone mineral density and bone metabolism markers. The agent has been also shown to be highly safe when used long.

Optimizing dosing frequencies for bisphosphonates in the management of postmenopausal osteoporosis: patient considerations

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John Sunyecz

2008-12-01

Full Text Available John SunyeczMenopauseRx, Inc., Hopwood, PA, USAAbstract: Postmenopausal osteoporosis is common and underrecognized among elderly women. Osteoporotic fractures cause disability and disfigurement and threaten patients’ mobility, independence, and survival. Care for incident fractures in this age group must go beyond orthopedic repair, to assessment and treatment of the underlying bone fragility. Fracture risk can be reduced by vitamin D and calcium supplementation along with antiresorptive drug treatment. First-line osteoporosis pharmacotherapy employs nitrogen-containing bisphosphonates. The inconvenience of daily oral treatment has motivated development of weekly, monthly, and intermittent oral regimens, as well as quarterly and yearly intravenous (iv regimens. Ibandronate is the first bisphosphonate to have shown direct anti-fracture efficacy with a non-daily regimen; it was approved for once-monthly oral dosing in 2005 and for quarterly iv dosing in 2006. Intermittent oral risedronate and yearly iv zoledronic acid were approved in 2007. Newly available regimens with extended dosing intervals reduce the inconvenience of bisphosphonate therapy and provide patients with a range of options from which to select a maximally sustainable course of treatment. This review discusses the development, efficacy, safety, and tolerability of extended-interval bisphosphonate regimens and examines their potential to improve patient acceptance and long-term success of osteoporosis treatment.Keywords: ibandronate, alendronate, risedronate, zoledronic acid, adherence, persistence

Long-term results of golimumab therapy for rheumatoid arthritis. Therapy compliance issues

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N. V. Chichasova

2016-01-01

Full Text Available The goal of therapy for rheumatoid arthritis (RA is to suppress inflammation, to prevent or delay destructive changes in the joints, and to normalize functions during the longest monitoring of the course of RA. The data of randomized controlled trials and national registries are of great importance to a clinician. The paper reviews the literature data characterizing the long-term results of RA therapy with the tumor necrosis factor-α inhibitor golimumab (GLM and patient compliance with the therapy. Treatment with GLM at the registered subcutaneous dose of 50 mg once every 4 weeks gives rise to an effect in the vast majority of patients regardless of the type of previous ineffective therapy, the dose of concurrently administered methotrexate, the number of previous ineffective disease-modifying antirheumatic drugs, and the use and nonuse of glucocorticoids. GLM is characterized by a long-term (as long as 5 years effect with suppressed progression of destruction, functional recovery, and satisfactory tolerability with no additional risk for adverse events as the therapy is continued.

Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.

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Anthony Grosso

Full Text Available A recent trial unexpectedly reported that atrial fibrillation, when defined as serious, occurred more often in participants randomized to an annual infusion of the relatively new parenteral bisphosphonate, zoledronic acid, than among those given placebo, but had limited power. Two subsequent population-based case-control studies of patients receiving a more established oral bisphosphonate, alendronic acid, reported conflicting results, possibly due to uncontrolled confounding factors.We used the United Kingdom General Practice Research Database to assess the risk of atrial fibrillation and flutter in women exposed to the oral bisphosphonates, alendronic acid and risedronate sodium. The self-controlled case-series method was used to minimise the potential for confounding. The age-adjusted incidence rate ratio for atrial fibrillation or flutter in individuals during their exposure to these oral bisphosphonates (n = 2195 was 1.07 (95% CI 0.94-1.21. The age-adjusted incidence rate ratio for alendronic acid (n = 1489 and risedronate sodium (n = 649 exposed individuals were 1.09 (95% CI 0.93-1.26 and 0.99 (95% CI 0.78-1.26 respectively. In post-hoc analyses, an increased risk of incident atrial fibrillation or flutter was detected for patients during their first few months of alendronic acid therapy.We found no robust evidence of an overall long-term increased risk of atrial fibrillation or flutter associated with continued exposure to the oral bisphosphonates, alendronic acid and risedronate sodium. A possible signal for an increase in risk during the first few months of therapy with alendronic acid needs to be re-assessed in additional studies.

Impact of long-term and short-term therapies on seminal parameters

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Jlenia Elia

2013-04-01

Full Text Available Aim: The aim of this work was: i to evaluate the prevalence of male partners of subfertile couples being treated with long/short term therapies for non andrological diseases; ii to study their seminal profile for the possible effects of their treatments on spermatogenesis and/or epididymal maturation. Methods: The study group was made up of 723 subjects, aged between 25 and 47 years. Semen analysis was performed according to World Health Organization (WHO guidelines (1999. The Superimposed Image Analysis System (SIAS, which is based on the computerized superimposition of spermatozoa images, was used to assess sperm motility parameters. Results: The prevalence of subjects taking pharmacological treatments was 22.7% (164/723. The prevalence was 3.7% (27/723 for the Short-Term Group and 18.9% (137/723 for the Long-Term Group. The subjects of each group were also subdivided into subgroups according to the treatments being received. Regarding the seminal profile, we did not observe a significant difference between the Long-Term, Short-Term or the Control Group. However, regarding the subgroups, we found a significant decrease in sperm number and progressive motility percentage in the subjects receiving treatment with antihypertensive drugs compared with the other subgroups and the Control Group. Conclusions: In the management of infertile couples, the potential negative impact on seminal parameters of any drugs being taken as Long-Term Therapy should be considered. The pathogenic mechanism needs to be clarified.

BONE TURNOVER IN OSTEOPOROTIC WOMEN DURING LONG-TERM ORAL BISPHOSPHONATES TREATMENT: IMPLICATIONS FOR TREATMENT FAILURE AND "DRUG HOLIDAY" IN THE REAL WORLD.

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Liel, Yair; Plakht, Ygal; Tailakh, Muhammad Abu

2017-07-01

Little data exist to support concerns over bone turnover suppression during prolonged oral bisphosphonate treatment and on consequences of the recommended "drug holiday." This study was performed to assess bone resorption rates in postmenopausal osteoporotic women on prolonged oral bisphosphonate treatment and in response to switching to "drug holiday" intravenous bisphosphonate, or continuation of oral bisphosphonates. The frequency distribution of the bone resorption marker urinary deoxypyridinoline crosslinks (uDPD), was obtained retrospectively from 211 osteoporotic women attended at an academic hospital endocrine clinic, treated for >2 years with oral bisphosphonates. In some patients, uDPD was re-assessed following modification or continuation of treatment. The mean duration of oral bisphosphonates treatment was 7.2 ± 3.1 years. uDPD was within reference range for premenopausal women in 61.6% of the patients, below in 7.6% of the patients, and above upper limit in 30.8%. uDPD decreased significantly following intravenous zoledronic acid, increased significantly during "drug holiday," and slightly decreased in those continued on oral bisphosphonate treatment. In this real-world study, the majority of women on prolonged oral bisphosphonates maintained bone resorption rates within the normal reference range for premenopausal women. The likelihood for inadequate suppression was considerably greater than that of over-suppression. Implementing a "drug holiday" resulted in a marked increase in bone resorption rates. Additional studies should explore the potential role of bone turnover markers in the evaluation of patients on prolonged oral bisphosphonates and during "drug holiday" in different settings and using additional markers. BMD = bone mineral density; IQR = interquartile range; uDPD = urinary deoxypyridinoline crosslinks.

Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.

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Gurudu, S R; Griffel, L H; Gialanella, R J; Das, K M

1999-09-01

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.

Atypical Femur Fractures in Patients Treated with Bisphosphonates: Identification, Management, and Prevention

Directory of Open Access Journals (Sweden)

Judith Sarah Bubbear

2016-10-01

Full Text Available Osteoporosis is a common condition with significant health care costs. First-line therapy is with bisphosphonates, which have proven anti-fracture efficacy. Around 10 years after the introduction of bisphosphonates reports began to be published of atypical femoral fractures (AFFs that may be associated with this therapy. These fractures are associated with significant morbidity although lower mortality than the more common osteoporotic neck-of-femur fractures. A case definition has been described to allow identification of this class of fracture. Further work has established a high relative risk of AFFs in patients treated with bisphosphonates, but a low absolute risk in comparison to that of osteoporotic fractures. Proposed pathological mechanisms include low bone turnover states leading to stress/insufficiency fractures. Clinicians should be aware of the risk of AFFs and in particular the high rate of prodromal thigh/groin pain that warrants investigation in a patient receiving a bisphosphonate. If an incomplete fracture is diagnosed then bisphosphonate therapy needs to be stopped and prophylactic surgery may be considered. Due to these rare side effects patients on bisphosphonates require regular review, and this is particularly advised after 5 years of oral or 3 years of intravenous therapy.

How much we know about bisphosphonate lesions

Directory of Open Access Journals (Sweden)

Pešić Zoran

2016-01-01

Full Text Available Introduction: Bisphosphonate drugs are used in the treatment of the osteoporosis and malignant processes in the bone tissue. As a result of this use bisphosphonate lesions are formed in bone tissue and oral mucosis, which representing a remarkable therapeutic problem. The aim of this study was to determine how many dentists in general practice are familiar with the character, diagnosis and therapy bisphosphonate lesions. Material and Methods: An anonymous questionnaire of 13 questions was conducted in dental practices in Nis County in the period from October 2015 to December 2015. The obtained data were statistically analyzed. Results: A total of 60% dentists knew what drugs are used in the treatment of osteoporosis and malignant processes in the bones. 25% knew what the bisphosphonate bone lesions are . 66, 6% of dentists knewn what is the prevention of bisphosphonate lesions. 63.3% of dentists are aware of the complications bisphosphonate lesions. Conclusion: Dentists in general practices are insufficiently familiar with the character, diagnosis and treatment of bisphosphonate lesions. We should activate all entities that participate in more continuous medical education, in order to achieve a higher level of prevention of these therapeutic ungrateful lesions.

Delayed healing of lower limb fractures with bisphosphonate therapy.

Science.gov (United States)

Yue, B; Ng, A; Tang, H; Joseph, S; Richardson, M

2015-07-01

Bisphosphonate therapy (BT) is used commonly in the management of osteoporosis. A systematic review was conducted investigating delayed union of lower limb, long bone fractures in patients on BT. We specifically assessed whether BT increases the risk of delayed union or non-union in lower limb, long bone fractures. A literature search was conducted in the PubMed and Embase™ on 4 November 2014. Articles that investigated lower limb fractures, history of BT and fracture union were included in the review. A total of 9,809 papers were retrieved and 14 were deemed suitable for this review. The mean time to union in patients on BT was 8.5 months. A longer time to union was reported in a study investigating BT users versus controls (6.5 vs 4.8 months respectively). The mean rate of delayed or non-union for BT associated atypical fractures was 20% per fracture. Specifically in one study, delayed union was more common in the cohort with more than three years of BT (67%) than in the group with less than three years of BT (26%). Surgical fixation was associated with improved outcomes compared with non-operative management. BT has been described to be associated with multiple adverse outcomes related to atypical fractures. Current evidence recommends operative management for this patient group. Further investigation is required to evaluate the exact effects of BT on lower limb fractures, in particular typical femoral fractures.

Bisphosphonate-associated osteonecrosis of jaw reoccurrence after methotrexate therapy: a case report.

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Alsalleeh, Fahd; Keippel, Jeffery; Adams, Lyde; Bavitz, Bruce

2014-09-01

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-known complication caused by amino-bisphosphonate therapy. We document one case of BRONJ associated with oral administration of methotrexate, a known immunosuppressive drug used to treat rheumatoid arthritis. A 66-year-old woman was referred for evaluation and endodontic surgery of recently re-treated tooth 13. Tooth 14 was extracted 3 months prior, and the extraction site had not completely healed. Her medical history revealed rheumatoid arthritis and osteoporosis. She had been taking Fosamax (alendronate) 70 mg daily. Because of adequate root canal therapy of tooth 13, endodontic surgery was performed. Five months after apicoectomy, her symptoms had not changed. Tooth 13 was extracted, and the socket healed without complications. The socket of extracted tooth 14 was also healing. At the 3-month recall visit, bone exposure and purulent discharge at the site of extracted tooth 14 were noted. The patient had recently received methotrexate. The methotrexate was discontinued, and she was given course of amoxicillin. At the 18-month follow-up, the healing progressed, and the wound was closed. A medication that suppresses the immune system such as methotrexate may complicate the management of BRONJ. Once a diagnosis of BRONJ is made, a closely monitored conservative approach is recommended. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw.

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Khan, Aliya A; Sándor, George K B; Dore, Edward; Morrison, Archibald D; Alsahli, Mazen; Amin, Faizan; Peters, Edmund; Hanley, David A; Chaudry, Sultan R; Dempster, David W; Glorieux, Francis H; Neville, Alan J; Talwar, Reena M; Clokie, Cameron M; Al Mardini, Majd; Paul, Terri; Khosla, Sundeep; Josse, Robert G; Sutherland, Susan; Lam, David K; Carmichael, Robert P; Blanas, Nick; Kendler, David; Petak, Steven; St-Marie, Louis Georges; Brown, Jacques; Evans, A Wayne; Rios, Lorena; Compston, Juliet E

2008-07-01

Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists. The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies. RECOMMENDATIONS regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case

MANAGEMENT OF ENDOCRINE DISEASE: Atypical femoral fractures: risks and benefits of long-term treatment of osteoporosis with anti-resorptive therapy.

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Adler, Robert A

2018-03-01

Modern osteoporosis treatment began in the mid-1990s with the approval of amino-bisphosphonates, anti-resorptive agents that have been shown to decrease osteoporotic fracture risk by about half. In 2005, the first cases of atypical femoral fractures (AFF), occurring in the shaft of the femur, were reported. Since then, more cases have been found, leading to great concern among patients and a dramatic decrease in bisphosphonate prescribing. The pathogenesis and incidence of AFF are reviewed herein. Management and an approach to prevention or early detection of AFF are also provided. Denosumab, a more recently approved anti-resorptive medication has also been associated with AFF. Long-term management of osteoporosis and prevention of fracture are challenging in light of this serious but uncommon side effect, yet with an aging population osteoporotic fracture is destined to increase in frequency. © 2018 European Society of Endocrinology.

Regional cerebral blood flow in Alzheimer's disease. Comparison between short and long-term donepezil therapy

International Nuclear Information System (INIS)

Ushijima, Yo; Okuyama, Chio; Kubota, Takao; Nakai, Takako; Nishimura, Tsunehiko; Mori, Satoru

2006-01-01

Treatment with donepezil improves cognitive function of patients with Alzheimer's disease (AD) when compared to a placebo-controlled group. The purpose of this study was to investigate changes in regional cerebral blood flow (rCBF) of AD patients in short-term and long-term treatment with donepezil. rCBF was measured by N-isopropyl-p- 123 I-iodoamphetamine (IMP) autoradiography method. CBF measurements were performed in 17 AD patients before treatment and after 3 months (short-term therapy) and 1 year (long-term therapy). Regions of interest were set at cerebral cortex and cerebellar hemisphere. We used absolute CBF and relative CBF expressed as ratio to cerebellar CBF. Significant increases in relative rCBF were noted in the frontal, parietal and temporal lobes at the end of short-term therapy. rCBF was decreased after the long-term therapy, whereas rCBF was still increased to a slight extent, as compared with the pre-treatment levels. Absolute rCBF showed minimal change and a tendency to decline. Relative rCBF significantly increased in the short-term donepezil therapy, while following the long-term therapy, rCBF decreased to the pre-treatment level. (author)

Pleiotropic effects of bisphosphonates on osteosarcoma.

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Ohba, Tetsuro; Cates, Justin M M; Cole, Heather A; Slosky, David A; Haro, Hirotaka; Ichikawa, Jiro; Ando, Takashi; Schwartz, Herbert S; Schoenecker, Jonathan G

2014-06-01

Osteosarcoma is the most common primary malignant tumor of bone and accounts for half of all primary skeletal malignancies in children and teenagers. The prognosis for patients who fail or progress on first-line chemotherapy protocols is poor, therefore, additional adjuvant therapeutic strategies are needed. A recent feasibility study has demonstrated that the nitrogen-containing bisphosphonate zoledronic acid (ZOL) can be combined safely with conventional chemotherapy. However, the pharmacodynamics of bisphosphonate therapy is not well characterized. Osteosarcoma is a highly angiogenic tumor. Recent reports of the anti-angiogenic effects of bisphosphonates prompted us to determine whether nitrogen-containing bisphosphonate (ZOL and alendronate) treatment attenuates osteosarcoma growth by inhibition of osteoclast activity, tumor-mediated angiogenesis, or direct inhibitory effects on osteosarcoma. Here, we demonstrate that bisphosphonates directly inhibit VEGFR2 expression in endothelial cells, as well as endothelial cell proliferation and migration. Additionally, bisphosphonates also decrease VEGF-A expression in osteosarcoma (K7M3) cells, resulting in reduced stimulation of endothelial cell migration in co-culture assays. ZOL also decreases VEGFR1 expression in aggressive osteosarcoma cell lines (K7M3, 143B) and induces apoptosis of these cells, but has negligible effects on less aggressive osteosarcoma cell lines (K12 and TE85). In vivo ZOL treatment results in significant reduction in osteosarcoma-initiated angiogenesis and tumor growth in a murine model of osteosarcoma. In conclusion, bisphosphonates have diverse growth inhibitory effects on osteosarcoma through: (1) activation of apoptosis and inhibition of cell proliferation, (2) inhibition of VEGF-A and VEGFR1 expression by tumor cells, (3) inhibition of tumor-induced angiogenesis, and (4) direct inhibitory actions on endothelial cells. Published by Elsevier Inc.

Safety issues with bisphosphonate therapy for osteoporosis

DEFF Research Database (Denmark)

Suresh, Ernest; Pazianas, Michael; Abrahamsen, Bo

2014-01-01

Randomized controlled trials have demonstrated the efficacy of bisphosphonates (BP) in improving BMD and reducing fracture risk. Various safety issues that were not noted in clinical trials have, however, now emerged with post-marketing surveillance and increasing clinical experience. The risk...

Urea dimethacrylates functionalized with bisphosphonate/bisphosphonic acid for improved dental materials

OpenAIRE

Güven, Melek Naz; Guven, Melek Naz; Akyol, Ece; Duman, Fatma Demir; Acar, Havva Yağcı; Acar, Havva Yagci; Karahan, Özlem; Karahan, Ozlem; Avcı, Duygu; Avci, Duygu

2017-01-01

Incorporation of bisphosphonate/bisphosphonic acid groups in dental monomer structures should increase interaction of these monomers with dental tissue as these groups have strong affinity for hydroxyapatite. Therefore, new urea dimethacrylates functionalized with bisphosphonate (1a, 1b) and bisphosphonic acid (2a, 2b) groups are synthesized and evaluated for dental applications. Monomers 1a and 1b are synthesized from 2isocyanatoethyl methacrylate (IEM) and two bisphosphonated amines (BPA1 a...

Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs.

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Edwards, Beatrice J; Hellstein, John W; Jacobsen, Peter L; Kaltman, Steven; Mariotti, Angelo; Migliorati, Cesar A

2008-12-01

and Overview. In 2005, the American Dental Association (ADA) Council on Scientific Affairs convened an expert panel to develop clinical recommendations for dentists treating patients who are receiving oral bisphosphonate therapy. The Journal of the American Dental Association published the resulting report in 2006. This 2008 advisory statement is the first of projected periodic updates of the 2006 clinical recommendations. This 2008 advisory statement concludes, on the basis of a review of the current literature, that for patients receiving bisphosphonate therapy, the risk of developing bisphosphonate-associated osteonecrosis (BON) of the jaw apparently remains low. It also newly concludes that current screening and diagnostic tests are unreliable for predicting a patient's risk of developing the condition. This statement updates the 2006 recommendations regarding general dentistry, management of periodontal diseases, implant placement and maintenance, oral and maxillofacial surgery, endodontics, restorative dentistry and prosthodontics, and orthodontics.

Pregnancy-associated spinal osteoporosis treated with bisphosphonates: long-term follow-up of maternal and infants outcome.

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Vujasinovic-Stupar, Nada; Pejnovic, Nada; Markovic, Ljiljana; Zlatanovic, Maja

2012-03-01

Pregnancy-associated spinal osteoporosis (PPSO) is a rare condition characterized by severe back pain occurring near the end of the first pregnancy or shortly afterward. The aim of this report is to present a 12-year follow-up of a patient with PPSO. Also, the outcomes of patient's two pregnancies and her infants after long-term treatment with bisphosphonates are assessed. A young woman was referred to our tertiary care hospital aged 30 years, due to intense pain in thoracic and lumbar region that started during the last month of her first pregnancy and got worse after delivery. Bone mineral density (BMD) measurement, clinical, and biochemical parameters were performed. Extremely low lumbar spine BMD, L2-L4: 0.627 g/cm(2), T-score -4.8, Z-score -4.3, 52% young adult indicated severe osteoporosis. Cyclical treatment with etidronate and then pamidronate was started, and a substantial increase in the BMD and the reduction in back pain intensity were observed. An increase in BMD of 44.8% over baseline was observed after 12 years of follow-up. Her two pregnancies were uneventful, and no neonatal adverse effects were observed. Control DXA scan in her girl child aged 6.8 years revealed low BMD at the lumbar spine. As PPSO seems to be an underdiagnosed severe disease, caution is recommended if back pain occurs in the last trimester or early post-partum period. Although pre-pregnancy use of bisphosponates does not pose a substantial fetal risk, their use in women of childbearing age might best be done only when strong clinical indications exist.

Bisphosphonates and osteonecrosis of the jaw.

Science.gov (United States)

Shannon, Jodi; Shannon, John; Modelevsky, Steven; Grippo, Anne A

2011-12-01

Bisphosphonates are used worldwide as a successful treatment for people with osteoporosis, which is the major underlying cause of fractures in postmenopausal women and older adults. These agents are successful at increasing bone mass and bone trabecular thickness, decreasing the risk of fracture, and decreasing bone pain, enabling individuals to have better quality of life. Bisphosphonates are also used to treat multiple myeloma, bone metastasis, and Paget's disease; however, bisphosphonate treatment may result in negative side effects, including osteonecrosis of the jaw (ONJ). ONJ involves necrotic, exposed bone in the jaw, pain, possible secondary infection, swelling, painful lesions, and various dysesthesias, although less-severe cases may be asymptomatic. First-generation bisphosphonates, which do not contain nitrogen, are metabolized into a nonfunctional, cytotoxic analogue of adenosine triphosphate and cause osteoclast death by starvation. Second-generation bisphosphonates are nitrogen-containing agents; these inhibit osteoclast vesicular trafficking, membrane ruffling, morphology, and cytoskeletal arrangement by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. Physicians treating older adults with osteoporosis and cancer should work together with dental practitioners, pharmacists, and other clinicians to inform individuals receiving bisphosphonates of their possible side effects and to suggest precautionary steps that may minimize the risk of osteonecrosis, particularly of the jaw. These include practicing good oral hygiene; scheduling regular dental examinations and cleanings; and cautioning people who are scheduling treatment for periodontal disease, oral and maxillofacial therapy, endodontics, implant placement, restorative dentistry, and prosthodontics. Recommendations for management of people with ONJ include an oral rinse, such as chlorhexidine, and antibiotics. © 2011, Copyright the Authors Journal compilation © 2011, The American

Patterns of Change in Interpersonal Problems During and After Short-term and Long-term Psychodynamic Group Therapy: A Randomized Clinical Trial.

Science.gov (United States)

Fjeldstad, Anette; Høglend, Per; Lorentzen, Steinar

2017-05-01

In this study, we compared the patterns of change in interpersonal problems between short-term and long-term psychodynamic group therapy. A total of 167 outpatients with mixed diagnoses were randomized to 20 or 80 weekly sessions of group therapy. Interpersonal problems were assessed with the Inventory of Interpersonal Problems at six time points during the 3-year study period. Using linear mixed models, change was linearly modelled in two steps. Earlier (within the first 6 months) and later (during the last 2.5 years) changes in five subscales were estimated. Contrary to what we expected, short-term therapy induced a significantly larger early change than long-term therapy on the cold subscale and there was a trend on the socially avoidant subscale, using a Bonferroni-adjusted alpha. There was no significant difference between short-term and long-term group therapy for improving problems in the areas cold, socially avoidant, nonassertive, exploitable, and overly nurturant over the 3 years.

Long-term opioid therapy in Denmark

DEFF Research Database (Denmark)

Birke, H; Ekholm, Ola; Sjøgren, P

2017-01-01

significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all......,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

The clinical utility of long-term humidification therapy in chronic airway disease.

Science.gov (United States)

Rea, Harold; McAuley, Sue; Jayaram, Lata; Garrett, Jeffrey; Hockey, Hans; Storey, Louanne; O'Donnell, Glenis; Haru, Lynne; Payton, Matthew; O'Donnell, Kevin

2010-04-01

Persistent airway inflammation with mucus retention in patients with chronic airway disorders such as COPD and bronchiectasis may lead to frequent exacerbations, reduced lung function and poor quality of life. This study investigates if long-term humidification therapy with high flow fully humidified air at 37 degrees C through nasal cannulae can improve these clinical outcomes in this group of patients. 108 patients diagnosed with COPD or bronchiectasis were randomised to daily humidification therapy or usual care for 12 months over which exacerbations were recorded. Lung function, quality of life, exercise capacity, and measures of airway inflammation were also recorded at baseline, 3 and 12 months. Patients on long-term humidification therapy had significantly fewer exacerbation days (18.2 versus 33.5 days; p = 0.045), increased time to first exacerbation (median 52 versus 27 days; p = 0.0495) and reduced exacerbation frequency (2.97/patient/year versus 3.63/patient/year; p = 0.067) compared with usual care. Quality of life scores and lung function improved significantly with humidification therapy compared with usual care at 3 and 12 months. Long-term humidification therapy significantly reduced exacerbation days, increased time to first exacerbation, improved lung function and quality of life in patients with COPD and bronchiectasis. Clinical trial registered with www.actr.org.au; Number ACTRN2605000623695. Copyright 2010 Elsevier Ltd. All rights reserved.

Position Statement: Drug Holiday in Osteoporosis Treatment with Bisphosphonates in South Korea

Science.gov (United States)

Lee, Seung Hun; Gong, Hyun Sik; Kim, Tae-Hee; Park, Si Young; Shin, Jung-Ho; Cho, Sun Wook

2015-01-01

Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from many placebo-controlled trials demonstrating its efficacy in fracture risk reduction over 3 to 5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about the adverse effects related to its long-term use, including osteonecrosis of the jaw and atypical femur fractures. Because bisphosphonates are incorporated into the skeleton and continue to exert an anti-resorptive effect for a period of time after the discontinuation of drugs, the concept of a "drug holiday" has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from anti-fracture efficacy. As randomized clinical trial evidence is not yet available on who may qualify for a drug holiday, there is considerable controversy regarding the selection of candidates for the drug holiday and monitoring during a drug holiday, both of which should be based on individual assessments of risk and benefit. This statement will provide suggestions for clinicians in South Korea on the identification of possible candidates and monitoring during a bisphosphonate drug holiday. PMID:26713307

Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates

Directory of Open Access Journals (Sweden)

Wang Sara

2008-12-01

Full Text Available Abstract Background Both raloxifene and bisphosphonates are indicated for the prevention and treatment of postmenopausal osteoporosis, however these medications have different efficacy and safety profiles. It is plausible that physicians would prescribe these agents to optimize the benefit/risk profile for individual patients. The objective of this study was to compare demographic and clinical characteristics of patients initiating raloxifene with those of patients initiating bisphosphonates for the prevention and treatment of osteoporosis. Methods This study was conducted using a retrospective cohort design. Female beneficiaries (45 years and older with at least one claim for raloxifene or a bisphosphonate in 2003 through 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified using a collection of large national commercial, Medicare supplemental, and Medicaid administrative claims databases (MarketScan®. Patients were divided into two cohorts, a combined commercial/Medicare cohort and a Medicaid cohort. Within each cohort, characteristics (demographic, clinical, and resource utilization of patients initiating raloxifene were compared to those of patients initiating bisphosphonate therapy. Group comparisons were made using chi-square tests for proportions of categorical measures and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used to simultaneously examine factors independently associated with initiation of raloxifene versus a bisphosphonate. Results Within both the commercial/Medicare and Medicaid cohorts, raloxifene patients were younger, had fewer comorbid conditions, and fewer pre-existing fractures than bisphosphonate patients. Raloxifene patients in both cohorts were less likely to have had a bone mineral density (BMD screening in the previous year than were bisphosphonate patients, and were also more likely to have used estrogen or estrogen/progestin therapy in the

Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen.

Science.gov (United States)

Biggin, Andrew; Briody, Julie N; Ormshaw, Elizabeth; Wong, Karen K Y; Bennetts, Bruce H; Munns, Craig F

2014-01-01

Intravenous bisphosphonate therapy is the mainstay of medical treatment in osteogenesis imperfecta (OI) and has been shown to increase bone mass, decrease bone pain, improve mobility, and reduce the incidence of fractures. Sclerotic metaphyseal lines parallel to the growth plate are seen on long bone radiographs following cyclical intravenous therapy. These areas create stress risers within the bone that may act as foci for subsequent fractures as exemplified in this clinical case. An 8-year-old girl with OI sustained a distal radial fracture following 3 years of treatment with 6-monthly intravenous zoledronate. Her diagnosis, response to treatment, and subsequent fracture at a sclerotic metaphyseal line is described. Peripheral quantitative computer tomography was used to characterise the presence of multiple stress risers at the distal forearm. Trabecular bone mineral density fluctuated from 34 to 126% compared to neighbouring 2-mm regions. There remain many unanswered questions about optimal bisphosphonate treatment regimens in children with OI. The formation of stress risers following intravenous bisphosphonate treatment raises the hypothesis that a more frequent and low-dose bisphosphonate regimen would provide more uniform dosing of bone in the growing child and reduce the likelihood of fractures compared to current treatment practices.

Being a long-term user of nicotine replacement therapy

DEFF Research Database (Denmark)

Borup, Gitte; Nørgaard, Lotte Stig; Tønnesen, Philip

Background During recent years a gradual shift in the application of nicotine replacement therapy (NRT) has taken place from NRT-products only being recommended to achieve smoking cessation, to now including smoking reduction, and long-term substitution of tobacco with NRT has taken place. This has...... been promoted as a way of achieving harm-reduction in highly nicotine dependent smokers who are unwilling or incapable of quitting all nicotine products, as continued use of NRT is widely accepted as being far less hazardous than continued smoking. To our knowledge no previous research has been done...... of feeling addicted, cost of NRT products and fear of adverse health consequences. Aim of study • To get a thorough understanding of the lived experiences of nicotine dependent long-term NRT users. • To investigate what motivates or discourages quitting NRT. Method Semi-structured interviews with long...

Long-term oxygen therapy: Are we prescribing appropriately?

Directory of Open Access Journals (Sweden)

Mª Rosa Güell Rous

2008-06-01

Full Text Available Mª Rosa Güell RousDepartament de Pneumologia, Hospital de la Santa Creu I de Sant Pau, Barcelona, SpainAbstract: Long-term oxygen therapy (LTOT is the treatment proven to improve survival in chronic obstructive pulmonary disease (COPD patients with chronic respiratory failure. It also appears to reduce the number of hospitalizations, increase effort capacity, and improve health-related quality of life. Standard LTOT criteria are related to COPD patients who have PaO2 <60 mmHg, are in a clinical stable situation, and are receiving optimal pharmacological treatment. According to LTOT guidelines, oxygen should be prescribed for at least 18 hours per day although some authors consider 24 hours would be more beneficial. The benefits of LTOT depend on correction of hypoxemia. Arterial blood gases should be measured at rest. During exercise, an effort test should be done to assure adequate SaO2. During sleep, continuous monitoring of SaO2 and PaCO2 should be performed to confirm correction of SaO2 overnight. An arterial blood gas sample should be taken at awakening to assess PaCO2 in order to prevent hypoventilation from the oxygen therapy. Several issues that need to be addressed are the use of LTOT in COPD patients with moderate hypoxemia, the efficacy of LTOT in patients who desaturate during exercise or during sleep, the optimal dosage of oxygen supplementation, LTOT compliance, and the LTOT prescription in diseases other than COPD.Keywords: long-term oxygen therapy, COPD, oxygen supplementation, chronic respiratory failure, hypoxemia

Stability of rapid maxillary expansion and facemask therapy: a long-term controlled study.

Science.gov (United States)

Masucci, Caterina; Franchi, Lorenzo; Defraia, Efisio; Mucedero, Manuela; Cozza, Paola; Baccetti, Tiziano

2011-10-01

The aim of this prospective controlled study was to evaluate the long-term effects of rapid maxillary expansion and facemask therapy in Class III subjects. Twenty-two subjects (9 boys, 13 girls; mean age, 9.2 years ± 1.6) with Class III disharmony were treated consecutively with rapid maxillary expansion and facemask therapy followed by fixed appliances. The patients were reevaluated at the end of the 2-phase treatment (mean age, 14.5 years ± 1.9) and then recalled about 8.5 years after the end of rapid maxillary expansion and facemask treatment (mean age, 18.7 years ± 2.1). Two groups of controls with untreated Class III malocclusion were used for statistical comparisons of the short-term and long-term intervals. Statistical comparisons were performed with the Mann-Whitney U test. In the long term, no significant differences in maxillary changes were recorded, whereas the treatment group showed significantly smaller increases in mandibular protrusion. The sagittal maxillomandibular skeletal variables maintained significant improvements in the treatment group vs the control groups. In the long term, rapid maxillary expansion and facemask therapy led to successful outcomes in about 73% of the Class III patients. Favorable skeletal changes were mainly due to significant improvements in the sagittal position of the mandible. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Recommendations for long-term home oxygen therapy in children and adolescents

Directory of Open Access Journals (Sweden)

Fabíola V. Adde

2013-01-01

Conclusions: Long-term home oxygen therapy is increasingly common in pediatrics and has many indications. There are relevant particularities when compared to its use in adults, regarding indications, directions for use, and monitoring.

Adjuvant psychological therapy in long-term endocrine conditions.

Science.gov (United States)

Daniels, J; Turner-Cobb, J M

2017-06-01

Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor mental health can lead to compromised self-care, higher utilization of health services, lower rates of adherence, reduced quality of life and ultimately poorer outcomes. Adjuvant psychological therapy offers an effective resource to reduce distress in endocrine conditions. While the vast majority of work in this area has focused on psychological screening and intervention in diabetes, identification and recognition of psychological distress are equally important in other endocrinological conditions, with supportive evidence in polycystic ovary syndrome and Addison's disease. Referral pathways and recommendations set out by UK guidelines and the Department of Health mandate requires greater attention across a wider range of long-term endocrine conditions to facilitate improved quality of life and health outcome. © 2017 John Wiley & Sons Ltd.

Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

Science.gov (United States)

Aleman, Jacomien; Moojen, Dirk Jan F; van Ogtrop, Marc L; Poolman, Rudolf W; Franssen, Eric J F

2018-01-01

Objectives : Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections. In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections. Methods : A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l. Results : 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395). Conclusions : In our population of patients with OIRI long-term treatment with conventionally dosed

Impact of bone turnover markers and/or educational information on persistence to oral bisphosphonate therapy: a community setting-based trial.

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Silverman, S L; Nasser, K; Nattrass, S; Drinkwater, B

2012-03-01

We examined how the use of bone turnover markers and educational information affects persistence of bisphosphonate use in osteoporotic patients. We found that reporting bone turnover results and/or educational information did not affect persistence. Long-term adherence and persistence to osteoporosis medication are poor. We examined whether reporting of bone turnover marker results, education about osteoporosis, or a combination of both would increase persistence to oral bisphosphonates. Two hundred and forty women who were 5 years postmenopausal with BMD at least 2.0 standard deviations below normal were recruited for the study. All women were given a new prescription for alendronate and randomly assigned to one of four groups: (1) bone marker results at baseline, 3 and 12 months; (2) educational materials every month and a membership in the National Osteoporosis Foundation; (3) bone marker and educational information; and (4) control, no information other than usual care. Persistence among randomization groups was tested using survival analysis adjusting for the delay between intervention methods. Of those filling their initial prescription, 95.5% refilled their prescription at the end of the first month, 87% at 3 months, 82% at 6 months, and 78% at 10 months. Overall persistence through 12 months was 54%. There was no difference found among the four groups for persistence time using (p > 0.58). Providing bone turnover marker results is not an effective way to enhance early compliance and persistence with drug therapy. While the women in our study felt that bone marker results and educational information were helpful to them, there was no difference in persistence between those who received either bone marker information and/or educational information and those who did not. Because of the unexpected rate of primary nonadherence, this study may be underpowered.

Bisphosphonate-related osteonecrosis of the jaw: historical, ethical, and legal issues associated with prescribing.

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Faiman, Beth; Pillai, Aiswarya Lekshmi Pillai Chandran; Benghiac, Ana Gabriela

2013-01-01

The long-term effects of many drugs are unknown. Established risks are communicated to patients who participate in clinical trials during the informed consent process. However, unknown and unanticipated side effects of medications may occur years after treatment. Patients with metastatic bone cancer experience an imbalance between tumor cells and the bone marrow microenvironment. Increased cytokine release, osteoclastic activity, and uncoupled osteoblastic activity lead to weakened bone structure and osteolytic lesions. The bisphosphonates are a class of drugs available in IV and oral formulations to treat and prevent bone loss and decrease the risk of skeletal-related events. Intravenous bisphosphonates such as zoledronic acid and pamidronate disodium are approved by the US Food and Drug Administration for the treatment of bone pain and hypercalcemia of malignancy and the prevention of painful bone fractures in patients with metastatic bone cancer. Oral bisphosphonates such as alendronate, risedronate, and etidronate are used to reduce the risk of skeletal fractures in patients with osteoporosis and in breast cancer. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but painful complication of treatment characterized by infection, exposed bone, and poor wound healing. In this article, we discuss BRONJ and identify past, present, and future ethical and legal issues surrounding bisphosphonate administration.

Bisphosphonates and oral pathology II. Osteonecrosis of the jaws: review of the literature before 2005.

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Estefanía Fresco, Ruth; Ponte Fernández, Ruth; Aguirre Urizar, José Manuel

2006-11-01

Bisphosphonates are bone-turnover modulating drugs which are used in the management of a number of bone diseases ranging from osteoporosis to neoplasic pathology-associated osteolysis. In the last years a number of cases of osteonecrosis of the jaws associated with these drugs have been reported. In this review we analyze the cases published in the literature indexed from 2003 to December 2005. During this period 246 cases were reported, being more frequently associated with women in the sixth decade of life. More frequently associated bisphosphonates were the nitrogenated bisphosphonates (pamidronate, zolendronic acid) and the most common oral antecedent was a dental extraction. Nevertheless more than 25% of the cases were spontaneous. The most frequent site was the mandible and most of the cases presented clinical evidence of bone exposure and pain. Different treatments have been proposed with different antibiotic therapies with or without surgery, showing in general terms an uncertain prognosis with low healing rates.

Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study.

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Lewis, Joshua R; Barre, Deka; Zhu, Kun; Ivey, Kerry L; Lim, Ee Mun; Hughes, Jeff; Prince, Richard L

2014-11-01

Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance-related function in a post hoc analysis of a longitudinal population-based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25-3.77; p = 0.006 and 1.95; 95% CI, 1.20-3.16; p = 0.007, respectively. In the replication study, long-term PPI use was associated with an increased risk of self-reported falling; AOR, 1.51; 95% CI, 1.00-2.27; p = 0.049. No association of long-term PPI therapy with bone structure was observed; however, questionnaire-assessed falls-associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p risk in subjects on long-term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy. © 2014 American Society for Bone and Mineral Research.

Ethnic Similarity, Therapist Adherence, and Long-Term Multisystemic Therapy Outcomes

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Chapman, Jason E.; Schoenwald, Sonja K.

2011-01-01

The current study investigated relations among ethnic similarity in caregiver-therapist pairs of youth participating in Multisystemic Therapy, therapist adherence, and youth long-term behavioral and criminal outcomes. Participants were 1,979 youth and families treated by 429 therapists across provider organizations in 45 sites. Relations were…

Bisphosphonate-associated atypical sub-trochanteric femur fractures: paired bone biopsy quantitative histomorphometry before and after teriparatide administration.

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Miller, Paul D; McCarthy, Edward F

2015-04-01

Bisphosphonate-associated atypical sub-trochanteric femur fractures (ASFF) may be seen with long-term bisphosphonate use, though these fractures are also seen in patients never exposed to bisphosphonates. One theory for the mechanism of action whereby bisphosphonates may induce these ASFF is over-suppression of bone turnover. Bisphosphonates suppress bone turnover, but in bisphosphonate clinical trials, over-suppression defined whether by maintaining the biochemical markers of bone turnover below the defined reference range or by quantitative bone histomorphometry, has not been observed. We studied 15 clinic patients referred to The Colorado Center for Bone Research (CCBR) after they had a bisphosphonate-associated ASFF and performed quantitative bone histomorphometry both before and after 12 months of teriparatide (20µg SQ/day). All patients had been on long-term alendronate (mean = 7 years, range: 6-11 years) and had already had intramedullary rods placed when first seen (6 weeks to 7 months after rod placement). Alendronate had been discontinued in all patients at the time of their first clinic visit to CCBR. All of the fractures fulfilled The American Society for Bone and Mineral Research major radiological criteria for ASFF. Three key dynamic histomorphometric features show that 7 of the 15 patients had unmeasurable bone formation, mineralizing surface, and mineral apposition, while the other 8 patients had measurable dynamic parameters; although for all 15 patients, the mean values for all 3 dynamic parameters was far below the average for the published normal population. Administration of teriparatide was associated with an increase in all 3 dynamic histomorphometric parameters. Baseline bone turnover markers did not correlate with the baseline histomorphometry. While there is heterogeneity in the bone turnover in patients with bisphosphonate ASFF, there is a large portion in this uncontrolled series that had absent bone turnover at the standard biopsy site

Off-trial evaluation of bisphosphonates in patients with metastatic breast cancer

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Liauw, Winston; Segelov, Eva; Lih, Anna; Dunleavy, Ms Ruth; Links, Matthew; Ward, Robyn

2005-01-01

Bisphosphonate therapy has been readily accepted as standard of care for individuals with bone metastases from breast cancer. In this study we determined whether the proportion of patients experiencing a skeletal related event (SRE) in a clinical practice population was similar to that observed in phase III randomized controlled studies. A retrospective chart review was conducted of 110 patients receiving intravenous bisphosphonates for advanced breast cancer. The proportion of patients experiencing at least one SRE after 12 months of therapy was determined. SRE included vertebral or non-vertebral fracture, cord compression, surgery and/or radiotherapy to bone. The proportion of patients who had an SRE was 30% (28 individuals) and the median time to first event was greater than 350 days. Non-vertebral events and radiotherapy were the most frequent type of SRE, while cord compression and hypercalcaemia were rare (1%). Most patients in the study had bone-only disease (58.2%) and most had multiple bone lesions. In the first 12 months the mean duration of exposure to intravenous bisphosphonates was 261 days and most patients remained on treatment until just before death (median 27 days). This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials. We attribute this lower rate to observational bias. In the clinical trial setting it is possible that over-detection of skeletal events occurs due to the utilisation of regular skeletal survey or radionucleotide bone scan, whereas these procedures are not routine in clinical practice. Phase IV observational studies need to be conducted to determine the true benefits of bisphosphonate therapy in order to implement rationale use of bisphosphonates

Long-term carbimazole pretreatment reduces the efficacy of radioiodine therapy

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C Shivaprasad

2015-01-01

Full Text Available Introduction: Data from several studies suggest that pretreatment with antithyroid drugs (ATD before 131 I increases the risk of treatment failure. This effect has been demonstrated more consistently with propylthiouracil than with carbimazole (CMZ or methimazole (MMI. Men with Graves′ disease (GD have a lower rate of remission with 131 I compared to women and the impact of long-term ATD pretreatment on the success of 131 I is unknown. The objective of our study was to compare the efficacy of fixed doses of radioiodine between patients with and without long-term CMZ pretreatment. Materials and Methods: We performed a retrospective study on 335 male patients with GD treated with 131 I from 1998 to 2008. 148 patients had been pretreated with CMZ, and the remaining 187 patients received 131 I without pretreatment. We compared the success rate of a single dose of 131 I, between patients with and without long-term CMZ pretreatment. Results: The success rate of a single dose of 131 I was significantly higher in patients without pretreatment than in patients who were pretreated with CMZ (91.4% vs. 82.3%, P = 0.01. The rate of hypothyroidism in the first 6 months after 131 I therapy was significantly higher in patients without pretreatment (55.1% vs. 44.6%, P = 0.05. There was also a trend for higher cumulative rate of hypothyroidism at last follow-up in nonpretreated patients (78.1% vs. 69.7%. Conclusion: Male patients with Graves′ hyperthyroidism pretreated with CMZ have lower efficacy with 131I therapy compared to nonpretreated patients. CMZ pretreatment given for a prolonged period reduces the efficacy of 131 I therapy.

Bisphosphonates and their clinical implications in endodontic therapy.

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Moinzadeh, A-T; Shemesh, H; Neirynck, N A M; Aubert, C; Wesselink, P R

2013-05-01

This review gives an overview of the factors that may play a role in the development of osteonecrosis of the jaw in patients treated with bisphosphonates (BPs) and undergoing nonsurgical endodontic treatment as well as some recommendations for its prevention. BPs are a widely prescribed group of drugs for diverse bone diseases. The occasional but devastating adverse effect of these drugs has been described as bisphosphonate-related osteonecrosis of the jaw (BRONJ). As this condition is debilitating and difficult to treat, all efforts should be made to prevent its occurence in patients at risk. The main triggering event is considered to be dental extraction. Even though nonsurgical endodontic treatment appears to be a relatively safe procedure, care remains essential. After an overview of this class of drugs, the clinical presentation, epidemiology and pathogenesis of BRONJ, as well as the possible risk factors associated with its development after nonsurgical endodontic treatment will be described. Finally, several strategies will be proposed for the prevention of BRONJ during nonsurgical endodontic treatment. © 2012 International Endodontic Journal. Published by Blackwell Publishing Ltd.

Anabolic Therapy for the Treatment of Osteoporosis in Childhood.

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Ward, Leanne M; Rauch, Frank

2018-06-01

Numerous forms of osteoporosis in childhood are characterized by low bone turnover (for example, osteoporosis due to neuromuscular disorders and glucocorticoid exposure). Anti-resorptive therapy, traditionally used to treat osteoporosis in the young, is associated with further reductions in bone turnover, raising concerns about the long-term safety and efficacy of such therapy. These observations have led to increasing interest in the role of anabolic therapy to treat pediatric osteoporosis. While growth hormone and androgens appears to be relatively weak anabolic modulators of bone mass, emerging therapies targeting bone formation pathways (anti-transforming growth factor beta antibody and anti-sclerostin antibody) hold considerable promise. Teriparatide remains an attractive option that merits formal study for patients post-epiphyseal fusion, although it must be considered that adult studies have shown its effect is blunted when administered following bisphosphonate therapy. Mechanical stimulation of bone through whole body vibration therapy appears to be much less effective than bisphosphonate therapy for treating osteoporosis in children. New anabolic therapies which target important pathways in skeletal metabolism merit further study in children, including their effects on fracture risk reduction and after treatment discontinuation.

Management strategy for symptomatic bisphosphonate-associated incomplete atypical femoral fractures.

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Saleh, Anas; Hegde, Vishal V; Potty, Anish G; Schneider, Robert; Cornell, Charles N; Lane, Joseph M

2012-07-01

Long-term bisphosphonate use has often been associated with atypical femoral fractures. These fractures evolve from incomplete femoral fractures. A previous study demonstrated that the presence of a radiolucent line in an incomplete fracture can indicate a high risk of progression to complete fracture. The aim of this study is to present a management strategy for symptomatic bisphosphonate-associated incomplete atypical femoral fractures. Specific study questions include the following: (1) Is there a difference in the prognosis of these fractures based on the presence or absence of a radiolucent fracture line? (2) Can treatment with teriparatide assist in clinical/radiographic healing of these incomplete fractures? (3) Is there a characteristic biochemical profile in these patients? We retrospectively examined all femur radiographs ordered by the metabolic bone disease service at our hospital between July 1, 2006 and July 1, 2011 and identified 10 patients with a total of 14 incomplete fractures. Nine patients received bisphosphonates for a mean duration of 10 ± 5 years (range, 4-17). The mean follow-up since the time of diagnosis was 20 ± 11 months (range, 6-36 months). Five fractures did not have a radiolucent fracture line and were treated conservatively with partial weight-bearing restrictions and pharmacologic therapy. All five of these fractures healed with conservative management. Nine fractures had a radiolucent fracture line, and only two of these were treated successfully with conservative management including teriparatide. Six of the eight patients with a radiolucent line elected for surgical prophylaxis after 3 months of conservative management, whereas one patient underwent surgical prophylaxis without a trial of conservative management. Regarding the biochemical profiles, bone turnover markers for our patient cohort were in the lower quartile. Fractures without a radiolucent line appear to respond to conservative management and not

The Pharmacological Profile of a Novel Highly Potent Bisphosphonate, OX14 (1-Fluoro-2-(Imidazo-[1,2-α]Pyridin-3-yl)-Ethyl-Bisphosphonate).

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Lawson, Michelle A; Ebetino, Frank H; Mazur, Adam; Chantry, Andrew D; Paton-Hough, Julia; Evans, Holly R; Lath, Darren; Tsoumpra, Maria K; Lundy, Mark W; Dobson, Roy Lm; Quijano, Michael; Kwaasi, Aaron A; Dunford, James E; Duan, Xuchen; Triffitt, James T; Jeans, Gwyn; Russell, R Graham G

2017-09-01

Bisphosphonates are widely used in the treatment of clinical disorders characterized by increased bone resorption, including osteoporosis, Paget's disease, and the skeletal complications of malignancy. The antiresorptive potency of the nitrogen-containing bisphosphonates on bone in vivo is now recognized to depend upon two key properties, namely mineral binding affinity and inhibitory activity on farnesyl pyrophosphate synthase (FPPS), and these properties vary independently of each other in individual bisphosphonates. The better understanding of structure activity relationships among the bisphosphonates has enabled us to design a series of novel bisphosphonates with a range of mineral binding properties and antiresorptive potencies. Among these is a highly potent bisphosphonate, 1-fluoro-2-(imidazo-[1,2 alpha]pyridin-3-yl)-ethyl-bisphosphonate, also known as OX14, which is a strong inhibitor of FPPS, but has lower binding affinity for bone mineral than most of the commonly studied bisphosphonates. The aim of this work was to characterize OX14 pharmacologically in relation to several of the bisphosphonates currently used clinically. When OX14 was compared to zoledronate (ZOL), risedronate (RIS), and minodronate (MIN), it was as potent at inhibiting FPPS in vitro but had significantly lower binding affinity to hydroxyapatite (HAP) columns than ALN, ZOL, RIS, and MIN. When injected i.v. into growing Sprague Dawley rats, OX14 was excreted into the urine to a greater extent than the other bisphosphonates, indicating reduced short-term skeletal uptake and retention. In studies in both Sprague Dawley rats and C57BL/6J mice, OX14 inhibited bone resorption, with an antiresorptive potency equivalent to or greater than the comparator bisphosphonates. In the JJN3-NSG murine model of myeloma-induced bone disease, OX14 significantly prevented the formation of osteolytic lesions (p < 0.05). In summary, OX14 is a new, highly potent bisphosphonate with lower bone binding

Long-term outcome of patients with chronic pancreatitis treated with micronutrient antioxidant therapy.

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Rupasinghe, Sukitha Namal; Siriwardena, Ajith K

2017-04-01

Micronutrient antioxidant therapy did not relieve pain in a European randomized trial of patients with chronic pancreatitis without malnutrition. However, intervention was undertaken only for 6 months leaving unanswered the question of whether long-term antioxidant therapy may modulate chronic pancreatitis. The aim of this study is to assess the outcome of long-term use of micronutrient antioxidant therapy in patients with chronic pancreatitis. This is a single center clinical cohort report of patients with chronic pancreatitis prescribed micronutrient antioxidant therapy and followed for up to 10 years. Data were collected on demographic detail, clinic pain assessment, insulin requirements, interventions and outcome. A group of 30 patients with a diagnosis of chronic pancreatitis constitute the study population. Median age at time of diagnosis was 40 years (range 14-66); 19 (63%) were male and the median duration of symptoms was 2 years (range 0-18). Alcohol was the dominant cause in 22 (73%) patients and 16 (53%) patients were Cambridge stage 1. Twenty-four (80%) patients had pain at presentation. During antioxidant treatment of 4 years (range 1-10), pain decreased but the proportion with abdominal pain compared to those who were pain-free remained constant (P=0.16; two-way ANOVA with Bonferroni correction). There was a significant increase in requirement for insulin (P=0.028) with time together with use of both endoscopic and surgical interventions. This is the first study to report long-term disease-specific outcome in patients with chronic pancreatitis prescribed micronutrient antioxidant therapy. There appears to be no effect of intervention on outcome.

Efficacy of long-term omalizumab therapy in patients with severe asthma.

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Saji, Junko; Yamamoto, Takahito; Arai, Motonaka; Mineshita, Masamichi; Miyazawa, Teruomi

2017-03-01

The efficacy of omalizumab, an anti-immunoglobulin E (IgE) antibody, has been studied in patients with severe bronchial asthma. We conducted a study to evaluate, on the basis of both objective and subjective measures, the efficacy of omalizumab as a long-term therapy in patients with severe and persistent asthma. Omalizumab was administered subcutaneously every two or four weeks. The results of pulmonary function tests, Asthma Control Test (ACT) and Asthma Health Questionnaire (AHQ)-33 scores, the dosage of methylprednisolone during the 12-month treatment period, and the number of emergency visits prior to the start of treatment with omalizumab were compared in patients pre- and post-treatment with omalizumab. Fourteen patients were enrolled in the study between June 2010 and February 2012. Ten patients completed the study. With omalizumab treatment, there was no improvement in lung function; however, the number of emergency visits (19.3 before treatment vs. 1.2 after treatment, p=0.020) and the dosage of methylprednisolone (871.5mg before treatment vs. 119.0mg after treatment, p=0.046) decreased significantly. ACT and AHQ-33 scores at 16 weeks after treatment were significantly better than baseline scores. Four patients continued treatment with omalizumab for four years, and a reduction in their corticosteroid usage was noted. Long-term omalizumab therapy in our patients was found to significantly reduce corticosteroid usage and the number of emergency visits. Long-term omalizumab therapy was effective and might have potential to reduce the frequency of asthma exacerbations. The trial has not been registered because it is not an intervention study. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

New bisphosphonate labeled with Iodine-131 for the palliative therapy for bone metastases pain

International Nuclear Information System (INIS)

Prats Capote, Anaís; Perera Pintado, Alejandro; León, Mariela; Hernández González, Ignacio; Leyva Montaña, René; Mocelo Castell, Raúl; O'Reilly, Beatriz; Calderón, Osmar; Griffith Pérez, Yoel; García Batle, Marisé; Rodríguez Tanty, Chryslaine

2016-01-01

The aim of this work was to obtain new bisphosphonate marked with 131I suitable for palliative treatment of bone metastases pain characteristics. Materials and Methods: It started with aromatic amino acids and the synthesis consisted of three stages: 1) Protection of amino groups by acetylation; 2) phosphonation protected amino acids with a mixture of phosphorous acid and phosphorus pentachloride; 3) Lack of protection of the amino groups by basic hydrolysis. The compounds obtained were characterized by IR, 1H NMR, RMN13-C mass. Los spectrometry bisphosphonic acids obtained were labeled with 131I using chloramine T and iodogen as oxidants. Stability of labeled compounds in aqueous solution was studied serum. 3 mg of 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1-bisphosphonic acid labeled of 131I were administered to male wistar rats (170-190 g) through a lateral tail vein. The scintigraphic study was conducted at 2, 6 and 12 hours. Results: The yield of the reactions of the amino group protection four compounds ranged from 75 to 80%, while the phosphonation was between 50 and 60%. The radiochemical purity of 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1- bisphosphonic acid labeled with 131I was (91.5 ± 1.4)% and its stability was satisfactory for 72h. Scintigraphic images suggest excretion by the kidneys of the compound and from 12 h post-administration begin to visualize bone structures of the animal, suggesting that the compound exhibits affinity for these tissues. Conclusions: A novel synthesis method with modifications that yielded the sodium salts of bisphosphonic acids starting from the respective aromatic amino acids was developed. 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1-bisphosphonic acid 131I labeled was stable up to 72h and showed affinity for bone tissue. (author)

Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

International Nuclear Information System (INIS)

Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

2006-01-01

Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

Long-term follow-up in dogs with idiopathic eosinophilic bronchopneumopathy treated with inhaled steroid therapy.

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Canonne, A M; Bolen, G; Peeters, D; Billen, F; Clercx, C

2016-10-01

Treatment of canine idiopathic eosinophilic bronchopneumopathy mainly consists of long-term oral corticosteroid therapy. To avoid side effects, inhaled steroid therapy has been increasingly used but long-term clinical response and potential side effects are sparsely described. Description of clinical response and side effects with long-term fluticasone in dogs with eosinophilic bronchopneumopathy. Case series of dogs with eosinophilic bronchopneumopathy and treated with fluticasone monotherapy for at least 6 months. Clinical response and side effects assessed by physical examination, standardised questionnaire and ACTH (corticotropin) stimulation test. Eight dogs were treated for between 6 months and 5 years. Cough initially improved in all dogs; two dogs remained free of clinical signs, three were well controlled, but three showed severe relapse. Pituitary-adrenal axis inhibition occurred in two dogs treated with fluticasone monotherapy for more than 2 years; only one dog had clinical signs of iatrogenic hyperadrenocorticism. Fluticasone monotherapy allows initial improvement or remission in the majority of dogs but long-term treatment fails to resolve the cough in some individuals. In addition, such therapy may induce pituitary-adrenal axis inhibition. Prospective larger and randomised studies including both fluticasone and orally-treated dogs are needed to define the optimal treatment. © 2016 British Small Animal Veterinary Association.

Stereotactic Radiation Therapy for Benign Meningioma: Long-Term Outcome in 318 Patients

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Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg, Marburg (Germany); Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt (Germany); Henzel, Martin [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg, Marburg (Germany); Surber, Gunar; Hamm, Klaus [Department for Stereotactic Neurosurgery and Radiosurgery, HELIOS Klinikum Erfurt, Erfurt (Germany); Engenhart-Cabillic, Rita [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg, Marburg (Germany)

2014-07-01

Purpose: To investigate the long-term outcome of stereotactic-based radiation therapy in a large cohort of patients with benign intracranial meningiomas. Methods and Materials: Between 1997 and 2010, 318 patients with histologically confirmed (44.7%; previous surgery) or imaging-defined (55.3%) benign meningiomas were treated with either fractionated stereotactic radiation therapy (79.6%), hypofractionated stereotactic radiation therapy (15.4%), or stereotactic radiosurgery (5.0%), depending on tumor size and location. Local control (LC), overall survival (OS), cause-specific survival (CSS), prognostic factors, and toxicity were analyzed. Results: The median follow-up was 50 months (range, 12-167 months). Local control, OS, and CSS at 5 years were 92.9%, 88.7%, and 97.2%, and at 10 years they were 87.5%, 74.1%, and 97.2%, respectively. In the multivariate analysis, tumor location (P=.029) and age >66 years (P=.031) were predictors of LC and OS, respectively. Worsening of pre-existing neurologic symptoms immediately after radiation therapy occurred in up to 2%. Clinically significant acute toxicity (grade 3°) occurred in 3%. Only grade 1-2 late toxicity was observed in 12%, whereas no new neurologic deficits or treatment-related mortality were encountered. Conclusions: Patients with benign meningiomas predominantly treated with standard fractionated stereotactic radiation therapy with narrow margins enjoy excellent LC and CSS, with minimal long-term morbidity.

Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials.

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Hald, Jannie D; Evangelou, Evangelos; Langdahl, Bente L; Ralston, Stuart H

2015-05-01

Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2  = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2  = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2  = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition. © 2014 American Society for

BISPHOSPHONATES IN LANGERHANS CELL HISTIOCYTOSIS: AN INTERNATIONAL RETROSPECTIVE CASE SERIES

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Deepak Chellapandian

2016-07-01

Full Text Available Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH, which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results: Ten patients (77% had a single system bone disease, and 3 (23% had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years. Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve  (92% achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years. One patient did not respond. No major adverse effects were reported in this series.  Conclusion: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted.

[Long-term digitalis therapy of elderly patients. Is digitalization unnecessary in the majority of cases?].

Science.gov (United States)

Häcki, M A; Angehrn, W; Cavegn, H R; Brändli, O

1982-12-18

More than 40% of patients hospitalized in the Wald Altitude Clinic of Zürich are already on long-term digitalis therapy upon admission. During a 6 month period long-term digoxin therapy was discontinued in 97 patients (age 74 +/- 9 years) with stable cardiac insufficiency (NYHA class I-III) and sinus rhythm. During the hospitalization (37 +/- 20 days), clinical signs and symptoms, body weight, radiological heart size, and systolic time intervals were monitored. After an observation period of one week, digoxin was discontinued in all patients. Body weight, cardio-thoracic ratio and left ventricular ejection time remained unchanged after cessation of digoxin therapy during hospitalization. The pre-ejection period showed a significant increase from 89 +/- 17 to 95 +/- 19 msec. Six patients were re-instituted on digoxin therapy, 3 due to progressive cardiac insufficiency, 2 due to atrial fibrillation, and 1 at his own request. After telephone follow-up six months later with the family physician an additional 20 patients were put back on digitalis. Among the total of 26 patients requiring further digitalization an absolute indication was found only in 12 (14%), 8 due to progressive cardiac insufficiency and 4 due to atrial fibrillation. In this study digitalis therapy could be discontinued without ill effects in 86% of elderly clinically stable patients in sinus rhythm. The authors therefore recommend a more cautious use of long-term digitalis therapy and, in already digitalized patients in sinus rhythm, a controlled trial period of discontinuation.

Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

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Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

2007-09-01

In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates.

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Olszynski, Wojciech P; Adachi, Jonathan D; Davison, K Shawn

2014-01-01

The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly (P disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies.

Differential response of idiopathic sporadic tumoral calcinosis to bisphosphonates

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Karthik Balachandran

2014-01-01

Full Text Available Context: Tumoral calcinosis is a disorder of phosphate metabolism characterized by ectopic calcification around major joints. Surgery is the current treatment of choice, but a suboptimal choice in recurrent and multicentric lesions. Aims: To evaluate the efficacy of bisphosphonates for the management of tumoral calcinosis on optimized medical treatment. Settings and Design: The study was done in the endocrine department of a tertiary care hospital in South India. We prospectively studied two patients with recurrent tumoral calcinosis who had failed therapy with phosphate lowering measures. Materials and Methods: After informed consent, we treated both patients with standard age adjusted doses of bisphosphonates for 18 months. The response was assessed by X ray and whole body 99mTc-methylene diphosphonate bone scan at the beginning of therapy and at the end of 1 year. We also estimated serum phosphate levels and urinary phosphate to document serial changes. Results: Two patients (aged 19 and 5 years with recurrent idiopathic hyperphosphatemic tumoral calcinosis, following surgery were studied. Both patients had failed therapy with conventional medical management − low phosphate diet and phosphate binders. They had restriction of joint mobility. Both were given standard doses of oral alendronate and parenteral pamidronate respectively for more than a year, along with phosphate lowering measures. At the end of 1 year, one of the patients had more than 95% and 90% reduction in the size of the lesions in right and left shoulder joints respectively with total improvement in range of motion. In contrast, the other patient (5-year-old had shown no improvement, despite continuing to maintain normophosphatemia following treatment. Conclusions: Bisphosphonate therapy in tumoral calcinosis is associated with lesion resolution and may be used as a viable alternative to surgery, especially in cases with multicentric recurrence or treatment failure to other

Optimal Timing of Bisphosphonate Administration in Combination with Samarium-153 Oxabifore in the Treatment of Painful Metastatic Bone Disease

International Nuclear Information System (INIS)

Rasulova, Nigora; Lyubshin, Vladimir; Arybzhanov, Dauranbek; Sagdullaev, Sh.; Krylov, Valery; Khodjibekov, Marat

2013-01-01

While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide therapy is widely used for treatment of painful bone metastases. Combined radionuclide therapy with bisphosphonates has demonstrated improved effectiveness in achieving bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates alone. However, there are conflicting reports as to whether bisphosphonates adversely influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline study, as well as in combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not provide any statistically significant difference in urinary excretion of Sm-153 between the two groups. It may be noted that the exact temporal sequence of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied. One of the side effects of bisphosphonates is transient flare effect on bone pain. Radionuclide therapy may also have similar side effect. Keeping in view the above the current study was designed with the main objective of determining the exact timing of bisphosphonate administration in patients receiving combined therapy so as to achieve optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP) and Zoledronic acid were divided into three groups according to the timing of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid 7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153 oxabifore was administered

Nonsurgical Outpatient Therapies for the Management of Female Stress Urinary Incontinence: Long-Term Effectiveness and Durability

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G. Willy Davila

2011-01-01

Results. Thirty-two clinical trial reports were included. Prospective long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months. Poor initial tolerability with duloxetine resulted in substantial discontinuation. Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements, generally good tolerability, and safety. Conclusions. Conservative therapy is an appropriate initial approach for female SUI, but if therapy fails, radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery.

The Pharmacological Profile of a Novel Highly Potent Bisphosphonate, OX14 (1‐Fluoro‐2‐(Imidazo‐[1,2‐α]Pyridin‐3‐yl)‐Ethyl‐Bisphosphonate)

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Ebetino, Frank H; Mazur, Adam; Chantry, Andrew D; Paton‐Hough, Julia; Evans, Holly R; Lath, Darren; Tsoumpra, Maria K; Lundy, Mark W; Dobson, Roy LM; Quijano, Michael; Kwaasi, Aaron A; Dunford, James E; Duan, Xuchen; Triffitt, James T; Jeans, Gwyn; Russell, R Graham G

2017-01-01

ABSTRACT Bisphosphonates are widely used in the treatment of clinical disorders characterized by increased bone resorption, including osteoporosis, Paget's disease, and the skeletal complications of malignancy. The antiresorptive potency of the nitrogen‐containing bisphosphonates on bone in vivo is now recognized to depend upon two key properties, namely mineral binding affinity and inhibitory activity on farnesyl pyrophosphate synthase (FPPS), and these properties vary independently of each other in individual bisphosphonates. The better understanding of structure activity relationships among the bisphosphonates has enabled us to design a series of novel bisphosphonates with a range of mineral binding properties and antiresorptive potencies. Among these is a highly potent bisphosphonate, 1‐fluoro‐2‐(imidazo‐[1,2 alpha]pyridin‐3‐yl)‐ethyl‐bisphosphonate, also known as OX14, which is a strong inhibitor of FPPS, but has lower binding affinity for bone mineral than most of the commonly studied bisphosphonates. The aim of this work was to characterize OX14 pharmacologically in relation to several of the bisphosphonates currently used clinically. When OX14 was compared to zoledronate (ZOL), risedronate (RIS), and minodronate (MIN), it was as potent at inhibiting FPPS in vitro but had significantly lower binding affinity to hydroxyapatite (HAP) columns than ALN, ZOL, RIS, and MIN. When injected i.v. into growing Sprague Dawley rats, OX14 was excreted into the urine to a greater extent than the other bisphosphonates, indicating reduced short‐term skeletal uptake and retention. In studies in both Sprague Dawley rats and C57BL/6J mice, OX14 inhibited bone resorption, with an antiresorptive potency equivalent to or greater than the comparator bisphosphonates. In the JJN3‐NSG murine model of myeloma‐induced bone disease, OX14 significantly prevented the formation of osteolytic lesions (p < 0.05). In summary, OX14 is a new, highly potent

Prediction of loss to follow-up in long-term supportive periodontal therapy in patients with chronic periodontitis.

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Di Wu

Full Text Available This study examined the predictors of loss to follow-up in long-term supportive periodontal therapy in patients with chronic periodontitis.A total of 280 patients with moderate to severe chronic periodontitis in a tertiary care hospital in China were investigated and followed over the course of study. Questionnaires on clinical and demographic characteristics, self-efficacy for oral self-care and dental fear at baseline were completed. Participants were followed to determine whether they could adhere to long-term supportive periodontal therapy. Binary logistic regression analysis was used to examine the association between clinical and demographic characteristics, self-efficacy for oral self-care, dental fear and loss to follow-up in long-term supportive periodontal therapy.The loss to follow-up in long-term supportive periodontal therapy was significantly associated with age [adjusted OR = 1.042, 95% confidence interval (CI: 1.012-1.074, p = 0.006], severe periodontitis [adjusted OR = 4.892, 95%CI: 2.280-10.499, p<0.001], periodontal surgery [adjusted OR = 11.334, 95% CI: 2.235-57.472, p = 0.003], and middle and low-scoring of self-efficacy scale for self-care groups. The adjusted ORs of loss to follow-up for the middle- (54-59 and low-scoring groups (15-53 were 71.899 (95%CI: 23.926-216.062, p<0.001 and 4.800 (95% CI: 2.263-10.182, p<0.001, respectively, compared with the high-scoring SESS group (60-75.Age, severity of periodontitis, periodontal surgery and the level of self-efficacy for self-care may be effective predictors of loss to follow-up in long-term supportive periodontal therapy in patients with chronic periodontitis.

Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic

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Y. Lalatonne

2010-01-01

Full Text Available A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI and a therapeutic agent (bisphosphonates into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe2O3 nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2∗ contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63 show that γFe2O3@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.

Comparison of Long-Term Outcomes in Adolescents with Anorexia Nervosa Treated with Family Therapy

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Lock, James; Couturier, Jennifer; Agras, W. Stewart

2006-01-01

Objective: To describe the relative effectiveness of a short versus long course of family-based therapy (FBT) for adolescent anorexia nervosa at long-term follow-up. Method: This study used clinical and structured interviews to assess psychological and psychosocial outcomes of adolescents (ages 12-18 years at baseline) who were previously treated…

Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus.

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Medeiros, Sheila de Oliveira; Abreu, Celina Monteiro; Delvecchio, Rodrigo; Ribeiro, Anísia Praxedes; Vasconcelos, Zilton; Brindeiro, Rodrigo de Moraes; Tanuri, Amilcar

2016-04-01

Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years. Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group. CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment. The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo. © ISFM and AAFP 2015.

Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

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2011-07-14

Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

Effect of Short- and Long-Term Play Therapy Services on Teacher-Child Relationship Stress

Science.gov (United States)

Ray, Dee C.; Henson, Robin K.; Schottelkorb, April A.; Brown, April Garofano; Muro, Joel

2008-01-01

The purpose of the present study was to explore the effect of both short- and long term Child-Centered Play Therapy on teacher-student relationship stress. Teachers identified 58 students exhibiting emotional and behavioral difficulties who were randomly assigned to one of two treatment groups. Students in the short-term intensive play therapy…

Long-term Compliance with Oral 5-aminosalicylic Acid Therapy and Risk of Disease Recurrence in Patients with Ulcerative Colitis

DEFF Research Database (Denmark)

Prosberg, Michelle V; Vester-Andersen, Marianne K; Andersson, Mikael

2016-01-01

BACKGROUND: Noncompliance to long-term medical therapy is a well-known problem among patients treated for ulcerative colitis, but studies of long-term consequences in unselected patients are lacking. The authors aimed to determine the risk of recurrence according to long-term compliance with oral 5...

Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.

Science.gov (United States)

Sato, Atsuko; Ouellet, Jean; Muneta, Takeshi; Glorieux, Francis H; Rauch, Frank

2016-05-01

Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. However, it is unclear whether this treatment decreases the risk of developing scoliosis. We retrospectively evaluated spine radiographs and charts of 437 patients (227 female) with OI caused by mutations in COL1A1 or COL1A2 and compared the relationship between scoliosis, genotype and bisphosphonate treatment history. At the last follow-up (mean age 11.9 [SD: 5.9] years), 242 (55%) patients had scoliosis. The prevalence of scoliosis was highest in OI type III (89%), followed by OI type IV (61%) and OI type I (36%). Moderate to severe scoliosis (Cobb angle ≥25°) was rare in individuals with COL1A1 haploinsufficiency mutations but was present in about two fifth of patients with triple helical glycine substitutions or C-propeptide mutations. During the first 2 to 4years of bisphosphonate therapy, patients with OI type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in OI types I and IV bisphosphonate treatment was not associated with a change in Cobb angle progression rates. At skeletal maturity, the prevalence of scoliosis (Cobb angle >10°) was similar in patients who had started bisphosphonate treatment early in life (before 5.0years of age) and in patients who had started therapy later (after the age of 10.0years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in OI type III but there was no evidence of a positive effect on scoliosis in OI types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any OI type. Copyright © 2016 Elsevier Inc. All rights reserved.

Atypical femur fractures associated with bisphosphonates: from prodrome to resolution

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Braulio Sastre-Jala

2015-10-01

Full Text Available Atypical fractures related to the prolonged use of bisphosphonates are caused by low energy mechanisms and are characterized by oblique and transverse lines and frequent bilateralism. We present a clinical case of a patient who we believe illustrates, both in clinical and radiological aspects, the new definition of atypical femur fracture related to treatment using bisphosphonates treated conservatively and successfully with discharge and teriparatide 20 mcg/80 mcl s.c./24h. The appearance of painful symptoms in the upper thigh, especially if bilateral, in patients treated with bisphosphonates for long periods of time, makes it necessary to dismiss bone lesions that might otherwise suggest atypical fracture. In those cases where the fracture is incomplete, restoring bone metabolism through the administration of teriparatide 20 mcg/80 mcl s.c./24h could prevent displaced fractures.

Comparison of raloxifene and bisphosphonates based on adherence and treatment satisfaction in postmenopausal Asian women.

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Pasion, Ellewellyn G; Sivananthan, Shanmugam K; Kung, Annie Wai-Chee; Chen, Sung-Hsiung; Chen, Yen-Jen; Mirasol, Roberto; Tay, Boon Keng; Shah, Ghazanfar Ali; Khan, Mansoor Ali; Tam, Frances; Hall, Belinda J; Thiebaud, Daniel

2007-01-01

We evaluated adherence with raloxifene therapy compared with daily bisphosphonate in Asian postmenopausal women at increased risk of osteoporotic fractures. In this 12-month observational study conducted in Asia (Hong Kong, Malaysia, Pakistan, Philippines, Singapore, Taiwan), 984 postmenopausal women (aged 55 years or older) were treated with raloxifene 60 mg/day (n = 707; 72%) or daily bisphosphonate (alendronate 10 mg/day; n = 206; 21%, or risedronate 5 mg/day; n = 71; 7%) during their normal course of care. Patients were assessed at baseline, 6, and 12 months. Baseline characteristics (including age, race, education, menopausal status, and baseline fractures) were comparable between the raloxifene and bisphosphonate groups. More women on raloxifene completed the study compared with those on bisphosphonate (50.2% versus 37.5%; P < 0.001). Patients also took raloxifene for a longer period than bisphosphonate (median, 356 versus 348 days; P = 0.011). Compared with those taking bisphosphonate, significantly fewer patients taking raloxifene discontinued the study because of stopping treatment (5.7% versus 10.1%, P = 0.017) or changing treatment (2.8% versus 9.7%, P < 0.001). Inconvenient dosing was reported as a primary reason for discontinuation due to stopping or changing treatment in 19 (6.9%) bisphosphonate patients compared with 0 raloxifene patients. The percentage of patients who had consumed 80% or more of their study medication was similar for raloxifene patients (48-56 weeks; 95.2%) and bisphosphonate patients (48-56 weeks; 93.3%). More raloxifene patients responded that they were satisfied with their medication than bisphosphonate patients at 48-56 weeks (P = 0.002). We concluded that Asian postmenopausal women at increased risk of osteoporotic fractures showed a greater propensity to remain on raloxifene compared with bisphosphonate. The women on raloxifene exhibited lower discontinuation rates and higher treatment satisfaction.

Bisphosphonate associated osteonecrosis of the jaw.

Science.gov (United States)

Khan, Aliya A; Sándor, George K B; Dore, Edward; Morrison, Archibald D; Alsahli, Mazen; Amin, Faizan; Peters, Edmund; Hanley, David A; Chaudry, Sultan R; Lentle, Brian; Dempster, David W; Glorieux, Francis H; Neville, Alan J; Talwar, Reena M; Clokie, Cameron M; Mardini, Majd Al; Paul, Terri; Khosla, Sundeep; Josse, Robert G; Sutherland, Susan; Lam, David K; Carmichael, Robert P; Blanas, Nick; Kendler, David; Petak, Steven; Ste-Marie, Louis Georges; Brown, Jacques; Evans, A Wayne; Rios, Lorena; Compston, Juliet E

2009-03-01

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%-12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Cost-effectiveness of increasing bisphosphonates adherence for osteoporosis in community pharmacies

NARCIS (Netherlands)

Van Boven, J.F.M.; Oosterhof, P.; Hiddink, E.G.; Stuurman-Bieze, A.G.G.; Postma, M.J.; Vegter, S.

2011-01-01

OBJECTIVES: Increasing real-life adherence to bisphosphonates therapy is important to achieve the clinical benefits of reducing fractures reported in randomized clinical trials (RCTs). The aim of this pharmacoeconomic analysis was to determine the cost-effectiveness of a pharmaceutical care

Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups.

Science.gov (United States)

Espeland, Mark A; Rapp, Stephen R; Manson, JoAnn E; Goveas, Joseph S; Shumaker, Sally A; Hayden, Kathleen M; Weitlauf, Julie C; Gaussoin, Sarah A; Baker, Laura D; Padula, Claudia B; Hou, Lifang; Resnick, Susan M

2017-06-01

Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age. Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos. Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase. CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Addressing Quality of Life Issues in Long Term Survivors of Head & Neck Cancer treated with Radiation Therapy

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Bishan Basu

2015-04-01

Full Text Available The rapid advancement of curative treatment modalities has resulted in improvement of cure rates of head neck cancer leaving us with a larger number of long term survivors from the disease. Unfortunately, long term complications of therapy continue to hurt patients even after cure, compromising their quality of life. This is particularly true for the patients treated with primary radiation/chemo-radiation therapy, where so called organ preservation does not necessarily translate into preservation of organ function. Long term sequelae of treatment, particularly xerostomia and swallowing difficulties compromise the survivors’ quality of life. More studies, particularly suited to our clinical scenario, are warranted to address the quality of life issues in these patients, so that better evidence-based guidelines may be developed for their benefit.

Immunomodulatory effects of macrolide antibiotics - part 2: advantages and disadvantages of long-term, low-dose macrolide therapy.

Science.gov (United States)

Altenburg, J; de Graaff, C S; van der Werf, T S; Boersma, W G

2011-01-01

The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide treatment. Macrolide maintenance therapy has been proven to be of benefit in diffuse panbronchiolitis and CF, presumably due to an anti-inflammatory mechanism of action in addition to its direct antimicrobial effect. Solid evidence to justify this treatment regimen for non-CF bronchiectasis, asthma, or sinusitis is still lacking, although a beneficial effect of long-term macrolide therapy has been found in small clinical trials on these subjects. Data from randomized trials of long-term macrolide treatment in COPD are conflicting. A sufficiently long duration of treatment and the careful selection of patients appears to be crucial. Aside from its beneficial effects, possible side effects of macrolide treatment should be taken into account, the most important of these being gastrointestinal upset and cardiac arrhythmias. Development of macrolide resistance among respiratory pathogens is very common during long-term macrolide treatment. Whether this finding is clinically significant is a matter of debate. Copyright © 2010 S. Karger AG, Basel.

Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates

International Nuclear Information System (INIS)

Malzoni, Carlos Eduardo

1996-01-01

The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author)

Long-term follow-up on Cushing disease patient after transsphenoidal surgery.

Science.gov (United States)

Jeong, Insook; Oh, Moonyeon; Kim, Ja Hye; Cho, Ja Hyang; Choi, Jin-Ho; Yoo, Han-Wook

2014-09-01

Cushing disease is caused by excessive adrenocorticotropic hormone (ACTH) production by the pituitary adenoma. Transsphenoidal surgery is its first-line treatment. The incidence of Cushing disease in children and adolescents is so rare that long-term prognoses have yet to be made in most cases. We followed-up on a 16-year-old male Cushing disease patient who presented with rapid weight gain and growth retardation. The laboratory findings showed increased 24-hour urine free cortisol and lack of overnight cortisol suppression by low-dose dexamethasone test. The serum cortisol and 24-hour urine free cortisol, by high-dose dexamethasone test, also showed a lack of suppression, and a bilateral inferior petrosal sinus sampling suggested lateralization of ACTH secretion from the right-side pituitary gland. However, after a right hemihypophysectomy by the transsphenoidal approach, the 24-hour urine free cortisol levels were persistently high. Thus the patient underwent a total hypophysectomy, since which time he has been treated with hydrocortisone, levothyroxine, recombinant human growth hormone, and testosterone enanthate. Intravenous bisphosphonate for osteoporosis had been administered for three years. At his current age of 26 years, his final height had attained the target level range; his bone mineral density was normal, and his pubic hair was Tanner stage 4. This report describes the long-term treatment course of a Cushing disease patient according to growth profile, pubertal status, and responses to hormone replacement therapy. The clinical results serve to emphasize the importance of growth optimization, puberty, and bone health in the treatment management of Cushing disease patients who have undergone transsphenoidal surgery.

Long Term Effectiveness of Cognitive Behavioral Group Therapy for Treatment of Major Depressive Disorder: A Systematic Review

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Ceren Gokdag

2016-03-01

Full Text Available The aim of the study was to conduct systematic review the articles on long term effectiveness of cognitive-behavioral group therapy for treatment of major depressive disorder. Articles in English and Turkish published between the years of 2000 and 2015 (January were searched in national and international databases. The articles that did not include follow-up studies were excluded. Although the main aim of this study is to evaluate permanent effect of the cognitive behavioral group therapy, 21 articles that met the criteria were examined also in terms of some other variables such as research method, therapy characteristics and post test results. The findings of the articles revealed that cognitive-behavioral group therapy is effective for major depressive disorder and post therapy gains are maintained for a long time. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(Supplement 1: 23-38

The thyroid axis 'setpoints' are significantly altered after long-term suppressive LT4 therapy

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Verburg, F.A.; Mader, U.; Grelle, I.; Visser, T.J.; Peeters, R.P.; Smit, J.W.A.; Reiners, C.

2014-01-01

The aim of the study was to investigate the changes in the thyroid axis setpoint after long-term suppressive levothyroxine therapy for differentiated thyroid carcinoma and the resulting changes in levothyroxine requirement. Ninety-nine differentiated thyroid cancer patients were reviewed. All

Opsismodysplasia: Phosphate wasting osteodystrophy responds to bisphosphonate therapy

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Ansab eKhwaja

2015-06-01

Full Text Available We present two siblings affected with opsismodysplasia, a rare skeletal dysplasia caused by mutations in the INPPL1 gene. The skeletal findings include short stature with postnatal onset micromelia, marked platyspondyly, squared metacarpals, delayed skeletal ossification, metaphyseal cupping and postnatal micromelia. Respiratory compromise, delayed ambulation, and progressive lower extremity deformities are described. The severity of findings is variable. Renal phosphate wasting is associated with severe bone demineralization and a more severe phenotype. This report represents the first described cases of opsismodysplasia treated with intravenous bisphosphonate (pamidronate. Surgical management for lower extremity deformities associated with OPS is also reviewed.

BISPHOSPHONATE - RELATED MUCOSITIS (BRM: A CASE REPORT

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Pavel Stanimirov

2017-03-01

Full Text Available Bisphosphonates (BPs are the most widely used and effective antiresorptive agents for the treatment of diseases in which there is an increase in osteoclastic resorption, including post-menopausal osteoporosis, Paget’s disease, and tumor-associated osteolysis. Oral and maxillofacial surgeons are well aware of the side effects of bisphosphonates and mainly with bisphosphonate-related osteonecrosis of the jaws (BRONJ. Less known are the mucosal lesions associated with the use of these agents. In the scientific literature, there are only few reports of mucosal lesions due to the direct contact of the oral form of BPs with the mucosa (bisphosphonate-related mucositis. They are mostly related to improper use of bisphosphonate tablets that are chewed, sucked or allowed to melt in the mouth before swallowing. Lesions are atypical and need to be differentiated from other mucosal erosions. We present a case of bisphosphonate-related mucositis due to the improper use of alendronate.

Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain

NARCIS (Netherlands)

Rombach, Saskia M.; Smid, Bouwien E.; Bouwman, Machtelt G.; Linthorst, Gabor E.; Dijkgraaf, Marcel G. W.; Hollak, Carla E. M.

2013-01-01

Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase A deficiency leading to renal, cardiac, cerebrovascular disease and premature death. Treatment with α-galactosidase A (enzyme replacement therapy, ERT) stabilises disease in some patients, but long term effectiveness

Geographic variation in long-term oxygen therapy in Denmark : factors related to adherence to guidelines for long-term oxygen therapy

DEFF Research Database (Denmark)

Ringbæk, Thomas Jørgen; Lange, Peter; Viskum, K

2001-01-01

STUDY OBJECTIVES: To evaluate regional differences in adherence to guidelines for long-term oxygen therapy (LTOT) in Denmark and to determine factors related to compliance with these guidelines. DESIGN: Cross-sectional study and analysis of a nationwide database (Danish Oxygen Register). SETTING...... to national guidelines for LTOT was found in 34.4% of the patients for the whole of Denmark and varied regionally from 14 to 63%. Mean compliance with guidelines was 5.3 (range, 2.9 to 9.1) times as likely if the oxygen was prescribed by a pulmonary department compared to LTOT initiated by a GP. CONCLUSIONS......: Marked geographic variations in compliance with LTOT guidelines are present even in a small country as Denmark. In general, the adherence to the guidelines is poor, especially when non-chest physicians prescribe LTOT. We therefore recommend that local and national thoracic societies together with health...

Current perspectives on bisphosphonate treatment in Paget’s disease of bone

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Wat WZM

2014-11-01

Full Text Available Winnie Zee Man Wat Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Abstract: Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus.

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Merrill, Joan T; Ginzler, Ellen M; Wallace, Daniel J; McKay, James D; Lisse, Jeffrey R; Aranow, Cynthia; Wellborne, Frank R; Burnette, Michael; Condemi, John; Zhong, Z John; Pineda, Lilia; Klein, Jerry; Freimuth, William W

2012-10-01

To evaluate the safety profile of long-term belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease. Patients who were randomized to receive intravenous placebo or belimumab 1, 4, or 10 mg/kg, plus standard therapy, and completed the initial 52-week double-blind treatment period were then allowed to enter a 24-week open-label extension phase. During the extension period, patients in the belimumab group either received the same dose or were switched to 10 mg/kg and patients in the placebo group were switched to belimumab 10 mg/kg. Patients who achieved a satisfactory response during the 24-week extension period were allowed to participate in the long-term continuation study of monthly belimumab 10 mg/kg. Adverse events (AEs) and abnormal laboratory results were analyzed per 100 patient-years in 1-year intervals. Of the 364 patients who completed the 52-week double-blind treatment period, 345 entered the 24-week extension, and 296 continued treatment with belimumab in the long-term continuation study. Safety data through 4 years of belimumab exposure (1,165 cumulative patient-years) are reported. Incidence rates of AEs, severe/serious AEs, infusion reactions, infections, malignancies, grades 3/4 laboratory abnormalities, and discontinuations due to AEs were stable or declined during 4-year belimumab exposure. The most common AEs included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea. Serious infusion reactions were rare: only 1 occurred during the 4-year followup period. Rates of serious infection decreased from 5.9/100 patient-years to 3.4/100 patient-years, and no specific type of infection predominated. Belimumab added to standard therapy was generally well-tolerated over the 4-year treatment period in patients with SLE, which suggests that belimumab can be administered long term with an acceptable safety profile. Copyright © 2012 by the American College of Rheumatology.

Discovery, clinical development, and therapeutic uses of bisphosphonates.

Science.gov (United States)

Licata, Angelo A

2005-04-01

To review the literature concerning the history, development, and therapeutic uses of bisphosphonates. English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined. Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses. Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R(1) and R(2)). The R(1) side chain determines binding affinity to hydroxyapatite, and the R(2) side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity. The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.

Effect of bisphosphonates on macrophagic THP-1 cell survival in bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Science.gov (United States)

Hoefert, Sebastian; Sade Hoefert, Claudia; Munz, Adelheid; Schmitz, Inge; Grimm, Martin; Yuan, Anna; Northoff, Hinnak; Reinert, Siegmar; Alexander, Dorothea

2016-03-01

Immune deficiency and bacterial infection have been suggested to play a role in the pathophysiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Zoledronate was previously found to promote THP-1 cell death. To examine this hypothesis with all commonly prescribed bisphosphonates, we tested the effect of (nitrogen-containing) ibandronate, risedronate, alendronate, pamidronate, and (non-nitrogen-containing) clodronate on macrophagic THP-1 cells. Activated THP-1 cells were exposed to .5 to 50 μM of nitrogen-containing bisphosphonates and .5 to 500 μM of clodronate. Cell adherence and survival were assessed in vitro using the xCELLigence real-time monitoring system. Results were confirmed histologically and verified with Live/Dead staining. All bisphosphonates inhibited THP-1 cell adherence and survival dose and time dependently, significant for zoledronate, alendronate, pamidronate, and clodronate in high concentrations (50 μM and 500 μM; P THP-1 cell survival compared with controls (P THP-1 cells exhibited no cytomorphologic changes at all concentrations. Commonly prescribed bisphosphonates inhibit the survival of macrophagic THP-1 cells dose-dependently without altering morphology. This may suggest a local immune dysfunction reflective of individual bisphosphonate potency leading to the pathogenesis of BRONJ. Copyright © 2016 Elsevier Inc. All rights reserved.

Atypical femoral fractures related to bisphosphonate therapy

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Tarun Pankaj Jain

2012-01-01

Full Text Available Bisphosphonates (BP are a commonly prescribed class of drugs for the prevention of osteoporosis-related fractures. Paradoxically, however, they have recently been linked to atypical fractures in the shaft of the femur. Since many physicians including radiologists, are not aware of this entity, the incidence is likely underreported. These fractures usually occur in the sub-trochanteric region of the femur in the setting of low-energy trauma. It starts as a fracture line involving the lateral cortex and then progresses medially to give rise to a complete fracture. The fracture line is usually transverse, and there is a medial spike associated with a complete fracture. These fractures can be bilateral. Awareness of these atypical fractures and their radiological appearance should enable their early and accurate detection and thus lead to specific treatment.

Mid- and long-term clinical results of surgical therapy in unicameral bone cysts

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Hagmann Sébastien

2011-12-01

Full Text Available Abstract Background Unicameral (or simple bone cysts (UBC are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. Methods A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Results Forty-six patients (17 female, 29 male with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%. All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws. Overall recurrence rate after the first surgical treatment was 39% (18/46, second (17.4% of all patients and third recurrence (4.3% were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Conclusions Our results suggest satisfactory overall long-term outcome for the

Mid- and long-term clinical results of surgical therapy in unicameral bone cysts.

Science.gov (United States)

Hagmann, Sébastien; Eichhorn, Florian; Moradi, Babak; Gotterbarm, Tobias; Dreher, Thomas; Lehner, Burkhard; Zeifang, Felix

2011-12-13

Unicameral (or simple) bone cysts (UBC) are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Forty-six patients (17 female, 29 male) with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%). All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws). Overall recurrence rate after the first surgical treatment was 39% (18/46), second (17.4% of all patients) and third recurrence (4.3%) were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Our results suggest satisfactory overall long-term outcome for the surgical treatment of UBC, although short-and mid-term

Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents.

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Lira, Fábio S; Rosa, Jose C; Pimentel, Gustavo D; Santos, Ronaldo V; Carnier, June; Sanches, Priscila L; de Piano, Aline; de Souza, Claudio T; Tock, Lian; Tufik, Sergio; de Mello, Marco T; Seelaender, Marília; Oller do Nascimento, Claudia M; Oyama, Lila M; Dâmaso, Ana R

2012-09-18

The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15-19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

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Lira Fábio S

2012-09-01

Full Text Available Abstract Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR. Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

Long-term outcomes for adult craniopharyngioma following radiation therapy

International Nuclear Information System (INIS)

Masson-Cote, Laurence; Masucci, Giuseppina Laura; Millar, Barbara-Ann; Laperriere, Normand J.; Atenafu, Eshetu G.; Cusimano, Michael; Croul, Sidney; Mason, Warren; Sahgal, Arjun; Dept. of Radiation Oncology, Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto

2013-01-01

Background. We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). Material and methods. Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. Results. Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age ( 2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. Conclusion. We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not

Bisphosphonate-Related Osteonecrosis of the Jaw: A Review of the Literature

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Eder Alberto Sigua-Rodriguez

2014-01-01

Full Text Available Bisphosphonates (BPs are a class of drugs used to treat osteoporosis and malignant bone metastasis. BPs show high binding capacity to the bone matrix, especially in sites of active bone metabolism. The American Society for Bone and Mineral Research defines BRONJ as “an area of exposed bone in the maxillofacial region that has not healed within 8 weeks after identification by a healthcare provider in a patient who is receiving or has been exposed to a bisphosphonate and has not had radiation therapy to the craniofacial region.” Bisphosphonate-related osteonecrosis of the jaw (BRONJ can adversely affect quality of life, as it may produce significant morbidity. The American Association of Oral and Maxillofacial Surgeons (AAOMS considers as vitally important that information on BRONJ be disseminated to other dental and medical specialties. The purpose of this work is to offer a perspective on how dentists should manage patients on BPs, to show the benefits of accurately diagnosing BRONJ, and to present diagnostic aids and treatments strategies for the condition.

Future of bisphosphonates and denosumab for men with advanced prostate cancer

International Nuclear Information System (INIS)

Iranikhah, Maryam; Stricker, Steve; Freeman, Maisha Kelly

2014-01-01

Prostate cancer is the most common cancer occurring in American men of all races. It is also the second leading cause of cancer death among men in the USA. Bone metastasis is a frequent occurrence in men with advanced prostate cancer, with skeletal-related events being a common complication and having negative consequences, leading to severe pain, increased health care costs, increased risk of death, and decreased quality of life for patients. Bone loss can also result from antiandrogen therapy, which can further contribute to skeletal-related events. Treatment with antiresorptive agents bisphosphonates, and the newly approved denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been shown to reduce the risk of skeletal-related complications and prevent treatment-induced bone loss in patients with advanced prostate cancer. This review discusses the role of antiresorptive agents bisphosphonates and RANK-L inhibitor in the current treatment of advanced prostate cancer by examining the primary literature and also focuses on the likely role of the bisphosphonates in the treatment of advanced prostate cancer in the future

A systematic review of the role of bisphosphonates in metastatic disease.

Science.gov (United States)

Ross, J R; Saunders, Y; Edmonds, P M; Patel, S; Wonderling, D; Normand, C; Broadley, K

2004-01-01

significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was GBP250 and GBP1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting.

The long-term effects of radiation therapy on patients with ovarian dysgerminoma

International Nuclear Information System (INIS)

Mitchell, M.F.; Gershenson, D.M.; Soeters, R.P.; Eifel, P.J.; Delclos, L.; Wharton, J.T.

1991-01-01

A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder

Pituitary function following megavoltage therapy for Cushings' disease; long term follow up

International Nuclear Information System (INIS)

Sharpe, G.F.; Kendall-Taylor, P.; Prescott, R.W.G.; Ross, W.M.; Davison, C.; Watson, M.J.; Cook, D.B.

1985-01-01

Eight patients who had received megavoltage therapy for Cushings' disease 5-12 years previously have been reviewed. The long term response to this therapy was assessed with respect to efficacy of treatment in inducing continued remission and disturbance of hypothalamic-pituitary function. One patient showed clear evidence of relapse of Cushings' disease. One patient had unequivocal hypopituitarism. Basal levels of growth hormone (GH), TSH, LH, and FSH were not statistically different from controls, but provocative testing revealed significant abnormalities of response of cortisol/ACTH, GH, prolactin and LH. Six out of eight patients had absent diurnal cortisol variation and five patients had elevated serum prolactin levels. Thus, in this group of patients normal pituitary-adrenal function has not been satisfactorily restored. It is clear that significant disturbances of hypothalamic-pituitary function follow megavoltage therapy and these may progress to overt hypopituitarism. (author)

Long-term effect of massage therapy on blood pressure in prehypertensive women.

Science.gov (United States)

Givi, Mahshid; Sadeghi, Masoumeh; Garakyaraghi, Mohammad; Eshghinezhad, Ameneh; Moeini, Mahin; Ghasempour, Zahra

2018-01-01

Prehypertension is one of the cardiovascular disease predicators. Management of prehypertension is an appropriate objective for clinicians in a wide range of medical centers. Massage therapy is primarily nonpharmacological treatment that is used to control blood pressure (BP). This study intends to investigate the long-term effect of massage therapy on BP in prehypertensive women. This was a single-blind clinical trial study conducted on 50 prehypertensive women who referred to Sedigheh Tahereh Cardiovascular Center, during 6 months in 2009. Participants were selected by simple random sampling and were divided into control and intervention groups. The test group (25 patients) received massage for 10-15 min, three times a week for 10 sessions, and the control group (25 patients) was relaxed in the same environment but with no massage. Their BP was measured before and after each session and 72 h and 2 weeks after finishing the massage therapy. Analyzing the data was done using descriptive and inferential statistical methods (Chi-square, Mann-Whitney, paired t -test, and Student's t -test) through SPSS software version 18 and a significant level was considered as P 0.05) between the two groups. Although massage therapy seems to be a safe, effective, applicable, and cost-effective intervention to control BP of prehypertensive women, its effects do not persist for a long time.

Long-term follow-up on Cushing disease patient after transsphenoidal surgery

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Insook Jeong

2014-09-01

Full Text Available Cushing disease is caused by excessive adrenocorticotropic hormone (ACTH production by the pituitary adenoma. Transsphenoidal surgery is its first-line treatment. The incidence of Cushing disease in children and adolescents is so rare that long-term prognoses have yet to be made in most cases. We followed-up on a 16-year-old male Cushing disease patient who presented with rapid weight gain and growth retardation. The laboratory findings showed increased 24-hour urine free cortisol and lack of overnight cortisol suppression by low-dose dexamethasone test. The serum cortisol and 24-hour urine free cortisol, by high-dose dexamethasone test, also showed a lack of suppression, and a bilateral inferior petrosal sinus sampling suggested lateralization of ACTH secretion from the right-side pituitary gland. However, after a right hemihypophysectomy by the transsphenoidal approach, the 24-hour urine free cortisol levels were persistently high. Thus the patient underwent a total hypophysectomy, since which time he has been treated with hydrocortisone, levothyroxine, recombinant human growth hormone, and testosterone enanthate. Intravenous bisphosphonate for osteoporosis had been administered for three years. At his current age of 26 years, his final height had attained the target level range; his bone mineral density was normal, and his pubic hair was Tanner stage 4. This report describes the long-term treatment course of a Cushing disease patient according to growth profile, pubertal status, and responses to hormone replacement therapy. The clinical results serve to emphasize the importance of growth optimization, puberty, and bone health in the treatment management of Cushing disease patients who have undergone transsphenoidal surgery.

Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma

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Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.; Busse, Paul M.; Goldberg, Saveli I. [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Varvares, Mark; Deschler, Daniel D.; Lin, Derrick T. [Head and Neck Surgical Oncology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts (United States); Delaney, Thomas F. [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Chan, Annie W., E-mail: awchan@partners.org [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2016-05-01

Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton

Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma

International Nuclear Information System (INIS)

Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.; Busse, Paul M.; Goldberg, Saveli I.; Varvares, Mark; Deschler, Daniel D.; Lin, Derrick T.; Delaney, Thomas F.; Chan, Annie W.

2016-01-01

Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton

Dosimetric Inhomogeneity Predicts for Long-Term Breast Pain After Breast-Conserving Therapy

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Mak, Kimberley S. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Chen, Yu-Hui; Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S.; Wong, Julia S.; Truong, Linh [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Bellon, Jennifer R., E-mail: jbellon@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States)

2015-12-01

Purpose: The objective of this cross-sectional study was to characterize long-term breast pain in patients undergoing breast-conserving surgery and radiation (BCT) and to identify predictors of this pain. Methods and Materials: We identified 355 eligible patients with Tis-T2N0M0 breast cancer who underwent BCT in 2007 to 2011, without recurrent disease. A questionnaire derived from the Late Effects Normal Tissue Task Force (LENT) Subjective, Objective, Management, Analytic (SOMA) scale was mailed with 7 items detailing the severity, frequency, duration, and impact of ipsilateral breast pain over the previous 2 weeks. A logistic regression model identified predictors of long-term breast pain based on questionnaire responses and patient, disease, and treatment characteristics. Results: The questionnaire response rate was 80% (n=285). One hundred thirty-five patients (47%) reported pain in the treated breast, with 19 (14%) having pain constantly or at least daily; 15 (11%) had intense pain. The pain interfered with daily activities in 11 patients (8%). Six patients (4%) took analgesics for breast pain. Fourteen (10%) thought that the pain affected their quality of life. On univariable analysis, volume of breast tissue treated to ≥105% of the prescribed dose (odds ratio [OR] 1.001 per cc, 95% confidence interval [CI] 1.000-1.002; P=.045), volume treated to ≥110% (OR 1.009 per cc, 95% CI 1.002-1.016; P=.012), hormone therapy use (OR 1.95, 95% CI 1.12-3.39; P=.02), and other sites of pain (OR 1.79, 95% CI 1.05-3.07; P=.03) predicted for long-term breast pain. On multivariable analysis, volume ≥110% (OR 1.01 per cc, 95% CI 1.003-1.017; P=.007), shorter time since treatment (OR 0.98 per month, 95% CI 0.96-0.998; P=.03), and hormone therapy (OR 1.84, 95% CI 1.05-3.25; P=.03) were independent predictors of pain. Conclusion: Long-term breast pain was common after BCT. Although nearly half of patients had pain, most considered it tolerable. Dosimetric inhomogeneity

Adjuvant bisphosphonates in early breast cancer

DEFF Research Database (Denmark)

Hadji, P; Coleman, R E; Wilson, C

2016-01-01

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have...... regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature...... was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus...

Successful long-term terbinafine therapy in an asthmatic patient with Aspergillus sensitization and bronchiectasis

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Isabel Rodriguez-Goncer

2017-06-01

Full Text Available Severe asthma with fungal sensitization (SAFS is estimated to affect ~25% of patients with poorly controlled asthma. Tri-azole therapy is effective in only 60–80% and side effects are common. We report a 25 years-old woman with severe asthma, Aspergillus sensitization and marked bronchiectasis that developed a rare Achilles-tendinopathy with both itraconazole and voriconazole. She started a trial with terbinafine as salvage therapy that led to a striking improvement and long-term control of her respiratory disease.

Socioeconomics of long-term glaucoma therapy in India

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Bhagabat Nayak

2015-01-01

Full Text Available Purpose: To determine the socioeconomic impact of long-term glaucoma therapy. Materials and Methods: One hundred and fifty consecutive glaucoma patients on medical therapy, following up at our glaucoma service for at least 6 months were recruited. A questionnaire regarding monthly income, cost of glaucoma medications prescribed, availability of medications, travel time, time spent in review clinics, compliance, education status, medical insurance and systemic or local side-effects was administered. Results: The patients seen at the tertiary government hospital had an average monthly income of Rs. 10,912/- (range: Rs. 500/- to Rs. 50,000/- with approximately 56% of the patients having an income of less than Rs. 5000/month. The expenditure on anti-glaucoma medications ranged from 0.3% in high income group to 123% of their monthly gross income in low income group (P < 0.0001. The total expenditure including travel, stay, and loss of wages of patients and accompanying persons ranged from 1.6% in high income group to 137% of the monthly income in low income group (P < 0.0001. Mean time required for a glaucoma clinic visit was 15.66 h, (range: 6-96 h/month. About 2.7% experienced systemic side-effects and 21.3% had complaints of ocular adverse effects. About 90% of the patients were compliant. 92% were not covered by any insurance plan/government reimbursement for their treatment. Conclusions: Medical therapy for glaucoma is an economic burden to many patients and should be individualized, according to the socioeconomic status, availability of drugs and the required distance to travel to reach the specialist clinics.

The effects of light therapy on depression and sleep disruption in older adults in a long-term care facility.

Science.gov (United States)

Wu, Mann-Chian; Sung, Huei-Chuan; Lee, Wen-Li; Smith, Graeme D

2015-10-01

This study aims to evaluate the effect of light therapy on depression and sleep disruption in older adults residing in a long-term care facility. Psychological morbidity is a problem commonly seen in older adults residing in long-term care facilities. Limited research has addressed the effect of light therapy on depression in this population. A quasi-experimental pretest and posttest design was used. Thirty-four participants in the experimental group received light therapy by sitting in front of a 10000-lux light box 30 min in the morning, three times a week for 4 weeks. Thirty-one participants in the control group received routine care without light therapy. Depression was measured by Geriatric Depression Scale-Short Form at baseline and week 4. After receiving 4 weeks of light therapy, the mean depression score in the experimental group decreased from 7.24 (SD3.42) at pretest to 5.91 (SD 3.40) at posttest, and had a significant reduction (t = 2.22, P = 0.03). However, there was no significant difference in depression score and sleep disruption between the experimental group and control group. Light therapy might have the potential to reduce depressive symptoms and sleep disruption and may be a viable intervention to improve mental health of older adults in the long-term care facilities. © 2014 Wiley Publishing Asia Pty Ltd.

Prestimulation with Recombinant Human Thyrotropin (rhTSH) Improves the Long-Term Outcome of Radioiodine Therapy for Multinodular Nontoxic Goiter

DEFF Research Database (Denmark)

Fast, Søren; Nielsen, Viveque Egsgaard; Grupe, Peter

2012-01-01

goiter volume reduction with rhTSH-augmented (131)I therapy improves the long-term reduction in goiter-related symptoms and reduces the need for additional therapy compared with plain (131)I therapy. Overall patient satisfaction is benefited, despite a higher rate of permanent hypothyroidism....

Growth hormone therapy for children born small for gestational age: height gain is less dose dependent over the long term than over the short term.

Science.gov (United States)

de Zegher, Francis; Hokken-Koelega, Anita

2005-04-01

Approximately 3% of children are born small for gestational age (SGA), and approximately 10% of SGA children maintain a small body size throughout childhood and often into adult life. Among short SGA children, growth hormone (GH) therapy increases short-term growth in a dose-dependent manner; experience with long-term therapy is limited. To delineate the dose dependency of long-term height gain among short SGA children receiving GH therapy. We performed an epianalysis of the first adult height data for SGA children (n = 28) enrolled in 3 randomized trials comparing the growth-promoting efficacy of 2 continuous GH regimens (33 or 67 microg/kg per day for approximately 10 years, starting at approximately 5 years of age); in addition, we performed a meta-analysis of the adult height results published previously and those presented here. Epianalysis outcomes (n = 28) suggested that adult height increased more with a higher-dose regimen than with a lower-dose regimen. In the meta-analysis (n = 82), the higher-dose regimen was found to elicit a long-term height gain superior to that achieved with the lower-dose regimen by a mean of 0.4 SD (approximately 1 inch). Children who were shorter at the start of therapy experienced more long-term height gain. These findings confirm GH therapy as an effective and safe approach to reduce the adult height deficit that short SGA children otherwise face. In addition, the first meta-analysis indicated that height gain is less dose dependent over the long term than over the short term, at least within the dose range explored to date. For SGA children whose stature is not extremely short, current data support the use of a GH dose of approximately 33 microg/kg per day from start to adult height, particularly if treatment starts at a young age; shorter children (for example, height below -3 SD) might benefit from an approach in which short-term catch-up growth is achieved with a higher dose (> or =50 microg/kg per day) and long-term growth

Validation of a novel device to objectively measure adherence to long-term oxygen therapy

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Sun-Kai V Lin

2008-10-01

Full Text Available Sun-Kai V Lin1, Daniel K Bogen1, Samuel T Kuna2,31Department of Bioengineering; 2Department of Medicine, Pulmonary, Allergy and Critical Care Division, and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, Pennsylvania, USA; 3Department of Medicine, Philadelphia Veterans Affairs Medical Center Philadelphia, Pennsylvania, USARationale: We have developed a novel oxygen adherence monitor that objectively measures patient use of long-term oxygen therapy. The monitor attaches to the oxygen source and detects whether or not the patient is wearing the nasal cannula.Objective: The study’s purpose was to validate the monitor’s performance in patients with chronic obstructive pulmonary disease during wakefulness and sleep.Methods: Ten adult males with stable chronic obstructive pulmonary disease (mean ± SD FEV1 37.7 ± 14.9% of predicted on long-term continuous oxygen therapy were tested in a sleep laboratory over a 12–13 hour period that included an overnight polysomnogram.Measurements: The monitor’s measurements were obtained at 4-minute intervals and compared to actual oxygen use determined by review of time-synchronized video recordings.Main results: The monitor made 1504/1888 (79.7% correct detections (unprocessed data across all participants: 957/1,118 (85.6% correct detections during wakefulness and 546/770 (70.9% during sleep. All errors were false negatives, ie, the monitor failed to detect that the participant was actually wearing the cannula. Application of a majority-vote filter to the raw data improved overall detection accuracy to 84.9%.Conclusions: The results demonstrate the monitor’s ability to objectively measure whether or not men with chronic obstructive pulmonary disease are receiving their oxygen treatment. The ability to objectively measure oxygen delivery, rather than oxygen expended, may help improve the management of patients on long-term oxygen therapy.Keywords: chronic obstructive pulmonary

Long-term outcomes for adult craniopharyngioma following radiation therapy

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Masson-Cote, Laurence; Masucci, Giuseppina Laura; Millar, Barbara-Ann; Laperriere, Normand J. [Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Atenafu, Eshetu G. [Dept. of Biostatistics, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Cusimano, Michael [Dept. of Surgery, Div. of Neurosurgery, St. Michaels Hospital, Toronto (Canada); Croul, Sidney [Dept. of Pathology, Univ. of Toronto, Toronto (Canada); Mason, Warren [Dept. of Medicine, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Sahgal, Arjun [Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada), E-mail: Arjun.sahgal@rmp.uhn.on.ca; Dept. of Radiation Oncology, Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto (Canada)

2013-01-15

Background. We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). Material and methods. Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. Results. Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age (<53 or {>=}53) as a prognostic factor for OS (p =0.0003) and CSS (p =0.05). PFS was observed to be worse in patients with >2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. Conclusion. We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not.

A review of the clinical implications of bisphosphonates in dentistry.

Science.gov (United States)

Borromeo, G L; Tsao, C E; Darby, I B; Ebeling, P R

2011-03-01

Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined. © 2010 Australian Dental Association.

Future long-term trials of postmenopausal hormone replacement therapy - what is possible and what is the optimal protocol and regimen?

Science.gov (United States)

Purbrick, B; Stranks, K; Sum, C; MacLennan, A H

2012-06-01

The ideal long-term, randomized, placebo-controlled trial of hormone replacement therapy (HRT) from near menopause for up to 30 years to assess major morbidity and mortality is impractical because of high cost, participant retention, therapy compliance, and continuity of research staff and funding. Also the trial regimen may become outdated. It is nihilistic to demand such a long-term trial before endorsing HRT. However, medium-term trials using surrogate measures for long-term morbidity and mortality are possible and two are near completion. If these studies have been able to maintain reasonable participant retention, therapy compliance and minimal breach of protocol, they will set standards for trials of new HRT regimens. This paper discusses lessons learnt from past attempts at long-term trials and suggests the currently optimal protocol and cost of assessing new HRT regimens to optimize potential benefits and minimize adverse effects. A 5-7-year randomized, placebo-controlled trial of a flexible transdermal estrogen regimen ± either a selective estrogen receptor modulator, e.g. bazedoxifene, or micronized progesterone is discussed. Mild to moderately symptomatic women, 1-4 years post menopause, can be recruited via general practice and group meetings. Future trials should be funded by independent agencies and are high priority in women's health.

Deferasirox: appraisal of safety and efficacy in long-term therapy

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Chaudhary P

2013-08-01

Full Text Available Preeti Chaudhary, Vinod PullarkatJane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USAAbstract: Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.Keywords: deferasirox, iron overload, thalassemia, sickle-cell disease, myelodysplastic syndrome

Neutrophil superoxide-anion generating capacity in chronic smoking: effect of long-term alpha-tocopherol therapy

NARCIS (Netherlands)

Tits, van L.; Waart, de F.; Hak-Lemmers, H.L.M.; Graaf, de J.; Demacker, P.N.; Stalenhoef, A.F.

2003-01-01

We investigated whether long-term alpha-tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 21 pack years of smoking) to treatment with placebo (n = 64) or alpha-tocopherol (400 IU

Bisphosphonate-related osteonecrosis of the jaw: specificities

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Siri Paulo

2014-09-01

Full Text Available Bisphosphonate-related osteonecrosis of the jaws (BRONJ is a severe complication that has recently emerged in patients treated with intravenous bisphosphonates for malignant diseases. This complication usually presents after a minor local trauma during a dental treatment. Several etiopathogenic mechanisms of this pathological condition have been proposed, but no model can explain all morphological changes observed at the macroscopic and microscopic level. BRONJ is likely to be related to direct toxicity in the bone and soft tissue cells, due to nitrogen-containing bisphosphonates. This review elucidates the clinical indications and mechanism of action of bisphosphonates, reports some clinical diagnostic criteria for BRONJ, describe the histopathological criteria for BRONJ diagnosis, the potential triggering pathways and the available treatment strategies.

Mild erythrocytopenia is the most frequent long-term sequel after peptide receptor radionuclide Therapy: Results of long-term follow-up in more than 500 Patients from a single centre

International Nuclear Information System (INIS)

Schmidt, J.; Kulkami, H.R.; Baum, R.P.; Menghui, Y.

2015-01-01

Full text of publication follows. Aim: Peptide receptor radionuclide therapy (PRRT) is highly effective in well differentiated neuroendocrine neoplasms (NENs) and lends a benefit in overall survival of several years. Renal toxicity is a well-known adverse effect of PRRNT. Hematological toxicity as possible long-term sequel has been hardly examined. Therefore we investigated the effect of PRRT on the hematological status (erythrocytes, leukocytes, thrombocytes) of patients who received individualized therapy at our centre. Materials and Methods: Out of over 500 patients, 59 chemotherapy naive patients with well-differentiated NENs who were treated with at least 3 cycles of PRRT with 177 Lu- and/or 90 Y- labeled DOTATATE/DOTATOC and long-term follow-up were selected for this analysis. Blood counts were documented before the first cycle and repeated at monthly intervals between further cycles and during re-staging examinations after PRRT for many years. Comparisons were done between the hematological status before the first cycle and the one 3 years after the last cycle of PRRT. Results: All 3 cell lines were significantly decreased 3 years after the last radionuclide therapy (erythrocytes, leukocytes: p=0,000; thrombocytes: p=0,002; confidence interval 95%). But only erythrocytes showed a significant decrement, i.e., below the reference level of our in-house laboratory (mean value ± standard deviation: (4.07 ± 0.69)/l; reference level: 4.1-5.4/l). Conclusions: Mild erythrocytopenia is the most frequent long-term sequel after PRRT. Although it has to be considered that repeated cycles probably cause impoverishment in bone marrow reserve (or red cell precursors), PRRT achieves both significant improvement in clinical symptoms and excellent palliation. Thus it remains a safe procedure if performed at specialized centres with interdisciplinary and long-term care. (authors)

Long-term use of short- and long-acting nitrates in stable angina pectoris.

Science.gov (United States)

Kosmicki, Marek Antoni

2009-05-01

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

Age and CD4 count at initiation of antiretroviral therapy in HIV-infected children: effects on long-term T-cell reconstitution.

Science.gov (United States)

Lewis, Joanna; Walker, A Sarah; Castro, Hannah; De Rossi, Anita; Gibb, Diana M; Giaquinto, Carlo; Klein, Nigel; Callard, Robin

2012-02-15

Effective therapies and reduced AIDS-related morbidity and mortality have shifted the focus in pediatric human immunodeficiency virus (HIV) from minimizing short-term disease progression to maintaining optimal long-term health. We describe the effects of children's age and pre-antiretroviral therapy (ART) CD4 count on long-term CD4 T-cell reconstitution. CD4 counts in perinatally HIV-infected, therapy-naive children in the Paediatric European Network for the Treatment of AIDS 5 trial were monitored following initiation of ART for a median 5.7 years. In a substudy, naive and memory CD4 counts were recorded. Age-standardized measurements were analyzed using monophasic, asymptotic nonlinear mixed-effects models. One hundred twenty-seven children were studied. Older children had lower age-adjusted CD4 counts in the long term and at treatment initiation (P memory CD4 counts increased less, albeit on a faster timescale. It appears the immature immune system can recover well from HIV infection via the naive pool. However, this potential is progressively damaged with age and/or duration of infection. Current guidelines may therefore not optimize long-term immunological health.

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021

Data.gov (United States)

National Aeronautics and Space Administration — The original intent of this study was to test 10 long-duration crewmembers taking one of two bisphosphonate regimens: either 70 mg per week alendronate or a single...

Making Music, Making Friends: Long-Term Music Therapy with Young Adults with Severe Learning Disabilities

Science.gov (United States)

Pavlicevic, Mercédès; O'Neil, Nicky; Powell, Harriet; Jones, Oonagh; Sampathianaki, Ergina

2014-01-01

This collaborative practitioner research study emerged from music therapists' concerns about the value of improvisational, music-centred music therapy for young adults with severe learning disabilities (SLDs), given the long-term nature of such work. Concerns included the relevance, in this context, of formulating, and reporting on, therapeutic…

Successful treatment of dwarfism secondary to long-term steroid therapy in steroid-dependent nephrotic syndrome.

Science.gov (United States)

Sun, Linlin; Chen, Dongping; Zhao, Xuezhi; Xu, Chenggang; Mei, Changlin

2010-01-01

Prolonged steroid therapy is generally used for steroid-dependent nephrotic syndrome in pediatric patients. However, dwarfism secondary to a long-term regimen and its successful reverse is rarely reported. The underlying mechanism of dwarfism is still poorly understood, as both long-term steroid use and nephrotic syndrome may interact or independently interfere with the process of growth. Here, we present a 17-year-old patient with dwarfism and steroid-dependent nephrotic syndrome and the successful treatment by recombinant human growth factor and cyclosporine A with withdrawal of steroid. We also briefly review the current understanding and the management of dwarfism in pediatric patients with nephrotic syndrome.

Managing treatment fatigue in patients with multiple sclerosis on long-term therapy: the role of multiple sclerosis nurses

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Crawford A

2014-08-01

Full Text Available Ann Crawford, Sally Jewell,* Holly Mara, Laura McCatty, Regina Pelfrey The Lash Group; Frisco, TX, USA *Sally Jewell is now retired Abstract: This article discusses the many ways that nurses can address the factors that lead to treatment fatigue in patients with multiple sclerosis (MS on long-term disease-modifying therapy, ultimately helping to preserve the patient’s health and quality of life. Patients with MS on long-term therapy may suffer from treatment fatigue and poor adherence due to a variety of different factors, including difficulties with injections, anxiety/depression, financial problems, and inaccurate beliefs about the MS disease process. Because MS nurses have regular interactions with patients, they are ideally situated to help patients cope with these and other factors that may limit adherence. Keywords: multiple sclerosis, disease-modifying therapy, injection, nurse

Long-term efficacy of reverse pull headgear therapy.

Science.gov (United States)

Wells, Andrew P; Sarver, David M; Proffit, William R

2006-11-01

To add to the data for long-term reverse pull headgear (RPHG) outcomes and further explore possible variables that could be predictors of long-term failure. Cephalometric radiographs of 41 Class III malocclusion children treated with RPHG (face mask) were evaluated before and immediately after treatment; at 5 years posttreatment; and, for 18 patients, at 10 years posttreatment. Patients were assigned to success or failure groups according to positive or negative overjet at the longest available recall. Seventy-five percent of the patients maintained positive overjet, whereas 25% outgrew the correction. In a stepwise discriminant analysis, a large mandible and vertical positioning of the maxilla and mandible so that mandibular growth would be projected more horizontally were the major indicators of unfavorable later mandibular growth. Patients who experienced downward-backward rotation of the mandible during RPHG treatment were more likely to be categorized in the failure group. The age at which treatment began had no effect on long-term success and failure for patients younger than 10 years, but the percentage of successful treatment decreased after that age. When RPHG treatment is used for all but the most obviously prognathic children to correct anterior cross-bite in the early mixed dentition, positive overjet is maintained long-term in 70%-75% of cases, whereas 25%-30% of cases relapse into reverse overjet mainly because of increased horizontally directed and often late mandibular growth. Up to age 10, the time at which RPHG treatment began does not appear to be a major factor in long-term success in maintaining positive overjet.

Heart failure in patients treated with bisphosphonates

DEFF Research Database (Denmark)

Grove, E L; Abrahamsen, B; Vestergaard, P

2013-01-01

The aim of this study was to investigate the occurrence of heart failure in patients treated with bisphosphonates.......The aim of this study was to investigate the occurrence of heart failure in patients treated with bisphosphonates....

Long-term single-center experience of defibrillator therapy in children and adolescents.

Science.gov (United States)

Frommeyer, Gerrit; Feder, Sebastian; Bettin, Markus; Debus, Volker; Köbe, Julia; Reinke, Florian; Uebing, Anselm; Eckardt, Lars; Kehl, Hans Gerd

2018-06-01

Implantable cardioverter-defibrillator (ICD) systems are established therapy for prevention of sudden cardiac death. Long-term data on ICD systems in children and adolescents is rare. The present study displays a long-term single-center follow-up of children and adolescents with ICD systems. The present study represents a single-center experience of patients younger than 18 years who received an ICD (n = 58). Follow-up data included in-house follow-up as well as examinations of collaborating specialists. Mean age at implantation was 14.0 ± 3.3 years and 33 patients (56.9%) were male. A transvenous ICD system was implanted in 54 patients (93.1%). In 33 patients (56.9%) electrical heart disease or idiopathic ventricular fibrillation represented the underlying condition of ICD implantation. Median follow-up duration was 70 months (45; 94). 3 patients (5.2%) died during the observation period. None of these deaths was associated with ICD failure. Appropriate shocks occurred in 32 patients (55.2%). Inappropriate shock delivery was recorded in 17 patients (29.3%). Supraventricular tachycardia represented the most frequent cause of inappropriate shock delivery (9 patients, 52.9%). T-wave oversensing led to inappropriate shock delivery in 3 patients (17.6%). In 5 patients (29.4%), lead failure caused inappropriate shock delivery. Of note, during follow-up lead failure was reported in 15 patients (25.9%) leading to surgical revision. ICD therapy in children and adolescents is effective for prevention of sudden cardiac death. The rate of appropriate shock deliveries was significantly higher as compared with large ICD trials. Inappropriate therapies occurred frequently. In particular supraventricular tachycardia, T-wave oversensing and lead failures were responsible for these episodes. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

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Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

2015-01-01

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy.

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Hatlebakk, Jan G; Zerbib, Frank; Bruley des Varannes, Stanislas; Attwood, Stephen E; Ell, Christian; Fiocca, Roberto; Galmiche, Jean-Paul; Eklund, Stefan; Långström, Göran; Lind, Tore; Lundell, Lars R

2016-05-01

We compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes. We analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole. In the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P acidity was stable in both groups. Patients who required a dose increase to 40 mg/d had more severe supine reflux at baseline, and decreased esophageal acid exposure (P acidity after dose escalation. Esophageal and intragastric pH parameters, off and on therapy, did not predict long-term symptom breakthrough. In a prospective study of patients with chronic GERD, esophageal acid reflux was reduced greatly by LARS or esomeprazole therapy. However, patients receiving LARS had significantly greater reductions in 24-hour esophageal acid exposure after 6 months and 5 years. Esophageal and gastric pH, off and on therapy, did not predict long-term outcomes of patients. Abnormal supine acid exposure predicted esomeprazole dose escalation. ClinicalTrials.Gov identifier: NCT00251927 (available: http://clinicaltrials.gov/ct2/show

Applying orthodontic tooth extrusion in a patient treated with bisphosphonate and irradiation: a case report.

Science.gov (United States)

Morita, Hiromitsu; Imai, Yuko; Yoneda, Masahiro; Hirofuji, Takao

2017-01-01

Bisphosphonates and irradiation are useful medical treatments, but can often cause oral complications such as medication-related oral necrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) during oral surgery, including tooth extraction. Therefore, we should take all risks into consideration carefully before choosing dental treatment for patients with a medical history of such therapies. A 55-year-old woman who underwent cord blood transplantation to treat extranodal natural killer T (NK/T) cell lymphoma (nasal type IVB) had a medical history of bisphosphonate and irradiation treatments. We treated her residual tooth root by applying orthodontic extrusion to avoid extraction and successfully restored the tooth. Application of an orthodontic tooth extrusion technique for conservative treatment of a residual tooth is a useful means of avoiding MRONJ or ORN in patients who have a medical history of bisphosphonate and irradiation treatments. © 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.

Bisphosphonates for osteoporosis in primary biliary cirrhosis

DEFF Research Database (Denmark)

Rudic, Jelena; Giljaca, Vanja; Krstic, Miodrag N

2011-01-01

Bisphosphonates are widely used for treatment of postmenopausal osteoporosis. Patients with primary biliary cirrhosis often have osteoporosis - either postmenopausal or secondary to the liver disease. No systematic review or meta-analysis has assessed the effects of bisphosphonates for osteoporosis...

Bisphosphonate adverse effects, lessons from large databases

DEFF Research Database (Denmark)

Abrahamsen, Bo

2010-01-01

To review the latest findings on bisphosphonate safety from health databases, in particular sources that can provide incidence rates for stress fractures, osteonecrosis of the jaw (ONJ), atrial fibrillation and gastrointestinal lesions including esophageal cancer. The main focus is on bisphosphon...

Bone Loss Prevention of Bisphosphonates in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

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Yan Hu

2017-01-01

Full Text Available Objective. The purpose of this study was to evaluate the effect of bisphosphonates in improving bone mineral density (BMD and decreasing the occurrence rate of fractures and adverse events in patients with inflammatory bowel disease (IBD. Methods. Randomized controlled trials (RCTs which use bisphosphonates in IBD patients were identified in PubMed, MEDLINE database, EMBASE database, Web of Knowledge, and the Cochrane Databases between 1990 and June 2016. People received bisphosphonate or placebos with a follow-up of at least one year were also considered. STATA 12.0 software was used for the meta-analysis. Results. Eleven randomized clinical trials were included in the meta-analysis. The data indicated that the percentage change in the increased BMD in the bisphosphonates groups was superior to that of the control groups at the lumbar spine and total hip. At the femoral neck, there was no significant difference between the two groups. The incidence of new fractures during follow-up showed significant reduction. The adverse event analysis revealed no significant difference between the two groups. Conclusion. Our results demonstrate that bisphosphonates therapy has an effect on bone loss in patients with IBD but show no evident efficiency at increasing the incidence of adverse events.

Long-term results of repeated anti-vascular endothelial growth factor therapy in eyes with retinal pigment epithelial tears.

Science.gov (United States)

Moreira, Carlos A; Arana, Luis A; Zago, Rommel J

2013-02-01

To evaluate the long-term results of retinal pigment epithelium tears in eyes treated with repeated anti-vascular endothelial growth factor (VEGF) therapy. Five patients with retinal pigment epithelial tears (without foveal center involvement) after anti-VEGF injection were studied retrospectively. Mean follow-up time was 52 months, with measurements of visual acuity and evaluation of macular findings by angiography and optical coherence tomography during this period. All eyes had a persistent submacular neovascular membrane 30 days after the tear. An anti-VEGF drug was reinjected until the membranes stopped leaking. The mean initial visual acuity immediately after the tear was 20/160, and the mean final visual acuity was 20/60. The number of anti-VEGF reinjections varied from two to eight during the follow-up period. Long-term optical coherence tomography analysis showed reduced fluid and remodeling of the torn retinal pigment epithelium. Long-term visual results with repeated anti-VEGF therapy are not as devastating as suggested previously. Visual acuity and metamorphopsia improve with time as long as the neovascular membrane is inactive. Optical coherence tomography changes in the macular area reflect the visual acuity improvement.

Beneficial Effects of Concentrated Growth Factors and Resveratrol on Human Osteoblasts In Vitro Treated with Bisphosphonates

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Elisa Borsani

2018-01-01

Full Text Available Bisphosphonates are primary pharmacological agents against osteoclast-mediated bone loss and widely used in the clinical practice for prevention and treatment of a variety of skeletal conditions, such as low bone density and osteogenesis imperfecta, and pathologies, such as osteoporosis, malignancies metastatic to bone, Paget disease of bone, multiple myeloma, and hypercalcemia of malignancy. However, long-term bisphosphonate treatment is associated with pathologic conditions including osteonecrosis of the jaw, named BRONJ, which impaired bone regeneration process. Clinical management of BRONJ is controversy and one recent approach is the use of platelet concentrates, such as Concentrated Growth Factors, alone or together with biomaterials or antioxidants molecules, such as resveratrol. The aim of the present study was to investigate the in vitro effects of Concentrated Growth Factors and/or resveratrol on the proliferation and differentiation of human osteoblasts, treated or not with bisphosphonates. Human osteoblasts were stimulated for 3 days in complete medium and for 21 days in mineralization medium. At the end of the experimental period, the in vitro effect on osteoblast proliferation and differentiation was evaluated using different techniques such as MTT, ELISA for the quantification/detection of osteoprotegerin and bone morphogenetic protein-2, immunohistochemistry for sirtuin 1 and collagen type I, and the Alizarin Red S staining for the rate of mineralization. Results obtained showed that Concentrated Growth Factors and/or resveratrol significantly increased osteoblast proliferation and differentiation and that the cotreatment with Concentrated Growth Factors and resveratrol had a protective role on osteoblasts treated with bisphosphonates. In conclusion, these data suggest that this approach could be promised in the clinical management of BRONJ.

Long-Term Care Services for Veterans

Science.gov (United States)

2017-02-14

includes but is not limited to home physical , occupational, or speech therapy ; wound care; and intravenous (IV) care. A VA physician determines that a...restoring/rehabilitating the veteran’s health, such as skilled nursing care, physical therapy , occupational therapy , and IV therapy Same as HBPC... geriatric evaluation,  palliative care,  adult day health care,  homemaker/home health aide care,  respite care, Long-Term Care Services for

Dispositional optimism as predictor of outcome in short- and long-term psychotherapy.

Science.gov (United States)

Heinonen, Erkki; Heiskanen, Tiia; Lindfors, Olavi; Härkäpää, Kristiina; Knekt, Paul

2017-09-01

Dispositional optimism predicts various beneficial outcomes in somatic health and treatment, but has been little studied in psychotherapy. This study investigated whether an optimistic disposition differentially predicts patients' ability to benefit from short-term versus long-term psychotherapy. A total of 326 adult outpatients with mood and/or anxiety disorder were randomized into short-term (solution-focused or short-term psychodynamic) or long-term psychodynamic therapy and followed up for 3 years. Dispositional optimism was assessed by patients at baseline with the self-rated Life Orientation Test (LOT) questionnaire. Outcome was assessed at baseline and seven times during the follow-up, in terms of depressive (BDI, HDRS), anxiety (SCL-90-ANX, HARS), and general psychiatric symptoms (SCL-90-GSI), all seven follow-up points including patients' self-reports and three including interview-based measures. Lower dispositional optimism predicted faster symptom reduction in short-term than in long-term psychotherapy. Higher optimism predicted equally rapid and eventually greater benefits in long-term, as compared to short-term, psychotherapy. Weaker optimism appeared to predict sustenance of problems early in long-term therapy. Stronger optimism seems to best facilitate engaging in and benefiting from a long-term therapy process. Closer research might clarify the psychological processes responsible for these effects and help fine-tune both briefer and longer interventions to optimize treatment effectiveness for particular patients and their psychological qualities. Weaker dispositional optimism does not appear to inhibit brief therapy from effecting symptomatic recovery. Patients with weaker optimism do not seem to gain added benefits from long-term therapy, but instead may be susceptible to prolonged psychiatric symptoms in the early stages of long-term therapy. © 2016 The British Psychological Society.

Long-term effect of exercise therapy in patients with osteoarthritis: a randomized controlled trial comparing two different physiotherapy interventions.

NARCIS (Netherlands)

Pisters, M.; Veenhof, C.; Schellevis, F.; Bakker, D. de; Dekker, J.

2011-01-01

Purpose: To determine if behavioural graded activity (BGA) results in better long-term effectiveness (5 years after inclusion) than usual exercise therapy (UC; usual care) in patients with OA of the hip or knee. Relevance: The positive effects of exercise therapy in patients with osteoarthritis seem

Safety of long-term PPI therapy

DEFF Research Database (Denmark)

Reimer, Christina

2013-01-01

Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been publishe...... to a careful evaluation of the indication for PPI treatment....

Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

NARCIS (Netherlands)

van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em

2014-01-01

Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on

Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study

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Meigs James B

2009-02-01

Full Text Available Abstract Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001 to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1 time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2 primary adherence (time from first prescription to prescription fill; (3 time until discontinuation of oral antidiabetic medication from first prescription; and (4 long-term adherence (amount dispensed versus amount prescribed over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7 and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes.

Bisphosphonate adverse effects, lessons from large databases

DEFF Research Database (Denmark)

Abrahamsen, Bo

2010-01-01

is on bisphosphonates used for osteoporosis. RECENT FINDINGS: Register studies have so far not confirmed a shift from classical to nonclassical femur fractures with bisphosphonates. However, studies were either small or without X-ray adjudication. Two new studies found no increase in jaw surgery for inflammatory...

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.

Science.gov (United States)

Herrera, L; Leal, I; Lapi, F; Schuemie, M; Arcoraci, V; Cipriani, F; Sessa, E; Vaccheri, A; Piccinni, C; Staniscia, T; Vestri, A; Di Bari, M; Corrao, G; Zambon, A; Gregori, D; Carle, F; Sturkenboom, M; Mazzaglia, G; Trifiro, G

2015-05-01

Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (reference point. A subgroup analysis by individual BP was then carried out. In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

The dental implications of bisphosphonates and bone disease.

Science.gov (United States)

Cheng, A; Mavrokokki, A; Carter, G; Stein, B; Fazzalari, N L; Wilson, D F; Goss, A N

2005-12-01

In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients.

[Disorders of lipid and glucose metabolism. Long-term adverse effects of antiretroviral therapy].

Science.gov (United States)

Landauer, N; Goebel, F D

2002-04-09

In addition to readily controllable short-term side effects, highly active antiretroviral therapy (HAART) also has long-term side effects: lipodystrophy syndrome, hyperlipoproteinemia, insulin resistance, elevated glucose tolerance sometimes leading to diabetes mellitus and lactic acidosis. The pathogenesis remains uncertain although various hypotheses have been advanced. A number of approaches for the treatment of lipodystrophy are available, the effects of which, however, have not been confirmed by study results. Hyperlipoproteinemia probably means an increased cardiovascular risk, but a final pronouncement on this is not yet possible. Fibrates and statins are currently applied for treatment, but interactions with HAART medicaments have to be considered. HAART-induced diabetes mellitus presents clinically as type 2 diabetes, and is treated accordingly.

Effects of long-term alendronate treatment on bone mineralisation, resorption parameters and biomechanics of single human vertebral trabeculae

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M Krause

2014-09-01

Full Text Available Due to their well-established fracture risk reduction, bisphosphonates are the most frequently used therapeutic agent to treat osteoporosis. Bisphosphonates reduce fracture risk by suppressing bone resorption, but the lower bone turnover could have a negative impact on bone quality at the tissue level. Here, we directly assess the structural and mechanical characteristics of cancellous bone from the lumbar vertebrae (L5 in non-treated osteoporotic controls (n = 21, mid-term alendronate-treated osteoporotic patients (n = 6, and long-term alendronate-treated osteoporotic patients (n = 7. The strength and toughness of single trabeculae were evaluated, while the structure was characterised through measurements of microdamage accumulation, mineralisation distribution, and histological indices. The alendronate-treated cases had a reduced eroded surface (ES/BS, p < 0.001 and a higher bone mineralisation in comparison to non-treated controls (p = 0.037, which is indicative of low turnover associated with treatment. However, the amount of microdamage and the mechanical properties were similar among the control and treatment groups. As the tissue mineral density (TMD increased significantly with alendronate treatment compared to non-treated osteoporotic controls, the reduction in resorption cavities could counterbalance the higher TMD allowing the alendronate-treated bone to maintain its mechanical properties and resist microdamage accumulation. A multivariate analysis of the possible predictors supports the theory that multiple factors (e.g., body mass index, TMD, and ES/BS can impact the mechanical properties. Our results suggest that long-term alendronate treatment shows no adverse impact on mechanical cancellous bone characteristics.

The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

Science.gov (United States)

Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

2011-10-01

The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience

Radiographic and MR Imaging Findings of the Spine after Bisphosphonate Treatment, in a Child with Idiopathic Juvenile Osteoporosis

Directory of Open Access Journals (Sweden)

Olympia Papakonstantinou

2015-01-01

Full Text Available Bisphosphonates are employed with increasing frequency in various pediatric disorders, mainly associated with osteoporosis. After cessation of bisphosphonate treatment in children, skeletal radiologic changes have been documented including dense metaphyseal lines of the long bones and “bone in bone” appearance of the vertebrae. However, the evolution of these radiographic changes has not been fully explored. We describe the MR imaging appearance of the spine that, to our knowledge, has not been previously addressed in a child with idiopathic juvenile osteoporosis who had received bisphosphonates and emphasize the evolution of the radiographic findings of the spine and pelvis over a four-year period.

T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

Science.gov (United States)

Da-Cruz, Alda Maria; Bittar, Rita; Mattos, Marise; Oliveira-Neto, Manuel P.; Nogueira, Ricardo; Pinho-Ribeiro, Vanessa; Azeredo-Coutinho, Rilza Beatriz; Coutinho, Sergio G.

2002-01-01

T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+ Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4+ than CD8+ T cells. In CL, the healing process was associated with a decrease of CD4+ and an increase of CD8+, leading to similar CD4+ and CD8+ proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4+/CD8+ ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-γ) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-γ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-γ, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4+ Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations. PMID:11874860

Hair and Nail Changes During Long-term Therapy With Ibrutinib for Chronic Lymphocytic Leukemia.

Science.gov (United States)

Bitar, Carole; Farooqui, Mohammed Z H; Valdez, Janet; Saba, Nakhle S; Soto, Susan; Bray, Amanda; Marti, Gerald; Wiestner, Adrian; Cowen, Edward W

2016-06-01

Ibrutinib, a Bruton tyrosine kinase inhibitor, is a new targeted agent approved by the US Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and Waldenström macroglobulinemia. Ibrutinib is overall well tolerated but long-term treatment is required until disease progression or intolerable toxic effects occur. Little is known regarding its cutaneous adverse effects. To describe the hair and nail manifestations associated with the long-term use of ibrutinib for the treatment of CLL. Prospective study of 66 patients with CLL enrolled in a single-arm phase 2 clinical trial of ibrutinib for CLL between March 2014 and October 2015 at the National Institutes of Health. The primary outcome, nail and hair changes associated with ibrutinib therapy, was assessed by an 11-question survey. In addition, the severity of nail changes was determined from a 0 to 3 rating scale for both onychoschizia and onychorrhexis. Among 66 patients (43 men and 23 women with ages ranging from 55 to 85 years), 44 (67%) reported brittle fingernails at a median of 6.5 (95% CI, 6-12) months after starting ibrutinib therapy. Fifteen patients (23%) developed brittle toenails after a median of 9 (95% CI, 6-15) months of ibrutinib therapy. Textural hair changes were reported in 17 patients (26%), at a median of 9 (95% CI, 6-12) months of ibrutinib treatment. Hair and nail abnormalities are commonly associated with ibrutinib and appear several months after initiating therapy. Ibrutinib inhibits Bruton tyrosine kinase by covalently binding to cysteine 481. Whether ibrutinib affects the hair and nails by binding and altering cysteine-rich proteins of hair and nails or by means of another mechanism remains unknown. clinicaltrials.gov Identifier: NCT01500733.

Long-term oxygen therapy for COPD. Improving longevity and quality of life in hypoxemic patients.

Science.gov (United States)

Weg, J G; Haas, C F

1998-04-01

Long-term oxygen therapy can increase life expectancy in hypoxemic patients with COPD. Accurate identification of hypoxemia requires arterial blood gas measurements. Pulse oximetry can be used to measure trends in oxygenation, oxygen needs, and oxygen requirements during exercise and sleep. A detailed oxygen prescription indicates: (1) the oxygen dose (L/min), (2) the number of hours per day that oxygen therapy is required, (3) the dose required during exercise, (4) the oxygen supply system: concentrator, compressed gas cylinder, or liquid oxygen reservoir, and (5) the delivery device: nasal cannula, demand-flow device, reservoir cannula, or transtracheal oxygen catheter.

Long-Term Outcomes of Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder.

Science.gov (United States)

Krebs, Georgina; de la Cruz, Lorena Fernández; Monzani, Benedetta; Bowyer, Laura; Anson, Martin; Cadman, Jacinda; Heyman, Isobel; Turner, Cynthia; Veale, David; Mataix-Cols, David

2017-07-01

Emerging evidence suggests that cognitive-behavioral therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomized controlled trial of CBT for BDD to determine whether treatment gains were maintained. Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, midtreatment, posttreatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month follow-up. Neither baseline insight nor baseline depression predicted long-term outcomes. The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes. Copyright © 2017. Published by Elsevier Ltd.

Lateral Cortical Thickening and Bone Heterogeneity of the Subtrochanteric Femur Measured With Quantitative CT as Indicators for Early Detection of Atypical Femoral Fractures in Long-Term Bisphosphonate Users.

Science.gov (United States)

Lee, Seung Hyun; Lee, Young Han; Suh, Jin-Suck

2017-10-01

The objective of our study was to compare subtrochanteric femur bone mineral density (BMD) and bone quality of long-term bisphosphonate (BP) users who sustained an atypical femoral fracture (AFF) with BP users who did not sustain a femoral fracture and BP-naïve patients with no history of femoral fracture using quantitative CT (QCT). Fourteen female BP users with an AFF (mean age, 72.6 years; mean duration of BP use, 6.2 years; mean body mass index, 21.9) who had undergone QCT before fracture events were sex-, age-, BP use duration-, and body mass index-matched to 14 BP users who did not sustain a fracture and 14 BP-naïve patients. The lateral cortical thickness index (CTI) and the mean BMD (BMD mean ) and SD of the BMD (BMD SD ) within the lateral cortex and within the entire cross-sectional area of the subtrochanteric femur were measured on axial QCT. Femoral neck-shaft angles were measured on the QCT scout image. Parameters were analyzed using the Kruskal-Wallis test. Lateral CTIs were greater in the BP users with an AFF (median, 0.28) than in the BP users without a femoral fracture (median, 0.21) (p = 0.038) and the BP-naïve group (median, 0.21) (p = 0.009). The lateral cortex BMD SD was significantly higher in the BP users with an AFF (median, 59.59 mg/cm 3 ) than the BP users without a femoral fracture (median, 39.27 mg/cm 3 ; p = 0.049) and the BP-naïve group (median, 31.02 mg/cm 3 ; p = 0.037). There was no significant difference among groups in lateral cortex BMD mean , BMD mean and BMD SD of the entire cross-sectional area, and femoral neck-shaft angle. Long-term BP users with a subsequent AFF had a thicker lateral cortex and higher lateral cortex BMD SD at the subtrochanteric area before the fracture on QCT than BP users who did not sustain a femoral fracture and BP-naïve patients.

Radiation therapy for wet type age-related macular degeneration. Long term follow-up results

Energy Technology Data Exchange (ETDEWEB)

Sasai, Keisuke; Hiraoka, Masahiro; Mandai, Michiyo; Takahashi, Masayo; Honda, Yoshihito [Kyoto Univ. (Japan). Faculty of Medicine

1998-12-01

Between April, 1994 and July, 1995, 33 patients with occult type choroidal neovascularization (CNV) with or without the classical type CNV of the wet type age-related macular degeneration ARMD were treated with radiation therapy (10 Gy/5 fx/1 week or 20 Gy/10 fx/2 weeks). This phase I/II study showed that radiation therapy seems to be useful for CNV during the first 12 months. Some eyes which initially showed good response to irradiation began to lose their visual acuity. However, the dose of 20 Gy in 10 fractions seemed useful to maintain the visual acuity better than 0.1 in this long term follow-up study (24 months). (author)

Long-term follow-up study of the therapeutic effect after iodine-131 therapy for hyperthyroidism

International Nuclear Information System (INIS)

Liu Changjiang; Li Long; Gao Jianqing; Xu Sumei; Chen Linna; Zhou Jianming

2006-01-01

To investigate the therapeutic effect through long-term visit and analyze the affecting factors of cure rate after iodine-131 therapy for hyperthyroidism, a long-term follow-up has been undertaken for the patients with hyperthyroidism after iodine-131 treatment. The following results have been obtained. (1) The cure rate of iodine-131 therapy for hyperthyroidism is 74.4%, and the incidence of permanent hypothyroidism is 7.5%. (2) There is no significant difference in the cure rate and incidence of hypothyroidism between the groups of male and female or 'not take ATD' and 'ATD withdrawn longer than 2 weeks' (P>0.05). (3) The difference of the cure rate among the groups of the courses of disease 3 a are significant (P 55 g are significant (P 0.05). The course of disease, age and thyroid mass are the major factors which influence the cure rate. Meanwhile, age and thyroid mass are the major factors which influence the incidence of hypothyroidism. To get high cure rate, the patients with hyperthyroidism should be treated with iodine-131 as early as possible. In the meantime, the incidence of permanent hypothyroidism must be paid attention to. (authors)

Impact of long-term corticosteroid therapy on the distribution pattern of lower limb atherosclerosis.

Science.gov (United States)

Willenberg, T; Diehm, N; Zwahlen, M; Kalka, C; Do, D-D; Gretener, S; Ortmann, J; Baumgartner, I

2010-04-01

Ectopic calcification and mediacalcinosis can be promoted by corticosteroid use. Aim of the present investigation is to describe macrovascular disease features in patients with long-term corticosteroid therapy and symptomatic lower limb peripheral arterial occlusive disease (PAD). A consecutive series of 2783 patients undergoing clinical and angiographic work-up of PAD were screened for long-term (>5 years) corticosteroid use (group A). Comparison was performed to a randomly selected age-, sex- and risk factor-matched PAD control cohort from the same series without corticosteroid use (group B). Patients with diabetes mellitus or severe renal failure were excluded. Arterial calcification was evaluated by qualitative assessment on radiographic images. Severity of atherosclerotic lesions was analysed from angiographic images using a semi-quantitative score (Bollinger score). In general, 12 patients (5 males, mean age 78.5 +/- 9.0 years) with 15 ischaemic limbs qualified to be enrolled in group A and were compared to 23 matching control patients (6 2 males, mean age 79.5 +/- 6 years) with 32 ischaemic limbs. Incompressibility of ankle arteries determined by measurement of the ankle-brachial index was seen in 12 limbs (80%) in group A compared to 3 limbs (9%) in group B (p = 0.0009). No significant difference was found comparing group A and B for segmental calcification, whereas comparison of the atherosclerotic burden using the angiographic severity score showed a significantly higher score at the infragenicular arterial level in group A (p = 0.001). Findings suggest that the long-term corticosteroid therapy is associated with a distally accentuated, calcifying peripheral atherosclerosis inducing arterial incompressibility. This occlusion pattern is comparable to patients with renal failure or diabetes. Further research is required to support our observations.

Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up of a randomized clinical trial.

Science.gov (United States)

Rutqvist, L E; Pettersson, D; Johansson, H

1993-02-01

This paper presents long-term results from a randomized trial of pre- or postoperative megavoltage radiation therapy versus surgery alone in pre- and postmenopausal women with operable breast cancer. Treatment outcome after relapse among patients who developed loco-regional recurrences was also analyzed. A total of 960 patients were included in the trial. The mean follow-up was 16 years (range: 13-19 years). The radiation therapy was individually planned. It included the chest wall (and the breast in the preoperative cases) and the regional lymph nodes. The tumor dose was 45 Gy/5 weeks. No adjuvant systemic therapy was used. The results showed a significant benefit with radiation therapy in terms of recurrence-free survival during the entire follow-up period. There was also an overall survival difference-corresponding to a 16% reduction of deaths-in favor of the irradiated patients which, however, was not statistically significant (p = 0.09). Among those 169 patients who developed locoregional recurrences long-term control was only achieved in about one-third of the cases. This figure was similar among those who had received adjuvant radiation therapy (34%) compared to those initially treated with surgery alone (32%). This implied that the overall proportion of patients who eventually developed uncontrolled local disease was significantly higher among those initially allocated to surgery alone (16%) compared to those allocated to pre- or postoperative radiation therapy (6%, p < 0.01). These results suggest that local undertreatment may be deleterious in subgroups of patients.

Short-term and long-term outcomes of intrathoracic vacuum therapy of empyema in debilitated patients

Directory of Open Access Journals (Sweden)

Zsolt Sziklavari

2016-10-01

Full Text Available Abstract Background This retrospective study analyzed the effectiveness of intrathoracic negative pressure therapy for debilitated patients with empyema and compared the short-term and long-term outcomes of three different intrapleural vacuum-assisted closure (VAC techniques. Methods We investigated 43 consecutive (preseptic patients with poor general condition (Karnofsky index ≤ 50 % and multimorbidity (≥ 3 organ diseases or immunosuppression, who had been treated for primary, postoperative, or recurrent pleural empyema with VAC in combination with open window thoracostomy (OWT-VAC with minimally invasive technique (Mini-VAC, and instillation (Mini-VAC-Instill. Results The overall duration of intrathoracic vacuum therapy was 14 days (5–48 days. Vacuum duration in the Mini-VAC and Mini-VAC-Instill groups (12.4 ± 5.7 and 10.4 ± 5.4 days was significantly shorter (p = 0.001 than in the group treated with open window thoracostomy (OWT-VAC (20.3 ± 9.4 days. No major complication was related to intrathoracic VAC therapy. Chest wall closure rates were significantly higher in the Mini-VAC and Mini-VAC-Instill groups than in the OWT-VAC group (p = 0.034 and p = 0.026. Overall, the mean postoperative length of stay in hospital (LOS was 21 days (median 18, 6–51 days. LOS was significantly shorter (p = 0.027 in the Mini-VAC-Instill group (15.1 ± 4.8 than in the other two groups (23.8 ± 12.3 and 22.7 ± 1.5. Overall, the 30-day and 60-day mortality rates were 4.7 % (2/43 and 9.3 % (4/43, and none of the deaths was related to infection. Conclusions For debilitated patients, immediate minimally invasive intrathoracic vacuum therapy is a safe and viable alternative to OWT. Mini-VAC-Instill may have the fastest clearance and healing rates of empyema.

Short-term and long-term outcomes of intrathoracic vacuum therapy of empyema in debilitated patients.

Science.gov (United States)

Sziklavari, Zsolt; Ried, Michael; Zeman, Florian; Grosser, Christian; Szöke, Tamas; Neu, Reiner; Schemm, Rudolf; Hofmann, Hans-Stefan

2016-10-21

This retrospective study analyzed the effectiveness of intrathoracic negative pressure therapy for debilitated patients with empyema and compared the short-term and long-term outcomes of three different intrapleural vacuum-assisted closure (VAC) techniques. We investigated 43 consecutive (pre)septic patients with poor general condition (Karnofsky index ≤ 50 %) and multimorbidity (≥ 3 organ diseases) or immunosuppression, who had been treated for primary, postoperative, or recurrent pleural empyema with VAC in combination with open window thoracostomy (OWT-VAC) with minimally invasive technique (Mini-VAC), and instillation (Mini-VAC-Instill). The overall duration of intrathoracic vacuum therapy was 14 days (5-48 days). Vacuum duration in the Mini-VAC and Mini-VAC-Instill groups (12.4 ± 5.7 and 10.4 ± 5.4 days) was significantly shorter (p = 0.001) than in the group treated with open window thoracostomy (OWT)-VAC (20.3 ± 9.4 days). No major complication was related to intrathoracic VAC therapy. Chest wall closure rates were significantly higher in the Mini-VAC and Mini-VAC-Instill groups than in the OWT-VAC group (p = 0.034 and p = 0.026). Overall, the mean postoperative length of stay in hospital (LOS) was 21 days (median 18, 6-51 days). LOS was significantly shorter (p = 0.027) in the Mini-VAC-Instill group (15.1 ± 4.8) than in the other two groups (23.8 ± 12.3 and 22.7 ± 1.5). Overall, the 30-day and 60-day mortality rates were 4.7 % (2/43) and 9.3 % (4/43), and none of the deaths was related to infection. For debilitated patients, immediate minimally invasive intrathoracic vacuum therapy is a safe and viable alternative to OWT. Mini-VAC-Instill may have the fastest clearance and healing rates of empyema.

What are the short-term and long-term effects of occupation-focused and occupation-based occupational therapy in the home on older adults' occupational performance?

DEFF Research Database (Denmark)

Nielsen, Tove Lise; Petersen, Kirsten Schultz; Nielsen, Claus Vinther

2016-01-01

critically appraised 13 of 995 detected papers. Extracted data were presented and summarised descriptively. Results Eight high-quality papers showed that occupation-focused and occupation-based occupational therapy using cognitive, behavioural and environmental strategies may significantly improve......Abstract Title What are the short-term and long-term effects of occupation-focused and occupation-based occupational therapy in the home on older adults’ occupational performance? A systematic review Background There is a lack of evidence-based knowledge about the effectiveness of home......-based occupational therapy for older adults aimed at improving occupational performance by practicing activities and tasks. Aim This review synthesizes and discusses evidence for the effectiveness of occupation-focused and occupation-based occupational therapy for older adults at home. Material and methods Peer...

The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro

Directory of Open Access Journals (Sweden)

Said Yekta Sareh

2011-02-01

Full Text Available Abstract Background Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ often requires surgical treatment and is accompanied with a disturbed wound healing. Therefore, the influence on adhesion and migration of human osteoblasts (hOB after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods. Methods By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10-5M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control. Results After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels. Conclusion Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.

Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

Science.gov (United States)

Wright, N C; Foster, P J; Mudano, A S; Melnick, J A; Lewiecki, M E; Shergy, W J; Curtis, J R; Cutter, G R; Danila, M I; Kilgore, M L; Lewis, E C; Morgan, S L; Redden, D T; Warriner, A H; Saag, K G

2017-08-01

The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide "drug holiday" clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a

Relationship of long-term highly active antiretroviral therapy on salivary flow rate and CD4 Count among HIV-infected patients.

Science.gov (United States)

Kumar, J Vijay; Baghirath, P Venkat; Naishadham, P Parameswar; Suneetha, Sujai; Suneetha, Lavanya; Sreedevi, P

2015-01-01

To determine if long-term highly active antiretroviral therapy (HAART) therapy alters salivary flow rate and also to compare its relation of CD4 count with unstimulated and stimulated whole saliva. A cross-sectional study was performed on 150 individuals divided into three groups. Group I (50 human immunodeficiency virus (HIV) seropositive patients, but not on HAART therapy), Group II (50 HIV-infected subjects and on HAART for less than 3 years called short-term HAART), Group III (50 HIV-infected subjects and on HAART for more than or equal to 3 years called long-term HAART). Spitting method proposed by Navazesh and Kumar was used for the measurement of unstimulated and stimulated salivary flow rate. Chi-square test and analysis of variance (ANOVA) were used for statistical analysis. The mean CD4 count was 424.78 ± 187.03, 497.82 ± 206.11 and 537.6 ± 264.00 in the respective groups. Majority of the patients in all the groups had a CD4 count between 401 and 600. Both unstimulated and stimulated whole salivary (UWS and SWS) flow rates in Group I was found to be significantly higher than in Group II (P flow rate between Group II and III subjects were also found to be statistically significant (P relationship in Group II (P flow rates of HIV-infected individuals who are on long-term HAART.

Inflammatory eye reactions with bisphosphonates and other osteoporosis medications

DEFF Research Database (Denmark)

Clark, Emma M; Durup, Darshana

2015-01-01

Inflammatory eye reactions (IERs) are rare but have been associated with medications to treat osteoporosis. The aim of this review is to summarize the current literature on the association between IERs and specific medications to treat osteoporosis (bisphosphonates, selective estrogen receptor...... of the information available is from spontaneous case reports and case series reporting associations between bisphosphonates and IERs. No case reports describe IERs after other anti-osteoporosis medications. Importantly, some case reports describe recurrence of the IER after affected patients were rechallenged...... with the same or another bisphosphonate, and that no reported cases resolved without discontinuation of the bisphosphonate. However, three large population-based cohort studies have shown conflicting results between osteoporosis treatments and IERs, but overall these studies suggest that IERs may actually...

Can long-term alopecia occur after appropriate pulsed-dye laser therapy in hair-bearing sites? Pediatric dermatologists weigh in.

Science.gov (United States)

Feldstein, Stephanie; Totri, Christine R; Friedlander, Sheila F

2015-03-01

The risk of long-term alopecia after pulsed-dye laser (PDL) therapy is unknown. To identify how many practitioners treat hair-bearing sites with PDL and how commonly long-term alopecia occurs, the authors queried pediatric dermatologists about their experiences using this modality. A survey was designed to evaluate the frequency of and factors contributing to long-term alopecia after PDL treatment of port-wine stains (PWS). "Long-term" was defined as no sign of hair regrowth after several years of nontreatment. The survey was administered to attendees at the 2014 Society for Pediatric Dermatology biannual meeting. Sixty-four pediatric dermatologists completed the survey, 50 of whom had experience using PDL. Of these physicians, 86% have used PDL to treat PWS of the eyebrow and 80% have treated PWS of the scalp. Over one-quarter of respondents (25.5%) using PDL on hair-bearing areas had at least 1 of their patients develop long-term alopecia after PDL treatment. The incidence of long-term alopecia after PDL treatment in the surveyed population was 1.5% to 2.6%. The occurrence of long-term alopecia at hair-bearing sites after treatment with PDL may be greater than previously thought. Because the majority of physicians using PDL treat hair-bearing areas, prospective studies are needed to more accurately determine the risk of long-term alopecia and the factors that contribute to it.

Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite.

Science.gov (United States)

Kos, Marcin; Junka, Adam; Smutnicka, Danuta; Szymczyk, Patrycja; Gluza, Karolina; Bartoszewicz, Marzenna

2015-07-01

Because of the suspicion that bisphosphonates enhance bacterial colonization, this study evaluated adhesion and biofilm formation by Streptococcus mutans 25175, Staphylococcus aureus 6538, and Pseudomonas aeruginosa 14454 reference strains on hydroxyapatite coated with clodronate, pamidronate, or zoledronate. Bacterial strains were cultured on bisphosphonate-coated and noncoated hydroxyapatite discs. After incubation, nonadhered bacteria were removed by centrifugation. Biofilm formation was confirmed by scanning electron microscopy. Bacterial colonization was estimated using quantitative cultures compared by means with Kruskal-Wallis and post-hoc Student-Newman-Keuls tests. Modeling of the interactions between bisphosphonates and hydroxyapatite was performed using the Density Functional Theory method. Bacterial colonization of the hydroxyapatite discs was significantly higher for all tested strains in the presence of bisphosphonates vs. Adherence in the presence of pamidronate was higher than with other bisphosphonates. Density Functional Theory analysis showed that the protonated amine group of pamidronate, which are not present in clodronate or zoledronate, forms two additional hydrogen bonds with hydroxyapatite. Moreover, the reactive cationic amino group of pamidronate may attract bacteria by direct electrostatic interaction. Increased bacterial adhesion and biofilm formation can promote osteomyelitis, cause failure of dental implants or bisphosphonate-coated joint prostheses, and complicate bone surgery in patients on bisphosphonates. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Long-term effectiveness of highly active antiretroviral therapy (HAART) in perinatally HIV-infected children in Denmark

DEFF Research Database (Denmark)

Bracher, Linda; Valerius, Niels Henrik; Rosenfeldt, Vibeke

2007-01-01

children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline......The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients ... characteristics were median CD4 percentage 14% and HIV-RNA viral load 4.9 log(10). Within the first 12 weeks of therapy approximately 60% achieved HIV-RNA viral load children changed the components of HAART. The proportion of children with CD4...

Using music therapy to help a client with Alzheimer's disease adapt to long-term care.

Science.gov (United States)

Kydd, P

2001-01-01

The purpose of this case study is to illustrate how music therapy can be used to help the elderly successfully adjust to living in a long-term care (LTC) facility. LTC residents, particularly those with Alzheimer's disease or related dementia, may exhibit behaviors such as depression, withdrawal, anxiety, emotional liability, confusion, and memory difficulties, frequently related to the disorder, but often exacerbated by difficulty in adjustment to the change in lifestyle. The subject of this case study demonstrated these symptoms. Music therapy helped him adjust to life in a LTC setting by improving his quality of life and enhancing his relationships with those around him. As chronicled in this study, music therapy may facilitate a resident's adjustment to life in a LTC facility. N.B. Names and identifying information have been changed to protect privacy.

Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage

DEFF Research Database (Denmark)

Ottosen, Tobias Pilgaard; Grijota, Miriam; Hansen, Morten Lock

2016-01-01

inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality......BACKGROUND AND PURPOSE: The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage...... and examined the impact of subsequent AT use on the long-term clinical outcome. METHODS: We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were...

Pros and Cons of Long-Term use of Nicotine Replacement Therapies: A Qualitative Study

DEFF Research Database (Denmark)

Borup, Gitte; Kaae, Susanne; Nørgaard, Lotte Stig

2016-01-01

, intrapersonal processes, the social environment of smoking vs. NRTs and finances. None of the ex-smokers feared to relapse to smoking, and few were motivated to quit NRTs. Non-nicotinic factors were found to have an important role in developing an addiction to NRTs. The use of NRTs yields some of the expected......, including perceived pros and cons of using NRTs, the risk of relapse to smoking and their motivation to quit using NRTs. The results identified five major themes that entailed pros and cons of the long-term use of NRTs. These were the non-nicotinic factors of NRTs, health risks of NRTs vs. smoking......In the last decade, harm reduction has been increasingly suggested as a method to reduce the harm caused by smoking in smokers who are unable or unwilling to quit all nicotine products. One of these methods includes long-term substitution of tobacco with nicotine replacement therapies (NRTs...

Bisphosphonate Treatment and Pregnancy

Science.gov (United States)

... rats given bisphosphonates during pregnancy developed calcium deficiency (hypocalcemia), which led to abnormal bone development, and also slow, difficult labor and delivery. Effects related to low calcium are not expected in ...

[Requirements for long-term follow-up on efficacy and safety of advanced therapy medicinal products. Risk management and traceability].

Science.gov (United States)

Klug, B; Reinhardt, J; Schröder, C

2010-01-01

Advanced therapy medicinal products (ATMPs) are an innovative treatment option. To promote timely access of the innovative medicinal product and to safeguard public health, new elements have been introduced into legislation. A key element of the ATMP regulation is the requirement for long-term follow-up on safety and efficacy of patients enrolled in clinical trials with ATMPs, which is beyond the routine requirements on pharmacovigilance. For gene therapy medicinal products, a guideline on long-term follow-up, which lays down the technical requirements, is available. A further key element of the ATMP regulation is the traceability of the starting materials used to manufacture the ATMP. A common European coding system is imperative to ensure the traceability of starting materials, especially across the borders of European Member States.

Long-term effects of radiation therapy on white matter of the corpus callosum: a diffusion tensor imaging study in children

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Makola, Monwabisi [University of Cincinnati, College of Medicine, Cincinnati, OH (United States); Douglas Ris, M. [Texas Children' s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States); Mahone, E.M. [Kennedy Krieger Institute, Department of Neuropsychology, Baltimore, MD (United States); Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD (United States); Yeates, Keith Owen [University of Calgary, Department of Psychology, Alberta Children' s Hospital Research Institute, Hotchkiss Brain Institute, Calgary, AB (Canada); Cecil, Kim M. [Imaging Research Center, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); University of Cincinnati College of Medicine, Department of Radiology, Cincinnati, OH (United States); University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, OH (United States); University of Cincinnati College of Medicine, Neuroscience Graduate Program, Cincinnati, OH (United States); University of Cincinnati College of Medicine, Department of Environmental Health, Cincinnati, OH (United States)

2017-12-15

Despite improving survival rates, children are at risk for long-term cognitive and behavioral difficulties following the diagnosis and treatment of a brain tumor. Surgery, chemotherapy and radiation therapy have all been shown to impact the developing brain, especially the white matter. The purpose of this study was to determine the long-term effects of radiation therapy on white matter integrity, as measured by diffusion tensor imaging, in pediatric brain tumor patients 2 years after the end of radiation treatment, while controlling for surgical interventions. We evaluated diffusion tensor imaging performed at two time points: a baseline 3 to 12 months after surgery and a follow-up approximately 2 years later in pediatric brain tumor patients. A region of interest analysis was performed within three regions of the corpus callosum. Diffusion tensor metrics were determined for participants (n=22) who underwent surgical tumor resection and radiation therapy and demographically matched with participants (n=22) who received surgical tumor resection only. Analysis revealed that 2 years after treatment, the radiation treated group exhibited significantly lower fractional anisotropy and significantly higher radial diffusivity within the body of the corpus callosum compared to the group that did not receive radiation. The findings indicate that pediatric brain tumor patients treated with radiation therapy may be at greater risk of experiencing long-term damage to the body of the corpus callosum than those treated with surgery alone. (orig.)

Long-term effects of radiation therapy on white matter of the corpus callosum: a diffusion tensor imaging study in children

International Nuclear Information System (INIS)

Makola, Monwabisi; Douglas Ris, M.; Mahone, E.M.; Yeates, Keith Owen; Cecil, Kim M.

2017-01-01

Despite improving survival rates, children are at risk for long-term cognitive and behavioral difficulties following the diagnosis and treatment of a brain tumor. Surgery, chemotherapy and radiation therapy have all been shown to impact the developing brain, especially the white matter. The purpose of this study was to determine the long-term effects of radiation therapy on white matter integrity, as measured by diffusion tensor imaging, in pediatric brain tumor patients 2 years after the end of radiation treatment, while controlling for surgical interventions. We evaluated diffusion tensor imaging performed at two time points: a baseline 3 to 12 months after surgery and a follow-up approximately 2 years later in pediatric brain tumor patients. A region of interest analysis was performed within three regions of the corpus callosum. Diffusion tensor metrics were determined for participants (n=22) who underwent surgical tumor resection and radiation therapy and demographically matched with participants (n=22) who received surgical tumor resection only. Analysis revealed that 2 years after treatment, the radiation treated group exhibited significantly lower fractional anisotropy and significantly higher radial diffusivity within the body of the corpus callosum compared to the group that did not receive radiation. The findings indicate that pediatric brain tumor patients treated with radiation therapy may be at greater risk of experiencing long-term damage to the body of the corpus callosum than those treated with surgery alone. (orig.)

Long-term outcomes of mandibular kinematics following class II malocclusion therapy with removable functional appliance therapy.

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Linsen, Sabine S; Wolf, Michael; Müßig, Dieter

2016-11-01

To evaluate mandibular kinematics in class I adults following class II therapy with removable functional appliances (RFAs) during the growth period in comparison with orthodontically untreated class I and II individuals. Condylar (CRoM) and incisal range of motion (InRoM), velocity during opening and closing, and the mandibular rotation angle were recorded using an ultrasound-based jaw-tracking system in 36 test patients (mean age = 28.03 ± 6.58 years). Significant group effects were found for CRoM towards the posterior in the right joint (p = 0.002) and InRoM towards the anterior (p = 0.043). The post hoc Tukey test indicates a significantly longer CRoM (posterior) for the right condyle in class II (p = 0.003) and RFA individuals (p = 0.023). The kinematic data imply greater dentoalveolar effects due to RFA therapy than adaptive remodeling of the temporomandibular joint. The class I relationship in the RFA group following treatment indicates stable long-term outcomes.

Long term control of a maxillary sinus mucoepidermoid carcinoma with low dose radiation therapy: a case report

International Nuclear Information System (INIS)

Vulpe, Horia; Giuliani, Meredith; Goldstein, David; Perez-Ordonez, Bayardo; Dawson, Laura A; Hope, Andrew

2013-01-01

Mucoepidermoid carcinoma of the maxillary sinus is a rare malignancy of the head and neck. The location of this tumour near vital structures and its large size at presentation makes surgical resection with negative margins challenging. In incurable cases, relief from symptoms such as epistaxis may be achieved with radiation therapy. We present a case of mucoepidermoid carcinoma of the maxillary sinus that was effectively palliated with a short course of radiation therapy, achieving complete cessation of bleeding, decrease in tumour size, and long term control. We surveyed the literature on mucoepidermoid carcinomas and propose that some tumours may be particularly radiosensitive, benefiting from even short courses of radiation therapy

Tubing length for long-term oxygen therapy.

Science.gov (United States)

Aguiar, Carolina; Davidson, Josy; Carvalho, Andréa K; Iamonti, Vinícius C; Cortopassi, Felipe; Nascimento, Oliver A; Jardim, José R

2015-02-01

Most patients on long-term oxygen therapy use stationary oxygen delivery systems. It is not uncommon for guidelines to instruct patients to use tubing lengths no longer than 19.68 ft (6 m) when using an oxygen concentrator and 49.21 ft (15 m) when using cylinders. However, these concepts are not based on sufficient evidence. Thus, our objective was to evaluate whether a 98.42-ft (30-m) tubing length affects oxygen flow and FIO2 delivery from 1 cylinder and 2 oxygen concentrators. The 3 oxygen delivery systems were randomly selected, and 1, 3, and 5 L/min flows and FIO2 were measured 5 times at each flow at the proximal and distal outlets of the tubing by a gas-flow analyzer. Paired Student t test was used to analyze the difference between flows and FIO2 at proximal and distal outlets of tubing length. A total of 45 flows were measured between proximal and distal outlets of the 98.42-ft (30-m) tubing. Flows were similar for 1 and 3 L/min, but distal flow was higher than proximal flow at 5 L/min (5.57×5.14 L/min, Ptubing at flows 1, 3, and 5 L/min, but the mean difference between measurements was less than 1%. Tubing length of 98.42 ft (30 m) may be used by patients for home delivery oxygen with flows up to 5 L/min, as there were no important changes in flows or FIO2. Copyright © 2015 by Daedalus Enterprises.

Long-term impairment of the lacrimal glands after radioiodine therapy: a cross-sectional study

International Nuclear Information System (INIS)

Zettinig, Georg; Fueger, Barbara J.; Pirich, Christian; Dudczak, Robert; Hanselmayer, Georg; Nepp, Johannes; Hofmann, Andrea

2002-01-01

Impairment of the lacrimal glands after external radiation has been well documented, but there are only a few reports on the effects of radioiodine therapy on the lacrimal glands. Long-term effects of high-dose radioiodine therapy on tear secretion have not previously been studied. We investigated 175 eyes of 88 patients with a history of radioiodine therapy for thyroid carcinoma (68 females, 20 males; mean age 55±16 years, range 17-81 years) and compared them with a sex- and age-matched control group (n=39). All patients had been given at least 2.96 GBq iodine-131 (maximal administered activity 22.3 GBq 131 I). An ophthalmological investigation was performed 64±71 months (range 3-317 months) after initial radioiodine therapy by a single ophthalmologist. Lacrimal gland function was evaluated with three different function tests. External eye morphology was considered, and detailed ophthalmological history-taking was performed. Patients with factors known to affect lacrimal gland function (contact lenses, autoimmune disorders, history of additional radiation exposure) were excluded from the study. A total of 81 patients (92%) had at least one abnormal function test indicating impaired lacrimal gland function. Schirmer's tear test was decreased (<10 mm/5 min) in 47 of the 88 patients and definitely abnormal (<5 mm/5 min) in 35 patients. A tear film break-up time of <10 s was found in 78 patients, and 62 patients had a definitely abnormal break-up time of <5 s. The lacrimal lipid layer was impaired in 43 patients. The function tests were all significantly altered in the study group as compared with the controls (P<0.005, P<0.001, P<0.001, respectively). Both subjective symptoms of dry eye (P<0.01) and changes in the external eye morphology (P<0.001) were significantly more prevalent in the study group. Our findings suggest that in the majority of patients, lacrimal gland function may be permanently impaired after high-dose radioiodine therapy. All three layers of the

Treatment of bisphosphonate related osteonecrosis following root canal therapy at the 1-year follow-up: report of two cases

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Kaptan F

2013-12-01

Full Text Available Figen Kaptan,1 Meric Karapinar Kazandag,1 Ufuk Iseri21Yeditepe University, Faculty of Dentistry, Department of Endodontics, 2Department of Prosthodontics, Istanbul, TurkeyAbstract: The objective of this report was to use topical gaseous ozone as an adjunct to conventional treatment methods and to describe the multidisciplinary management of bisphosphonate associated bone necrosis, which developed following endodontic treatment. No complaints were noted by the patients at their 1-year follow-up and the treatment showed favorable prognosis.Keywords: bisphosphonate, osteonecrosis, BRONJ, endodontics, oxygen, ozone

Oroantral fistula from bisphosphonate induced osteonecrosis of the jaw

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Henry Sharp

2010-07-01

Full Text Available Bisphosphonates like alendronic acid, disodium etidronate, and risedronate are effective for preventing postmenopausal and corticosteroid induced osteoporosis. They are also useful in the treatment of Paget’s disease, hypercalcaemia of malignancy and in bony metastases. However osteonecrosis of the jaw has been reported following intravenous bisphosphonate use and rarely in those taking them orally.Increasingly, oroantral fistulae have been shown to occur as sequelae of bisphosphonate-induced osteonecrosis of the jaw and this case report highlights a patient that presented to our ENT department and required sinus surgery in collaboration with maxillofacial surgeons.This case report aims to raise awareness among ENT surgeons to these patients on bisphosphonates that could present to them with sinus disease from oroantral fistulae. There is an on-going audit in the maxillofacial community on this emerging trend.

Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

Science.gov (United States)

Arponen, Heidi; Vuorimies, Ilkka; Haukka, Jari; Valta, Helena; Waltimo-Sirén, Janna; Mäkitie, Outi

2015-03-01

Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology

Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

Directory of Open Access Journals (Sweden)

Luca Dalle Carbonare

2010-08-01

Full Text Available Luca Dalle Carbonare, Mirko Zanatta, Adriano Gasparetto, Maria Teresa ValentiClinic of Internal Medicine D, Department of Medicine, University of Verona, ItalyAbstract: Bisphosphonates (BPs are widely used in the treatment of postmenopausal ­osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively. The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis, and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.Keywords: bisphosphonates, osteoporosis, safety, tolerability, zoledronic acid

Iron Deficiency in Long-Term Parenteral Nutrition Therapy.

Science.gov (United States)

Hwa, Yi L; Rashtak, Shahrooz; Kelly, Darlene G; Murray, Joseph A

2016-08-01

Iron is not routinely added to parenteral nutrition (PN) formulations in the United States because of the risk of anaphylaxis and concerns about incompatibilities. Studies have shown that iron dextran in non-lipid-containing PN solutions is safe. Data are limited on iron status, prevalence of iron deficiency anemia (IDA), and efficacy of intravenous iron infusion in long-term home PN (HPN). We aimed to determine the incidence of IDA and to examine the effectiveness of parenteral iron replacement in patients receiving HPN. Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated. Of 185 patients (122 women), 60 (32.4%) were iron deficient. Five patients were iron deficient, and 18 had unknown iron status before HPN. Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2-149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P Parenteral and Enteral Nutrition.

Testosterone Replacement Therapy: Long-Term Safety and Efficacy

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Giovanni Corona

2017-08-01

Full Text Available Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG or late-onset hypogonadism (LOH. The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T therapy (TTh. In addition, concerns related to cardiovascular (CV safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented.

Bisphosphonates and risk of cardiovascular events: a meta-analysis.

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Dae Hyun Kim

Full Text Available Some evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV events, atrial fibrillation, myocardial infarction (MI, stroke, and CV death in adults with or at risk for low bone mass.A systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs and 95% confidence intervals (CIs of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.Absolute risks over 25-36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84-1.14]; I2 = 0.0%, atrial fibrillation (41 trials; 1.08 [0.92-1.25]; I2 = 0.0%, MI (10 trials; 0.96 [0.69-1.34]; I2 = 0.0%, stroke (10 trials; 0.99 [0.82-1.19]; I2 = 5.8%, and CV death (14 trials; 0.88 [0.72-1.07]; I2 = 0.0% with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96-1.61]; I2 = 0.0%, not for oral bisphosphonates (26 trials; 1.02 [0.83-1.24]; I2 = 0.0%. The CV effects did not vary by subgroups or study quality.Bisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in

Effects of long-term vasodilator therapy in patients with carotid sinus hypersensitivity.

Science.gov (United States)

Brignole, M; Menozzi, C; Gaggioli, G; Musso, G; Foglia-Manzillo, G; Mascioli, G; Fradella, G; Bottoni, N; Mureddu, R

1998-08-01

In patients affected by carotid sinus hypersensitivity, long-term vasodilator therapy might increase the risk of syncopal episodes by reducing systolic blood pressure and venous return to the heart. Thirty-two patients (mean age 73 +/- 9 years; 20 men) who met all the following criteria were included: (1) one or more episodes of syncope occurring during long-term (>6 months) treatment with angiotensin-converting enzyme inhibitors, long-acting nitrates, calcium antagonists, or a combination of these; (2) a positive response to carotid sinus massage, defined as the reproduction of spontaneous syncope in the presence of ventricular asystole > or =3 seconds or a fall in systolic blood pressure > or =50 mm Hg; (3) negative workup for other causes of syncope. The patients were randomly assigned to continue or to discontinue use of vasodilators; carotid sinus massage was repeated 2 weeks after randomization. By the end of the study period, the baseline values of systolic blood pressure were significantly different between the 2 groups of patients both in supine (P=.01) and upright (P=.03) positions. Syncope had been induced by carotid sinus massage in 81% of patients in the "on-vasodilator" group and in 62% of patients in the "off-vasodilator" group (P=.21). The cardioinhibitory reflex was of similar magnitude in the 2 groups, being found in 50% of the patients in each group, with a maximum ventricular pause of 7.1 +/- 2.7 and 6.7 +/- 1.8 seconds, respectively. The percentage decrease of blood pressure did not differ between the 2 groups, even if, in absolute values, the baseline difference of blood pressure roughly persisted for the duration of the test. In consequence of that, the rise of blood pressure to similar values was delayed approximately 30 seconds in the "on-vasodilator" group and took more than 2 minutes to return to baseline values. In patients affected by carotid sinus hypersensitivity, chronic vasodilator therapy does not have a direct effect on carotid

Clinical Aspects, Imaging Features, and Considerations on Bisphosphonate-Related Osteonecrosis Risk in a Pediatric Patient with Osteogenesis Imperfecta

Directory of Open Access Journals (Sweden)

Fábio Wildson Gurgel Costa

2014-01-01

Full Text Available Osteogenesis imperfecta (OI is a rare hereditary condition caused by changes in collagen metabolism. It is classified into four types according to clinical, genetic, and radiological criteria. Clinically, bone fragility, short stature, blue sclerae, and locomotion difficulties may be observed in this disease. OI is often associated to severe dental problems, such as dentinogenesis imperfecta (DI and malocclusions. Radiographically, affected teeth may have crowns with bulbous appearance, accentuated constriction in the cementoenamel junction, narrowed roots, large root canals due to defective dentin formation, and taurodontism (enlarged pulp chambers. There is no definitive cure, but bisphosphonate therapy is reported to improve bone quality; however, there is a potential risk of bisphosphonate-related osteonecrosis of the jaw. In this study we report a case of OI in a male pediatric patient with no family history of OI who was receiving ongoing treatment with intravenous perfusion of bisphosphonate and who required dental surgery. In addition, we discussed the clinical and imaging findings and briefly reviewed the literature.

Which patients with moderate hypoxemia benefit from long-term oxygen therapy? Ways forward

Directory of Open Access Journals (Sweden)

Ekström M

2018-01-01

Full Text Available Magnus Ekström,1 Thomas Ringbaek2 1Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 2Respiratory Department, Hvidovre Hospital, Copenhagen, Denmark Abstract: Long-term oxygen therapy (LTOT improves prognosis in patients with COPD and chronic severe hypoxemia. The efficacy in moderate hypoxemia (tension of arterial oxygen; on air, 7.4−8.0 kPa was questioned by a recent large trial. We reviewed the evidence to date (five randomized trials; 1,191 participants, all with COPD. Based on the current evidence, the survival time may be improved in patients with moderate hypoxemia with secondary polycythemia or right-sided heart failure, but not in the absence of these signs. Clinically, LTOT is not indicated in moderate hypoxemia except in the few patients with polycythemia or signs of right-sided heart failure, which may reflect more chronic and severe hypoxemia. Keywords: survival, oxygen therapy, hypoxemia, COPD

Long-Term Perspectives of Family Quality of Life Following Music Therapy With Young Children on the Autism Spectrum: A Phenomenological Study.

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Thompson, Grace A

2018-01-13

Parents of children on the autism spectrum have consistently reported feeling uncertain in their parenting role, and desire more practical advice from service providers about how to support their child in the home. There is growing recognition of the need for interventions to provide support to the family as well as fostering child development outcomes. This study explores mothers' follow-up perspectives of family-centered music therapy (FCMT) four years after participating in a 16-week home-based program, and therefore provides a unique long-term viewpoint on FCMT outcomes. Eight mothers who previously participated in FCMT sessions with their young children on the autism spectrum were interviewed to explore their perception of any long-term outcomes. A descriptive phenomenological analysis revealed five global themes, including: improvement in mothers' confidence to engage their child; rare opportunities for mutual mother-child enjoyment; improved child social communication and quality of life; mothers' new understanding of the child's interests and strengths; and more opportunities for continuing the child's interest in music. Mothers perceived long-term benefits to social relationships within the family, leading to perceived enrichment in child and family quality of life following music therapy sessions. © American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Factors indicating need of rehabilitation--occupational therapy among persons with long-term and/or recurrent pain.

Science.gov (United States)

Müllersdorf, M

2000-12-01

The aim of the study was to elucidate selection criteria for need of rehabilitation/occupational therapy, and to state criteria for participation in occupational therapy, among persons with long-term and/or recurrent pain causing activity limitations or restricting participation in daily life. The study involved 914 persons aged 18-58 years who answered a postal questionnaire concerning demography, pain, occupations in daily life, work, treatments and health care staff visited. The direct method in logistic regression analysis was used to test two models: (1) need of rehabilitation/occupational therapy and (2) participation in occupational therapy. The results for the first model revealed the selection criteria (1) 'feelings of irresolution', (2) 'gnawing/searing pain' and (3) 'use of technical aids'. The odds for need of rehabilitation/occupational therapy were higher for women than for men. The criteria derived from the second model, participation in occupational therapy, were whether (1) the participants had 'used tricks and/or compensated ways to perform tasks', (2) the participants had 'pain in shoulders' and (3) 'changes had been made at work due to health conditions'.

Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday.

Science.gov (United States)

Xu, L H R; Adams-Huet, B; Poindexter, J R; Maalouf, N M

2016-05-01

In a retrospective analysis of 208 osteoporotic patients followed during a bisphosphonate holiday, lower body weight and risedronate use were associated with a more rapid decline in bone mineral density during the bisphosphonate holiday, while bone mineral density (BMD) trends were similar in patients who sustained vs. did not sustain a fracture. A drug holiday has been suggested for some bisphosphonate-treated patients with osteoporosis to minimize potential side effects from prolonged use. However, there is limited information on the evolution of BMD during a bisphosphonate holiday. Our study analyzed the longitudinal course of BMD following bisphosphonate discontinuation and assessed its determinants. Retrospective single-center cohort study of osteoporosis patients treated with alendronate or risedronate for at least 2 years and then discontinued their bisphosphonate for a drug holiday. Patients were stratified by bisphosphonate type and by fracture occurrence during drug holiday. A total of 208 patients were included in this analysis (87.5 % female). At the time of bisphosphonate cessation, mean ± SD age was 66.9 ± 8.9 years and BMI 24.5 ± 4.4 kg/m(2). Duration of bisphosphonate treatment was 5.2 ± 2.3 years, and follow-up during holiday was 3.3 ± 1.7 years. During the first 2 years of the holiday, BMD remained stable at the lumbar spine and femoral neck, but declined significantly at the total hip. BMD declined significantly at all sites thereafter. Significant predictors of BMD decline during bisphosphonate holiday included lower BMI at the start of the holiday and change in body weight during the holiday. BMD decline was more pronounced in former risedronate compared to former alendronate users. BMD trends were similar in patients who sustained vs. did not sustain a fracture during the holiday. BMD at the total hip declines significantly within 1 year of bisphosphonate discontinuation, particularly in lean patients

[Long-term outcomes of children treated with continuous renal replacement therapy].

Science.gov (United States)

Almarza, S; Bialobrzeska, K; Casellas, M M; Santiago, M J; López-Herce, J; Toledo, B; Carrillo, Á

2015-12-01

The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Long-term Therapy With Tenofovir Is Effective for Patients Co-Infected With Human Immunodeficiency Virus and Hepatitis B Virus

NARCIS (Netherlands)

de Vries-Sluijs, Theodora E. M. S.; Reijnders, Jurriën G. P.; Hansen, Bettina E.; Zaaijer, Hans L.; Prins, Jan M.; Pas, Suzan D.; Schutten, Martin; Hoepelman, Andy I. M.; Richter, Clemens; Mulder, Jan W.; de Man, Rob A.; Janssen, Harry L. A.; van der Ende, Marchina E.

2010-01-01

BACKGROUND & AIMS: We investigated the long-term efficacy and renal safety of tenofovir disoproxil fumarate (TDF), administered to patients co-infected with human immunodeficiency virus and hepatitis B virus (HBV) as part of an antiretroviral therapy. METHODS: We performed a multicenter, prospective

Bisphosphonate ISS Flight Experiment

Science.gov (United States)

LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey; Shapiro, Jay; Lang, Thomas; Shackleford, Linda; Smith, Scott M.; Evans, Harlan; Spector, Elizabeth; Ploutz-Snyder, Robert;

Low-intensity continuous ultrasound triggers effective bisphosphonate anticancer activity in breast cancer.

Science.gov (United States)

Tardoski, Sophie; Ngo, Jacqueline; Gineyts, Evelyne; Roux, Jean-Paul; Clézardin, Philippe; Melodelima, David

2015-11-18

Ultrasound (US) is a non-ionizing pressure wave that can produce mechanical and thermal effects. Bisphosphonates have demonstrated clinical utility in bone metastases treatment. Preclinical studies suggest that bisphosphonates have anticancer activity. However, bisphosphonates exhibit a high affinity for bone mineral, which reduces their bioavailability for tumor cells. Ultrasound has been shown to be effective for drug delivery but in interaction with gas bubbles or encapsulated drugs. We examined the effects of a clinically relevant dose of bisphosphonate zoledronate (ZOL) in combination with US. In a bone metastasis model, mice treated with ZOL+US had osteolytic lesions that were 58% smaller than those of ZOL-treated animals as well as a reduced skeletal tumor burden. In a model of primary tumors, ZOL+US treatment reduced by 42% the tumor volume, compared with ZOL-treated animals. Using a fluorescent bisphosphonate, we demonstrated that US forced the release of bisphosphonate from the bone surface, enabling a continuous impregnation of the bone marrow. Additionally, US forced the penetration of ZOL within tumors, as demonstrated by the intratumoral accumulation of unprenylated Rap1A, a surrogate marker of ZOL antitumor activity. Our findings made US a promising modality to trigger bisphosphonate anticancer activity in bone metastases and in primary tumors.

Quantitative determination of bone mineral concentrations using quotient densitometry in patients under long-term anticonvulsant therapy

International Nuclear Information System (INIS)

Schulz, H.

1980-01-01

The effect on bone mineral concentration of anticonvulsive long-term therapy was investigated in order to find out if there is a relation between the occurence and extent of osteomalacial lesions on the one hand and the type and time of application of anticonvulsants. The hydroxyl apatite content was determined by X-ray densitometry. The method is considered to be suitable for yearly skeletal monitoring of epilepticians treated with anticonvulsants. (orig./HP) [de

Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features

International Nuclear Information System (INIS)

Lee, Byung Do; Kwon, Kyung Hwan; Park, Moo Rim

2015-01-01

A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature

Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features.

Science.gov (United States)

Lee, Byung-Do; Park, Moo-Rim; Kwon, Kyung-Hwan

2015-09-01

A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features

Energy Technology Data Exchange (ETDEWEB)

Lee, Byung Do; Kwon, Kyung Hwan [College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Park, Moo Rim [Dept. of Internal Medicine, School of Medicine, Wonkwang University, Iksan (Korea, Republic of)

2015-09-15

A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

The long-term effectiveness of Cognitive Behaviour Therapy for Psychosis (CBTp within a routine psychological therapies service

Directory of Open Access Journals (Sweden)

Emmanuelle ePeters

2015-10-01

Full Text Available Randomised Controlled Trials (RCTs have shown the efficacy of CBTp, however few studies have considered its long-term effectiveness in routine services. This study reports the outcomes of clients seen in a psychological therapies clinic, set up following positive results obtained from an RCT (Peters et al. 2010. The aims were to evaluate the effectiveness of CBTp, using data from the service’s routine assessments for consecutive referrals over a 12 year period, and assess whether gains were maintained at a 6+ months’ follow-up. Of the 476 consenting referrals, all clients (N=358 who received ≥5 therapy sessions were offered an assessment at 4 time points (baseline, pre-, mid- and end of therapy on measures assessing current psychosis symptoms, emotional problems, general well-being and life satisfaction. A sub-set (N=113 was assessed at a median of 12 months after finishing therapy. Following the waiting list (median of 3 months clients received individualised, formulation-based CBTp for a median number of 19 sessions from 121 therapists with a range of experience receiving regular supervision. Clients showed no meaningful change on any measure while on the waiting list (Cohen’s d<=0.23. In contrast, highly significant improvements following therapy, all of which were significantly greater than changes during the waiting list, were found on all domains assessed (Cohen’s d: 0.44-0.75. All gains were maintained at follow-up (Cohen’s d: 0.29-0.82, with little change between end of therapy and follow-up (Cohen’s d<=0.18. Drop-out rate from therapy was low (13%. These results demonstrate the positive and potentially enduring impact of psychological therapy on a range of meaningful outcomes for clients with psychosis. The follow-up assessments were conducted on only a sub-set, which may not generalise to the full sample. Nevertheless this study is the largest of its kind in psychosis, and has important implications for the practice of

Comparison of serum Dkk1 (Dickkopf-1) and bone mineral density in patients on bisphosphonate treatment vs no treatment.

LENUS (Irish Health Repository)

Memon, Adeel R

2013-05-17

Complex pathways affect bone metabolism at the cellular level, and a balance between osteoblast and osteoclast activity is critical to bone remodeling. One of the major pathways affecting bone metabolism is Wnt\\/β-catenin signaling, and its disturbances lead to a wide range of bone abnormalities. An important antagonist of this pathway is Dickkopf-1 (Dkk1). Higher Dkk1 levels have been associated with increased bone loss due to inhibition of Wnt pathway. Currently, bisphosphonates are the most commonly used agents to treat primary osteoporotic patients. This study demonstrates the effect of bisphosphonates on Dkk1 levels and its correlation with bone mineral density (BMD). Eighty patients with low BMD were recruited and divided into 2 groups of 40 each (bisphosphonate treatment group and control group). The mean Dkk1 level in the treatment group was significantly reduced to 2358.18 vs 3749.80 pg\\/mL in the control group (p<0.001). Pearson correlation coefficient showed negative correlation between Dkk1 and BMD at lumbar spine (r=-0.55) and femoral neck in the control group; however, no such correlation was found in the treatment group (r=-0.05). Hence, bisphosphonate therapy leads to reduction in Dkk1 levels, but it does not correlate with BMD in such patients.

Persistence with weekly and monthly bisphosphonates among postmenopausal women: analysis of a US pharmacy claims administrative database

Directory of Open Access Journals (Sweden)

Fan T

2013-11-01

Full Text Available Tao Fan, Qiaoyi Zhang, Shuvayu S Sen Global Health Outcomes, Merck, Whitehouse Station, NJ, USA Background: Bisphosphonates are available in daily, weekly, and monthly dosing formulations to treat postmenopausal osteoporosis. Some researchers suggested that adherence to monthly bisphosphonate might be different from that with weekly or daily bisphosphonate because of different dosing regimens. However, the actual persistency rates in regular practice settings are unknown. Objectives: To compare persistence rates with alendronate 70 mg once weekly (AOW, risedronate 35 mg once weekly (ROW, and ibandronate 150 mg once monthly (IOM in a US pharmacy claims database. Methods: In this retrospective cohort study, pharmacy claims data of patients with new bisphosphonate prescriptions were extracted for women aged ≥ 50 years who had an AOW, ROW, or IOM prescription (index prescription between December 30, 2004 and May 31, 2005 (the index period and did not have the index Rx during the previous 12 months. Patients’ records were reviewed for at least 5 months from their index date to November 2, 2005 (the follow-up period. Patients were considered persistent if they neither discontinued (failed to refill the index Rx within a 45-day period following the last supply day of the previous dispensing nor switched (changed to another bisphosphonate during the follow-up period. Medication-possession ratio was defined as days with index prescription supplies/total days of follow-up. Results: Among 44,635 patients, 25,207 (56.5% received prescriptions of AOW, 18,689 (41.9% ROW, and 739 (1.7% IOM as the index prescription. In all, 35.1% of AOW patients, 32.5% of ROW patients, and 30.4% of IOM patients (P < 0.0001 AOW vs ROW or IOM had persisted with their initial therapy, whereas 64.0% of AOW, 66.4% of ROW, and 68.2% of IOM patients discontinued (P < 0.0001 during follow-up. The medication-possession ratio (days with index prescription supplies/total days of

Efficacy of Bisphosphonates for the Treatment of Osteoporosis in Patients with Multiple Sclerosis

Directory of Open Access Journals (Sweden)

İlke Coşkun Benlidayı

2015-08-01

Full Text Available Objective: The aim of this study was to evaluate the effectiveness of bisphosphonates in osteoporotic patients with multiple sclerosis. Materials and Methods: Patients with multiple sclerosis, who were started on treatment with a diagnosis of osteoporosis, at the Department of Physical Medicine and Rehabilitation, Faculty of Medicine Çukurova University, between January 2011 and January 2014, were included in this study. Patients were allocated into control (calcium-vitamin D alone and active treatment (calcium-vitamin D and bisphosphonate groups according to their medications. Response to the 12-month treatment in terms of bone mineral density (BMD values and biological marker levels were evaluated, both within and between groups. Results: The study group consisted of 29 patients (14 controls and 15 active treatment. Evaluation performed within each group revealed no significant difference between baseline and post-treatment values of BMD and biological markers in controls. However, regarding the active treatment group, a significant increase in L1-L4 T-score and 25(OHD was detected. When delta values were taken into account, comparison between groups revealed no significant difference in terms of BMD and biological marker levels. Conclusion: The effect of calcium-vitamin D alone on BMD and biologic markers was similar to that of calcium-vitamin D and bisphosphonate combination, in multiple sclerosis patients with osteoporosis. However, prospective, randomized, controlled studies are required on this issue. (Turkish Journal of Osteoporosis 2015;21: 53-7

[Psychosocial issues of long-term cancer survivors].

Science.gov (United States)

Weis, J; Faller, H

2012-04-01

Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

Burn injury during long-term oxygen therapy in Denmark and Sweden

DEFF Research Database (Denmark)

Tanash, Hanan A; Ringbaek, Thomas; Huss, Fredrik

2017-01-01

% confidence interval [CI], 126-225) vs 85 (95% CI, 44-148) per 100,000 person-years; rate ratio 2.0 (95% CI, 1.0-4.1). The risk remained higher after adjustment for gender, age, and diagnosis in multivariate Cox regression, hazard ratio 1.8 (95% CI, 1.0-3.5). Thirty-day mortality after burn injury was 8......BACKGROUND: Long-term oxygen therapy (LTOT) increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury...... end point was burn injury during LTOT. RESULTS: A total of 23,741 patients received LTOT in Denmark and 7,754 patients in Sweden. Most patients started LTOT due to COPD, both in Sweden (74%) and in Denmark (62%). The rate of burn injury while on LTOT was higher in Denmark than in Sweden; 170 (95...

Long-term effects of tocilizumab therapy for refractory uveitis-related macular edema.

Science.gov (United States)

Mesquida, Marina; Molins, Blanca; Llorenç, Victor; Sainz de la Maza, Maite; Adán, Alfredo

2014-12-01

To report the long-term efficacy and safety of the interleukin-6 receptor antagonist tocilizumab for refractory uveitis-related macular edema (ME). Retrospective cohort study. Eyes with uveitis seen at a single tertiary referral center for which ME was the principal cause of reduced visual acuity. Data were obtained by standardized chart review. Central foveal thickness (CFT) measured by optical coherence tomography, degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), and visual acuity (logarithm of the minimum angle of resolution [logMAR]) were recorded during tocilizumab therapy at months 1, 3, 6, and 12. Eleven eyes from 7 patients (all women) were included. Mean age was 43.4 years. Mean duration of ME was 14.2 years. Mean follow-up with tocilizumab therapy was 15.2 months (range, 12-18 months). Before tocilizumab therapy, conventional immunosuppressive therapy and 1 or more biologic agents failed in all patients. Uveitis diagnoses were birdshot chorioretinopathy (n = 3), juvenile idiopathic arthritis-associated uveitis (n = 3), and idiopathic panuveitis (n = 1). Mean CFT was 550 ± 226 μm at baseline, 389 ± 112 μm at month 1 (P = 0.007), 317 ± 88 μm at month 3 (P = 0.01), 292 ± 79 μm at month 6 (P = 0.006), and 274 ± 56 μm at month 12 of follow-up (P = 0.002). Mean logMAR best-corrected visual acuity improved from 0.67 ± 0.53 at baseline to 0.4 ± 0.56 at month 12 (P = 0.008). Tocilizumab therapy was withdrawn in 2 patients because of sustained remission at month 12. In both patients, ME relapsed 3 months after tocilizumab withdrawal. Reinitiation of tocilizumab therapy led to good uveitis control and ME resolution. Tocilizumab generally was well tolerated and no serious adverse events were reported. In this study, tocilizumab was effective in the treatment of refractory inflammatory ME. No serious adverse events were observed. Copyright © 2014 American Academy of Ophthalmology

Atrial fibrillation in fracture patients treated with oral bisphosphonates

DEFF Research Database (Denmark)

Abrahamsen, B; Eiken, P; Brixen, K

2009-01-01

OBJECTIVES: To determine if patients receiving oral bisphosphonates are at excess risk of atrial fibrillation (AF), stroke and myocardial infarction. DESIGN: Register-based restricted cohort study. SETTING: National Hospital Discharge Register and National Prescriptions Database (1995-2005). SUBJ......OBJECTIVES: To determine if patients receiving oral bisphosphonates are at excess risk of atrial fibrillation (AF), stroke and myocardial infarction. DESIGN: Register-based restricted cohort study. SETTING: National Hospital Discharge Register and National Prescriptions Database (1995...... to adherence. There was no increased risk of ischaemic stroke and an increased risk of myocardial infarction was not significant after adjustment for comorbidity. CONCLUSIONS: The increased occurrence of AF in fracture patients who are users of oral bisphosphonates should be attributed to targeting...

Bisphosphonates for treatment of Complex Regional Pain Syndrome type 1: A systematic literature review and meta-analysis of randomized controlled trials versus placebo.

Science.gov (United States)

Chevreau, Maxime; Romand, Xavier; Gaudin, Philippe; Juvin, Robert; Baillet, Athan

2017-07-01

Complex Regional Pain Syndrome Type 1 is a severely disabling pain syndrome with no definite established treatment. We have performed a systematic literature review and meta-analysis of all randomized controlled trials to assess the benefit of bisphosphonates on pain and function in patients with Complex Regional Pain Syndrome Type 1. A systematic literature search was performed in the Medline, Embase and Cochrane databases. Two authors selected independently blinded randomized trials comparing bisphosphonates to placebo on short-term (J30 to J40) and medium term pain (M2-M3), safety and function in patients with CRPS 1. The methodological quality of the studies was analyzed. Data were aggregated using the method of the inverse of the variance. 258 articles were identified. Four trials of moderate to good quality comprising 181 patients (90 in the bisphosphonate group and 91 in the placebo group) were included in this meta-analysis. Short-term pain Visual Analog Scale was significantly lower in the bisphosphonate group versus the placebo group (SMD=-2.6, 95%CI [-1.8, -3.4], Ppain (SMD=-2.5, 95%CI [-1.4, -3.6], Ppain in patients with Complex Regional Pain Syndrome type 1. Other studies are needed to determine their effectiveness. Copyright © 2017. Published by Elsevier SAS.

Case of femoral diaphyseal stress fracture after long-term risedronate administration diagnosed by iliac bone biopsy

Directory of Open Access Journals (Sweden)

Nagai T

2013-04-01

imaging had decreased and her pain while walking or undergoing the stress test disappeared as well. Thus, long-term administration of bisphosphonates may lead to easy fracture, although bone turnover markers were observed to be within the normal range. During bisphosphonate administration, physicians need to monitor closely and treat their patients for any pain experienced in the femoral region while walking or undergoing a stress test. Keywords: bisphosphonate, severely suppressed bone turnover, risedronate

Bisphosphonates and osteonecrosis of jaws

Directory of Open Access Journals (Sweden)

Geetha Vijay

2012-01-01

The purpose of the present article is to enlighten the dental fraternity about this frequently prescribed class of drugs with regard to its types and mode of action, and the implication of bisphosphonates-induced ONJ.

Uptake of a fluorinated bisphosphonate by cultured bones

International Nuclear Information System (INIS)

Rowe, D.J.; Etre, L.A.

1988-01-01

The uptake of bisphosphonates into bone was studied using 19-day-old fetal rat bones cultured with a new fluorinated bisphosphonate, difluoromethylidene bisphosphonate (F2MBP). F2MBP uptake was assessed by determining the weight percent of fluoride using electron probe microanalysis. By 30 min the weight percent of fluoride was significantly greater in the F2MBP-treated bones than in controls and continually increased throughout the duration of the experiment to reach a fluoride concentration 6-fold greater than controls after 120 h of incubation. When the peripheral cortical bone was analyzed separately from the interior trabecular bone in the F2MBP-treated bones, the fluoride concentration in the periphery increased until 24 h and then remained somewhat constant, while the interior, which is more actively remodeling, showed a continual increase. The uptake of F2MBP during the 1 to 6 h time intervals demonstrated no differences between vital and devitalized bone and, thus, is not cell-mediated. Because analysis of free fluoride in F2MBP media incubated with bones showed that the concentration of fluoride was less than 1% of the total amount of fluoride, the fluoride detected by the probe was most likely that of the intact molecule and not free fluoride. The rapid uptake of the F2MBP molecule was supported by assessing the effects of short-term F2MBP treatment on subsequent bone resorption, as determined by the release of 45Ca from prelabeled bones. Bones treated with F2MBP for only 5 min exhibited reductions in the percentage of 45Ca released during the remainder of the 120 h incubation period similar to that when F2MBP was continuously in the medium

Stevens-Johnson syndrome in a patient with rheumatoid arthritis during long-term etanercept therapy.

Science.gov (United States)

Owczarczyk-Saczonek, Agnieszka; Zdanowska, Natalia; Znajewska-Pander, Aleksandra; Placek, Waldemar

2016-03-31

Etanercept and other anti-TNF-alpha agents have been indicated as a therapeutic option in severe drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Etanercept has been shown to quickly reduce the detachment of the epidermis and shorten healing time. Cases of etanercept-induced severe adverse drug reactions were also described. A 27-year-old woman with a 4-year history of etanercept and sulfasalazine treatment for rheumatoid arthritis was admitted with Stevens-Johnson syndrome. The patient received one dose of an OTC drug containing acetaminophen, phenylephrine and pheniramine two days prior to developing fist mucocutaneous symptoms. The most probable causative agent was paracetamol. Throughout the successful routine therapy of Stevens-Johnson syndrome etanercept therapy was continued. Sulfosalazin administration was stopped and administered again after recovery with no recurrence of the skin and mucosal symptoms. This case indicates that there is no justification for discontinuation of long-term anti-TNF-alpha treatment in patients who develop Stevens- Johnson syndrome / toxic epidermal necrolysis.

Long-term treatment effect of trauma-affected refugees with flexible cognitive behavioural therapy and antidepressants.

Science.gov (United States)

Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstroem, Morten; Carlsson, Jessica; Mortensen, Erik Lykke

2018-04-04

Few studies exist on the long-term effect of treatment of trauma-affected refugees. The purpose of this study was to estimate the long-term treatment effects of cognitive behavioural therapy and antidepressants (sertraline and mianserin) in trauma-affected refugees. Follow-ups were conducted 6 and 18 months after a randomised controlled clinical trial. The included patients were refugees with war-related traumatic experiences, PTSD and without psychotic disorders. We found a small improvement over time in PTSD, depression and anxiety symptoms and level of functioning, but the improvement was not associated with any specific treatment. Personality change after catastrophic experiences and life events influenced the symptom level at all follow-ups while depression at completion of treatment was associated with a steeper decline in symptom load at the follow-ups. In spite of the limited decline in symptom scores and treatment effects immediately after treatment, the condition of the treated trauma-affected refugees was significantly improved 6 and 18 months after treatment although the improvement was small. Copyright © 2018 Elsevier B.V. All rights reserved.

Fondaparinux in the initial and long-term treatment of venous thromboembolism.

Science.gov (United States)

Pesavento, Raffaele; Amitrano, Maria; Trujillo-Santos, Javier; Di Micco, Pierpaolo; Mangiacapra, Sara; López-Jiménez, Luciano; Falgá, Conxita; García-Bragado, Fernando; Piovella, Chiara; Prandoni, Paolo; Monreal, Manuel

2015-02-01

Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice. We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer. Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05). An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-Term Outcome of Low-Energy Extracorporeal Shock Wave Therapy for Plantar Fasciitis: Comparative Analysis According to Ultrasonographic Findings

Science.gov (United States)

Park, Jong-Wan; Yoon, Kyungjae; Chun, Kwang-Soo; Lee, Joon-Youn; Park, Hee-Jin; Lee, So-Yeon

2014-01-01

Objective To investigate the long-term effect of low-energy extracorporeal shock wave therapy (ESWT) for plantar fasciitis (PF) according to ultrasonography (US) findings. Methods Thirty feet of 25 patients with clinical diagnosis of PF were enrolled and divided into two groups (Apparent-US and Uncertain-US) according to US findings, such as plantar fascia thickening or hypoechogenicity. Inclusion criteria were symptom duration >6 months and a fair or poor grade in Roles-Maudsley score (RMS). ESWT (0.10 mJ/mm2, 600 shocks) was given once a week for 6 weeks. Numeric rating scale (NRS) and RMS were evaluated prior to each ESWT session, at short-term follow-up (one week after all ESWT sessions) and long-term follow-up telephone interview (mean 24 months after ESWT). Good and excellent grade in RMS were considered as treatment success. Results Repeated measure ANOVA demonstrated that NRS significantly decreased with time after ESWT up to the long-term follow-up (time effect, p<0.001) without group-time interaction (p=0.641), indicating that ESWT equally decreased pain in both groups. Overall success rate was 63.3% (short-term follow-up) and 80.0% (long-term follow-up). In comparative analysis between groups, success rate of Apparent-US and Uncertain-US at short-term follow-up was 61.9% and 66.7%, respectively, and 85.7% and 66.7%, respectively, at long-term follow-up. Conclusion If other causes of heel pain are ruled out through meticulous physical examination and ultrasonography, low-energy ESWT in PF seems to be beneficial regardless of US findings. In terms of success rate, however, long-term outcome of Apparent-US appears to be superior to Uncertain-US. PMID:25229032

CARDIORENAL RELATIONS AND QUALITY OF LIFE IN ELDERLY PATIENTS WITH CHRONIC HEART FAILURE IN LONG TERM THERAPY WITH CARVEDILOL AND BISOPROLOL

Directory of Open Access Journals (Sweden)

M. A. Statsenko

2005-01-01

Full Text Available Aim. To compare effects of long term therapy with сarvedilol and bisoprolol on heart and renal functions, heart rate variability (HRV and quality of life in elderly patients with chronic heart failure (CHF.Material and methods. We examined 40 patients aged 60-75 years on the 15-30 day after myocardial infarction complicated with CHF. All the patients taking basic therapy with enalapril, aspirin, simvastatin and diuretics were randomized to either bisoprolol (n=20 or сarvedilol (n=20 therapy group. The average daily doses were 5,7+0,8 mg for and 32,6+3,4 mg for carvedilol. The duration of the observation period was 12 months. Cardiac morphofunctional parameters, HRV, renal function and quality of life were determined at baseline, after 12 weeks and at the end of the study.Results. Complex therapy of CHF including both beta-blockers resulted in clinical improvement, increase in myocardial contractility. However, carvedilol group showed more pronounced increase in ejection fraction in comparison with bisoprolol group, 8,97% and 5,14%, respectively. Local contractility index decreased significantly only in carvedilol group by 29,9% (p<0,05. Carvedilol demonstrated more significant nephroprotective effects: glomerular filtration rate increased by 32,2%, renal functional reserve restored in 70% of patients. Tubular reabsorbtion, sodium clearance and excretion also increased in carvedilol group. After 12 month of treatment microalbuminuria reduced in both groups of patients, but more significant in carvedilol group. Carvedilol provided more strong blocking effect on sympathetic part of autonomic nervous system according to HRV data.Conclusion. In elderly patients with CHF long term therapy with both carvedilol and bisoprolol provided with improvement in clinical conditions and renal function, increased in HRV and was well tolerated. However, carvedilol compared with bisoprolol showed more significant beneficial effects on cardiac morphofunctional

Predictors of Adherence to Oral Bisphosphonate Therapy: A Register-based National Open Cohort Study

DEFF Research Database (Denmark)

Hansen, Carrinna; Pedersen, B D; Konradsen, Hanne

Abstract: Aim: To assess adherence to oral bisphosphonates and determine what predicts early cessation of treatment as opposed to low refill compliance. We hypothesized that patients who stopped treatment very early would differ in demographics and comorbidity from other patients with poor...... with increasing age and in patients taking proton pump inhibitors. These findings suggest that other factors — such as patient understanding, education level and socioeconomics may be more important determinants of adherence to osteoporosis treatment....

Long-term primary patency prognostic factors after endovascular therapy for acute lower limb ischemia

International Nuclear Information System (INIS)

Zhang Di; Gu Jianping; Lou Wensheng; He Xu; Chen Liang; Chen Guoping; Su Haobo; Song Jinhua; Wang Tao

2012-01-01

Objective: To assess prognostic factors regarding long-term primary patency for patients who underwent intra-arterial thrombolysis and/or adjuvant endovascular techniques due to acute lower limb ischemia. Methods: Consecutive patients with ALI of the lower extremities treated via interventional methods between January 2005 and June 2010 were identified and reviewed (exclude patient suffered from aortic dissection involved artery of lower extremity or trauma). Analyze the potential variables with univariable analysis and only factors associated with long-term primary patency with a P value less than 0.1 in univariable analysis were introduced into the Cox regression mode. Total long-term primary patency and grouped primary patency were assessed using Kaplan-Meier estimation. Results: The analyzed dataset included 107 limbs treated in 101 patients presenting with ALI (class Ⅰ 15, class Ⅱ A 36, class Ⅱ B to Ⅲ 56, according to Rutherford classification). Eight nine limbs were enrolled in follow-up.The mean followup was 34 months (range: 1 to 53 months). Primary patency at 12, 24 and 36 months was 87%, 68% and 55%, respectively. Multivariable analyses identified patients presenting with diabetes mellitus (P=0.00), PAOD (P<0.02) and thrombolysis time (P<0.02) were associated with primary patency. Compare the patency rate of patients with different thrombolysis time, the results showed that the patency rate of the patients thrombolysis time less than 4 d was higher than those more than 4 c. Conclusions: Interventional therapy remains an effective treatment option for patients presenting with lower extremity ALI. Diabetes mellitus and PAOD negatively affect the rates of limb primary patency. Thrombolysis should be limited to <4 days. (authors)

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates

DEFF Research Database (Denmark)

Diez-Perez, Adolfo; Naylor, K E; Abrahamsen, B

2017-01-01

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug....

Relapse and long-term cognitive performance after brief pulse or ultrabrief pulse right unilateral electroconvulsive therapy: A multicenter naturalistic follow up

NARCIS (Netherlands)

Verwijk, E.; Spaans, H.P.; Comijs, H.C.; Kho, K.H.; Sienaert, P.; Bouckaert, F.; Obbels, J.; Scherder, E.J.A.; Stek, M.L.; Kok, R.M.

2015-01-01

Background Superior cognitive functioning for electroconvulsive therapy (ECT) with right unilateral (RUL) ultrabrief pulse (UBP) stimulation compared to RUL brief pulse (BP) stimulation is not clearly established and long-term data is needed. Methods We conducted a prospective naturalistic follow-up

Assessment of cognitive impairment in long-term oxygen therapy-dependent COPD patients.

Science.gov (United States)

Karamanli, Harun; Ilik, Faik; Kayhan, Fatih; Pazarli, Ahmet Cemal

2015-01-01

A number of studies have shown that COPD, particularly in its later and more severe stages, is associated with various cognitive deficits. Thus, the primary goal of the present study was to elucidate the extent of cognitive impairment in patients with long-term oxygen therapy-dependent (LTOTD) COPD. In addition, this study aimed to determine the effectiveness of two cognitive screening tests, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), for COPD patients and the ability of oxygen therapy to mitigate COPD-related deficits in cognitive function. The present study enrolled 45 subjects: 24 nonuser and 21 regular-user LTOTD-COPD patients. All subjects had a similar grade of education, and there were no significant differences regarding age or sex. The MoCA (cutoff: therapy increased the risk of cognitive impairment (MoCA, P=0.007 and MMSE, P=0.014), and the MoCA and MMSE scores significantly correlated with the number of emergency admissions and the number of hospitalizations in the last year. In the present study, the nonuser LTOTD-COPD group exhibited a significant decrease in cognitive status compared with the regular-user LTOTD-COPD group. This suggests that the assessment of cognitive function in nonuser LTOTD-COPD patients and the use of protective strategies, such as continuous supplemental oxygen treatment, should be considered during the management of COPD in this population. In addition, the MoCA score was superior to the MMSE score for the determination of cognitive impairment in the nonuser LTOTD-COPD patients.

Long-term coital behaviour in women treated with cognitive behaviour therapy for superficial coital pain and vaginismus.

Science.gov (United States)

Engman, Maria; Wijma, Klaas; Wijma, Barbro

2010-01-01

The purpose of the present study was to investigate long-term coital behaviour in women treated with cognitive behaviour therapy (CBT) for superficial coital pain and vaginismus. Data were taken from a questionnaire concerning long-term coital behaviour sent to 59 women who presented to Linköping University Hospital because of superficial coital pain, had been diagnosed with vaginismus, and had been treated with CBT. Data were also traced from therapy records: mean follow-up time was 39 months, the women had suffered for an average of almost 4 years, and required a mean of 14 treatment sessions. Forty-four of the 59 women returned the questionnaire, for a response rate of 74.6%. At follow-up, 81% of the treated women had had intercourse. A majority (61%) rated their ability to have intercourse without pain as 6 or higher (on a scale from 0-10), and 61% rated their ability to enjoy intercourse as 6 or higher (on a scale from 0-10). The proportion of women with positive treatment outcome at follow-up ranged from 81% (able to have intercourse) to 6% (able to have pain-free intercourse). An ability to have intercourse at end of therapy was maintained at follow-up. Two-thirds of the women reported high fulfillment of individual treatment goals. At follow-up, the women estimated a significantly higher self-worth as sex partners, and as women and human beings, than before treatment. Twelve per cent of the original sample had healed after a few assessment sessions and without treatment.

Crown lengthening procedure following intentional endodontic therapy for correction of supra-erupted posterior teeth: Case series with long-term follow-up

Science.gov (United States)

Patil, Shruti Arun; Kulkarni, Sudhindra; Thakur, Srinath; Naik, Balaram

2016-01-01

Context: The crown lengthening procedure (CLP) is routinely carried out to correct gingival levels and achieve esthetic contours and adequate crown lengths for restorative purposes. Though the short-term outcomes have been found to be stable, long-term results are not much reported. Aims: To evaluate the long-term stability of the marginal bone levels, gingival levels, and the status of the teeth, which underwent endodontic therapy, followed by CLP and final restorations. Settings and Design: Institutional setting, long-term case series. Materials and Methods: Case records of the patients who underwent CLP and endodontic therapy for corrections of the supra-erupted teeth to regain the lost interocclusal spaces were retrieved, and the cases with complete set of the clinical and radiographs were taken. All the cases were recalled and bone levels on the radiographs, bleeding on probing, probing pocket depths, and changes in the soft tissue margins were evaluated. Statistical Analysis Used: Descriptive analysis. Results: A total of 25 teeth had undergone CLP and endodontic therapy and final restorations for a minimum of 24 months. The mean post-restorative duration was 50.8 ± 22.48 months (range 24–96 months). All the teeth were functional and asymptomatic with 100% survival. Interdental bone loss of 1 mm, probing pockets of 5 mm, and 1 mm buccal recession were observed in 16% of the sites. The amount of interocclusal space regained was adequate to restore the missing teeth in the opposing arch. Conclusions: The CLP is a predictive procedure for correction of supra-erupted teeth. The survival of the teeth that underwent the procedure in the present study was 100% over 24–96 months. PMID:27041850

Examining the Influence of Occupational Therapy and Its Effectiveness in Long-Term Care on Dementia Patients Through Ontology-Based Clustering

Science.gov (United States)

Fang, Kwoting; Change, Chingwei; Yuliao, Miao; Chi, Yenping

Over the past decade, the number of long-term care (LTC) residents has increased, and many have accepted treatments such as medication, rehabilitation and occupational therapy. This study discusses the effectiveness of occupational therapy when given to dementia patients of different contexts. The results of this study showed that patients of a good condition in the first stage present a more positive attitude towards participation in the occupational therapy designed by the institution; therefore, they have a greater chance of their condition improving or remaining the same. However, patients of an average condition have a more passive attitude towards taking part in any therapy; therefore, they have a greater chance of their condition deteriorating. In conclusion, occupational therapy has an effect on all kinds of patients.

LONG-TERM THERAPY WITH INDAPAMIDE IN ELDERLY AND SENILE PATIENTS WITH HYPERTENSION: CARDIORENOPROTECTIVE EFFECTS AND INFLUENCE ON QUALITY OF LIFE

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M. E. Statsenko

2009-01-01

Full Text Available Aim. To estimate cardiorenoprotective effect of 12-month therapy by indapamide in elderly and senile patients with arterial hypertension (HT and its influence on quality of life.Material and methods. 40 elderly and senile patients with HT were examined. 70% of patients received monotherapy by indapamide 2,5 mg once daily and 30% of patients were treated with indapamide and lisinopril combination. Duration of observation was 12 months. Ambulatory blood pressure (BP monitoring, echocardiography, plasma lipid profile, glycemia and uricemia levels and potassium serum level was evaluated initially and after 12 months of therapy. Glomerular filtration rate and albuminuria as well as patient quality of life also was evaluated.Results. Target BP level was reached in all patients during 12 month therapy. Reduction of average 24-hour, day and night BP, BP load, rate of morning BP rising was observed. Negative influence on BP variability was not found. Improvement of daily BP profile also was found. The indapamide reduced left ventricle mass, improved renal function, vessel resistance and quality of life. Negative influence of long-term therapy with indapamide on lipid, glucose, purine metabolism and serum potassium level was not observed.Conclusion. Indapamide is an effective antihypertensive drug for long-term treatment of elderly and senile patients with HT of 1-2 degree.

Incidence of hypothyroidism occurring long after iodine-131 therapy for hyperthyroidism

International Nuclear Information System (INIS)

Holm, L.E.; Lundell, G.; Israelsson, A.; Dahlgvist, I.

1982-01-01

We have studied the long-term incidence of hypothyroidism in 4,473 formerly hyperthyroid patients given I-131 therapy between 1951 and 1975. The mean age at the first I-131 treatment was 56 yr. Six percent developed hypothyroidism within one year of therapy, and 72% within 26 yr. Prior antithyroid medication did not affect the incidence of hypothyroidism. Patients cured with one dose of I-131 had a lower cumulative long-term incidence of hypothyroidism than those requiring more than one dose

Long-term causes of death in patients with infective endocarditis who undergo medical therapy only or surgical treatment

DEFF Research Database (Denmark)

Østergaard, Lauge; Oestergaard, Louise Bruun; Lauridsen, Trine Kiilerich

2018-01-01

OBJECTIVES: It is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization. METHODS: Using Danish administrative registries, we identified patients...... admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We...... examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group...

The excessive caloric intake and micronutrient deficiencies related to obesity after a long-term interdisciplinary therapy.

Science.gov (United States)

Poli, Vanessa Fadanelli Schoenardie; Sanches, Ricardo Badan; Moraes, Amanda Dos Santos; Fidalgo, João Pedro Novo; Nascimento, Maythe Amaral; Bresciani, Paula; Andrade-Silva, Stephan Garcia; Cipullo, Marcos Alberto Taddeo; Clemente, José Carlos; Caranti, Danielle Arisa

2017-06-01

The aim of this study was to assess the effectiveness of a long-term interdisciplinary lifestyle modification therapy on food intake, body composition, and anthropometric measurements of obese women. Seventy obese women (age 41 ± 5.9 y) attended the interdisciplinary therapy, with nutrition, physical exercise, physiotherapy, and psychological support during the course of 1 y. Usual food intake was estimated by 3-d dietary record. Dual-energy x-ray absorptiometry was performed to determine body fat and fat-free mass. Waist and hip circumferences also were measured. Student's t test and Wilcoxon test were used for comparisons among categories; P obesity; however, the present study reinforced the need to address the micronutrient deficiency in the target population. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication

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Bander Balkhi

2018-02-01

Conclusions: The 2010 FDA bisphosphonates safety communication appeared to have influenced Osteoporosis utilization in Medicaid recipients. The 2010 FDA bisphosphonates safety communication was associated with a significant reduction in the utilization of bisphosphonates in the Medicaid program.

A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

Science.gov (United States)

Davis, Sarah; Martyn-St James, Marrissa; Sanderson, Jean; Stevens, John; Goka, Edward; Rawdin, Andrew; Sadler, Susi; Wong, Ruth; Campbell, Fiona; Stevenson, Matt; Strong, Mark; Selby, Peter; Gittoes, Neil

2016-10-01

-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies. This study is registered as PROSPERO CRD42013006883. The National Institute for Health Research Health Technology Assessment programme.

Complexes of DOTA-bisphosphonate conjugates: probes for determination of adsorption capacity and affinity constants of hydroxyapatite.

Science.gov (United States)

Vitha, Tomas; Kubícek, Vojtech; Hermann, Petr; Kolar, Zvonimir I; Wolterbeek, Hubert Th; Peters, Joop A; Lukes, Ivan

2008-03-04

The adsorption on hydroxyapatite of three conjugates of a bisphosphonate and a macrocycle having C1, C2, and C3 spacers and their terbium complexes was studied by the radiotracer method using 160Tb as the label. The radiotracer-containing complex of the conjugate with the C3 spacer was used as a probe for the determination of the adsorption parameters of other bisphosphonates that lack a DOTA unit. A physicochemical model describing the competitive adsorption was successfully applied in the fitting of the obtained data. The maximum adsorption capacity of bisphosphonates containing bulky substituents is determined mainly by their size. For bisphosphonates having no DOTA moiety, the maximum adsorption capacity is determined by the electrostatic repulsion between negatively charged bisphosphonate groups. Compounds with a hydroxy or amino group attached to the alpha-carbon atom show higher affinities. Macrocyclic compounds containing a short spacer between the different bisphosphonic acid groups and the macrocyclic unit exhibit high affinities, indicating a synergic effect of the bisphosphonic and the macrocyclic groups during adsorption. The competition method described uses a well-characterized complex and allows a simple evaluation of the adsorption behavior of bisphosphonates. The application of the macrocycle-bisphosphonate conjugates allows easy radiolabeling via complexation of a suitable metal isotope.

Bisphosphonates-induced osteonecrosis of the jaw: pharmacology and clinical procedures.

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Candice Belchior Duplat

2012-01-01

Full Text Available Osteonecrosis of the jaw is a consequent condition of a variety of local and systemic factors that compromises the bone blood flow. Bisphosphonates are a class of compounds widely used for the treatment of disorders of bone metabolism, such as bone metastasis and osteoporosis. Bisphosphonates-induced osteonecrosis of the jaw is a new complication, published for the first time at 2003, and can be defined as an unexpected necrosis development on the oral cavity in patients who received bisphosphonates and were not being treated with head and neck radiotherapy. Radiographies show radiolucent zones or sclerotic bone and, in some cases, show areas with delayed or absent bone remodeling after extraction, remain the socket cavity. The treatment can be done in accordance with the condition stage, since management of 0,12% chlorhexidine and antibiotics until laser utilization, hyperbaric oxygen, surgical debridement and resection. It is important to promote more communication between physicians and dentists to guarantee dental attention during the bisphosphonate administration, establishing oral health and preventing complications, such as osteonecrosis induced by this medication.

BISPHOSPHONATES-INDUCED OSTEONECROSIS OF THE JAW: PHARMACOLOGY AND CLINICAL PROCEDURES.

Directory of Open Access Journals (Sweden)

Candice Belchior Duplat

2012-08-01

Full Text Available Osteonecrosis of the jaw is a consequent condition of a variety of local and systemic factors that compromises the bone blood flow. Bisphosphonates are a class of compounds widely used for the treatment of disorders of bone metabolism, such as bone metastasis and osteoporosis. Bisphosphonates-induced osteonecrosis of the jaw is a new complication, published for the first time at 2003, and can be defined as an unexpected necrosis development on the oral cavity in patients who received bisphosphonates and were not being treated with head and neck radiotherapy. Radiographies show radiolucent zones or sclerotic bone and, in some cases, show areas with delayed or absent bone remodeling after extraction, remain the socket cavity. The treatment can be done in accordance with the condition stage, since management of 0,12% chlorhexidine and antibiotics until laser utilization, hyperbaric oxygen, surgical debridement and resection. It is important to promote more communication between physicians and dentists to guarantee dental attention during the bisphosphonate administration, establishing oral health and preventing complications, such as osteonecrosis induced by this medication.

Evaluation of long-term cosmetic results and complications following breast conserving surgery and radiation therapy for breast cancer

International Nuclear Information System (INIS)

Fujishiro, Satsuki; Mitsumori, Michihide; Kokubo, Masaki; Nagata, Yasushi; Sasai, Keisuke; Hiraoka, Masahiro; Kodama, Hiroshi

1999-01-01

Long-term cosmetic outcomes and complications were evaluated in 109 patients with breast cancer who had been treated by breast conservation therapy. Patients received radiation therapy at Kyoto University Hospital following quadrantectomy and level II or III axillary node dissection. Factors that might influence long-term cosmetic results were also analyzed. Irradiation to the breast was administered in 2 Gy fractions, 5 times a week for a total of 50 Gy in all patients. Cobalt-60 γ-rays were used in 108 patients with the exception of 1 patient who received 6 Mev X-ray. Some patients with positive or close margins received boost irradiation of 10 Gy using electron beams to the primary tumor bed. Cosmetic outcome was assessed by both a scoring method and breast retraction assessment (BRA). Forty-seven percent of patients were assessed as excellent to good before radiation therapy. The percent of excellent to good decreased shortly after termination of radiation therapy, but gradually improved and stabilized by 3 years. Seventy percent of patients showed a score of excellent to good 5 years after treatment. The average BRA of the 109 patients was 3.0 cm. This did not change between 3 and 5 years after treatment. A significant correlation between cosmetic score and BRA was shown at all follow-up times. Factors such as age over 50 years (p=0.008), tumor location in the outer quadrant (p=0.02) and boost irradiation (p=0.03) significantly affected the cosmetic score. Arm edema and restriction of shoulder movement were observed in 22% and 49% at the start of radiation therapy, these improved within approximately 3 years and 1 year after treatment, respectively. Mild skin change was observed in 60% of patients even 5 years after treatment. The results indicate that cosmetic outcome after breast conservation therapy is clinically acceptable, and the complication rate is low. (author)

Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study.

Science.gov (United States)

Shahab, Lion; Goniewicz, Maciej L; Blount, Benjamin C; Brown, Jamie; McNeill, Ann; Alwis, K Udeni; Feng, June; Wang, Lanqing; West, Robert

2017-03-21

Given the rapid increase in the popularity of e-cigarettes and the paucity of associated longitudinal health-related data, the need to assess the potential risks of long-term use is essential. To compare exposure to nicotine, tobacco-related carcinogens, and toxins among smokers of combustible cigarettes only, former smokers with long-term e-cigarette use only, former smokers with long-term nicotine replacement therapy (NRT) use only, long-term dual users of both combustible cigarettes and e-cigarettes, and long-term users of both combustible cigarettes and NRT. Cross-sectional study. United Kingdom. The following 5 groups were purposively recruited: combustible cigarette-only users, former smokers with long-term (≥6 months) e-cigarette-only or NRT-only use, and long-term dual combustible cigarette-e-cigarette or combustible cigarette-NRT users (n = 36 to 37 per group; total n = 181). Sociodemographic and smoking characteristics were assessed. Participants provided urine and saliva samples and were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs). After confounders were controlled for, no clear between-group differences in salivary or urinary biomarkers of nicotine intake were found. The e-cigarette-only and NRT-only users had significantly lower metabolite levels for TSNAs (including the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) and VOCs (including metabolites of the toxins acrolein; acrylamide; acrylonitrile; 1,3-butadiene; and ethylene oxide) than combustible cigarette-only, dual combustible cigarette-e-cigarette, or dual combustible cigarette-NRT users. The e-cigarette-only users had significantly lower NNAL levels than all other groups. Combustible cigarette-only, dual combustible cigarette-NRT, and dual combustible cigarette-e-cigarette users had largely similar levels of TSNA and VOC metabolites. Cross-sectional design with self-selected sample. Former

Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene.

Science.gov (United States)

Melo, Luis G; Agrawal, Reitu; Zhang, Lunan; Rezvani, Mojgan; Mangi, Abeel A; Ehsan, Afshin; Griese, Daniel P; Dell'Acqua, Giorgio; Mann, Michael J; Oyama, Junichi; Yet, Shaw-Fang; Layne, Matthew D; Perrella, Mark A; Dzau, Victor J

2002-02-05

Ischemia and oxidative stress are the leading mechanisms for tissue injury. An ideal strategy for preventive/protective therapy would be to develop an approach that could confer long-term transgene expression and, consequently, tissue protection from repeated ischemia/reperfusion injury with a single administration of a therapeutic gene. In the present study, we used recombinant adeno-associated virus (rAAV) as a vector for direct delivery of the cytoprotective gene heme oxygenase-1 (HO-1) into the rat myocardium, with the purpose of evaluating this strategy as a therapeutic approach for long-term protection from ischemia-induced myocardial injury. Human HO-1 gene (hHO-1) was delivered to normal rat hearts by intramyocardial injection. AAV-mediated transfer of the hHO-1 gene 8 weeks before acute coronary artery ligation and release led to a dramatic reduction (>75%) in left ventricular myocardial infarction. The reduction in infarct size was accompanied by decreases in myocardial lipid peroxidation and in proapoptotic Bax and proinflammatory interleukin-1beta protein abundance, concomitant with an increase in antiapoptotic Bcl-2 protein level. This suggested that the transgene exerts its cardioprotective effects in part by reducing oxidative stress and associated inflammation and apoptotic cell death. This study documents the beneficial therapeutic effect of rAAV-mediated transfer, before myocardial injury, of a cytoprotective gene that confers long-term myocardial protection from ischemia/reperfusion injury. Our data suggest that this novel "pre-event" gene transfer approach may provide sustained tissue protection from future repeated episodes of injury and may be beneficial as preventive therapy for patients with or at risk of developing coronary ischemic events.

New 68Ga-PhenA bisphosphonates as potential bone imaging agents

International Nuclear Information System (INIS)

Wu, Zehui; Zha, Zhihao; Choi, Seok Rye; Plössl, Karl; Zhu, Lin; Kung, Hank F.

2016-01-01

Introduction: In vivo positron emission tomography (PET) imaging of the bone using [ 68 Ga]bisphosphonates may be a valuable tool for cancer diagnosis and monitoring therapeutic treatment. We have developed new [ 68 Ga]bisphosphonates based on the chelating group, AAZTA (6-[bis(hydroxycarbonyl-methyl)amino]-1,4-bis(hydroxycarbonyl methyl)-6-methylperhydro-1,4-diazepine). Method: Phenoxy derivative of AAZTA (2,2′-(6-(bis(carboxymethyl)amino)-6-((4-(2-carboxyethyl)phenoxy) methyl)-1,4-diazepane-1,4-diyl)diacetic acid), PhenA, 2, containing a bisphosphonate group (PhenA-BPAMD, 3, and PhenA-HBP, 4) was prepared. Labeling of these chelating agents with 68 Ga was evaluated. Results: The ligands reacted rapidly in a sodium acetate buffer with [ 68 Ga]GaCl 3 eluted from a commercially available 68 Ge/ 68 Ga generator (pH 4, > 95% labeling at room temperature in 5 min) to form [ 68 Ga]PhenA-BPAMD, 3, and [ 68 Ga]PhenA-HBP, 4. The improved labeling condition negates the need for further purification. The 68 Ga bisphosphonate biodistribution and autoradiography of bone sections in normal mice after an iv injection showed excellent bone uptake. Conclusion: New 68 Ga labeled bisphosphonates may be useful as in vivo bone imaging agents in conjunction with positron emission tomography (PET).

Long-term success of dental implants in patients with head and neck cancer after radiation therapy.

Science.gov (United States)

Curi, M M; Condezo, A F B; Ribeiro, K D C B; Cardoso, C L

2018-06-01

The purpose of this study was to analyze the long-term success and factors potentially influencing the success of dental implants placed in patients with head and neck cancer who underwent radiation therapy with a minimum total dose of 50Gy during the years 1995-2010. Thirty-five patients (169 dental implants) were included in this study. Data on demographic characteristics, tumour type, radiation therapy, implant sites, implant dimensions, and hyperbaric oxygen therapy (HBOT) were obtained from the medical records and analyzed. Implant survival was estimated using Kaplan-Meier survival curves. Seventy-nine dental implants were placed in the maxilla and 90 in the mandible. The mean follow-up after implant installation was 7.4 years (range 0.3-14.7 years). The overall 5-year survival rate for all implants was 92.9%. Sex (Pradiation therapy delivery (P=0.005) had a statistically significant influence on implant survival. Age, time of implantation after irradiation, implant brand and dimensions, and HBOT had no statistically significant influence on implant survival. Osseointegrated dental implants can be used successfully in the oral rehabilitation of patients with head and neck cancer with a history of radiation therapy. Risk factors such as sex and the mode of radiation therapy delivery can affect implant survival. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Animal-Assisted Therapy and Application to Older Adults in Long Term Care

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Kimberly Ann Mercer

2015-05-01

Full Text Available In the past thirty years animal-assisted therapy (AAT has moved beyond anecdotal status to a scientific evidence-based intervention. AAT comes in many shapes and sizes. There are a variety of animals which can be used such as dogs, cats, rabbits, horses, guinea pigs, goats, dolphins, and even fish aquariums. Loneliness is a common theme among older adults in long term care (LTC. Many older adults living in LTC facilities feel isolated. Some have little contact with family members or friends. Many describe feelings of loneliness and withdraw from social activities and interaction with others. Some feel as if they have nothing to look forward to and find no useful purpose in life.  The absence of having another to care for or nurture can also be distressing. The purpose of this project was to explore the use of AAT as an intervention to decrease loneliness in residents living in a LTC setting by introducing visits from a Sphynx cat registered by the Delta Society as a therapy animal. The project sample consisted of seven participants all over the age of 60 years who resided in a LTC facility in Texas. Pre-intervention and post-intervention checklists and open-ended questions were employed to collect data from participants. Analysis of the project findings revealed a notable decrease in loneliness.

What Animal Models Have Taught Us About the Safety and Efficacy of Bisphosphonates in Chronic Kidney Disease.

Science.gov (United States)

Allen, Matthew R; Aref, Mohammad W

2017-06-01

Bisphosphonates (BPs) have long been the gold-standard anti-remodeling treatment for numerous metabolic bone diseases. Since these drugs are excreted unmetabolized through the kidney, they are not recommended for individuals with compromised kidney function due to concerns of kidney and bone toxicity. The goal of this paper is to summarize the preclinical BP work in models of kidney disease with particular focus on the bone, kidney, and vasculature. Summative data exists showing positive effects on bone and vascular calcifications with minimal evidence for bone or kidney toxicity in animal models. Preclinical data suggest it may be worthwhile to take a step back and reconsider the use of bisphosphonates to lessen skeletal/vascular complications associated with compromised kidney function.

Long-term Primary Medical Therapy with Somatostatin Analogs in Acromegaly

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Deng-Huang Su

2006-01-01

Full Text Available To cure acromegalic patients, transsphenoidal surgery is considered first, especially for microadenoma. However, less than 50% of patients with macroadenoma achieve satisfactory biochemical control. Moreover, surgery may cause hypopituitarism. Medical therapy may offer the prospect of near normalization of growth hormone (GH/insulin-like growth factor-1 levels with substantial tumor shrinkage in a significant number of patients. Here, we report two cases of acromegaly under treatment with somato-statin analogs alone for more than 10 years. Case 1 was a 54-year-old man with a pituitary macro-adenoma. He received 4 years of octreotide treatment followed by 6 years of prolonged-release (PR lanreotide resulting in normal GH level. Case 2 was a 60-year-old woman with a 1.3 cm pituitary tumor. She received 8 years of octreotide treatment followed by 6 years of PR lanreotide resulting in subnormal GH level and gallbladder sludge. She had received bilateral total hip replacement for hip osteoarthritis at the age of 59 years. These cases illustrate that long-term treatment with somatostatin analogs offers an alternative choice in selected acromegalic patients, such as those with pituitary tumor who cannot be cured by surgery, those who have unacceptable anesthetic risk and those who refuse surgery.

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

International Nuclear Information System (INIS)

Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David; Rineer, Justin

2014-01-01

To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Long-term Morbidity of Testicular Cancer Treatment.

Science.gov (United States)

Fung, Chunkit; Fossa, Sophie D; Williams, Annalynn; Travis, Lois B

2015-08-01

Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.

Science.gov (United States)

Kovalyov, Oleksiy O; Kostyuk, Oleksandr G; Tkachuk, Tetyana V

To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy. Peripheral venous bed status in 41 oncology patients taking long-term chemotherapy treatment is analyzed in the article. Doppler sonography, morphologic and immune histochemical analyses were used in the study. Doppler sonography found qualitative and quantitative changes in forearm veins at different time periods after initiation of chemotherapy in the majority of patients. The major morphologic manifestations of venous wall damage were chemical phlebitis, local or extended hardening of venous wall, venous thrombosis and extravasations with necrosis and subsequent paravasal tissue sclerosis. Alternative vascular access created in 12 patients completely met the adequacy criteria (safety, multiple use, longevity, realization of the designed therapy program). The conclusion was made about inapplicability of forearm veins for long-term administration of cytostatic agents. If it is impossible to use central veins, arteriovenous fistula can become an alternative vascular access.

Do bisphosphonates inhibit direct fracture healing?: A laboratory investigation using an animal model.

Science.gov (United States)

Savaridas, T; Wallace, R J; Salter, D M; Simpson, A H R W

2013-09-01

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (sd 7.63) vs 24.65 Nmm(-2) (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Primary tacrolimus (FK506) therapy and the long-term risk of post-transplant lymphoproliferative disease in pediatric liver transplant recipients.

Science.gov (United States)

Cacciarelli, T V; Reyes, J; Jaffe, R; Mazariegos, G V; Jain, A; Fung, J J; Green, M

2001-10-01

While the overall incidence of post-transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients has been reported to be 4-11%, the long-term risk of PTLD associated with primary tacrolimus therapy is unknown. Therefore, in order to determine the incidence and long-term risk of PTLD, the present study examined 131 pediatric recipients who underwent liver transplantation (LTx) between October 1989 and December 1991 and received primary tacrolimus therapy. This cohort of children was evaluated over an extended time-period (until December 31 1996) with a mean follow-up of 6.3 yr. Actuarial Kaplan-Meier analysis was utilized to determine the risk of PTLD over time. The overall incidence of PTLD was 13% (17/131) with an average age of 4.3 +/- 0.75 yr at diagnosis. Pretransplant Epstein-Barr virus (EBV) serologies were negative in 82%, positive in 12%, and not available in 6% of the patients. The median time to diagnosis of PTLD post-Tx was 11.9 months (mean 16.4 +/- 3.9, range 1.7-63.0 months). Mean tacrolimus dose and plasma trough level (as evaluated by enzyme-linked immunosorbent assay [ELISA]) at the time of diagnosis was 0.32 +/- 0.06 mg/kg/day and 1.3 +/- 0.3 ng/mL, respectively. The cumulative long-term risk of PTLD was found to increase over time: 3% at 6 months, 8% at 1 yr, 12% at 2 yr, 14% at 3 yr, and 15% at 4 and 5 yr. Mortality from PTLD was 12% (two of 17 patients). Primary tacrolimus use in pediatric LTx has a long-term risk of PTLD approaching 15%, with the majority of episodes (78%) occurring in the first 2 yr, suggesting that intense EBV surveillance should occur early post-transplantation.

Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning

NARCIS (Netherlands)

Mansson, K.N.T.; Frick, A.; Boraxbekk, C.J.; Marquand, A.F.; Williams, S.C.; Carlbring, P.; Andersson, G.; Furmark, T.

2015-01-01

Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge.

Brain size and neuropsychological functioning in long-term survivors of pediatric acute lymphoblastic leukemia.

Science.gov (United States)

Mulcahy Levy, Jean M; Hunger, Stephen P

2013-10-01

With the increased survival of pediatric cancer patients the interest in the late effects of treatments is rapidly increasing. Long-term survival rates for children with acute lymphoblastic leukemia (ALL) now approach 90%. Treatment for ALL includes intensified central nervous system (CNS)-directed therapy, which is associated with risks for long-term neurocognitive effects. It is becoming clear that current therapies can have not only a detrimental effect on IQ, processing speed, and memory, but also on structural changes that lead to permanent alterations of the organization of the CNS. Understanding how the CNS is affected by the treatments is a critical step in evaluating current therapies and developing interventions to decrease the incidence and severity of long-term changes in brain anatomy and function.

Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium.

Science.gov (United States)

Hiligsmann, Mickaël; Reginster, Jean-Yves

2011-10-01

less and no prior fractures. The cost effectiveness of denosumab compared with generic alendronate was estimated at &U20AC;38 514, &U20AC;22 220 and &U20AC;27 862 per QALY for women aged 60, 70 and 80 years, respectively, with T-scores of -2.5 or less. The equivalent values were &U20AC;37 167, &U20AC;19 718 and &U20AC;19 638 per QALY for women with prevalent vertebral fractures. This study suggests, on the basis of currently available data, that denosumab is a cost-effective strategy compared with oral bisphosphonates (including generic alendronate) for the treatment of post-menopausal osteoporotic women, aged ≥60 years in Belgium. Denosumab therefore appears to have the potential to become a first-line treatment for post-menopausal women with osteoporosis. However, further studies would be required to evaluate the long-term safety and adherence of denosumab in real-world clinical practice as well as head-to-head effectiveness compared with oral bisphosphonates.

Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis.

Science.gov (United States)

Winny, Markus; Paroglou, Vagia; Bektas, Hüseyin; Kaltenborn, Alexander; Reichert, Benedikt; Zachau, Lea; Kleine, Moritz; Klempnauer, Jürgen; Schrem, Harald

2014-02-01

This retrospective, single-center, observational study on postoperative long-term results aims to define yet unknown factors for long-term outcome after operation for chronic pancreatitis. We analyzed 147 consecutive patients operated for chronic pancreatitis from 2000 to 2011. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Complete long-term survival data were provided by the German citizen registration authorities for all patients. A quality-of-life questionnaire was sent to surviving patients after a mean follow-up of 5.7 years. Surgical principles were resection (n = 86; 59%), decompression (n = 29; 20%), and hybrid procedures (n = 32; 21%). No significant influences of different surgical principles and operative procedures on survival, long-term quality of life and pain control could be detected. Overall 30-day mortality was 2.7%, 1-year survival 95.9%, and 3-year survival 90.8%. Multivariate Cox regression analysis revealed that only postoperative insulin dependence at the time of hospital discharge (P = .027; Exp(B) = 2.111; 95% confidence interval [CI], 1.089-4.090) and the absence of pancreas enzyme replacement therapy at the time of hospital discharge (P = .039; Exp(B) = 2.102; 95% CI, 1.037-4.262) were significant, independent risk factors for survival with significant hazard ratios for long-term survival. Long-term improvement in quality of life was reported by 55 of 76 long-term survivors (73%). Pancreatic enzyme replacement should be standard treatment after surgery for chronic pancreatitis at the time of hospital discharge, even when no clinical signs of exocrine pancreatic failure exist. This study underlines the potential importance of early operative intervention in chronic pancreatitis before irreversible endocrine dysfunction is present. Copyright © 2014 Mosby, Inc. All rights reserved.

Tapering off benzodiazepines in long-term users : an economic evaluation

NARCIS (Netherlands)

Oude Voshaar, Richard C; Krabbe, Paul F M; Gorgels, Wim J M J; Adang, Eddy M M; van Balkom, Anton J L M; van de Lisdonk, Eloy H; Zitman, Frans G

2006-01-01

BACKGROUND: Discontinuation of benzodiazepine usage has never been evaluated in economic terms. This study aimed to compare the relative costs and outcomes of tapering off long-term benzodiazepine use combined with group cognitive behavioural therapy (TO+CBT), tapering off alone (TOA) and usual

Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy

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Allan W. Taylor

2013-01-01

Full Text Available Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART are not established in human-immunodeficiency-virus-(HIV- infected women who experience pregnancy during the course of therapy. Design. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Results. Among 196 pregnant women, 103 (52.6% were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095 of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.. Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.

Radiation Therapy Did Not Induce Long-Term Changes in Rectal Mucosa: Results From the Randomized Scandinavian Prostate Cancer Group 7 Trial

Energy Technology Data Exchange (ETDEWEB)

Slagsvold, Jens Erik, E-mail: Jens.Erik.Slagsvold@stolav.no [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Viset, Trond [Department of Pathology, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Wibe, Arne [Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim (Norway); Department of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Kaasa, Stein [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); European Palliative Care Research Center, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim (Norway); Widmark, Anders [Department of Radiation Sciences, Cancercentrum, Umeå (Sweden); Lund, Jo-Åsmund [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); European Palliative Care Research Center, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim (Norway)

2016-07-15

Purpose: To investigate long-term changes in the rectal mucosa after curative external beam radiation therapy in the treatment of prostate cancer. Methods and Materials: In the Scandinavian Prostate Cancer Group 7 trial, 880 men with locally advanced prostate cancer were randomized to hormonal therapy alone versus hormonal therapy plus radiation therapy to 70 Gy. A subcohort from this trial being randomized at our center (n=178) was invited to a study on late anorectal side effects during 2003-2005, approximately 5 years after treatment, including measuring health-reported quality of life and physician-assessed toxicity score by the Late Effects Normal Tissue Task Force/Subjective, Objective, Management, Analytic (LENT/SOMA) and European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group score. Sixty-seven patients had a rectal mucosa biopsy. Sixty-four biopsies were included in the final analysis, of which 33 patients were randomized to hormonal treatment and 31 to hormonal treatment plus radiation therapy. The presence of fibrosis, number of capillaries, and lymphocyte infiltration was then evaluated by light microscopy. Results: The group receiving radiation therapy had significantly higher LENT/SOMA and function/bother scale scores than the group that only received hormonal treatment, but there was no significant difference in the presence of fibrosis, ectasia, number of capillaries in the lamina propria, or lymphocyte infiltration between the groups. Conclusion: Radiation therapy to 70 Gy to the prostate does not induce long-term microscopic mucosal changes in the rectum 5 years after treatment. This is in contrast to the general assumption that structural changes, including fibrosis, seen after radiation therapy include the mucosa. We speculate that the main late effects of radiation therapy on the structure of the rectum are located in the deeper layers of the rectal wall than the mucosa.

Intraoperative Radiation Therapy in Resected Pancreatic Carcinoma: Long-Term Analysis

International Nuclear Information System (INIS)

Valentini, Vincenzo; Morganti, Alessio G.; Macchia, Gabriella; Mantini, Giovanna; Mattiucci, Gian C.; Brizi, M. Gabriella; Alfieri, Sergio; Bossola, Maurizio; Pacelli, Fabio; Sofo, Luigi; Doglietto, Giovanbattista; Cellini, Numa

2008-01-01

Purpose: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT + IORT). Methods and Materials: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative 'flash' RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. Results: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p = 0.019). Conclusions: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (∼50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT + external RT)

Osteonecrosis de los maxilares asociada al empleo de bifosfonatos Bisphosphonate-associated osteonecrosis of the jaw

Directory of Open Access Journals (Sweden)

J.L. del Castillo Pardo de Vera

2007-10-01

Full Text Available Los bifosfonatos constituyen un grupo de fármacos inhibidores de la resorción ósea, utilizados en el tratamiento de numerosas patologías como la osteoporosis, la enfermedad de Paget, el mieloma múltiple, la hipercalcemia maligna y las metástasis óseas asociadas al cáncer de mama o de próstata. El principal efecto farmacológico de los bifosfonatos es la inhibición de la resorción ósea, mediante una disminución de la actividad de los osteoclastos, sin intervenir en la formación y mineralización del hueso. Son fármacos utilizados a nivel mundial con unos claros beneficios contrastados clínicamente. Numerosas publicaciones durante los últimos tres años, y debido a su utilización masiva, consideran que la osteonecrosis de los maxilares está asociada al tratamiento con bifosfonatos. Es importante que los pacientes sean informados del riesgo de presentarse esta complicación, para tener la oportunidad de someterse a procedimientos dentales previos al inicio del tratamiento. Las medidas preventivas deben realizarse antes, durante y después del tratamiento con bifosfonatos. El tratamiento quirúrgico debe reservarse para aquellos pacientes que presenten síntomas. Son necesarias nuevas investigaciones que clarifiquen esta complicación.Bisphosphonates constitute a group of inhibitors of bone resorption that are used for treating many disor-ders such as osteoporosis, Paget´s disease, multiple myeloma, malignant hypercalcemia and bone metas-tases associated with breast and prostate cancer. The main pharmacological effect of bisphosphonates is the inhibition of bone resorption, mediated by a decreased function of osteoclasts without interfering in bone formation and mineralization. These drugs are used worldwide, with clear and clinically proven benefits. Several publications within the last three years consider osteonecrosis of the jaw to be associated with bisphosphonate therapy as a result of their extensive use. It is important

Effects of Transdermal Tulobuterol in Pediatric Asthma Patients on Long-Term Leukotriene Receptor Antagonist Therapy: Results of a Randomized, Open-Label, Multicenter Clinical Trial in Japanese Children Aged 4–12 Years

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Toshio Katsunuma

2013-01-01

Conclusions: These results suggest that short-term use of a transdermal β2 agonist is an effective therapy for pediatric asthma without inducing airway inflammation in children on long-term LTRA therapy.

Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging

NARCIS (Netherlands)

Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Steingrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, José A. M.; Miedema, Frank

2008-01-01

It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

Restoration of the CD4 T cell compartment after long-term highly active Antiretroviral therapy without phenotypical signs of accelerated immunological aging

NARCIS (Netherlands)

Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Stemgrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, Jose A. M.; Miedema, Frank

2008-01-01

It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

Self-Reported Long-Term Benefits of Mindfulness-Based Cognitive Therapy in Patients with Bipolar Disorder.

Science.gov (United States)

Weber, Béatrice; Sala, Loretta; Gex-Fabry, Marianne; Docteur, Aurélie; Gorwood, Philip; Cordera, Paolo; Bondolfi, Guido; Jermann, Françoise; Aubry, Jean-Michel; Mirabel-Sarron, Christine

2017-07-01

This study focused on patients with bipolar disorder (BD), several years after their participation in mindfulness-based cognitive therapy (MBCT). It aimed at documenting sustained mindfulness practice, perceived long-term benefit from the program, and changes regarded as direct consequences of the intervention. This cross-sectional survey took place at least 2 years after MBCT for 70.4% of participants. It was conducted in two specialized outpatient units for BDs that are part of the Geneva University Hospitals (Switzerland) and the Sainte-Anne Hospital in Paris (France). Eligibility criteria were a diagnosis of BD according to DSM-IV and participation in at least four MBCT sessions. Response rate was 66.4%. The final sample included 71 outpatients (71.8% bipolar I, 28.2% bipolar II). A questionnaire retrospectively assessed patient-perceived change, benefit from MBCT, and current mindfulness practice. Proportions of respondents who practiced mindfulness at least once a week were 54.9% for formal practice (body scan, sitting meditation, mindful walking, or movements) and 57.7% for informal practice (mindful daily activities). Perceived benefit for the prevention of relapse was moderate, but patients acknowledged long-lasting effects and persistent changes in their way of life. Formal mindfulness practice at least once a week tended to be associated with increased long-lasting effects (p = 0.052), whereas regular informal practice and mindful breathing were significantly associated with persistent changes in daily life (p = 0.038) and better prevention of depressive relapse (p = 0.035), respectively. The most frequently reported positive change was increased awareness of being able to improve one's health. Despite methodological limitations, this survey allowed documenting mindfulness practice and perceived sustained benefit from MBCT in patients with BD. Participants particularly valued increased awareness that they can influence their own health. Both

Long-term oxygen therapy in COPD patients: population-based cohort study on mortality

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Pavlov N

2018-03-01

Full Text Available Nikolay Pavlov,1 Alan Gary Haynes,2,3 Armin Stucki,4 Peter Jüni,5 Sebastian Robert Ott1 1Department of Pulmonary Medicine, University Hospital (Inselspital, University of Bern, Bern, Switzerland; 2CTU Bern, University of Bern, Bern, Switzerland; 3Institute of Social and Preventive Medicine (ISPM, University of Bern, Bern, Switzerland; 4Department of Internal Medicine, Spital Thun, Thun, Switzerland; 5Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada Purpose: Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death worldwide and is associated with a growing and substantial socioeconomic burden. Long-term oxygen therapy (LTOT, recommended by current treatment guidelines for COPD patients with severe chronic hypoxemia, has shown to reduce mortality in this population. The aim of our study was to assess the standardized mortality ratios of incident and prevalent LTOT users and to identify predictors of mortality. Patients and methods: We conducted a 2-year follow-up population-based cohort study comprising all COPD patients receiving LTOT in the canton of Bern, Switzerland. Comparing age- and sex-adjusted standardized mortality ratios, we examined associations between all-cause mortality and patient characteristics at baseline. To avoid immortal time bias, data for incident (receiving LTOT <6 months and prevalent users were analyzed separately. Results: At baseline, 475 patients (20% incident users, n=93 were receiving LTOT because of COPD (48/100,000 inhabitants. Mortality of incident and prevalent LTOT users was 41% versus 27%, respectively, p<0.007, and standardized mortality ratios were 8.02 (95% CI: 5.64–11.41 versus 5.90 (95% CI: 4.79–7.25, respectively. Type 2 respiratory failure was associated with higher standardized mortality ratios among incident LTOT users (60.57, 95% CI: 11.82–310.45, p=0

Do the frequencies of adverse events increase, decrease, or stay the same with long-term use of statins?

Science.gov (United States)

Huddy, Karlyn; Dhesi, Pavittarpaul; Thompson, Paul D

2013-02-01

Statins are widely used for their cholesterol-lowering properties and proven reduction of cardiovascular disease risk. Many patients take statins as long-term treatment for a variety of conditions without a clear-cut understanding of how treatment duration affects the frequency of adverse effects. We aimed to evaluate whether the frequencies of documented adverse events increase, decrease, or remain unchanged with long-term statin use. We reviewed the established literature to define the currently known adverse effects of statin therapy, including myopathy, central nervous system effects, and the appearance of diabetes, and the frequency of these events with long-term medication use. The frequency of adverse effects associated with long-term statin therapy appears to be low. Many patients who develop side effects from statin therapy do so relatively soon after initiation of therapy, so the frequency of side effects from statin therapy when expressed as a percentage of current users decreases over time. Nevertheless, patients may develop side effects such as muscle pain and weakness years after starting statin therapy; however, the absolute number of patients affected by statin myopathy increases with treatment duration. Also, clinical trials of statin therapy rarely exceed 5 years, so it is impossible to determine with certainty the frequency of long-term side effects with these drugs.

Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.

Science.gov (United States)

Wehrhan, F; Hyckel, P; Amann, K; Ries, J; Stockmann, P; Schlegel, Ka; Neukam, Fw; Nkenke, E

2011-05-01

Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone. An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels. Labelling indices were significantly lower for Msx-1 (P Msx-1, 22-fold lower (P Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future. © 2011 John Wiley & Sons A/S.

Subtrochanteric fractures in bisphosphonate-naive patients

DEFF Research Database (Denmark)

Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven

2011-01-01

Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained ...

Root canal therapy for the prevention of osteonecrosis of the jaws: an evidence-based clinical update.

Science.gov (United States)

Kyrgidis, Athanassios; Arora, Amit; Lyroudia, Kleoniki; Antoniades, Konstantinos

2010-12-01

Osteonecrosis of the jaws is an adverse effect of bone preservation treatment. There is a sufficient body of evidence to associate osteonecrosis of the jaws development with dental extractions and trauma caused from ill-fitting dentures. In this review, we critically appraise available evidence about the clinical efficacy of root canal therapy in patients receiving bisphosphonates.We review a series of theories to explain why endodontic treatment is a safe clinical intervention to prevent osteonecrosis of the jaws in patients receiving bisphosphonates. Root canal therapy could postpone or even eradicate the need for dental extractions of carious teeth in patients on bisphosphonates who may develop osteonecrosis of the jaws. Patients receiving bisphosphonates should be offered the full range of preventive care to reduce their risk to both dental caries and periodontal disease, so that the need for both endodontic therapy and dental extractions will be reduced. Implementing such a strategy would require both practitioner and patient education through the combined efforts of medical and dental societies. Such an approach is justified, as the risk of compromising the oral health of patients on bisphosphonates undertaking endodontic treatment is negligible compared with the benefit from avoiding dental extractions.

Report of a Rare Case of Gorham-Stout Disease of Both Shoulders: Bisphosphonate Treatment and Shoulder Replacement

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Eike Garbers

2011-01-01

Full Text Available Massive osteolysis known as Gorham-Stout disease is a rare idiopathic disorder typically affecting long bones in a unifocal pattern. Angiomatosis is strongly connected to the osteolysis. Weather angiomatosis is the cause or the result of osteolysis is subject of intense discussion (Kawasaki et al. (2003, Möller et al. (1999, Radhakrishnan and Rockson (2008. There are about 200 cases described since 1955. Our patient is a 77-year-old female patient with osteolyses of both shoulders involving the proximal humerus, lateral clavicle, and the glenoid. Under bisphosphonate therapy, the progressive osteolysis stopped on the right side and showed progression on the left. With the patient complaining about severe rest pain and impaired function, we performed surgical reconstruction by implantation of total shoulder prosthesis three months after onset of symptoms. Our case shows a possibility of primary and early surgical reconstruction with good clinical outcome.

A large case-control study reveals a positive association between bisphosphonate use and delayed dental healing and osteonecrosis of the jaw.

Science.gov (United States)

Borromeo, Gelsomina L; Brand, Caroline; Clement, John G; McCullough, Michael; Crighton, Lisa; Hepworth, Graham; Wark, John D

2014-06-01

This study sought to investigate, using a case-control study design, the association between bisphosphonate therapy and delayed dental healing and osteonecrosis of the jaw. Identification of potential cases of delayed dental healing was by consecutive screening of Specialist Oral and Maxillofacial and Special Needs Dentist clinic records for patients aged older than 50 years, during a 6-month window, in Victoria, Australia. Cases were confirmed by a case adjudication panel blinded to bisphosphonate status. Cases associated with malignancy or local radiotherapy were excluded. Controls were matched for age, sex, and source of dental referral (1:4, n = 160 controls). Variables of interest were dental precipitants, dental clinic type, smoking history, and medical comorbidities. A total of 4212 of 22,358 patients met inclusion criteria, of which 69 were potential cases with 40 (0.95%) confirmed cases. The odds ratio (OR) for developing delayed dental healing when taking an oral bisphosphonate was 13.1 (95% confidence interval [CI] 4.4 to 39.3; p associated with intravenous bisphosphonate use. There was some evidence of an interaction with age, sex, and clinic type. When adjusted for smoking, the estimated odds ratio was 11.6 (95% CI 1.9 to 69.4; p = 0.01). There was an association between having another illness and delayed dental healing (OR = 2.3; 95% CI 1.0 to 5.2). A dental precipitant was present in 39 of 40 (97.5%) delayed dental healing cases. An important association between bisphosphonate use and delayed dental healing in the setting of benign bone disease, predominately in individuals with a dental precipitant, has been demonstrated. © 2014 American Society for Bone and Mineral Research.

Long-term efficacy of microbiology-driven periodontal laser-assisted therapy.

Science.gov (United States)

Martelli, F S; Fanti, E; Rosati, C; Martelli, M; Bacci, G; Martelli, M L; Medico, E

2016-03-01

Periodontitis represents a highly prevalent health problem, causing severe functional impairment, reduced quality of life and increased risk of systemic disorders, including respiratory, cardiovascular and osteoarticular diseases, diabetes and fertility problems. It is a typical example of a multifactorial disease, where a polymicrobial infection inducing chronic inflammation of periodontal tissues is favoured by environmental factors, life style and genetic background. Since periodontal pathogens can colonise poorly vascularised niches, antiseptics and antibiotics are typically associated with local treatments to manage the defects, with unstable outcomes especially in early-onset cases. Here, the results of a retrospective study are reported, evaluating the efficacy of a protocol (Periodontal Biological Laser-Assisted Therapy, Perioblast™) by which microbial profiling of periodontal pockets is used to determine the extent and duration of local neodymium-doped yttrium aluminium garnet (Nd:YAG) laser irradiation plus conventional treatment. The protocol was applied multicentrically on 2683 patients, and found to produce a significant and enduring improvement of all clinical and bacteriological parameters, even in aggressive cases. Microbiome sequencing of selected pockets revealed major population shifts after treatment, as well as strains potentially associated with periodontitis in the absence of known pathogens. This study, conducted for the first time on such a large series, clearly demonstrates long-term efficacy of microbiology-driven non-invasive treatment of periodontal disease.

Eliminating the need for fasting with oral administration of bisphosphonates

DEFF Research Database (Denmark)

Pazianas, Michael; Abrahamsen, Bo; Ferrari, Serge

2013-01-01

or beverages create complexes that cannot be absorbed. For this reason, they must be taken on an empty stomach, and a period of up to 2 hours must elapse before the consumption of any food or drink other than plain water. This routine is not only inconvenient but can lead to discontinuation of treatment......Bisphosphonates are the major treatment of choice for osteoporosis, given that they are attached preferentially by bone and significantly reduce the risk of fractures. Oral bisphosphonates are poorly absorbed (usually less than 1% for nitrogen-containing bisphosphonates) and when taken with food......, and when mistakenly taken with food, may result in misdiagnosis of resistance to or failure of treatment. The development of an enteric-coated delayed-release formulation of risedronate with the addition of the calcium chelator, ethylenediaminetetraacetic acid (EDTA), a widely used food stabilizer...

Comparison of orally administered bisphosphonate drugs in reducing the risk of hip fracture in older adults: a population-based cohort study.

Science.gov (United States)

Cadarette, Suzanne M; Lévesque, Linda; Mamdani, Muhammad; Perreault, Sylvie; Juurlink, David N; Paterson, J Michael; Carney, Greg; Gunraj, Nadia; Hawker, Gillian A; Tadrous, Mina; Wong, Lindsay; Dormuth, Colin R

2013-09-01

selection bias. The long-term comparative effects of orally administered bisphosphonate drugs warrant further study.

Bisphosphonate drug holidays in postmenopausal osteoporosis: effect on clinical fracture risk.

Science.gov (United States)

Mignot, M A; Taisne, N; Legroux, I; Cortet, B; Paccou, J

2017-12-01

A cohort of 183 postmenopausal women, who had either discontinued or continued bisphosphonates (BPs) after first-line therapy, was used to investigate the relationships between "drug holiday" and clinical fracture. The risk of new clinical fractures was found to be 40% higher in women who had taken a BP "drug holiday." BPs are the most widely used treatment for postmenopausal osteoporosis. The optimal treatment duration, however, remains unclear. The purpose of this study was to evaluate the fracture risk in postmenopausal women with osteoporosis after discontinuing BP treatment (BP "drug holiday"). A retrospective analysis was performed at Lille University Hospital (LUH) on postmenopausal women with osteoporosis who had taken a "drug holiday" or continued treatment after first-line BP therapy (3 to 5 years). The occurrence of new clinical fractures during follow-up was also explored. Cox proportional hazards models were used to investigate the relationships between BP "drug holiday" and the occurrence of clinical fractures, while controlling for confounding factors. Survival without new clinical fractures was analyzed using Kaplan-Meier curves and log-rank tests. One hundred eighty-three women (mean age: 61.8 years; SD: 8.7) who had previously undergone BP treatment for 3 to 5 years were enrolled in our study. The patients had received alendronate (n = 81), risedronate (n = 73), zoledronic acid (n = 20), and ibandronate (n = 9). In 166 patients ("drug holiday" group: n = 31; continuous-treatment group: n = 135), follow-up ranged from 6 to 36 months (mean duration: 31.8 months; SD: 8.2). The incidences of new clinical fractures during follow-up were 16.1% (5/31) and 11.9% (16/135). After full adjustment, the hazard ratio of new clinical fractures among "drug holiday" patients was 1.40 (95% CI: 1.12-1.60; p = 0.0095). After first-line BP therapy in postmenopausal women with osteoporosis, the risk of new clinical fractures was 40% higher in

Long-term follow-up study of compensated low-dose 131I therapy for Graves' disease

International Nuclear Information System (INIS)

Sridama, V.; McCormick, M.; Kaplan, E.L.; Fauchet, R.; DeGroot, L.J.

1984-01-01

We treated 187 patients who had Graves' disease with low-dose radioactive iodide ( 131 I), using a protocol that included a compensation for thyroid size. The incidence of early hypothyroidism (12 per cent) was acceptably low in the first year after 131 I treatment, but we found a cumulative high incidence (up to 76 per cent) at the end of the 11th year. In contrast, the incidence of permanent hypothyroidism was relatively stable in 166 surgically treated patients, increasing from 19 to 27 per cent at the end of 11 years. Among 122 medically treated patients, only 40 per cent entered remission, and hypothyroidism developed in 2 per cent during the same period of follow-up. The long-term incidence of hypothyroidism in our patients treated with low-dose 131 I therapy was much higher than that found in earlier studies using a comparable dose. Our study suggests that it will be difficult to modify therapy with 131 I alone to produce both early control of thyrotoxicosis and a low incidence of hypothyroidism

Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy.

Science.gov (United States)

Nakai, Kentaro; Fujii, Hideki; Yoshikawa, Mikiko; Kono, Keiji; Yonekura, Yuriko; Goto, Shunsuke; Ishimura, Takeshi; Takeda, Masashi; Fujisawa, Masato; Nishi, Shinichi

2015-12-01

Cinacalcet is a promising therapy widely used in dialysis patients with hyperparathyroidism resistant to conventional therapy. However, reports regarding the influence of cinacalcet cessation after long-term use on kidney transplantation patients are few. This retrospective observational study included 40 dialysis patients who underwent kidney transplantation. Creatinine, corrected calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone levels were assessed before and after kidney transplantation according to pretransplant treatment of chronic kidney disease-mineral and bone disorder. Ultrasonography revealed enlargement of the parathyroid in all patients treated with cinacalcet. Although the data at the time of kidney transplantation were comparable, the serum levels of calcium, alkaline phosphatase, and intact parathyroid hormone after kidney transplantation were higher in patients treated with cinacalcet than in those treated without. However, serum phosphate levels in the cinacalcet group were slightly higher at the time of kidney transplantation and significantly lower 3 months later. Mineral abnormalities persisted in kidney transplant patients with enlarged parathyroid glands after discontinuation of cinacalcet treatment. Parathyroidectomy should be considered in kidney transplant candidates with the risk of developing refractory hyperparathyroidism after transplantation.

CD19 CAR-T cell therapy for relapsed/refractory acute lymphoblastic leukemia: factors affecting toxicities and long-term efficacies.

Science.gov (United States)

Zhang, Li-Na; Song, Yongping; Liu, Delong

2018-03-15

The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy. CD-19 CAR-T cells have been recently approved for high-risk R/R ALL and lymphoma. The data from long-term follow-up of a single-center phase I study of 19-28z CAR-T cell therapy for adult R/R ALL were just published. At the same time, a multicenter phase II study of 19-41BB CAR-T cell therapy for children and young adults with R/R B cell ALL was also published. The two studies provided fresh information with long-term follow-up. This research highlight analyzed the data and proposed future perspectives for further investigation in this rapidly evolving field.

Long-Term Effects of Two Formats of Cognitive Behavioral Therapy for Insomnia Comorbid with Breast Cancer.

Science.gov (United States)

Savard, Josée; Ivers, Hans; Savard, Marie-Hélène; Morin, Charles M

2016-04-01

The goal of this randomized controlled trial, conducted in breast cancer patients, was to assess the long-term efficacy of a video-based cognitive behavioral therapy for insomnia (VCBT-I), as compared to a professionally administered intervention (PCBT-I) and to a no-treatment group (CTL). An earlier report revealed that, at posttreatment, VCBT-I patients showed significantly greater sleep improvements than CTL, but that PCBT-I produced superior effects than VCBT-I on some sleep and secondary outcomes. In this report, long-term effects are compared. Two hundred forty-two women with breast cancer and with insomnia symptoms or using hypnotic medications participated to this three-arm randomized controlled trial: (1) PCBT-I (n = 81); (2) VCBT-I (n = 80); or (3) no treatment (CTL; n = 81) group. PCBT-I was composed of six weekly, individual sessions of approximately 50 min, whereas VCBT-I comprised a 60-min animated video and six booklets. Study measures (sleep and secondary variables) were administered at pretreatment and posttreatment, and at a 3-, 6-, and 12-mo follow-up. Treatment gains were well sustained at follow-up in both PCBT-I and VCBT-I. As at posttreatment, the remission rate of insomnia at follow-up was greater in PCBT-I than in VCBT-I, which was greater than in CTL. Although face-to-face therapy remains the optimal format to efficaciously administer CBT for insomnia in cancer patients, a minimal intervention, such as the video-based intervention tested in this study, produces significant and sustainable treatment effects. ClinicalTrials.gov identifier NCT00674830. © 2016 Associated Professional Sleep Societies, LLC.

Bone targeting compounds for radiotherapy and imaging: *Me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid.

Science.gov (United States)

Meckel, M; Bergmann, R; Miederer, M; Roesch, F

2017-01-01

Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing 68 Ga-labelled analogues, endoradiotheraphy with 177 Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA PAM and DOTA ZOL (MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide 68 Ga and the β - emitting nuclide 177 Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [ 18 F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed 68 Ga and >98 % with 177 Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [ 68 Ga]DOTA ZOL (SUV Femur  = 5.4 ± 0.6) followed by [ 18 F]NaF (SUV Femur  = 4.8 ± 0.2), [ 68 Ga]DOTA PAM (SUV Femur  = 4.5 ± 0.2) and [ 68 Ga]BPAPD (SUV Femur  = 3.2 ± 0.3). [ 177 Lu]DOTA ZOL showed a similar distribution as the diagnostic 68 Ga complex. The 68 Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [ 68 Ga]DOTA ZOL , which makes this compound probably an interesting bone targeting agent for a therapeutic approach with 177 Lu. The therapeutic compound [ 177 Lu]DOTA ZOL showed a high target-to-background ratio. SPECT experiments showed concordance

BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma.

Science.gov (United States)

Rossi, Adriana; Mark, Tomer; Jayabalan, David; Christos, Paul; Zafar, Faiza; Pekle, Karen; Pearse, Roger; Chen-Kiang, Selina; Coleman, Morton; Niesvizky, Ruben

2013-03-14

The combination of clarithromycin, lenalidomide, and dexamethasone (BiRd) was evaluated as therapy for treatment-naive symptomatic multiple myeloma (MM), with overall response at 2 years of 90%. We reviewed the long-term follow-up of initial BiRd therapy. Seventy-two patients were given dexamethasone 40 mg weekly, clarithromycin 500 mg twice daily, and lenalidomide 25 mg daily on days 1 to 21 of a 28-day cycle. After a median follow-up of 6.6 years, overall response rates were 93%, with a very good partial response or better of 68%. Median progression-free survival was 49 months. Evaluation for the development of second primary malignancies (SPMs) was conducted, and no increase in incidence was noted in our cohort of patients who received frontline immunomodulatory therapy. BiRd remains a highly potent and safe regimen for frontline therapy in patients with MM without apparent increase in risk of SPMs. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

The Electroporation as a Tool for Studying the Role of Plasma Membrane in the Mechanism of Cytotoxicity of Bisphosphonates and Menadione.

Science.gov (United States)

Šilkūnas, Mantas; Saulė, Rita; Batiuškaitė, Danutė; Saulis, Gintautas

2016-10-01

In this study, the role of the cell plasma membrane as a barrier in the mechanism of the cytotoxicity of nitrogen-containing bisphosphonates and menadione was studied, and the possibility of increasing the efficiency of bisphosphonates and menadione (vitamin K 3 ) as chemotherapeutic agents by permeabilizing the cell plasma membrane has been investigated in vitro. The plasma membrane barrier was reduced by electropermeabilization with the pulse of strong electric field. Two membrane-impermeant bisphosphonates with different hydrophilicities were chosen as study objects: ibandronate and pamidronate. For the comparison, an amphiphilic vitamin K 3 , which is able to cross the cell membrane, was studied as well. The impact of nitrogen-containing bisphosphonates and vitamin K 3 on MH-22A cells viability was evaluated for the case of long (9 days) and short (20 min) exposure. When cells were cultured in the medium with vitamin K 3 for 9-10 days, it exhibited toxicity of 50 % over the control at 6.2 µM for mouse hepatoma MH-22A cells. Ibandronate and pamidronate were capable of reducing drastically the cell viability only in the case of long 9-days incubation and at high concentrations (~20 µM for pamidronate and over 100 µM for ibandronate). Single, square-wave electric pulse with the duration of 100 µs and the field strength of 2 kV/cm was used to electroporate mouse hepatoma MH-22A cells in vitro. The results obtained here showed that the combination of the exposure of cells to membrane-impermeable bisphosphonates pamidronate and ibandronate with electropermeabilization of the cell plasma membrane did not increase their cytotoxicity. In the case of membrane-permeable vitamin K 3 , cell electropermeabilization did increase vitamin K 3 killing efficiency. However, this increase was not substantial, within the range of 20-30 % depending on the duration of the exposure. Electropermeabilization improved cytotoxic effect of vitamin K 3 but not of pamidronate

Long-term effectiveness of surgical treatment of ectopic atrial tachycardia.

Science.gov (United States)

Prager, N A; Cox, J L; Lindsay, B D; Ferguson, T B; Osborn, J L; Cain, M E

1993-07-01

The purpose of this study was to determine the long-term clinical outcome of patients with ectopic atrial tachycardias treated surgically. Ectopic atrial tachycardia is an uncommon arrhythmia that can be symptomatic and is associated with the development of a cardiomyopathy. Management strategies are not well defined because of the paucity of data on the long-term effectiveness of pharmacologic and nonpharmacologic therapies. The long-term clinical impact of medical and surgical therapy was determined in 15 consecutive patients with ectopic atrial tachycardia. All 15 patients were initially treated with antiarrhythmic drugs (mean 5.7 +/- 2.2 drugs/patient). An effective drug regimen was identified in only 5 (33%) of the 15 patients; the remaining 10 patients were treated surgically. In each, individualized surgical procedures were guided by computer-assisted intraoperative mapping, with atrial plaques comprising up to 156 electrodes. Focal ablation was performed in four patients and atrial isolation procedures in six. The 10 patients treated surgically were followed up a mean of 4 +/- 3.2 years. Ectopic atrial tachycardia recurred in one patient. A permanent pacemaker was implanted in two patients, one of whom also required reoperation for constrictive pericarditis. There were no operative deaths. Ectopic atrial tachycardia recurred in three (60%) of the five patients discharged on antiarrhythmic drug therapy during a mean follow-up interval of 6.4 +/- 4.3 years. There was one nonarrhythmic death. Map-guided surgery demonstrated long-term efficacy in abolishing symptoms in 9 of the 10 patients with ectopic atrial tachycardia. Results demonstrate that surgery is effective for patients with ectopic atrial tachycardias who are not easily treated with antiarrhythmic drugs.

Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning.

Science.gov (United States)

Månsson, K N T; Frick, A; Boraxbekk, C-J; Marquand, A F; Williams, S C R; Carlbring, P; Andersson, G; Furmark, T

2015-03-17

Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2-97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale-Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC-amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC-amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.

The effect, moderators, and mediators of resistance and aerobic exercise on health-related quality of life in older long-term survivors of prostate cancer.

Science.gov (United States)

Buffart, Laurien M; Newton, Robert U; Chinapaw, Mai J; Taaffe, Dennis R; Spry, Nigel A; Denham, James W; Joseph, David J; Lamb, David S; Brug, Johannes; Galvão, Daniel A

2015-08-15

The current study examined effects, moderators (for whom), and mediators (working mechanisms) of 12 months of exercise on health-related quality of life (HRQoL) in older long-term survivors of prostate cancer. In total, 100 men aged 71.7 years (standard deviation, 6.4 years) were randomly assigned to 6 months of supervised aerobic and resistance exercise followed by 6 months of a home-based exercise maintenance program (EX group) or printed education material regarding physical activity for 12 months (PA group). Assessments took place at baseline and after 6 and 12 months. Generalized estimating equations were used to study the effects of EX versus PA on HRQoL at 6 and 12 months, adjusting for baseline HRQoL. The authors examined potential sociodemographic and clinical moderators by adding interaction terms, and potential physical and psychological mediators using the product-of-coefficients test. At 6 months, significant beneficial effects were found for global QoL, physical function, and social function in the EX group compared with the PA group. For physical function, beneficial effects were sustained at 12 months. Moderation analyses demonstrated larger effects of EX versus PA for patients who were married, started exercising sooner after their diagnosis, and previously used bisphosphonates. Changes in lower body functional performance significantly mediated the effect of EX on global QoL, physical function, and social function. No mediating effects on HRQoL were found for aerobic fitness, physical activity, fatigue, distress, or falls self-efficacy. Aerobic and resistance exercise appears to have beneficial effects on HRQoL among older, long-term survivors of prostate cancer. Effects were moderated by marital status, time since diagnosis, and use of bisphosphonates, and were mediated by lower body functional performance. © 2015 American Cancer Society.

Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

OpenAIRE

Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

2007-01-01

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight...

Long-term observations of operated and irradiated breast carcinoma

International Nuclear Information System (INIS)

Decker-Mroz, G.; Schroeder, R.

1983-01-01

498 patients with histologically established and surgically removed breast carcinomas received post-operative irradiation treatment at Moabit hospital, Berlin, between 1965 and 1975. The long-term results of this largely standardized therapy have been compiled and evaluated. (orig./MG) [de

Bisphosphonate-associated osteonecrosis of the jaws

Directory of Open Access Journals (Sweden)

Pankaj Agarwal

2012-01-01

Full Text Available Bisphosphonates constitute a group of drugs capable of modulating bone turnover and reduce its remodeling when an excessive resorption occurs. This is why they are indicated in a large group of bone diseases like postmenopausal osteoporosis or osteolysis associated with breast cancer or multiple myeloma. Over the last few years and due to their extensive use, many cases of complications associated with their use have been published. Among the most important possible adverse effects are the oral ones, with the appearance of ulcerations and, especially, osteonecrosis of the jaws associated with this therapy. In this paper, we have analyzed the general characteristics of these drugs and their mechanisms of action as well as the described adverse effects, especially oral and maxillofacial, have been made special reference, regarding the prevention of osteonecrosis of the jaws, heightened by cases described in the medical and odontological literature. The preventive protocol backs up the fundamental role of the odontologist in the effective prevention of this process before, during and after the treatment.

Self-concept and quality of object relations as predictors of outcome in short- and long-term psychotherapy.

Science.gov (United States)

Lindfors, Olavi; Knekt, Paul; Heinonen, Erkki; Virtala, Esa

2014-01-01

Quality of object relations and self-concept reflect clinically relevant aspects of personality functioning, but their prediction as suitability factors for psychotherapies of different lengths has not been compared. This study compared their prediction on psychiatric symptoms and work ability in short- and long-term psychotherapy. Altogether 326 patients, 20-46 years of age, with mood and/or anxiety disorder, were randomized to short-term (solution-focused or short-term psychodynamic) psychotherapy and long-term psychodynamic psychotherapy. The Quality of Object Relations Scale (QORS) and the Structural Analysis of Social Behavior (SASB) self-concept questionnaire were measured at baseline, and their prediction on outcome during the 3-year follow-up was assessed by the Symptom Check List Global Severity Index and the Anxiety Scale, the Beck Depression Inventory and by the Work Ability Index, Social Adjustment Scale work subscale and the Perceived Psychological Functioning scale. Negative self-concept strongly and self-controlling characteristics modestly predicted better 3-year outcomes in long-term therapy, after faster early gains in short-term therapy. Patients with a more positive or self-emancipating self-concept, or more mature object relations, experienced more extensive benefits after long-term psychotherapy. The importance of length vs. long-term therapy technique on the differences found is not known. Patients with mild to moderate personality pathology, indicated by poor self-concept, seem to benefit more from long-term than short-term psychotherapy, in reducing risk of depression. Long-term therapy may also be indicated for patients with relatively good psychological functioning. More research is needed on the relative importance of these characteristics in comparison with other patient-related factors. © 2013 Published by Elsevier B.V.

The long-term effects of naprapathic manual therapy on back and neck pain - Results from a pragmatic randomized controlled trial

Directory of Open Access Journals (Sweden)

Bohman Tony

2010-02-01

Full Text Available Abstract Background Back and neck pain are very common, disabling and recurrent disorders in the general population and the knowledge of long-term effect of treatments are sparse. The aim of this study was to compare the long-term effects (up to one year of naprapathic manual therapy and evidence-based advice on staying active regarding non-specific back and/or neck pain. Naprapathy, a health profession mainly practiced in Sweden, Finland, Norway and in the USA, is characterized by a combination of manual musculoskeletal manipulations, aiming to decrease pain and disability in the neuromusculoskeletal system. Methods Subjects with non-specific pain/disability in the back and/or neck lasting for at least two weeks (n = 409, recruited at public companies in Sweden, were included in this pragmatic randomized controlled trial. The two interventions compared were naprapathic manual therapy such as spinal manipulation/mobilization, massage and stretching, (Index Group, and advice to stay active and on how to cope with pain, provided by a physician (Control Group. Pain intensity, disability and health status were measured by questionnaires. Results 89% completed the 26-week follow-up and 85% the 52-week follow-up. A higher proportion in the Index Group had a clinically important decrease in pain (risk difference (RD = 21%, 95% CI: 10-30 and disability (RD = 11%, 95% CI: 4-22 at 26-week, as well as at 52-week follow-ups (pain: RD = 17%, 95% CI: 7-27 and disability: RD = 17%, 95% CI: 5-28. The differences between the groups in pain and disability considered over one year were statistically significant favoring naprapathy (p ≤ 0.005. There were also significant differences in improvement in bodily pain and social function (subscales of SF-36 health status favoring the Index Group. Conclusions Combined manual therapy, like naprapathy, is effective in the short and in the long term, and might be considered for patients with non-specific back and/or neck

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study

NARCIS (Netherlands)

L. Herrera (Lizbeth); I. Leal (Ingrid); F. Lapi (Francesco); M.J. Schuemie (Martijn); V. Arcoraci (Vincenzo); F. Cipriani (Francesco); E. Sessa (E.); A. Vaccheri (Alberto); C. Piccinni (C.); T. Staniscia (Tommaso); A. Vestri (Annarita); M. Di Bari (M.); G. Corrao (Giovanni); A. Zambon (A.); D Gregori (Dario); F. Carle (F.); M.C.J.M. Sturkenboom (Miriam); G. Mazzaglia (Giampiero); G. Trifirò (Gianluca)

2015-01-01

textabstractSummary: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with

Combining garden therapy and supported employment - a method for preparing women on long-term sick leave for working life.

Science.gov (United States)

Lidén, Eva; Alstersjö, Karin; Gurné, Frida L; Fransson, Sandra; Bergbom, Ingegerd

2016-06-01

Women are overrepresented among the group people suffering from long-term illness. In addition to their illness, suffering long-term sick leave leads to economical restraints as well social distress. There are gaps in our understanding of the challenges these women face. There is also lack of knowledge about how these challenges can be effectively addressed in rehabilitation. This deficiency is problematic from an ethical, justice and a caring perspective. In this study, changes in health-related quality of life (HRQoL) among women on long-term sick leave were investigated during and after participating in a rehabilitation programme combining two validated methods, Garden Therapy and Supported Employment (SE). The study also discusses difficulties in realising research related to vulnerable under-privileged people. From a population of 329 women who had reported their interest to participate, 245 were randomised to the programme. Of these 144 accepted participation in the research project and of these 123 women accepted to answer the SF-36 questionnaire. The participants were between 21 and 62 years with poor physical and mental health. They had received public financial support from 10 years. The SF-36 measurement was carried out at baseline, after completion of Garden Therapy and after completion of SE. The results are based on data of respondents who participated at all the three occasions (n = 52). When comparing HRQoL baseline with the following occasions, the participants' General Health (GH), Vitality (VT), Social Functioning (SF) and mental health had improved significantly. The Four Leaf Clover (FLC) programme could be an appropriate method for reducing socially induced suffering. However, to conduct intervention studies where vulnerable persons are involved, it is off vital importance to consider whether the participants have the strength to complete the intervention. © 2015 Nordic College of Caring Science.

Long-term efficacy of recombinant human growth hormone therapy in short-statured patients with Noonan syndrome

Directory of Open Access Journals (Sweden)

Insook Jeong

2016-03-01

Full Text Available PurposeNoonan syndrome (NS is characterized by short stature, heart anomalies, developmental delays, dysmorphic features, cryptorchidism, and coagulation defects. Several studies reported the short-term effects of recombinant human growth hormone (rhGH treatment on the improvement of height. This study was performed to evaluate the long-term efficacy of rhGH in children with NS in Korea.MethodsThis study included 15 prepubertal NS children who received rhGH subcutaneously at a dose of 50–75 µg/kg/day for 6 days a week for at least >3 years. Preand posttreatment data, such as height, weight, bone age, insulin-like growth factor 1 (IGF-1, and IGF binding protein 3 (IGFBP-3 levels, were collected every 6 months.ResultsChronologic age and bone age at the start of treatment were 7.97±1.81 and 5.09±2.12 years, respectively. Height standard deviation score (SDS was increased from –2.64±0.64 to –1.54±1.24 years after 3 years (P<0.001. Serum IGF-1 SDS levels were elevated from –1.28±1.03 to –0.10±0.94 (P<0.001. Height SDS was more increased in subjects without PTPN11 mutations compared to those with mutations after 3 years (P=0.012. However, the other parameters, including bone age, IGF-1 SDS, and IGFBP-3 SDS, were not significantly different between patients with and without PTPN11 mutations.ConclusionAlthough this study included a relatively small number of patients, long-term rhGH therapy in NS patients was safe and effective at improving height, growth velocity, and serum IGF-1 levels, in accordance with previous studies. However, the meticulous monitoring of potential adverse events is still needed because of high dose of rhGH and preexisting hyperactivity of RAS-MAPK pathway. Patients with PTPN11 mutations demonstrated a decreased response to rhGH therapy compared to those without mutations.

Implications of bisphosphonate calcium ion depletion interfering with desmosome epithelial seal in osseointegrated implants and pressure ulcers.

Science.gov (United States)

Touyz, Louis Z G; Afrashtehfar, Kelvin I

2017-09-01

Osteoporosis (OP) is a global bone disease prevalent in aging in humans, especially in older women. Bisphosphonates (BPs) are commonly used as therapy for OP as it influences hard and soft tissues calcium metabolism. Mucosal and dermal ulceration with exposure of underlying bone arises from incomplete epithelial recovery due to reduced desmosome formation deriving from lack of available calcium. Pathological situations such as bisphosphonate-related osteonecrosis of the jaw have been described. This hypothesis states other situations which demand intact functional desmosomes such as healing skin over chronic pressure points leading to pressure ulcers (as well-known as bedsores, pressure sores, pressure injuries, decubitus ulcers), and hemidesmosomes such as epithelial seals in contact with titanium surfaces will have a higher prevalence of breakdown among patients being treated with BPs. This may be proven through the diminished modulation of calcium ions due to BPs, and its effect on the formation of intercellular gap junctions. Copyright © 2017. Published by Elsevier Ltd.

Long-term etanercept therapy favors weight gain and ameliorates cachexia in rheumatoid arthritis patients: roles of gut hormones and leptin.

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Chen, Chih-Yen; Tsai, Chang-Youh; Lee, Pui-Ching; Lee, Shou-Dong

2013-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNF-α therapy on body weight, appetite, plasma gut hormones and leptin have not been investigated. Twenty RA patients received subcutaneous injections of etanercept, a chimeric protein of human IgG1 Fc and TNF receptor p75, twice weekly for 12 consecutive months. Sequential changes in body weight, body fat, appetite rating, lipid profiles, gut hormones and leptin were measured at baseline and at 3 and 12 months after treatment. Ten RA patients who received non-biological disease modifying anti-rheumatic drugs were enrolled as the controls and were appraised at baseline and at 12 months after treatment (a nonrandomized study). Significant weight gain, hyperuricemia, decreased fasting plasma glucose-dependent insulinotropic polypeptide (GIP) levels, and loss of post-oral glucose suppression of plasma leptin concentration were found in the patients after the 12-month course of etanercept therapy, but not in the controls. A transient decrease in fasting plasma acyl ghrelin occurred at 3 months during etanercept treatment. Appetite score and serum lipid profiles did not change in either group. Long-term therapy with anti-TNF-α is promising in ameliorating body mass decrease in patients with active RA. Plasma levels of ghrelin, GIP and leptin may play significant roles in maintaining energy homeostasis in the anti-inflammatory responses during RA remission.

Disability and health outcomes - from a cohort of people on long-term anti-retroviral therapy.

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Myezwa, Hellen; Hanass-Hancock, Jill; Ajidahun, Adedayo Tunde; Carpenter, Bradley

2018-12-01

Human-immunodeficiency virus (HIV)/Acquired immunodeficiency Syndrome (AIDS) remains a major health problem in South Africa - even after two decades since the introduction of antiretroviral therapy (ART). Long-term survival with HIV is associated with new health-related issues and a risk of functional limitation/disability. The aim of this study was to assess functional limitation associated with HIV/AIDS among people living with HIV (PLHIV) in South Africa. This study is a cross-sectional survey using a cohort in an urban area in Gauteng province, South Africa. Data were collected using questionnaires through an interview process. The information collected included aspects such as demographics, livelihood, the state of mental and physical health, adherence and disability. A total of 1044 participants with an average age of 42 ± 12 years were included in the study, with 51.9% of the participants reporting functional limitations (WHODAS ≥ 2). These were reported mainly in the domains of participation (40.2%) and mobility (38.7%). In addition, adherence to ART, symptoms of poor physical health and depression were strongly associated with their functional limitations/disability. HIV as a chronic disease is associated with functional limitations that are not adequately addressed and pose a risk of long-term disability and negative adherence outcomes. Therefore, wellness for PLHIV/AIDS needs to include interventions that can prevent and manage disability.

Long-term outcomes of two rescue therapies in lamivudine-refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir

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EunYoung Ze

2014-09-01

Full Text Available Background/AimsAdefovir (ADV and lamivudine (LAM combination therapy (ADV+LAM has been a useful option for patients with LAM-resistant (LAM-r chronic hepatitis B (CHB. However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies.MethodsSixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36 or 1-mg ETV (n=24. We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV DNA by PCR (lower limitation of detection, < 140 copies/mL, biochemical response (alanine aminotransferase < 40 IU/mL, and the incidence of hepatitis B virus e antigen (HBeAg seroconversion and virologic breakthrough.ResultsBaseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months in the ADV+LAM group and 42 months (range, 12-73 months in the ETV group (P=0.036. The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001.ConclusionsCombination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.

Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial

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Rahu Mati

2008-08-01

Full Text Available Abstract Background Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment. Methods The Estonian Postmenopausal Hormone Therapy trial (EPHT, originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT on health services utilization. Results After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT. Conclusion Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials. The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old drug for a new preventive indication? In preventive drug trials companies may

Long-Term Improvement of Neurological Signs and Metabolic Dysfunction in a Mouse Model of Krabbe's Disease after Global Gene Therapy.

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Marshall, Michael S; Issa, Yazan; Jakubauskas, Benas; Stoskute, Monika; Elackattu, Vince; Marshall, Jeffrey N; Bogue, Wil; Nguyen, Duc; Hauck, Zane; Rue, Emily; Karumuthil-Melethil, Subha; Zaric, Violeta; Bosland, Maarten; van Breemen, Richard B; Givogri, Maria I; Gray, Steven J; Crocker, Stephen J; Bongarzone, Ernesto R

2018-03-07

We report a global adeno-associated virus (AAV)9-based gene therapy protocol to deliver therapeutic galactosylceramidase (GALC), a lysosomal enzyme that is deficient in Krabbe's disease. When globally administered via intrathecal, intracranial, and intravenous injections to newborn mice affected with GALC deficiency (twitcher mice), this approach largely surpassed prior published benchmarks of survival and metabolic correction, showing long-term protection of demyelination, neuroinflammation, and motor function. Bone marrow transplantation, performed in this protocol without immunosuppressive preconditioning, added minimal benefits to the AAV9 gene therapy. Contrasting with other proposed pre-clinical therapies, these results demonstrate that achieving nearly complete correction of GALC's metabolic deficiencies across the entire nervous system via gene therapy can have a significant improvement to behavioral deficits, pathophysiological changes, and survival. These results are an important consideration for determining the safest and most effective manner for adapting gene therapy to treat this leukodystrophy in the clinic. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Long-term effects of localized spinal radiation therapy on vertebral fractures and focal lesions appearance in patients with multiple myeloma

International Nuclear Information System (INIS)

Lecouvet, Frederic; Richard, Francoise; Berg, B. Vande; Malghem, Jacques; Maldague, Baudouin; Ferrant, Augustin; Michaux, J.-L.

1997-01-01

The occurrence of new vertebral fractures and focal marrow lesions was determined and compared in irradiated and nonirradiated vertebrae of 12 patients with multiple myeloma (MM), prospectively followed using magnetic resonance imaging (MRI) of the thoraco-lumbar spine after localized spinal radiation therapy. During follow-up (mean 35 months), fractures appeared in 5% of irradiated vertebrae and in 20% of nonirradiated vertebrae; new focal lesions appeared in 4% of irradiated vertebrae and in 27% of nonirradiated vertebrae. This study demonstrates a beneficial long-term effect of localized radiation therapy, consisting of a reduced incidence of vertebral fractures and focal marrow lesions in irradiated vertebrae. (author)

Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

International Nuclear Information System (INIS)

Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis; Stirnemann, Jerome; Belmatoug, Nadia; Petrover, David

2015-01-01

To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

Energy Technology Data Exchange (ETDEWEB)

Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Stirnemann, Jerome [Universite Paris-Diderot Hopital Bichat, AP-HP, Department of Biostatistics and Medical Data Processing, INSERM UMR 738, Paris (France); Geneva University Hospital, Division of General Internal Medicine, Faculty of Medicine, Geneva (Switzerland); Belmatoug, Nadia [Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France); Hopital Beaujon, AP-HP, Department of Internal Medicine, Clichy (France); Petrover, David [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France)

2015-10-15

To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

Osteonecrosis de los maxilares inducida por bifosfonatos: prevención y actitud terapéutica Bisphosphonate induced osteonecrosis of the jaws: prevention and therapeutic approach

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F.J. Barrientos Lezcano

2007-10-01

Full Text Available Introducción. La osteonecrosis maxilar o mandibular por bifosfonatos puede convertirse en una epidemia debido a la amplia difusión de estos fármacos entre la población. Material y método. Se muestra un protocolo para la prevención y el tratamiento de esta enfermedad. Se presentan tres casos de osteonecrosis maxilar/mandibular. Resultados. Es difícil lograr una curación completa; sin embargo es posible detener la progresión de la enfermedad. Discusión. La cirugía y la suspensión de la terapia con bifosfonatos han demostrado poca utilidad. Los antibióticos y los enjuagues con clorhexidina son las únicas medidas eficaces. Conclusiones. Es imprescindible una planificación adecuada previa a la instauración del tratamiento con bifosfonatos. Ante una osteonecrosis establecida, la actitud debe ser conservadora.Introduction. Bisphosphonate-induced osteonecrosis of the jaws might reach epidemic proportions due to the widespread use of this therapy. Materials and methods. A protocol for prevention and treatment of this pathology is shown. Three clinical cases are reported. Results. It is quite difficult to reach restitutio ad integrum, but stopping the progress of the disease is possible. Discussion. Surgical treatment and cessation of bisphosphonate therapy are of no use. Only antibiotics and oral chlorhexidine have shown some benefits. Conclusions. An accurate preventive attitude is mandatory prior to undergoing bisphosphonate therapy. If osteonecrosis of the jaws is present, management should be conservative.

The predictive value of current haemoglobin levels for incident tuberculosis and/or mortality during long-term antiretroviral therapy in South Africa: a cohort study

NARCIS (Netherlands)

Kerkhoff, Andrew D.; Wood, Robin; Cobelens, Frank G.; Gupta-Wright, Ankur; Bekker, Linda-Gail; Lawn, Stephen D.

2015-01-01

Low haemoglobin concentrations may be predictive of incident tuberculosis (TB) and death in HIV-infected patients receiving antiretroviral therapy (ART), but data are limited and inconsistent. We examined these relationships retrospectively in a long-term South African ART cohort with multiple

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

Science.gov (United States)

Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

1999-02-04

Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported

Clinical trials with rasagiline: evidence for short-term and long-term effects.

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Siderowf, Andrew; Stern, Matthew

2006-05-23

Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency

NARCIS (Netherlands)

ter Maaten, JC; De Boer, H; Kamp, O; Stuurman, L; Van der Veen, EA

Short term GH replacement therapy has been shown to improve body composition and exercise capacity. It is not yet known whether GH replacement remains beneficial over the long term. We assessed the effects of long term GH replacement on body composition, bone mineral density, and cardiac function.

COMPLIANCE TO LONG-TERM TREATMENT OF CARDIOLOGIC PATIENTS WITH MILD TO MODERATE DEPRESSION: INEFFECTIVENESS OF ANTIDEPRESSIVE THERAPY WITH PIRLINDOL IN RANDOMIZED STUDY

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E. V. Strokova

2015-12-01

Full Text Available Aim. To evaluate the influence of antidepressant therapy with pirlindol on compliance to the long-term treatment and quality of life in patients with cardiovascular diseases and mild to moderate depression. Material and methods. 61 patients with cardiovascular diseases and mild to moderate depression (according to Beck depression scale were randomized into two groups. Patients of intervention group received pirlindol, while patients of control group did not receive this drug. Compliance to cardiovascular and antidepressant treatment were estimated in 3 and 6 months. Adverse reactions and patients self-assessment of their well-being and global satisfaction in treatmen were also registered.  Results. 24 (75%, 2 (6% and 0 patients of intervention group continue pirlindol treatment in 1, 3 and 6 months, respectively. In 3 months of observation patients of intervention group took drugs for cardiovascular diseases more often than these in control group (81% vs 72%, respectively , р<0.05, they also less frequently showed adverse reactions (56% vs 72%, respectively ,p=0.01 and more often — improvement of their well-being (65% vs 50%, respectively , р=0.03. Compliance to cardiovascular therapy did not differ significantly in patients of both groups by the end the study.  Conclusion. Antidepressant therapy with pirlindol did not influence compliance to long-term cardiovascular treatment in patients with cardiovascular diseases and mild to moderate depression, apparently because of low compliance to pirlindol therapy.

Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

DEFF Research Database (Denmark)

Prabakaran, Thaneas; Birn, Henrik; Bibby, Bo M

2014-01-01

dysfunction in women with Fabry disease treated with ERT. METHODS: A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...... in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. CONCLUSIONS: The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestations....

Treatment of bisphosphonate related osteonecrosis following root canal therapy at the 1-year follow-up: report of two cases.

Science.gov (United States)

Kaptan, Figen; Kazandag, Meric Karapinar; Iseri, Ufuk

2013-01-01

The objective of this report was to use topical gaseous ozone as an adjunct to conventional treatment methods and to describe the multidisciplinary management of bisphosphonate associated bone necrosis, which developed following endodontic treatment. No complaints were noted by the patients at their 1-year follow-up and the treatment showed favorable prognosis.

Intravenous aminohydroxypropylidene bisphosphonate does not modify 99mTc-hydroxymethylene bisphosphonate bone scintigraphy. A prospective study

International Nuclear Information System (INIS)

Macro, M.; Bouvard, G.; Le Gangneux, E.; Colin, T.; Loyau, G.

1995-01-01

Bisphosphonates have market affinity for bone that makes them useful in both the treatment and imaging of bone lesions. Bone scintigraphy is very sensitive for the detection of bone metastases, which can cause life-threatening hypercalcemia requiring emergency treatment. This prospective study was done to determine whether intravenous administration of pamidronate, a second-generation bisphophonate used to treat hypercalcemia, affects the affinity of the radiopharmaceutical 99m technetium-labeled hydroxymethylene bisphosphonate (99m Tc- HMDP) for bone and bone lesions. Six patients with metastatic bone disease and five with Paget's disease of bone had a 99m Tc-HMDP bone scan before and two to four days after an intravenous infusion of pamidronate. The number and activity of metastatic bone lesions were unchanged after pamidronate, even when the second bone scan was done only 24 hours after the pamidronate infusion. Our data suggest that emergency treatment of life-threatening hypercalcemia by intravenous pamidronate does not decrease the sensitivity of subsequent bone scanning done to detect bone metastases. (authors). 17 refs. 1 tab. 2 figs

Long-term psychological impact and perceived efficacy of pulsed-dye laser therapy for patients with port-wine stains.

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Hansen, Kristen; Kreiter, Clarence D; Rosenbaum, Marcy; Whitaker, Duane C; Arpey, Christopher J

2003-01-01

The rationale for treatment of patients with port-wine stain (PWS) birthmarks has focused on the belief that eventual soft-tissue hypertrophy and negative psychological effects might be diminished or avoided. Pulsed-dye laser (PDL) therapy has become widely accepted as the treatment of choice for PWS, and a variety of studies have been conducted that evaluate its short-term efficacy. Long-term data regarding outcome and patient satisfaction are lacking. Our objective was to evaluate the long-term efficacy of pulsed-dye laser therapy from the patient's perspective. A survey was mailed to all patients or parents of minor patients whose last known laser treatment was performed between January 1, 1989, and January 1, 1996. Patients were asked to quantify changes in their PWS as well as their psychological well-being. A formal qualitative analysis was performed on their written comments as well. A total of 164 surveys were mailed to the most recent address available by the patient record. Fifty-two surveys were returned as undeliverable, and 55 evaluable surveys were returned, yielding a 49% overall return rate for patients who could be located. The mean age of respondents was 28.8 years, 96% of whom were white and 62% female. The mean number of years since last treatment was 7.04. The vast majority of patients noted little or no change in texture, height, or dimension of their PWS, whereas 62% noted color improvement. A majority or patients (60%) worried less about their appearance after treatment, whereas a similar number (61%) believed their ability to make friends or meet others was unaffected by treatment. Only 19% thought others looked at or treated them differently because of their PWS. Overall, 48% of patients indicated satisfaction with treatment, 24% dissatisfaction, and 28% neutral. On a 10-point scale indicating their likelihood of recommending treatment to someone similarly affected, the mean score was 7.42. Men were significantly and consistently less

Bisphosphonate-associated Osteonecrosis of the jaws and endodontic treatment: two case reports.

Science.gov (United States)

Goodell, Gary

2006-01-01

Bisphosphonates are commonly used in the management of bone diseases, such as osteoporosis and Paget's disease, and to prevent bone complications and treat malignant hypercalcemia in certain types of cancer. Although this class of drugs has clear evidence of medical efficacy, there are an, increasing number of reports of bisphosphonate-associated osteonecrosis of the jaws that have substantial implications for the patient and for the treating dentist. This article reviews proposed possible mechanisms of bisphosphonate-associated osteonecrosis of the jaws and describes two case reports where non-surgical and surgical root canal treatment were precipitating factors. Recommendations for prevention and treatment of the disease follow. Thorough history-taking and timely consultation with the patient's oral surgeon and oncologist are emphasized.

A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease management.

Science.gov (United States)

Thornton, J; Ashcroft, D; O'Neill, T; Elliott, R; Adams, J; Roberts, C; Rooney, M; Symmons, D

2008-03-01

To review outcome measures and treatment costs in children with juvenile idiopathic arthritis (JIA) and low bone mineral density (BMD) and/or fragility fractures. To review evidence for effectiveness and safety of bisphosphonates and calcium and/or vitamin D in these children. To assess long-term bone health in adults with JIA. Major databases were searched up to July 2005 for effectiveness studies and up to January 2005 for costs. A structured search strategy was conducted. For the evaluation of long-term bone health, outcome data were derived from two cohorts of adult patients with JIA. As there were few published cost data, an ongoing UK longitudinal study (CAPS) provided background data on the cost of managing JIA. Sixteen studies (78 children with JIA) were included. At baseline, the children had BMD below the expected values for age- and sex-matched children; treatment with bisphosphonates increased BMD with mean percentage increases in spine BMD varying from 4.5 to 19.1%. None of the studies with control groups compared results between the intervention and control groups, they only compared each group with its own baseline. Overall, studies were heterogeneous in design, of variable quality and with no consistency in methods of assessing and reporting outcomes. Hence, data could not be combined or an effect size calculated. A further 43 papers were included in the safety review; side-effects were generally transient. Two studies assessed treatment with calcium and/or vitamin D; BMD was increased from 0.75 to 0.830 g/cm2 after 6 months and BMD Z-score from -2.8 to -2.3 after 6 months and -2.4 after 1 year. There are relatively few long-term studies on the occurrence of low BMD and fragility fractures in children with JIA, with most studies only following children for 1 or 2 years. However, the long- and short-term data indicate that children with JIA have a lower BMD and more fractures than children without JIA. There are very few data on long-term bone health

Sleep Quality, Short-Term and Long-Term CPAP Adherence

Science.gov (United States)

Somiah, Manya; Taxin, Zachary; Keating, Joseph; Mooney, Anne M.; Norman, Robert G.; Rapoport, David M.; Ayappa, Indu

2012-01-01

Study Objectives: Adherence to CPAP therapy is low in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). The purpose of the present study was to evaluate the utility of measures of sleep architecture and sleep continuity on the CPAP titration study as predictors of both short- and long-term CPAP adherence. Methods: 93 patients with OSAHS (RDI 42.8 ± 34.3/h) underwent in-laboratory diagnostic polysomnography, CPAP titration, and follow-up polysomnography (NPSG) on CPAP. Adherence to CPAP was objectively monitored. Short-term (ST) CPAP adherence was averaged over 14 days immediately following the titration study. Long-term (LT) CPAP adherence was obtained in 56/93 patients after approximately 2 months of CPAP use. Patients were grouped into CPAP adherence groups for ST ( 4 h) and LT adherence ( 4 h). Sleep architecture, sleep disordered breathing (SDB) indices, and daytime outcome variables from the diagnostic and titration NPSGs were compared between CPAP adherence groups. Results: There was a significant relationship between ST and LT CPAP adherence (r = 0.81, p CPAP adherence groups had significantly lower %N2 and greater %REM on the titration NPSG. A model combining change in sleep efficiency and change in sleep continuity between the diagnostic and titration NPSGs predicted 17% of the variance in LT adherence (p = 0.006). Conclusions: These findings demonstrate that characteristics of sleep architecture, even on the titration NPSG, may predict some of the variance in CPAP adherence. Better sleep quality on the titration night was related to better CPAP adherence, suggesting that interventions to improve sleep on/prior to the CPAP titration study might be used as a therapeutic intervention to improve CPAP adherence. Citation: Somiah M; Taxin Z; Keating J; Mooney AM; Norman RG; Rapoport DM; Ayappa I. Sleep quality, short-term and long-term CPAP adherence. J Clin Sleep Med 2012;8(5):489-500. PMID:23066359

Radio(chemo)therapy for locally advanced squamous cell carcinoma of the esophagus. Long-term outcome

Energy Technology Data Exchange (ETDEWEB)

Ordu, Arif Deniz; Deymann, Lisa Felicia; Scherer, Vera; Combs, Stephanie E. [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Nieder, Carsten [University of Tromsoe, Department of Oncology and Palliative Medicine, Nordland Hospital Trust, Bodoe (Norway); Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Geinitz, Hans [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Krankenhaus der Barmherzigen Schwestern Linz, Department of Radiation Oncology, Linz (Austria); Kup, Philipp Guenther [Marien Hospital Herne, Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Herne (Germany); Fakhrian, Khashayar [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Marien Hospital Herne, Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Herne (Germany); Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Sankt Josef Hospital Bochum, Bochum (Germany)

2014-11-18

The purpose of this work is to report the long-term outcomes of three-dimensional conformal radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). A retrospective analysis of patients treated with radio(chemo)therapy between 1988 and 2011 at Klinikum rechts der Isar, Technische Universitaet Muenchen was performed. In all, 168 patients received radio(chemo)therapy for ESCC in curative intention. The median follow-up time was 91 months (range 1-212 months). There were 128 men and 40 women with a median age of 63 years. Selection criteria for radio(chemo)therapy were unfit for surgery and/or unresectable primary tumor (n = 146, 87 %) or patients' choice (n = 22, 13 %). The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 54 Gy in 30 fractions of radiotherapy. The median overall survival (OS) was 20 months (95 % confidence interval 17-23 months). The OS at 2 and 5 years for the whole cohort was 41 ± 4 % and 22 ± 3 %, respectively. Forty patients (24 %) suffered an in-field recurrence. The most common acute nonhematologic toxicity >grade 2 was dysphagia in 35 % of the patients. Acute hematologic toxicity > grade 2 was recorded in 14 % of the patients. There was no grade 5 toxicity observed during the study. Poor ECOG performance status (0-1 vs. 2-3, HR = 1.70, p = 0.002) and weight loss ≥ 10 % before the start of therapy (HR = 1.99, p = 0.001) were among the factors significantly associated with poor OS in multivariate analysis. Three-dimensional conformal definitive radio(chemo)therapy is well tolerated and leads to long-term survival in more than 20 % of patients with advanced disease and/or contraindication to surgery. However, 24 % in-field recurrence remains a major concern. Prospective trials are warranted to assess if a well-tailored conformal radiochemotherapy can improve the local control and obviate the need for surgical resection in patients with good general

Long-term outcomes of vertebroplasty for osteoporotic compression fractures

International Nuclear Information System (INIS)

Thillainadesan, G.; Schlaphoff, G.; Gibson, K.A.; Hassett, G.M.; McNeil, H.P.

2010-01-01

This study aimed to determine outcomes of percutaneous vertebroplasty for osteoporotic vertebral compression fractures (VCFs). Prospective assessment of short-term (≤6 weeks), medium-term (6 months) and long-term (29 months) outcomes of vertebroplasty, followed by a retrospective long-term follow-up of patients treated with vertebroplasty compared with conservative therapy. Outcomes measured were visual analogue scale pain scores, analgesic use, disability scores using the Roland Morris Disability questionnaire and a number of new VCFs. In 27 patients with acute VCFs followed prospectively, vertebroplasty resulted in significant reductions in pain levels (56-mm reduction on a 100-mm scale) and disability scores (11.8-point reduction on a 24-point scale) at all follow-up points up to a mean of 29 months compared with pre-vertebroplasty levels (P < 0.001). Analgesic use was significantly less intense in the short and medium term after vertebroplasty (P < 0.005). In 25 patients who had vertebroplasty for VCF, a sustained reduction in all outcomes was demonstrated at a mean follow-up of 30 months, with less pain, significantly lower disability scores (P < 0.05) and less analgesic use (P < 0.05) compared with nine conservatively treated subjects. During the follow-up period, six new VCFs occurred in 4/25 vertebroplasty patients compared with four new VCFs in 2/9 control subjects. Vertebroplasty provides significant and clinically meaningful reductions in pain, analgesic use, and disability in the short, medium and long term. Compared with conservative therapy, vertebroplasty provides significantly greater functional improvement and reduction in analgesic use. The procedure is relatively safe with no clearly increased risk of new vertebral fractures.

Insulin requirement profiles of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes and its association with long-term glycemic remission.

Science.gov (United States)

Liu, Liehua; Ke, Weijian; Wan, Xuesi; Zhang, Pengyuan; Cao, Xiaopei; Deng, Wanping; Li, Yanbing

2015-05-01

To investigate the insulin requirement profiles during short-term intensive continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes and its relationship with long-term glycemic remission. CSII was applied in 104 patients with newly diagnosed type 2 diabetes. Daily insulin doses were titrated and recorded to achieve and maintain euglycemia for 2 weeks. Measurements of blood glucose, lipid profiles as well as intravenous glucose tolerance tests were performed before and after the therapy. Afterwards, patients were followed up for 1 year. Total daily insulin dose (TDD) was 56.6±16.1IU at the first day when euglycemia was achieved (TDD-1). Thereafter, TDD progressively decreased at a rate of 1.4±1.0IU/day to 36.2±16.5IU at the end of the therapy. TDD-1 could be estimated with body weight, FPG, triglyceride and waist circumference in a multiple linear regression model. Decrement of TDD after euglycemia was achieved (ΔTDD) was associated with reduction of HOMA-IR (r=0.27, P=0.008) but not with improvement in β cell function. Patients in the lower tertile of ΔTDD had a significantly higher risk of hyperglycemia relapse than those in the upper tertile within 1 year (HR 3.4, 95%CI [1.4, 8.4], P=0.008). There is a steady decline of TDD after euglycemia is achieved in patients with newly diagnosed type 2 diabetes treated with CSII, and ΔTDD is associated with a better long-term glycemic outcome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Osteonecrose dos maxilares associada ao uso de bisfosfonatos: importante complicação do tratamento oncológico Bisphosphonate-associated jaws osteonecrosis: an important complication of oncology treatment

Directory of Open Access Journals (Sweden)

Marco Antonio T. Martins

2009-02-01

Full Text Available Os bisfosfonatos são um grupo de medicamentos utilizados no tratamento de doenças malignas metastáticas e em outras doenças ósseas como osteoporose e doença de Paget. A despeito dos seus benefícios, uma importante complicação denominada de osteonecrose dos maxilares vem sendo observada nos pacientes usuários crônicos dos bisfosfonatos que se caracteriza clinicamente por exposições ósseas na região maxilofacial persistente, acompanhadas de osteomielite, geralmente sintomáticas e cujo tratamento é complexo. Este estudo tem por objetivo revisar a literatura sobre a osteonecrose associada ao uso dos bisfosfonatos, em especial, em oncologia, no período de 2003 a 2008. Serão apresentados e discutidos os fatores de risco, aspectos etiopatogênicos, clínicos, imagenológicos, terapêuticos e preventivos desta doença. Devido à dificuldade de tratamento da osteonecrose associada aos bisfosfonatos, o foco deve ser a prevenção, sendo o ideal a eliminação de quadros infecciosos orais antes da terapia com os bisfosfonatos ter sido iniciada e minimizar traumas em boca após o uso destes medicamentos.Bisphosphonates are drugs used in the treatment of malignant metastatic diseases and in other bone lesions such as osteoporosis and Paget´s disease. Besides their benefits, jaw osteonecrosis, an important side effect, has been observed in long-term users of these drugs. Jaw osteonecrosis is clinically characterized by prolonged maxillary and mandible bone exposure accompanied by osteomyelitis. These lesions are usually symptomatic and difficult to treat. This study has the objective of reviewing publications from 2003 to 2008 about bisphosphonate-associated jaw osteonecrosis, in particular in relation to oncology. Risk factors, and etiopathological, clinical, radiographic, therapeutic, and preventive aspects of this condition are presented and discussed. Due to the difficulty to treat this disease, the focus must be prevention, with the

Esker Ri Nursing Home, Kilnabinnia, Clara, Offaly.

LENUS (Irish Health Repository)

McKenna, Malachi

2017-03-01

Atypical femur fractures (AFFs) are associated with long-term bisphosphonate (BP) therapy. Early identification of AFF prior to their completion provides an opportunity to intervene, potentially reducing morbidity associated with these fractures. Single-energy X-ray absorptiometry (SE) is an imaging method recently shown to detect incomplete AFF (iAFF) prior to fracture completion.

Identifying Incomplete Atypical Femoral Fractures With Single-Energy Absorptiometry: Declining Prevalence

LENUS (Irish Health Repository)

McKenna, Malachi

2017-03-01

Atypical femur fractures (AFFs) are associated with long-term bisphosphonate (BP) therapy. Early identification of AFF prior to their completion provides an opportunity to intervene, potentially reducing morbidity associated with these fractures. Single-energy X-ray absorptiometry (SE) is an imaging method recently shown to detect incomplete AFF (iAFF) prior to fracture completion.

Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy.

Science.gov (United States)

Yang, Shuo; Ma, Si-Qi; Wan, Xing; He, Heng; Pei, Han; Zhao, Min-Jian; Chen, Chen; Wang, Dao-Wen; Dong, Xiao-Yan; Yuan, Jia-Jia; Li, Bin

2016-08-01

Leber's hereditary optic neuropathy (LHON) is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP), optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2-9) received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8) and untreated eyes (Patients 2, 3, 4, 6 and 8). Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1) who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains stable in the

Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy

Directory of Open Access Journals (Sweden)

Shuo Yang

2016-08-01

Full Text Available Leber's hereditary optic neuropathy (LHON is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12 months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP, optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2–9 received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8 and untreated eyes (Patients 2, 3, 4, 6 and 8. Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1 who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3 months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains

Bisphosphonate-Linked TrkB Agonist: Cochlea-Targeted Delivery of a Neurotrophic Agent as a Strategy for the Treatment of Hearing Loss.

Science.gov (United States)

Kempfle, Judith S; Nguyen, Kim; Hamadani, Christine; Koen, Nicholas; Edge, Albert S; Kashemirov, Boris A; Jung, David H; McKenna, Charles E

2018-04-18

Hearing loss affects more than two-thirds of the elderly population, and more than 17% of all adults in the U.S. Sensorineural hearing loss related to noise exposure or aging is associated with loss of inner ear sensory hair cells (HCs), cochlear spiral ganglion neurons (SGNs), and ribbon synapses between HCs and SGNs, stimulating intense interest in therapies to regenerate synaptic function. 7,8-Dihydroxyflavone (DHF) is a selective and potent agonist of tropomyosin receptor kinase B (TrkB) and protects the neuron from apoptosis. Despite evidence that TrkB agonists can promote survival of SGNs, local delivery of drugs such as DHF to the inner ear remains a challenge. We previously demonstrated in an animal model that a fluorescently labeled bisphosphonate, 6-FAM-Zol, administered to the round window membrane penetrated the membrane and diffused throughout the cochlea. Given their affinity for bone mineral, including cochlear bone, bisphosphonates offer an intriguing modality for targeted delivery of neurotrophic agents to the SGNs to promote survival, neurite outgrowth, and, potentially, regeneration of synapses between HCs and SGNs. The design and synthesis of a bisphosphonate conjugate of DHF (Ris-DHF) is presented, with a preliminary evaluation of its neurotrophic activity. Ris-DHF increases neurite outgrowth in vitro, maintains this ability after binding to hydroxyapatite, and regenerates synapses in kainic acid-damaged cochlear organ of Corti explants dissected in vitro with attached SGNs. The results suggest that bisphosphonate-TrkB agonist conjugates have promise as a novel approach to targeted delivery of drugs to treat sensorineural hearing loss.

Long-term pain relief with optimized medical treatment including antioxidants and step-up interventional therapy in patients with chronic pancreatitis.

Science.gov (United States)

Shalimar; Midha, Shallu; Hasan, Ajmal; Dhingra, Rajan; Garg, Pramod Kumar

2017-01-01

Abdominal pain is difficult to treat in patients with chronic pancreatitis (CP). Medical therapy including antioxidants has been shown to relieve pain of CP in the short-term. Our aim was to study the long-term results of optimized medical and interventional therapy for pain relief in patients with CP with a step-up approach. All consecutive patients with CP were included prospectively in the study. They were treated medically with a well-balanced diet, pancreatic enzymes, and antioxidants (9000 IU beta-carotene, 0.54 g vitamin C, 270 IU vitamin E, 600 µg organic selenium, and 2 g methionine). Endoscopic therapy and/or surgery were offered if medical therapy failed. Pain relief was the primary outcome measure. A total of 313 patients (mean age 26.16 ± 12.17; 244 males) with CP were included; 288 (92%) patients had abdominal pain. The etiology of CP was idiopathic in 224 (71.6%) and alcohol in 82 (26.2%). At 1-year follow-up, significant pain relief was achieved in 84.7% of patients: 52.1% with medical therapy, 16.7% with endoscopic therapy, 7.6% with surgery, and 8.3% spontaneously. The mean pain score decreased from 6.36 ± 1.92 to 1.62 ± 2.10 (P pain free at those follow-up periods. Significant pain relief is achieved in the majority of patients with optimized medical and interventional treatment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Recovery of menstruation after long-term chemotherapy and endocrine therapy in pre-menopausal patients with breast cancer.

Science.gov (United States)

Sakurai, Kenichi; Enomoto, Katsuhisa; Amano, Sadao

2011-04-01

A luteinizing hormone-releasing hormone (LH-RH) agonist and tamoxifen (TAM) are used in hormonal therapy following pre- and post-operative chemotherapy in pre-menopausal advanced breast cancer patients who are positive for hormone receptors. However, it remains to be clarified how often patients recover menstruation after long-term LH-RH agonist plus TAM therapy. In this study, the incidence of menstruation recovery after therapy was examined. The subjects included 125 pre-menopausal patients with breast cancer who were positive for hormone receptors and had undergone surgery at our institution. They were treated with four cycles of the CEF regimen and four cycles of docetaxel (Doc) before surgery as adjuvant chemotherapy. Thereafter, they were treated with an LH-RH agonist plus TAM for 24 months and followed to determine menstruation recovery. Menstruation resumed in 24 cases (19.2%) after the last LH-RH agonist treatment session. It took 7.3 ± 2.8 months for the patients to recover menstruation. The rate of menstruation recovery was 42.1% in patients aged 40 or younger and 9.2% in those aged 41 or older; the difference was significant. The period until menstruation recovery tended to be longer in older patients at the end of treatment. The menstruation recovery rate after therapy was higher in younger women. However, since ovarian function may be lost even in younger patients, the potential consequences of this therapy should be fully explained beforehand to patients who may wish to become pregnant.

Conditioning radium needles for long term storage : Sri Lankan experience

International Nuclear Information System (INIS)

Ranjith, H.L.A.; Shantha, T.H.S.; Gunaratne, M.G.J.; De Silva, U.W.K.H.; Perera, H.P.H.

2000-01-01

Radium the first radioisotope invented by Madame Curie was used for cancer therapy for the intracavitory treatment of cervical cancers and as oral implants etc. Radium needles and other geometries were made in standard strengths and Radium therapy enjoyed a heyday during the 1st half of the 20th century. Radium-226 is a long-lived radioactive material with a half-life of 1600 years. The use of radium was abandoned in the world in 1980s with the invention of short lived radioactive materials offering remote after loading systems which minimise radiation protection and waste disposal problems associated with long lived radioactive materials. This paper reports the conditioning procedure of the spent radium sources for long term storage (less than 20 years) and transport to national/ international stores if needed. The dose received by those involved in this exercise is also discussed in terms of radiation protection. The Ra was contained for long term storage according to international radiation safety regulations with a surface dose of less than 2 mSv per hour in a conditioned package having 17.5 GBq activity and can be transported to national/international stores if needed. The highest dose received during the exercise is well within the recommended dose limits for occupational exposures (20 and 500 mSv per year) for whole body and extremities respectively

Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

International Nuclear Information System (INIS)

Coventry, Brendon J; Baume, Dominique; Lilly, Carrie

2015-01-01

Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Cases of long-term survival of ≥3 years’ duration (from diagnosis of metastatic disease) were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Eighteen cases were identified that identified survival of ≥3 years’ duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94%) had survived ≥5 years, and eleven patients (61%) had survived ≥10 years (range: 3–15 years). The median survival duration with metastatic disease was 11 years; 15 remained alive and three had died. Published studies of melanoma therapies were tabled for comparison. The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself

Fatigue and quality of life in breast cancer survivors: temporal courses and long-term pattern

NARCIS (Netherlands)

Schmidt, M.E.; Chang-Claude, J.; Vrieling, A.; Heinz, J.; Flesch-Janys, D.; Steindorf, K.

2012-01-01

INTRODUCTION: Fatigue is a frequent problem during and after cancer treatment. We investigated different courses of fatigue from pre-diagnosis, through therapy, to long-term survivorship and evaluated potential implications on long-term quality of life (QoL). METHODS: Breast cancer patients

Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

International Nuclear Information System (INIS)

Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

1997-01-01

Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

Audit of long-term and short-term liabilities

Directory of Open Access Journals (Sweden)

Korinko M.D.

2017-03-01

Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

Bisphosphonate Therapy (and Osteonecrosis of the Jaw)

Science.gov (United States)

... you to a specialist in oral medicine or oral surgery to evaluate the best possible therapy. Generally, therapy ... the risk of needing invasive procedures (extractions and oral surgery). Frequent professional cleanings, attention to home care, and ...

Long-Term Results of a Highly Performing Conformal Electron Therapy Technique for Chest Wall Irradiation After Mastectomy

Energy Technology Data Exchange (ETDEWEB)

Grellier Adedjouma, Noemie, E-mail: grellier.noemie@gmail.com [Department of Radiation Oncology, Institut Curie, Paris (France); Chevrier, Marion [Department of Biostatistics, Institut Curie, Paris (France); Fourquet, Alain; Costa, Emilie; Xu, Haoping [Department of Radiation Oncology, Institut Curie, Paris (France); Berger, Frederique [Department of Biostatistics, Institut Curie, Paris (France); Campana, Francois [Department of Radiation Oncology, Institut Curie, Paris (France); Laki, Fatima [Department of Surgical Oncology, Institut Curie, Paris (France); Beuzeboc, Philippe [Department of Medical Oncology, Institut Curie, Paris (France); Lefeuvre, Delphine [Department of Biostatistics, Institut Curie, Paris (France); Fournier-Bidoz, Nathalie; Kirova, Youlia M. [Department of Radiation Oncology, Institut Curie, Paris (France)

2017-05-01

Purpose: To evaluate locoregional control and survival after mastectomy, as well as toxicity, in patients irradiated by a previously described postmastectomy highly conformal electron beam radiation therapy technique (PMERT). Methods and Materials: We included all women irradiated by postmastectomy electron beam radiation therapy for nonmetastatic breast cancer between 2007 and 2011 in our department. Acute and late toxicities were retrospectively assessed using Common Terminology Criteria for Adverse Events version 3.0 criteria. Results: Among the 796 women included, 10.1% were triple-negative, 18.8% HER2-positive, and 24.6% received neoadjuvant chemotherapy (CT). Multifocal lesions were observed in 51.3% of women, and 64.6% had at least 1 involved lymph node (LN). Internal mammary chain, supraclavicular, infraclavicular, and axillary LNs were treated in 85.6%, 88.3%, 77.9%, and 14.9% of cases, respectively. With a median follow-up of 64 months (range, 6-102 months), 5-year locoregional recurrence–free survival and overall survival were 90% (95% confidence interval 88.1%-92.4%) and 90.9% (95% confidence interval 88.9%-93%), respectively. Early skin toxicity was scored as grade 1 in 58.5% of patients, grade 2 in 35.9%, and grade 3 in 4.5%. Concomitant CT was associated with increased grade 3 toxicity (P<.001). At long-term follow-up, 29.8% of patients presented temporary or permanent hyperpigmentation or telangiectasia or fibrosis (grade 1: 23.6%; grade 2: 5.2%; grade 3: 1%), with higher rates among smokers (P=.06); 274 patients (34.4%) underwent breast reconstruction. Only 24 patients (3%) had early esophagitis of grade 1. Only 3 patients developed ischemic heart disease: all had been treated by anthracycline-based CT with or without trastuzumab, all had been irradiated to the left chest wall and LN, and all presented numerous cardiovascular risk factors (2-4 factors). Conclusions: This study demonstrated the good efficacy of this technique in terms of

Long-term Therapeutic Impact of the Timing of Antiretroviral Therapy in Patients Diagnosed With Primary Human Immunodeficiency Virus Type 1 Infection.

Science.gov (United States)

Novelli, Sophie; Lécuroux, Camille; Avettand-Fenoel, Véronique; Seng, Rémonie; Essat, Asma; Morlat, Philippe; Viard, Jean-Paul; Rouzioux, Christine; Meyer, Laurence; Goujard, Cécile

2018-05-02

We aimed to determine the consequences of delayed human immunodeficiency virus type 1 (HIV-1) infection diagnosis by comparing long-term outcomes depending on the time of combination antiretroviral therapy (cART) initiation in patients diagnosed during primary HIV infection (PHI). We selected patients from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) PRIMO cohort, treated for ≥36 months, with sustained HIV RNA 12 months after infection (deferred ART). We measured inflammatory biomarkers from PHI through the last visit on cART, and CD4+ and CD8+ T-cell activation and plasma ultrasensitive HIV RNA at the last visit. Inflammation/activation levels were compared with those of uninfected controls. We modeled CD4+ count, CD4:CD8 ratio, and HIV DNA dynamics on cART. The decrease of HIV DNA levels was more marked in the immediate than deferred ART group, leading to a sustained mean difference of -0.6 log10 copies/106 peripheral blood mononuclear cells. Immediate ART led to improved CD4+ T-cell counts and CD4:CD8 ratios over the first 4 years of cART. At the last visit (median, 82 months), there was no difference between groups in CD4+ counts, CD4:CD8 ratio, ultrasensitive HIV RNA, or inflammation/activation marker levels. Long-term suppressive cART failed to normalize inflammation levels, which were not associated with immunovirological markers. Antiretroviral therapy initiated during PHI promotes long-term reduction of HIV reservoir size. In patients with sustained virologic suppression, inflammation may be driven by non-HIV-related factors.

Interaction of Left Ventricular Remodeling and Regional Dyssynchrony on Long-Term Prognosis after Cardiac Resynchronization Therapy

DEFF Research Database (Denmark)

Tayal, Bhupendar; Sogaard, Peter; Delgado-Montero, Antonia

2017-01-01

BACKGROUND: Left ventricular (LV) remodeling in heart failure (HF) manifested by chamber dilatation is associated with worse clinical outcomes. However, the impact of LV dilatation on the association of measures of dyssynchrony with long-term prognosis and resynchronization potential after cardiac...... resynchronization therapy (CRT) remains unclear. METHODS: Two hundred sixty CRT patients in New York Heart Association classes II to IV, with ejection fractions ≤ 35% and QRS intervals ≥ 120 msec, were prospectively studied. Quantitative echocardiographic assessment of LV volumes and mechanical dyssynchrony...... of the baseline indexed LV end-diastolic volume (EDVI). Patients with less dilated left ventricles (EDVI left ventricles (EDVI ≥ 90 mL/m(2)) for both primary (adjusted hazard ratio [HR], 2.20; 95% CI, 1.44-3.38; P

The mid-to-long term therapeutic efficacy of Graves' disease after interventional embolization

International Nuclear Information System (INIS)

Li Weiduo; Yang Jianyong; Zhuang Wenquan; Chen Wei; Li Heping

2002-01-01

Objective: To explore the mid-to-long term therapeutic efficacy of Graves' disease after interventional embolization. Methods: Twenty-five patients of Graves' disease treated with interventional embolization were followed up for 24-57 months. T 3 and T 4 were monitored at pre-operation, six months, 12 months, 2, 3 and 4 years after operation, respectively. Other references included pulse, thyroid size, and vessel's murmur. Results: Twenty-two patients completely relieved from the hyperthyroidism during the follow-up. Only one patient suffered from recurrence. Other two patients were still on maintaining dosage of antithyroid drug therapy. No hypothyroidism or hypoparathyroidism was found during this term. Conclusion: Mid-to-long term follow-up showed satisfactory efficacy of interventional therapy, offering another alternative for treatment of refractory Graves' disease

Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease

Science.gov (United States)

Yao, Liwei; Wang, Haiqing; Dong, Wenwei; Liu, Zhenxin; Mao, Haijiao

2017-01-01

Abstract This study aims to determine whether bisphosphonates are safe, as well as effective against bone mineral loss in inflammatory bowel disease (IBD). A computerized search of electronic databases from 1966 to 2016 was performed. Randomized controlled trials (RCTs) were included in this review to evaluate the role of bisphosphonates in the management of osteoporosis in IBD patients. A revised 7-point Jadad scale was used to evaluate the quality of each study. Overall, 13 RCTs and 923 patients met the inclusion criteria of this meta-analysis. The result showed that bisphosphonates decreased bone mass density (BMD) loss at the lumbar spine (P = 0.0002), reduced the risk of new fractures (P = 0.01), and retained the similar adverse events (P = 0.86). Bisphosphonates may provide protection and safety against bone mineral loss in IBD patients. PMID:28099343

Long-Term Effect of HAART on Biochemical Profiles of HIV/AIDS ...

African Journals Online (AJOL)

Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. ... Purpose: To assess the long-term effect of highly active antiretroviral therapy (HAART) on .... allowed to clot at room temperature for 45 min.

EFFECTIVENESS OF NITROGEN-CONTAINING BISPHOSPHONATES IN THE REGULATION OF MINERAL METABOLISM DISTURBANCES ASSOCIATED WITH ALIMENTARY OSTEOPOROSIS IN RATS

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Komisarenko S. V.

2015-08-01

Full Text Available The aim of the study was to investigate the effectiveness of nitrogen-containing bisphosphonates synthesized as promising substances for correction of mineral metabolism in osteoporosis. The study was carried out on a model of alimentary osteoporosis that was characterized by hypocalcaemia, hypophosphatemia, decreased 25-Hydroxyvitamin D3 content in blood serum and severe bone tissue demineralization (reduced ash content and mineral components. It was found that synthesized novel nitrogen bisphosphonates (pyrazole-containing analogues, like reference drugs — metylene bisphosphonate (disodium salt of metylene bisphosphonic acid and alendronate (4-amino-1-hidroxybutyliden bisphosphonate, inhibit with the different efficiency demineralization of the bone tissue and increase the mineral metabolism in rats with alimentary (nutritional osteoporosis that was assessed by the marker parameters of bone formation. In particular, drug administration (bisphosphonates І-12, І-40, І-42 resulted in elevation of calcium and phosphate levels and decreased the total activity of alkaline phosphatase and its isoenzymes in blood serum. The ash content and the levels of calcium and phosphorus in the ash of tibia and femur bones were shown to be markedly elevated. Bisphosphonate І-12 has shown more profound antiresorbtive activity and ability to correct mineral metabolism in alimentary osteoporosis, including such of reference drugs. It was found a significant decrease of 25-Hydroxyvitamin D3 content in the serum that is considered as a profound vitamin D3 deficiency associated with nutritional osteoporosis. As it was not compensated by bisphosphonates, we suggest that further investigations should be directed to the combined use of both: bisphosphonates as inhibitors of osteoclast activity that diminish bone resorption and vitamin D3 as a key regulator of bone remodeling process and osteosynthesis activator.

Long-term follow-up study and long-term care of childhood cancer survivors

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Hyeon Jin Park

2010-04-01

Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

Antiparasitic Activity of Sulfur- and Fluorine-Containing Bisphosphonates against Trypanosomatids and Apicomplexan Parasites

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Tamila Galaka

2017-01-01

Full Text Available Based on crystallographic data of the complexes 2-alkyl(aminoethyl-1,1-bisphosphonates–Trypanosoma cruzi farnesyl diphosphate synthase, some linear 1,1-bisphosphonic acids and other closely related derivatives were designed, synthesized and biologically evaluated against T. cruzi, the responsible agent of Chagas disease and against Toxoplasma gondii, the etiologic agent of toxoplasmosis and also towards the target enzymes farnesyl pyrophosphate synthase of T. cruzi (TcFPPS and T gondii (TgFPPS, respectively. The isoprenoid-containing 1,1-bisphosphonates exhibited modest antiparasitic activity, whereas the linear α-fluoro-2-alkyl(aminoethyl-1,1-bisphosphonates were unexpectedly devoid of antiparasitic activity. In spite of not presenting efficient antiparasitic activity, these data turned out to be very important to establish a structural activity relationship.

Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts

NARCIS (Netherlands)

Cohen, Sophie; Innes, Steve; Geelen, Sibyl P. M.; Wells, Jonathan C. K.; Smit, Colette; Wolfs, Tom F. W.; van Eck-Smit, Berthe L. F.; Kuijpers, Taco W.; Reiss, Peter; Scherpbier, Henriette J.; Pajkrt, Dasja; Bunders, Madeleine J.

2015-01-01

Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in

Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy : A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts

NARCIS (Netherlands)

Cohen, Sophie; Innes, Steve; Geelen, SPM; Wells, Jonathan C. K.; Smit, Colette; Wolfs, Tom F. W.; van Eck-Smit, Berthe L. F.; Kuijpers, Taco W.; Reiss, Peter; Scherpbier, Henriette J.; Pajkrt, Dasja; Bunders, Madeleine J.

2015-01-01

Objective Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected

Search for genetic markers determining the efficiency of therapy with bisphosphonates in Russian women with postmenopausal osteoporosis: A pilot study

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M. Yu. Krylov

2016-01-01

Full Text Available Many clinical observations show that patient’s genetic background is of great importance in determining the efficiency of treatment.Subjects and methods. The instigation included 50 postmenopausal women with osteoporosis (OP, who were followed up at the Laboratory of osteoporosis, V.A. Nasonova Research Institute of Rheumatology. Body mineral density (BMD in the lumbar spine (LI-IV, femoral neck (FN, and total hip was measured using dual-energy X-ray absorptiometry before and 12 months after treatment with bisphosphonates (BP. To estimate BMD changes, the investigators used ΔBMD in percent (Δ, %.Results and discussion. The whole group showed a positive effect of BP therapy during a year, which was most pronounced in the lumbar spine (mean ΔBMD, about 4%, and a small increment in the proximal hip BMD (mean ΔBMD, about 2%. An analysis indicated a statistically significant correlation of MCP1 -2518A>G polymorphism with changes in LI-IV BMD after 12-month BP therapy. Thus, the female patients who were A allele carriers had a twice lower increase in LI-IV BMD due to BP therapy than those without this allele. The genetic variants of the CCR5 gene, which were related to Δ32 deletion, and IL1β -511C/T polymorphism were also associated with changes in FN BMD following 12-month BP therapy. The BMD increase due to BP therapy in the carriers of the CCR5 Δ32 mutation (wt/Δ32 genotype was 3.5-fold than that in the carriers of the wild type gene (wt/wt genotype. Examination of IL1 -511C/T polymorphism demonstrated that the FN BMD increment in the carriers of the CC genotype was significantly higher than in those of the CT genotype (4.2±4.8 and 1.0±3.7%, respectively; р = 0.023. Our investigation revealed no significant relationship between VDR, LEPR, IL10, MHTFR, PPARG, SPP1, and CCR5(G/A gene polymorphisms and 12-month BP therapy-induced BMD changes in the three study skeletal regions. The findings may suggest that genetic testing may be used to

The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.

Science.gov (United States)

Melles, Ronald B; Marmor, Michael F

2014-12-01

Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull's eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques. To reassess the prevalence of and risk factors for hydroxychloroquine retinal toxicity and to determine dosage levels that facilitate safe use of the drug. Retrospective case-control study in an integrated health organization of approximately 3.4 million members among 2361 patients who had used hydroxychloroquine continuously for at least 5 years according to pharmacy records and who were evaluated with visual field testing or spectral-domain optical coherence tomography. Hydroxychloroquine use for at least 5 years. Retinal toxicity as determined by characteristic visual field loss or retinal thinning and photoreceptor damage, as well as statistical measures of risk factors and prevalence. Real body weight predicted risk better than ideal body weight and was used for all calculations. The overall prevalence of hydroxychloroquine retinopathy was 7.5% but varied with daily consumption (odds ratio, 5.67; 95% CI, 4.14-7.79 for >5.0 mg/kg) and with duration of use (odds ratio, 3.22; 95% CI, 2.20-4.70 for >10 years). For daily consumption of 4.0 to 5.0 mg/kg, the prevalence of retinal toxicity remained less than 2% within the first 10 years of use but rose to almost 20% after 20 years of use. Other major risk factors include kidney disease (odds ratio, 2.08; 95% CI, 1.44-3.01) and concurrent tamoxifen citrate therapy (odds ratio, 4.59; 95% CI, 2.05-10.27). These data suggest that hydroxychloroquine retinopathy is more common than previously recognized, especially at high dosages and long duration of use. While no completely safe dosage is identified from this study, daily consumption of

Cephalometric variables predicting the long-term success or failure of combined rapid maxillary expansion and facial mask therapy.

Science.gov (United States)

Baccetti, Tiziano; Franchi, Lorenzo; McNamara, James A

2004-07-01

The aim of this study was to select a model of cephalometric variables to predict the results of early treatment of Class III malocclusion with rapid maxillary expansion and facemask therapy followed by comprehensive treatment with fixed appliances. Lateral cephalograms of 42 patients (20 boys, 22 girls) with Class III malocclusion were analyzed at the start of treatment (mean age 8 years 6 months +/- 2 years, at stage I in cervical vertebral maturation). All patients were reevaluated after a mean period of 6 years 6 months (at stage IV or V in cervical vertebral maturation) that included active treatment plus retention. At this time, the sample was divided into 2 groups according to occlusal criteria: a successful group (30 patients) and an unsuccessful group (12 patients). Discriminant analysis was applied to select pretreatment predictive variables of long-term treatment outcome. Stepwise variable selection of the cephalometric measurements at the first observation identified 3 predictive variables. Orthopedic treatment of Class III malocclusion might be unfavorable over the long term when a patient's pretreatment cephalometric records exhibit a long mandibular ramus (ie, increased posterior facial height), an acute cranial base angle, and a steep mandibular plane angle. On the basis of the equation generated by the multivariate statistical method, the outcome of interceptive orthopedic treatment for each new patient with Class III malocclusion can be predicted with a probability error of 16.7%.

Rape-related symptoms in adolescents: short- and long-term outcome after cognitive behavior group therapy.

Science.gov (United States)

Bicanic, Iva; de Roos, Carlijn; van Wesel, Floryt; Sinnema, Gerben; van de Putte, Elise

2014-01-01

Efficacy studies on treatment in adolescent victims of single rape are lacking, even though sexual victimization is most likely to occur during adolescence and despite the fact that adolescents are at risk to develop subsequent posttraumatic stress disorder. The aim of this prospective observational study was to evaluate the short- and long-term outcomes of a nine-session cognitive behavior group therapy (STEPS), including a parallel six-session parents' group on rape-related symptomatology in female adolescents (13-18 years). STEPS includes psychoeducation, exposure in sensu as well as in vivo, cognitive restructuring, and relapse prevention. Fifty-five female adolescents with mental health problems due to single rape, but without prior sexual trauma, received STEPS while their parents participated in a support group. Subjects were assessed on posttraumatic stress (PTS) and comorbid symptoms using self-report questionnaires prior to and directly after treatment, and at 6 and 12 months follow-up. Repeated measures analysis showed a significant and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation, sexual concerns, and behavior problems directly after treatment, which maintained at 12 months follow-up. Time since trauma did not influence the results. Dropout during STEPS was 1.8%. The results potentially suggest that the positive treatment outcomes at short- and long-term may be caused by STEPS. The encouraging findings need confirmation in future controlled studies on the effectiveness of STEPS because it may be possible that the treatment works especially well for more chronic symptoms, while the less chronic part of the sample showed considerable improvement on its own.

Radiographic findings of bisphosphonate-related osteonecrosis of ...

African Journals Online (AJOL)

Objective: The aim of this study is to assess radiographic findings of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to evaluate the efficiency of cone-beam computed tomography (CBCT) and panoramic radiography (PR) by comparing with each other. Materials and Methods: The data of 46 patients treated ...

Effect of Comprehensive Geriatric Training for The Long-term Care Insurance user.

OpenAIRE

磯崎, 弘司; 石井, 佐和子; 高橋, 美千子

2007-01-01

Comprehensive geriatric training (CGT) is training devised for the elderly persons which uses exercise therapy together with instrumental training. The comprehensive geriatric training was provided to a Long-term Care Insurance user group in order to evaluate the effect of the training. The subjects of the training include 12 Long-term Care Insurance users (mean 80.9 age, SD 7.6 years). Physical strength examinations were made before and after the training and their results were used to evalu...

Long-Term Outcome of Cognitive Behavior Therapy for Body Dysmorphic Disorder: A Naturalistic Case Series of 1 to 4 Years After a Controlled Trial.

Science.gov (United States)

Veale, David; Miles, Sarah; Anson, Martin

2015-11-01

There is some evidence for the efficacy of cognitive behavior therapy (CBT) for body dysmorphic disorder (BDD) after 1 to 6months but none in the long term. The aim of this study was to follow up the participants in a randomized controlled trial of CBT versus anxiety management to determine whether or not the treatment gains were maintained over time. Thirty of the original 39 participants who had CBT were followed up over 1 to 4years and assessed using a number of clinician and self-report measures, which included the primary outcome measure of the Yale-Brown Obsessive Compulsive Scale modified for BDD. Outcome scores generally maintained over time from end of treatment to long-term follow-up. There was a slight deterioration from n=20 (51.3%) to n=18 (46.2%) who met improvement criteria at long-term follow-up. Eleven (28.2%) were in full remission and 22 (56.4%) were in partial remission. The gains made were generally maintained at long-term follow-up. However, there were a significant number of participants who maintained chronic symptoms after treatment and may need a longer-term or more complex intervention and active medication management. Copyright © 2015. Published by Elsevier Ltd.

Malignancy associated hypercalcaemia-responsiveness to IV bisphosphonates and prognosis in a palliative population.

Science.gov (United States)

Mallik, Shreyashee; Mallik, Girijasankar; Macabulos, Shireen Teves; Dorigo, Andrew

2016-04-01

Hypercalcaemia is a potentially fatal paraneoplastic complication of malignancy. It primarily manifests during the advanced phase of cancer, with the life expectancy of patients ranging from weeks to months. The mainstay of treatment is with bisphosphonates, but these are not frequently used in a palliative population due to potential conflict with goals of care. The goals of this study was to determine the reversibility of hypercalcaemia amongst patients whose underlying malignancy is not being treated and assess whether correction results in improvement in symptoms attributable to hypercalcaemia, while identifying risk factors that can predict responsiveness. We conducted a retrospective cohort study of 63 patients aged >18 years who were admitted to the St Joseph's Palliative Care Unit, Australia between 2007 and 2013, having evidence of malignancy-associated hypercalcaemia which was treated with bisphosphonates. We assessed the response to bisphosphonates based on improvement of symptoms attributable to hypercalcaemia, as well as a reduction in serum calcium. We used the Kaplan-Meier survival method and parametric survival analysis to estimate the effect of the independent variables on time till death. Thirty-six of sixty three patients achieved normocalcaemia following treatment with an intravenous bisphosphonate. Complete response was influenced by the number of instances of hypercalcaemia in the past and patient factors, such as age and albumin levels. We found that a reduction in calcium level was associated with a significantly prolonged survival, as well as symptomatic improvement, irrespective of whether normocalcaemia was achieved. Our study suggests that bisphosphonates can be recommended as a palliative measure for selected patients to improve symptoms and prolong survival.

Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study.

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Asier Sáez-Cirión

2013-03-01

Full Text Available Combination antiretroviral therapy (cART reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs] whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs; instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.

Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.

Science.gov (United States)

Prochaska, Megan; Taylor, Eric; Vaidya, Anand; Curhan, Gary

2017-08-07

Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). Low bone density is an independent risk factor for incident kidney stone and is associated with

Long-term persistence with injectable therapy in relapsing-remitting multiple sclerosis: an 18-year observational cohort study.

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Simon Zhornitsky

Full Text Available Disease modifying therapies (DMTs reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS. Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA or interferon-β 1a/1b (IFN-β between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2% were lost to follow-up and 160 (11% moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54% started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations.

Science.gov (United States)

Tosteson, Anna N A; Burge, Russel T; Marshall, Deborah A; Lindsay, Robert

2008-09-01

To evaluate the cost-effectiveness of osteoporosis treatments for women at high fracture risk and estimate the population-level impact of providing bisphosphonate therapy to all eligible high-risk US women. Fractures, healthcare costs, and quality-adjusted life-years (QALYs) were estimated over 10 years using a Markov model. No therapy, risedronate, alendronate, ibandronate, and teriperatide (PTH) were compared among 4 risk groups. Sensitivity analyses examined the robustness of model results for 65-year-old women with low bone density and previous vertebral fracture. Women treated with a bisphosphonate experienced fewer fractures and more QALYs compared with no therapy or PTH. Total costs were lowest for the untreated cohort, followed by risedronate, alendronate, ibandronate, and PTH in all risk groups except women aged 75 years with previous fracture. The incremental cost-effectiveness of risedronate compared with no therapy ranged from cost saving for the base case to $66,722 per QALY for women aged 65 years with no previous fracture. Ibandronate and PTH were dominated in all risk groups. (A dominated treatment has a higher cost and poorer outcome.) Treating all eligible women with a bisphosphonate would cost an estimated additional $5563 million (21% total increase) and would result in 390,049 fewer fractures (35% decrease). In the highest risk group, the additional cost of therapy was offset by other healthcare cost savings. Osteoporosis treatment of high-risk women is cost-effective, with bisphosphonates providing the most benefit at lowest cost. For highest risk women, costs are offset by savings from fracture prevention.

Long-term regional control after radiation therapy and neck dissection for base of tongue carcinoma

International Nuclear Information System (INIS)

Lee, Henry J.; Zelefsky, Michael J.; Kraus, Dennis H.; Pfister, David G.; Strong, Elliot W.; Raben, Adam; Shah, Jatin P.; Harrison, Louis B.

1997-01-01

Purpose: Minimal literature exists with 10-year data on neck control in advanced head and neck cancer. The purpose of this study is to determine long-term regional control for base of tongue carcinoma patients treated with primary radiation therapy plus neck dissection. Methods and Materials: Between 1981-1996, primary radiation therapy was used to treat 68 patients with squamous cell carcinoma of the base of tongue. Neck dissection was added for those who presented with palpable lymph node metastases. The T-stage distribution was T1, 17; T2, 32; T3, 17; and T4, 2. The N-stage distribution was N0, 10; N1, 24; N2a, 6; N2b, 11, N2c, 8; N3, 7; and Nx, 2. Ages ranged from 35 to 77 (median 55 years) among the 59 males and nine females. Therapy generally consisted of initial external beam irradiation to the primary site (54 Gy) and neck (50 Gy). Clinically positive necks were boosted to 60 Gy with external beam irradiation. Three weeks later, the base of tongue was boosted with an Ir-192 interstitial implant (20-30 Gy). A neck dissection was done at the same anesthesia for those who presented with clinically positive necks, even if a complete clinical neck response was achieved with external beam irradiation. Neoadjuvant cisplatin-based chemotherapy was administered to nine patients who would have required a total laryngectomy if their primary tumors had been surgically managed. The median follow-up was 36 months with a range from 1 to 151 months. Eleven patients were followed for over 8 years. No patients were lost to follow-up. Results: Actuarial 5- and 10-year neck control was 96% overall, 86% after radiation alone, and 100% after radiation plus neck dissection. Pathologically negative neck specimens were observed in 70% of necks dissected after external beam irradiation. The remaining 30% of dissected necks were pathologically positive. These specimens contained multiple positive nodes in 83% despite a 56% overall complete clinical neck response rate to irradiation

A case of early detection of bisphosphonate-related osteonecrosis of the jaw

OpenAIRE

Mori, Miyu; Koide, Tetsuro; Matsui, Yuriyo; Matsuda, Toru

2015-01-01

Osteonecrosis of the jaws is an adverse reaction associated with the use of bisphosphonates. Although the diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is based on symptomatology, it is often detected late because the patients become symptomatic only after osteonecrosis is well established. We describe a case of early oral BRONJ detected by magnetic resonance imaging (MRI) accidentally. Head MRI revealed low signal of T1-weight images in left mandibula. Patient had been...

Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

Directory of Open Access Journals (Sweden)

Coventry BJ

2015-04-01

Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I

Directory of Open Access Journals (Sweden)

Iwamoto J

2012-12-01

Full Text Available Jun Iwamoto,1 Yoshihiro Sato,2 Mitsuyoshi Uzawa,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Neurology, Mitate Hospital, Fukuoka, 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 µg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 µg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.Keywords: etidronate, alendronate, fragility fracture, bone mineral density, osteogenesis imperfecta

Long-term Follow-up Results of a Multi-institutional Phase 2 Study of Concurrent Chemoradiation Therapy for Locally Advanced Cervical Cancer in East and Southeast Asia

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Kato, Shingo, E-mail: s_kato@saitama-med.ac.jp [Department of Radiation Oncology, International Medical Center, Saitama Medical University, Saitama (Japan); National Institute of Radiological Sciences of Japan, Chiba (Japan); Ohno, Tatsuya [Gunma University Heavy Ion Medical Center, Gunma University, Gunma (Japan); Thephamongkhol, Kullathorn; Chansilpa, Yaowalak [Division of Radiation Oncology, Department of Radiology, Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok (Thailand); Cao, Jianping [School of Radiation Medicine and Public Health, Soochow University, Soochow (China); Xu, Xiaoting [Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Devi, C. R. Beena; Swee, Tang Tieng [Department of Radiotherapy and Oncology, Hospital Umum Sarawak, Kuching (Malaysia); Calaguas, Miriam J.C. [Department of Radiation Oncology, St. Luke' s Medical Center, Quezon City, the Philippines (Philippines); Reyes, Rey H. de los [Department of Obstetrics and Gynecology, Dr Jose R. Reyes Memorial Medical Center, Manila, the Philippines (Philippines); Cho, Chul-Koo [Department of Radiation Oncology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Dung, To Anh [Department of Breast and Gynecology Radiotherapy, National Cancer Institute, Hanoi (Viet Nam); Supriana, Nana [Department of Radiation Therapy, Faculty of Medicine, University of Indonesia, Dr Cipto Mangunkusumo General Hospital, Jakarta (Indonesia); Erawati, Dyah [Division of Radiotherapy, Dr Soetomo General Hospital, Surabaya (Indonesia); Mizuno, Hideyuki [National Institute of Radiological Sciences of Japan, Chiba (Japan); Nakano, Takashi [Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma (Japan); Tsujii, Hirohiko [National Institute of Radiological Sciences of Japan, Chiba (Japan)

2013-09-01

Purpose: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. Methods and Materials: Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m{sup 2}) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. Results: Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. Conclusions: The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.

The long-term effectiveness of generic adult fixed-dose combination ...

African Journals Online (AJOL)

Background: Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs. Objective: To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment. Methods: ...

Impact of long-term HPN on daily life in adults.

NARCIS (Netherlands)

Persoon, A.; Huisman-de Waal, G.J.; Naber, A.H.J.; Schoonhoven, L.; Tas, T.; Sauerwein, H.P.; Achterberg, T. van

2005-01-01

BACKGROUND AND AIMS: Home parenteral nutrition (HPN) is a therapy that changes life radically and often means lifelong dependence on parenteral feeding. The aim of this study was to gain insight into problems experienced by adult patients who were dependent on long-term HPN. METHODS: A survey was

Client interpersonal impacts as mediators of long-term outcome in cognitive-behavioral therapy integrated with motivational interviewing for generalized anxiety disorder.

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Constantino, Michael J; Romano, Felicia M; Coyne, Alice E; Westra, Henny A; Antony, Martin M

2017-03-24

A recent trial of generalized anxiety disorder treatment (Westra, H. A., Constantino, M. J., & Antony, M. M. (2016). Integrating Motivational Interviewing With Cognitive-Behavioral Therapy for Severe Generalized Anxiety Disorder: An Allegiance-Controlled Randomized Clinical Trial. Journal of Consulting and Clinical Psychology, 84, 768-782. doi: 10.1037/ccp0000098 ) revealed that cognitive-behavioral therapy (CBT) integrated with motivational interviewing (MI) outperformed CBT alone across a 12-month follow up. The present study examined whether this treatment effect was mediated by MI-CBT clients engaging over time in during-session interpersonal behaviors reflecting more friendly dominance, or agentic actions, and less friendly submissiveness (FS), or trustingly compliant actions both theory-specific MI mechanisms. Clients received 15 sessions of MI-CBT (n = 42) or CBT alone (n = 43). Therapists rated client interpersonal behavior following five sessions, and clients rated their worry at baseline, each session, and 6- and 12-month follow up. Mediator and outcome variables were derived from multilevel models. Mediation was tested using a bootstrapping procedure. There was a significant indirect effect for FS. As expected, CBT clients evidenced greater increases in FS than MI-CBT clients, which in turn, though unexpectedly, related to lower 12-month worry. However, long-term CBT outcomes remained inferior to MI-CBT outcomes even with CBT clients'greater increase in FS. Results suggest that CBT outcomes are more positive when clients trustingly comply; however, MI-CBT remained superior, but for as yet unexplained reasons. Clinical or methodological significance of this article: The findings highlight the clinical importance of GAD clients becoming more friendly dominant in the therapy relationship irrespective of whether they received CBT or integrative MI-CBT. Moreover, it seems clinically indicated to incorporate MI spirit and techniques into CBT when

Long-term efficacy of polyethylene glycol 3350 for the treatment of chronic constipation in children with and without encopresis.

Science.gov (United States)

Pashankar, Dinesh S; Bishop, Warren P; Loening-Baucke, Vera

2003-01-01

Seventy-four children (43 with chronic constipation, 31 with constipation and encopresis) treated with polyethylene glycol 3350 (PEG) for longer than 3 months were studied to assess long-term efficacy. The mean duration of PEG therapy was 8.4 months (range, 3-30). Weekly stool frequency, stool consistency, and symptoms associated with constipation improved significantly with PEG therapy in all 74 patients. In 31 children with encopresis, soiling ceased completely in 16 patients and frequency of soiling decreased significantly in all others. The average effective long-term dose of PEG was 0.7 g/kg/day. Long-term PEG therapy is effective for the treatment of chronic constipation with and without encopresis in children.

Bone mineral density changes of lumbar spine and femur in osteoporotic patient treated with bisphosphonates and beta-hydroxy-beta-methylbutyrate (HMB): Case report.

Science.gov (United States)

Tatara, Marcin R; Krupski, Witold; Majer-Dziedzic, Barbara

2017-10-01

Currently available approaches to osteoporosis treatment include application of antiresorptive and anabolic agents influencing bone tissue metabolism. The aim of the study was to present bone mineral density (BMD) changes of lumbar spine in osteoporotic patient treated with bisphosphonates such as ibandronic acid and pamidronic acid, and beta-hydroxy-beta-methylbutyrate (HMB). BMD and volumetric BMD (vBMD) of lumbar spine were measured during the 6 year observation period with the use of dual-energy X-ray absorptiometry (DEXA) and quantitative computed tomography (QCT). The described case report of osteoporotic patient with family history of severe osteoporosis has shown site-dependent response of bone tissue to antiosteoporotic treatment with bisphosphonates. Twenty-five-month treatment with ibandronic acid improved proximal femur BMD with relatively poor effects on lumbar spine BMD. Over 15-month therapy with pamidronic acid was effective to improve lumbar spine BMD, while in the proximal femur the treatment was not effective. A total of 61-week long oral administration with calcium salt of HMB improved vBMD of lumbar spine in the trabecular and cortical bone compartments when monitored by QCT. Positive effects of nearly 2.5 year HMB treatment on BMD of lumbar spine and femur in the patient were also confirmed using DEXA method. The results obtained indicate that HMB may be applied for the effective treatment of osteoporosis in humans. Further studies on wider human population are recommended to evaluate mechanisms influencing bone tissue metabolism by HMB.

Long-term results of percutaneous ethanol injection therapy for hepatocellular carcinoma in cirrhosis: a European experience

International Nuclear Information System (INIS)

Lencioni, R.; Pinto, F.; Armillotta, N.; Bassi, A.M.; Moretti, M.; Di Giulio, M.; Marchi, S.; Uliana, M.; Della Capanna, S.; Lencioni, M.; Bartolozzi, C.

1997-01-01

The objective of our work was to evaluate the long-term results of percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. A total of 184 cirrhotic patients with HCC underwent PEI as the only anticancer treatment over an 8-year period. Patients were followed after therapy by means of clinical examinations, laboratory tests, and US and CT studies performed at regular time intervals. Survival rates were determined according to the Kaplan-Meier method. The overall survival was 67% at 3 years, 41% at 5 years, and 19% at 7 years. The 3-, 5-, and 7-year survival rates of patients with single HCC≤3 cm (78, 54, and 28%, respectively) were significantly higher (p<0.01) than those of patients with single HCC of 3.1-5 cm (61, 32, and 16, respectively) or multiple HCCs (51, 21, and 0%, respectively). Survival of Child-Pugh A patients (79% at 3 years, 53% at 5 years, and 32% at 7 years) was significantly longer (p<0.01) than that of Child-Pugh B patients (50% at 3 years, 28% at 5 years, and 8% at 7 years). A selected group of 70 patients with Child-Pugh A cirrhosis and single HCC≤3 cm had a 7-year survival of 42%. Long-term survival of cirrhotic patients with HCC treated with PEI is comparable to that reported in published series of matched patients submitted to surgical resection. (orig.)

Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome.

Science.gov (United States)

Wang, Liping; Guo, Tian-Zhi; Hou, Saiyun; Wei, Tzuping; Li, Wen-Wu; Shi, Xiaoyou; Clark, J David; Kingery, Wade S

2016-10-01

. Alendronate (60 μg/kg/d subcutaneously [s.c.]) or zoledronate (3 mg/kg/d orally) treatment for 28 days, started at the time of fracture, completely inhibited the development of hindpaw allodynia and reduced hindpaw unweighting by 44% ± 13% and 58% ± 5%, respectively. Orally administered zoledronate (3 mg/kg/d for 21 days) treatment also completely reversed established allodynia and unweighting when started at 4 weeks postfracture. Histomorphometric and microcomputed tomography analysis demonstrated that both the 3 and 60 μg/kg/d alendronate treatments reversed trabecular bone loss (an 88% ± 25% and 188% ± 39% increase in the ipsilateral distal femur BV/TV, respectively) and blocked the increase in osteoclast numbers and erosion surface observed in bilateral distal femurs and in L5 vertebra of the fracture rats. Alendronate treatment inhibited fracture-induced increases in hindpaw inflammatory mediators, reducing postfracture levels of tumor necrosis factor by 43% ± 9%, IL-1 by 60% ± 9%, IL-6 by 56% ± 14%, and NGF by 37% ± 14%, but had no effect on increased spinal cord Fos expression, or skin and sciatic nerve immunocomplex deposition. Collectively, these results indicate that bisphosphonate therapy inhibits pain, osteoclast activation, trabecular bone loss, and cutaneous inflammation in the rat fracture model of CRPS, data supporting the hypothesis that bisphosphonate therapy can provide effective multimodal treatment for CRPS.

A Long-Term Follow-Up of the Efficacy of Nature-Based Therapy for Adults Suffering from Stress-Related Illnesses on Levels of Healthcare Consumption and Sick-Leave Absence: A Randomized Controlled Trial

Science.gov (United States)

Corazon, Sus Sola; Nyed, Patrik Karlsson; Sidenius, Ulrik

2018-01-01

Stress-related illnesses are a growing health problem in the Western world; which also has economic significance for society. As a consequence; there is a growing demand for effective treatments. The study investigates the long-term efficacy of the Nacadia® nature-based therapy (NNBT) by comparing it to the efficacy of a validated cognitive behavioral therapy, called STreSS. The study is designed as a randomized controlled trial in which 84 participants are randomly allocated between the treatments. Long-term efficacy is investigated through data extracts from the national database of Statistics Denmark on the sick leave and the health-care consumption. The results show that both the NNBT and the STreSS lead to a significant decrease in number of contacts with a general practitioner in the period from twelve months prior to treatment to twelve months after treatment; and, a significant decrease in long-term sick leave from the month prior to treatment to twelve months after treatment. The positive long-term effects provide validation for the NNBT as an efficient treatment of stress-related illnesses. PMID:29342952

A Long-Term Follow-Up of the Efficacy of Nature-Based Therapy for Adults Suffering from Stress-Related Illnesses on Levels of Healthcare Consumption and Sick-Leave Absence: A Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Sus Sola Corazon

2018-01-01

Full Text Available Stress-related illnesses are a growing health problem in the Western world; which also has economic significance for society. As a consequence; there is a growing demand for effective treatments. The study investigates the long-term efficacy of the Nacadia® nature-based therapy (NNBT by comparing it to the efficacy of a validated cognitive behavioral therapy, called STreSS. The study is designed as a randomized controlled trial in which 84 participants are randomly allocated between the treatments. Long-term efficacy is investigated through data extracts from the national database of Statistics Denmark on the sick leave and the health-care consumption. The results show that both the NNBT and the STreSS lead to a significant decrease in number of contacts with a general practitioner in the period from twelve months prior to treatment to twelve months after treatment; and, a significant decrease in long-term sick leave from the month prior to treatment to twelve months after treatment. The positive long-term effects provide validation for the NNBT as an efficient treatment of stress-related illnesses.

A Long-Term Follow-Up of the Efficacy of Nature-Based Therapy for Adults Suffering from Stress-Related Illnesses on Levels of Healthcare Consumption and Sick-Leave Absence: A Randomized Controlled Trial.

Science.gov (United States)

Corazon, Sus Sola; Nyed, Patrik Karlsson; Sidenius, Ulrik; Poulsen, Dorthe Varning; Stigsdotter, Ulrika Karlsson

2018-01-15

Stress-related illnesses are a growing health problem in the Western world; which also has economic significance for society. As a consequence; there is a growing demand for effective treatments. The study investigates the long-term efficacy of the Nacadia ® nature-based therapy (NNBT) by comparing it to the efficacy of a validated cognitive behavioral therapy, called STreSS. The study is designed as a randomized controlled trial in which 84 participants are randomly allocated between the treatments. Long-term efficacy is investigated through data extracts from the national database of Statistics Denmark on the sick leave and the health-care consumption. The results show that both the NNBT and the STreSS lead to a significant decrease in number of contacts with a general practitioner in the period from twelve months prior to treatment to twelve months after treatment; and, a significant decrease in long-term sick leave from the month prior to treatment to twelve months after treatment. The positive long-term effects provide validation for the NNBT as an efficient treatment of stress-related illnesses.

In vitro comparison of new bisphosphonic acids and zoledronate effects on human gingival fibroblasts viability, inflammation and matrix turnover.

Science.gov (United States)

De Colli, Marianna; Tortorella, Paolo; Marconi, Guya Diletta; Agamennone, Mariangela; Campestre, Cristina; Tauro, Marilena; Cataldi, Amelia; Zara, Susi

2016-11-01

Bisphosphonates (BPs) are drugs clinically used in resorptive diseases. It was already proved that some clinically relevant BPs can inhibit a class of enzymes called matrix metalloproteinases (MMPs), required during tissue remodelling. Combining the arylsulfonamide function with the bisphosphonic group, several compounds were synthesized to obtain selective inhibitors of MMPs. The aim of the present study was to compare the effect of zoledronic acid (ZA), the most potent bisphosphonate available as therapy, with new sulfonamide containing BPs in an in vitro model of human gingival fibroblasts (HGFs). Western blot was used to measure procollagen I, β1 integrin MMP-8 and MMP-9, phase contrast and MTT for cell viability; L-lactate-dehydrogenase (LDH) measurement was performed for toxicity evaluation and ELISA for prostaglandin E 2 (PGE 2 ) secretion assessment. When compared with ZA, the treatment with the newly synthesized compounds shows increasing viability, procollagen I expression and decreased expression of β1 integrin in HGFs. Higher levels of released LDH, PGE 2 and MMP-9 expression are recorded in ZA-treated HGFs. Increased levels of MMP-8 are recorded in newly synthesized compounds-treated samples. These findings allowed to conclude that new tested BPs did not affect HGFs viability and adhesion, did not induce cellular toxicity, were not responsible for inflammatory event induction and could preserve the physiological matrix turnover. It could be hypothesized that the new molecules were better tolerated by soft tissues, resulting in lesser side effects.

Long-term survival benefit of revascularization compared with medical therapy in patients with coronary chronic total occlusion and well-developed collateral circulation.

Science.gov (United States)

Jang, Woo Jin; Yang, Jeong Hoon; Choi, Seung-Hyuk; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Kim, Wook Sung; Lee, Young Tak; Gwon, Hyeon-Cheol

2015-02-01

The purpose of this study was to compare the long-term clinical outcomes of patients with chronic total occlusion (CTO) and well-developed collateral circulation treated with revascularization versus medical therapy. Little is known about the clinical outcomes and optimal treatment strategies of CTO with well-developed collateral circulation. We screened 2,024 consecutive patients with at least 1 CTO detected on coronary angiogram. Of these, we analyzed data from 738 patients with Rentrop 3 grade collateral circulation who were treated with medical therapy alone (n = 236), coronary artery bypass grafting (n = 170) or percutaneous coronary intervention (n = 332; 80.1% successful). Patients who underwent revascularization and medical therapy (revascularization group, n = 502) were compared with those who underwent medical therapy alone (medication group, n = 236) in terms of cardiac death and major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, and repeat revascularization. During a median follow-up duration of 42 months, multivariate analysis revealed a significantly lower incidence of cardiac death (hazard ratio [HR]: 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p collateral circulation, aggressive revascularization may reduce the risk of cardiac mortality and MACE. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Long-term safety and efficacy of fractionated stereotactic body radiation therapy for spinal metastases

Energy Technology Data Exchange (ETDEWEB)

Mantel, Frederick; Glatz, Stefan; Toussaint, Andre; Flentje, Michael; Guckenberger, Matthias [University Hospital Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany)

2014-12-15

Patients with long life expectancy despite metastatic status might benefit from long-term local control of spinal metastases. Dose-intensified radiotherapy (RT) is believed to control tumor growth better and thus offers longer pain relief. This single-institution study reports on fractionated stereotactic body radiation therapy (SBRT) for spinal metastases in patients with good life expectancy based on performance status, extent of metastases, histology, and time to metastasis. Between 2004 and 2010, 36 treatment sites in 32 patients (median age 55 years; male 61 %; median Karnofsky performance score 85) were treated with fractionated SBRT. The median treatment dose was 60 Gy (range, 48.5-65 Gy) given in a median of 20 fractions (range, 17-33); the median maximum dose to the planning risk volume for the spinal cord (PRV-SC) was 46.6 Gy. All patients suffering from pain prior to RT reported pain relief after treatment; after a median follow-up of 20.3 months, 61 % of treatment sites were pain-free, another 25 % associated with mild pain. In 86 % of treatments, patients were free from neurological symptoms at the time of the last clinical follow-up. Acute grade 1 toxicities (CTCAE 3.0) were observed in 11 patients. Myelopathy did not occur in any patient. Radiologically controlled freedom from local progression was 92 and 84 % after 12 and 24 months, respectively. Median overall survival (OS) was 19.6 months. Patient selection resulted in long OS despite metastatic disease, and dose-intensified fractionated SBRT for spinal metastases was safe and achieved long-term local tumor control and palliation of pain. (orig.) [German] Patienten mit guter Lebenserwartung trotz metastasierter Erkrankung koennten von einer lang andauernden lokalen Kontrolle von Wirbelsaeulenmetastasen profitieren. Eine dosisintensivierte Radiotherapie (RT) kann vermutlich eine bessere Tumorkontrolle und daher eine laengere Schmerzpalliation erreichen. Ausgewertet wurden die monozentrischen

Impact of long-term HPN on daily life in adults

NARCIS (Netherlands)

Persoon, Anke; Huisman-de Waal, Getty; Naber, Ton A.; Schoonhoven, Lisette; Tas, Tirzah; Sauerwein, Hans; van Achterberg, Theo

2005-01-01

Home parenteral nutrition (HPN) is a therapy that changes life radically and often means lifelong dependence on parenteral feeding. The aim of this study was to gain insight into problems experienced by adult patients who were dependent on long-term HPN. A survey was performed on all patients at the

Long-term effects of pegvisomant on comorbidities in patients with acromegaly: a retrospective single-center study

Science.gov (United States)

Kuhn, Emmanuelle; Maione, Luigi; Bouchachi, Amir; Rozière, Myriam; Salenave, Sylvie; Brailly-Tabard, Sylvie; Young, Jacques; Kamenicky, Peter; Assayag, Patrick; Chanson, Philippe

2015-01-01

Context The effect of pegvisomant on IGF1 levels in patients with acromegaly is well documented, but little is known of its long-term impact on comorbidity. Aim The aim of this retrospective study was to evaluate the effects of long-term pegvisomant therapy on cardiorespiratory and metabolic comorbidity in patients with acromegaly. Patients and methods We analyzed the long-term (up to 10 years) effect of pegvisomant therapy given alone (n=19, 45%) or in addition to somatostatin analogues and/or cabergoline (n=23, 55%) on echocardiographic, polysomnographic and metabolic parameters in respectively 42, 12 and 26 patients with acromegaly followed in Bicêtre hospital. Results At the first cardiac evaluation, 20±16 months after pegvisomant introduction, IGF1 levels normalized in 29 (69%) of the 42 patients. The left ventricular ejection fraction (LVEF) improved significantly in patients whose basal LVEF was ≤60% and decreased in those whose LVEF was >70%. The left ventricular mass index (LVMi) decreased from 123±25 to 101±21 g/m2 (P<0.05) in the 17 patients with a basal LVMi higher than the median (91 g/m2), while it remained stable in the other patients. Pegvisomant reduced the apnoea–hypopnea index and cured obstructive sleep apnea (OSA) in four of the eight patients concerned. Long-term follow-up of 22 patients showed continuing improvements in cardiac parameters. The BMI and LDL cholesterol level increased minimally during pegvisomant therapy, and other lipid parameters were not modified. Conclusions Long-term pegvisomant therapy not only normalizes IGF1 in a large proportion of patients but also improves cardiac and respiratory comorbidity. PMID:26429918

[Long-term psychiatric hospitalizations].

Science.gov (United States)

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Reproductive status in adult male long-term survivors of childhood cancer

NARCIS (Netherlands)

Tromp, K.; Claessens, J. J. M.; Knijnenburg, S. L.; van der Pal, H. J. H.; van Leeuwen, F. E.; Caron, H. N.; Beerendonk, C. C. M.; Kremer, L. C. M.

2011-01-01

This study assessed the long-term effects of cancer therapies on reproductive status in adult male childhood cancer survivors, evaluated the treatment-related risk factors for hypergonadotropic hypogonadism and assessed the association between the FSH levels and the later need for assisted

Reproductive status in adult male long-term survivors of childhood cancer

NARCIS (Netherlands)

Tromp, K.; Claessens, J.J.M.; Knijnenburg, S.L.; Pal, H.J. van der; Leeuwen, F.E. van; Caron, H.N.; Beerendonk, C.C.M.; Kremer, L.C.

2011-01-01

BACKGROUND: This study assessed the long-term effects of cancer therapies on reproductive status in adult male childhood cancer survivors, evaluated the treatment-related risk factors for hypergonadotropic hypogonadism and assessed the association between the FSH levels and the later need for

Long-term patterns of adherence to medication therapy among patients with type 2 diabetes mellitus in Denmark

DEFF Research Database (Denmark)

Jensen, Majken Linnemann; Jørgensen, Marit Eika; Hansen, Ebba Holme

2017-01-01

: Adherence to six medicine groups (metformin, sulfonylureas, acetylsalicylic acid, thiazide diuretics, renin angiotensin system inhibitors, and statins) were analysed among 5,232 patients with type 2 diabetes at a tertiary referral hospital during 1998-2009. Rate-ratios of initiation of treatment, recurrent......AIMS: Poor adherence to medication therapy among type 2 diabetes patients is a clinical challenge. We aimed to determine which factors are associated with the three phases of long-term adherence to medication: initiation, implementation and discontinuation in a register-based study. METHODS...... gaps in supply of medication, and discontinuation of treatment were analysed using Poisson regression. RESULTS: Poor initiation rather than poor implementation or discontinuation was the main contributor to medication nonadherence. Polypharmacy was a risk factor for slower initiation of treatment...

Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

Directory of Open Access Journals (Sweden)

Keisuke Imafuku

2017-04-01

Full Text Available Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs. We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4. We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors.

Long-Term Quality of Life After Swallowing and Salivary-Sparing Chemo–Intensity Modulated Radiation Therapy in Survivors of Human Papillomavirus–Related Oropharyngeal Cancer

Energy Technology Data Exchange (ETDEWEB)

Vainshtein, Jeffrey M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Moon, Dominic H. [University of Michigan Medical School, Ann Arbor, Michigan (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Chepeha, Douglas B. [Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan (United States); Eisbruch, Avraham, E-mail: eisbruch@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Stenmark, Matthew H. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

2015-04-01

Purpose: To evaluate long-term health-related quality of life (HRQOL) in 2 prospective studies of chemo–intensity modulated radiation therapy (chemo-IMRT) for oropharyngeal cancer (OPC). Methods and Materials: Of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT, 69 were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL (HNQOL) questionnaire, the University of Washington quality of life (UWQOL) questionnaire, and the Xerostomia Questionnaire (XQ), previously administered from baseline through 2 years in the parent studies, were readministered at long-term follow-up, along with the Short-Form 36. Long-term changes in HRQOL from before treatment and 2 years were evaluated. Results: Forty patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed human papillomavirus–positive OPC. Long term, no clinically significant worsening was detected in mean HRQOL scores compared with 2 years, with stable or improved HRQOL from before treatment in nearly all domains. “Moderate” or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom from percutaneous endoscopic gastrostomy tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. Eleven percent and 14% of patients reported “moderate” or “severe” long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors. Conclusions: At more than 6 years' median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared with both before treatment and 2-year follow-up. New late toxicity after 2 years was

Short- and long-term response to corticosteroid therapy in chronic beryllium disease.

Science.gov (United States)

Marchand-Adam, S; El Khatib, A; Guillon, F; Brauner, M W; Lamberto, C; Lepage, V; Naccache, J-M; Valeyre, D

2008-09-01

Chronic beryllium disease (CBD) is a granulomatous disorder that affects the lung after exposure to beryllium. The present study reports short- and long-term evolution of granulomatous and fibrotic components in eight patients with severe CBD receiving corticosteroid therapy. Eight patients with confirmed CBD were studied at baseline, after initial corticosteroid treatment (4-12 months), at relapse and at the final visit. Beryllium exposure, Glu(69) (HLA-DPB1 genes coding for glutamate at position beta69) polymorphism, symptoms, pulmonary function tests (PFT), serum angiotensin-converting enzyme (SACE) and high-resolution computed tomography (HRCT) quantification of pulmonary lesions were analysed. The CBD patients were observed for a median (range) of 69 (20-180) months. After stopping beryllium exposure, corticosteroids improved symptoms and PFT (vital capacity +26%, diffusing capacity of the lung for carbon monoxide +15%), and decreased SACE level and active lesion HRCT score. In total, 18 clinical relapses occurred after the treatment was tapered and these were associated with SACE and active lesion HRCT score impairment. At the final visit, corticosteroids had completely stabilised all parameters including both HRCT scores of active lesions and fibrotic lesions in six out of eight patients. Corticosteroids were beneficial in chronic beryllium disease. They were effective in suppressing granulomatosis lesions in all cases and in stopping the evolution to pulmonary fibrosis in six out of eight patients.

Rape-related symptoms in adolescents: short- and long-term outcome after cognitive behavior group therapy

Directory of Open Access Journals (Sweden)

Iva Bicanic

2014-06-01

Full Text Available Background: Efficacy studies on treatment in adolescent victims of single rape are lacking, even though sexual victimization is most likely to occur during adolescence and despite the fact that adolescents are at risk to develop subsequent posttraumatic stress disorder. Aim: The aim of this prospective observational study was to evaluate the short- and long-term outcomes of a nine-session cognitive behavior group therapy (STEPS, including a parallel six-session parents’ group on rape-related symptomatology in female adolescents (13–18 years. STEPS includes psychoeducation, exposure in sensu as well as in vivo, cognitive restructuring, and relapse prevention. Methods: Fifty-five female adolescents with mental health problems due to single rape, but without prior sexual trauma, received STEPS while their parents participated in a support group. Subjects were assessed on posttraumatic stress (PTS and comorbid symptoms using self-report questionnaires prior to and directly after treatment, and at 6 and 12 months follow-up. Results: Repeated measures analysis showed a significant and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation, sexual concerns, and behavior problems directly after treatment, which maintained at 12 months follow-up. Time since trauma did not influence the results. Dropout during STEPS was 1.8%. Conclusions: The results potentially suggest that the positive treatment outcomes at short- and long-term may be caused by STEPS. The encouraging findings need confirmation in future controlled studies on the effectiveness of STEPS because it may be possible that the treatment works especially well for more chronic symptoms, while the less chronic part of the sample showed considerable improvement on its own.

Long-term potentiation and long-term depression: a clinical perspective

Directory of Open Access Journals (Sweden)

Timothy V.P. Bliss

2011-01-01

Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography

International Nuclear Information System (INIS)

Johnston, D.G.; Hall, K.; Kendall-Taylor, P.; Ross, W.M.; Crombie, A.L.; Cook, D.B.; Watson, M.J.

1986-01-01

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). It was concluded that radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume. (author)

The role of protein and carbohydrates for long-term weight control

DEFF Research Database (Denmark)

Perez-Cornago, Aurora; van Baak, Marleen A.; Saris, Wim H. M.

2014-01-01

Current therapies to manage obesity are based on energy restriction and physical activity promotion. However, the role of specific dietary components for long-term weight maintenance is under debate. This review aims to illustrate some lessons from the pan-European Diogenes study, a randomized, c...

Long-term follow-up of psilocybin-facilitated smoking cessation.

Science.gov (United States)

Johnson, Matthew W; Garcia-Romeu, Albert; Griffiths, Roland R

2017-01-01

A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration. The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin. All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

Effect of Bisphosphonates on the Levels of Rankl and Opg in Gingival Crevicular Fluid of Patients With Periodontal Disease and Post-menopausal Osteoporosis.

Science.gov (United States)

Verde, María E; Bermejo, Daniela; Gruppi, Adriana; Grenón, Miriam

2015-12-01

The Receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/Osteoprotegerine (OPG) system has been proposed as essential for osteoclast biology and identified as key part in regulating the physiology and pathology of the skeletal system. The study of the RANKL/RANK/OPG system has increased the understanding of the mechanisms involved in the bone remodeling process, especially in postmenopausal osteoporosis and periodontal disease. Bisphosphonates have become the mainstay of the treatment and prevention of post-menopausal osteoporosis. They inhibit the formation and dissolution of calcium phosphate crystals in bone and also osteoclasts, thus reducing bone turnover.Current investigations relate osteoporosis with the appearance and progression of periodontal disease. Although the etiology of both is different, the bone loss present in both shares several characteristics. Thus, therapy used for osteoporosis can be considered of value in the treatment of periodontal disease. The aim of this study was to evaluate the levels of RANKL, OPG and their relationship in gingival crevicular fluid (GCF) in patients with periodontal disease and postmenopausal osteoporosis/ osteopenia in relation to consumption of bisphosphonates. We studied 66 periodontal active sites obtained from 17 post- menopausal women patients aged between 45-70 years old with osteoporosis/osteopenia and periodontal disease. GCF samples were collected using sterile filter paper strips. To determine the concentration of RANKL and OPG, a commercial ELISA assay was used. The values of RANKL, OPG and their ratio (RANKL/ OPG) were compared with Mann-Whitney U Test. The values of RANKL, OPG and their ratio obtained in patients with osteoporosis/osteopenia and periodontal disease with or without bisphosphonates treatment showed no differences. Bisphosphonates do not alter the concentration of RANKL and OPG and their ratio in the GCF of patients with osteoporosis/ osteopenia and periodontal disease

Anticancer Activity of Polyoxometalate-Bisphosphonate Complexes: Synthesis, Characterization, In Vitro and In Vivo Results.

Science.gov (United States)

Boulmier, Amandine; Feng, Xinxin; Oms, Olivier; Mialane, Pierre; Rivière, Eric; Shin, Christopher J; Yao, Jiaqi; Kubo, Tadahiko; Furuta, Taisuke; Oldfield, Eric; Dolbecq, Anne

2017-07-03

We synthesized a series of polyoxometalate-bisphosphonate complexes containing Mo VI O 6 octahedra, zoledronate, or an N-alkyl (n-C 6 or n-C 8 ) zoledronate analogue, and in two cases, Mn as a heterometal. Mo 6 L 2 (L = Zol, ZolC 6 , ZolC 8 ) and Mo 4 L 2 Mn (L = Zol, ZolC 8 ) were characterized by using single-crystal X-ray crystallography and/or IR spectroscopy, elemental and energy dispersive X-ray analysis and 31 P NMR. We found promising activity against human nonsmall cell lung cancer (NCI-H460) cells with IC 50 values for growth inhibition of ∼5 μM per bisphosphonate ligand. The effects of bisphosphonate complexation on IC 50 decreased with increasing bisphosphonate chain length: C 0 ≈ 6.1×, C 6 ≈ 3.4×, and C 8 ≈ 1.1×. We then determined the activity of one of the most potent compounds in the series, Mo 4 Zol 2 Mn(III), against SK-ES-1 sarcoma cells in a mouse xenograft system finding a ∼5× decrease in tumor volume than found with the parent compound zoledronate at the same compound dosing (5 μg/mouse). Overall, the results are of interest since we show for the first time that heteropolyoxomolybdate-bisphosphonate hybrids kill tumor cells in vitro and significantly decrease tumor growth, in vivo, opening up new possibilities for targeting both Ras as well as epidermal growth factor receptor driven cancers.

Influence of Bisphosphonate Treatment on Medullary Macrophages and Osteoclasts: An Experimental Study

Directory of Open Access Journals (Sweden)

Natalia Daniela Escudero

2012-01-01

Full Text Available Nitrogen-containing bisphosphonates are widely used for treating diverse bone pathologies. They are anticatabolic drugs that act on osteoclasts inhibiting bone resorption. It remains unknown whether the mechanism of action is by decreasing osteoclast number, impairing osteoclast function, or whether they continue to effectively inhibit bone resorption despite the increase in osteoclast number. There is increasing evidence that bisphosphonates also act on bone marrow cells like macrophages and monocytes. The present work sought to evaluate the dynamics of preosteoclast fusion and possible changes in medullary macrophage number in bisphosphonate-treated animals. Healthy female Wistar rats received olpadronate, alendronate, or vehicle during 5 weeks, and 5-bromo-2-deoxyuridine (BrdU on day 7, 28, or 34 of the experiment. Histomorphometric studies were performed to study femurs and evaluate: number of nuclei per osteoclast (N.Nu/Oc; number of BrdU-positive nuclei (N.Nu BrdU+/Oc; percentage of BrdU-positive nuclei per osteoclast (%Nu.BrdU+/Oc; medullary macrophage number (mac/mm2 and correlation between N.Nu/Oc and mac/mm2. Results showed bisphosphonate-treated animals exhibited increased N.Nu/Oc, caused by an increase in preosteoclast fusion rate and evidenced by higher N.Nu BrdU+/Oc, and significantly decreased mac/mm2. Considering the common origin of osteoclasts and macrophages, the increased demand for precursors of the osteoclast lineage may occur at the expense of macrophage lineage precursors.

Hyaline cartilage regeneration by combined therapy of microfracture and long-term bone morphogenetic protein-2 delivery.

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Yang, Hee Seok; La, Wan-Geun; Bhang, Suk Ho; Kim, Hak-Jun; Im, Gun-Il; Lee, Haeshin; Park, Jung-Ho; Kim, Byung-Soo

2011-07-01

Microfracture of cartilage induces migration of bone-marrow-derived mesenchymal stem cells. However, this treatment often results in fibrocartilage regeneration. Growth factors such as bone morphogenetic protein (BMP)-2 induce the differentiation of bone-marrow-derived mesenchymal stem cells into chondrocytes, which can be used for hyaline cartilage regeneration. Here, we tested the hypothesis that long-term delivery of BMP-2 to cartilage defects subjected to microfracture results in regeneration of high-quality hyaline-like cartilage, as opposed to short-term delivery of BMP-2 or no BMP-2 delivery. Heparin-conjugated fibrin (HCF) and normal fibrin were used as carriers for the long- and short-term delivery of BMP-2, respectively. Rabbit articular cartilage defects were treated with microfracture combined with one of the following: no treatment, fibrin, short-term delivery of BMP-2, HCF, or long-term delivery of BMP-2. Eight weeks after treatment, histological analysis revealed that the long-term delivery of BMP-2 group (microfracture + HCF + BMP-2) showed the most staining with alcian blue. A biochemical assay, real-time polymerase chain reaction assay and Western blot analysis all revealed that the long-term delivery of BMP-2 group had the highest glucosaminoglycan content as well as the highest expression level of collagen type II. Taken together, the long-term delivery of BMP-2 to cartilage defects subjected to microfracture resulted in regeneration of hyaline-like cartilage, as opposed to short-term delivery or no BMP-2 delivery. Therefore, this method could be more convenient for hyaline cartilage regeneration than autologous chondrocyte implantation due to its less invasive nature and lack of cell implantation.

Treatment of bisphosphonate related osteonecrosis following root canal therapy at the 1-year follow-up: report of two cases

OpenAIRE

Kaptan, Figen; Kazandag, Meric Karapinar; Iseri, Ufuk

2013-01-01

Figen Kaptan,1 Meric Karapinar Kazandag,1 Ufuk Iseri21Yeditepe University, Faculty of Dentistry, Department of Endodontics, 2Department of Prosthodontics, Istanbul, TurkeyAbstract: The objective of this report was to use topical gaseous ozone as an adjunct to conventional treatment methods and to describe the multidisciplinary management of bisphosphonate associated bone necrosis, which developed following endodontic treatment. No complaints were noted by the patients at their 1-year follow-u...

Long-Term Symbolic Learning

National Research Council Canada - National Science Library

Kennedy, William G; Trafton, J. G

2007-01-01

What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

Pediatric polytrauma : Short-term and long-term outcomes

NARCIS (Netherlands)

vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial.

Science.gov (United States)

Sugano, Kentaro; Kontani, Teiji; Katsuo, Shinichi; Takei, Yoshinori; Sakaki, Nobuhiro; Ashida, Kiyoshi; Mizokami, Yuji; Asaka, Masahiro; Matsui, Shigeyuki; Kanto, Tatsuya; Soen, Satoshi; Takeuchi, Tsutomu; Hiraishi, Hideyuki; Hiramatsu, Naoki

2012-05-01

Low-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain. This multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice daily (n = 181) and followed up for 12 months or longer prospectively. The cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400-0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event. Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy.

Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

Science.gov (United States)

Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

2016-04-01

Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

Hormone replacement therapy: short-term versus long-term use.

Science.gov (United States)

Rousseau, Mary Ellen

2002-01-01

Midwives manage health care of women throughout the life cycle including prescribing hormone replacement therapy (HRT). This article presents a history of research on the use of HRT, as well as risks and benefits. Older research on the effects of HRT on heart disease, osteoporosis, and breast cancer is included. The results and recommendations of the Women's Health Initiative are examined.

A Comparison of Short- And Long-Term Family Therapy for Adolescent Anorexia Nervosa.

Science.gov (United States)

Lock, James; Agras, W. Stewart; Bryson, Susan; Kraemer, Helena C.

2005-01-01

Objective: Research suggests that family treatment for adolescents with anorexia nervosa may be effective. This study was designed to determine the optimal length of such family therapy. Method: Eighty-six adolescents (12-18 years of age) diagnosed with anorexia nervosa were allocated at random to either a short-term (10 sessions over 6 months) or…

Bisphosphonate Drug Holiday and Fracture Risk: A Population-Based Cohort Study.

Science.gov (United States)

Adams, Annette L; Adams, John L; Raebel, Marsha A; Tang, Beth T; Kuntz, Jennifer L; Vijayadeva, Vinutha; McGlynn, Elizabeth A; Gozansky, Wendolyn S

2018-03-12

Holidays from bisphosphonates (BPs) may help to prevent rare adverse events like atypical femoral fractures, but may be appropriate only if risk of osteoporosis-related fractures does not increase. Our objective was to compare the incidence of osteoporosis-related fractures among women who had a bisphosphonate (BP) holiday to those who continued use BPs. This retrospective cohort study, conducted within 4 Kaiser Permanente integrated health system regions, included 39,502 women aged ≥45 years with ≥3 years exposure to BP. Participants with a BP holiday (≥12 months with no use) were compared to persistent (use with ≥50% adherence) and non-persistent (use with holiday (n = 11,497), non-persistent user (n = 10,882), and persistent user groups (n = 17,123) were observed for 156,657 person-years. A total of 5,199 osteoporosis-related fractures (including 1,515 hip fractures and 2,147 vertebral fractures) were observed. Compared to the persistent use group, there was a slight difference in overall osteoporosis-related fracture risk (HR 0.92, 95% CI 0.84-0.99)and no difference in hip fracture risk (HR 0.95, 95% CI 0.83-1.10) for the BP holiday group. A slight reduction in risk of vertebral fracture was observed (HR 0.83, 95% CI 0.74-0.95). Compared to the non-persistent user group, the BP holiday group was at decreased risk for osteoporosis-related fractures (HR 0.71, 95% CI 0.65-0.79), vertebral fractures (HR 0.68, 95% CI 0.59-0.78), and hip fractures (HR 0.59; 95% CI 0.50-0.70). Women who undertake a BP holiday from BP of ≥12 months duration for any reason after ≥3 years of BP use do not appear to be at greater risk of osteoporosis-related fragility fracture, hip, or vertebral fractures compared to ongoing BP users. In our cohort, BP holiday remains a viable strategy for balancing the benefits and potential harms associated with long-term BP use. This article is protected by copyright. All rights reserved. This article is protected by copyright

Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

Science.gov (United States)

Pendergraft, William F.; Cortazar, Frank B.; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.

2014-01-01

Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. PMID:24626432

The long term effect and outcome of preoperative chemotherapy combined with radiation therapy for bladder cancer

International Nuclear Information System (INIS)

Nasu, Takahito; Nakane, Hiroshi; Kamata, Seiji; Mitsui, Hiroshi; Hayashida, Shigeaki; Shinohara, Youichi.

1996-01-01

The object of this study is to evaluate the efficacy of preoperative chemotherapy combined with radiation therapy for bladder cancer. A total of 44 patients with bladder cancer were treated by preoperative chemotherapy combined with radiation therapy between October, 1981 and December, 1986. Clinical stages included 4 patients in Ta, 25 in T1, 11 in T2, and 4 in T3. Each patient was treated twice with 15 gray of radiation to the small pelvic cavity and a chemotherapy combination of adriamycin, cis-platinum, tegaful, and peplomycin. The average observation time after the therapy was 83 month, with the maximum being 146 months. Complete remission was included in 5 patients, partial remission in 27, and no change in 12. Thus, the overall effective rate was 72.8%. Operations, selected by the results of the preoperative therapy, included transurethral resection on 28 patients, transurethral fulguration on 2, partial cystectomy on 4, resection of tumor on 4, and total cystectomy on 3. Operations were not performed on 2 patients and not allowed on 1 patient. The outcome during the long-term follow-up included cancer related deaths in 4 patients, and death resulting from other disorders in 9. The 5-year survival rates for superficial and invasive bladder cancer were 92.4%, and 83.9%, respectively. The 10-year survival rates for superficial and invasive bladder cancer were also 92.4% and 83.9%, respectively. The 3-year and 5-year non-recurrence rates for superficial bladder cancer were 75.8%, and 66.9% respectively, according to the Kaplan-Meier method. On the other hand, the 3-year and 5-year non-recurrence rates for invasive bladder cancer were both 73.8%. During the follow-up between 9 and 11 years, 3 upper tract tumor were diagnosed (2 ureteral cancer, and 1 renal pelvic cancer). We concluded that preoperative chemotherapy combined with radiation therapy may be effective for the treatment of bladder cancer. (author)

Evaluation of retinal nerve fiber layer thickness in vernal keratoconjunctivitis patients under long-term topical corticosteroid therapy.

Science.gov (United States)

Cingu, Abdullah Kursat; Cinar, Yasin; Turkcu, Fatih Mehmet; Sahinoglu-Keskek, Nedime; Sahin, Alparslan; Sahin, Muhammed; Yuksel, Harun; Caca, Ihsan

2014-09-01

The aim of this study was to evaluate the retinal nerve fiber layer (RNFL) thickness in vernal keratoconjunctivitis (VKC) patients who were under long-term topical corticosteroid therapy. Thirty-six eyes of 36 VKC patients with clear cornea and normal videokeratography and 40 eyes of 40 age- and gender-matched normal children were included in the study. Clinical and demographic characteristics of the patients were noted and detailed ophthalmological examination was performed. Visual acuity (VA), spherical equivalent (SE), axial length (AL) and RNFL thickness measurements were compared between the groups. To correct ocular magnification effect on RNFL, we used Littmann's formula. All VKC patients had history of topical corticosteroid use and the mean duration of the topical corticosteroid use was 23.8 ± 9.09 months. There was no significant difference between the groups in terms of intraocular pressure (IOP). VKC group had significantly worse VA, greater SE and AL and thinner mean global, superior and inferior RNFL thickness. There were significant negative correlations between the duration of topical corticosteroid use and the mean global, superior and temporal RNFL thickness in VKC group. After correction of magnification effect, VKC group still had thinner mean global, superior and inferior RNFL thickness, and significant difference between the groups in inferior RNFL thickness did not disappear. Significant RNFL thickness difference between the groups suggests a possible effect of long-term corticosteroid use in VKC patients. Because visual field (VF) analysis in pediatric patients is difficult to perform and IOP may be illusive, RNFL thickness measurements in addition to routine examinations in VKC patients may help clinicians in their practice.

Long-Term Reduction of Sacroiliac Joint Pain With Peripheral Nerve Stimulation.

Science.gov (United States)

Guentchev, Marin; Preuss, Christian; Rink, Rainer; Peter, Levente; Sailer, Martin H M; Tuettenberg, Jochen

2017-10-01

We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment. To investigate the long-term (up to 4 years) response rate of this novel treatment. Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient. Quality of life, pain, and patient satisfaction were assessed using the Oswestry Disability Index 2.0, Visual Analog Scale (VAS), and International Patient Satisfaction Index. Patients reported a pain reduction from 8.8 to 1.6 (VAS) at 1 year ( P < .001), and 13 of 14 patients (92.9%) rated the therapy as effective (International Patient Satisfaction Index score ≤ 2). At 2 years, average pain score was 1.9 ( P < .001), and 9 of 10 patients (90.0%) considered the treatment a success. At 3 years, 8 of 9 patients (88.9%) were satisfied with the treatment results, reporting an average VAS of 2.0 ( P < .005). At 4 years, 2 of 3 patients were satisfied with the treatment results. We have shown for the first time that PNS is a successful long-term therapy for SIJ pain. Copyright © 2017 by the Congress of Neurological Surgeons

Long-Term Outcomes of Cognitive-Behavioral Treatments for Posttraumatic Stress Disorder among Female Rape Survivors

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Resick, Patricia A.; Williams, Lauren F.; Suvak, Michael K.; Monson, Candice M.; Gradus, Jaimie L.

2012-01-01

Objective: We conducted a long-term follow-up (LTFU) assessment of participants from a randomized controlled trial comparing cognitive processing therapy (CPT) with prolonged exposure (PE) for posttraumatic stress disorder (PTSD). Competing hypotheses for positive outcomes (i.e., additional therapy, medication) were examined. Method:…

Physician personal characteristics influencing long-term treatment of patients with cardiovascular diseases

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Strokova E.V.

2013-06-01

Full Text Available The main purpose of the article is to identify the peculiarities of a doctor personality, affecting long-term therapy in patients with cardiovascular diseases. Materials and methods: To determine the type of temperament, the presence and intensity of the syndrome of emotional burnout and capacity for empathy therapists and cardiologists were asked to fill in a number of questionnaires. Each doctor had a group of patients contacting by telephone for a year after the discharge from the hospital. During the telephone contact, the patients were asked about the continuation of their therapy recommended in the hospital, the regularity of therapy, the frequency of absence, and the assessment of a physician by the patients. Results: 35 questionnaires were suitable for interpretation. Through one year after the discharge from the hospital it was able to contact with 147 patients, 18.4% (27 of patients completely stopped the treatment by recommended drugs. Positive assessment of physicians was associated with the continuation of the therapy by recommended drugs and regularity of drug taking (p=0,03. Patients assessed physicians positively more often in cases of low level of emotional state, high level of depersonalization (cynicism and the reduction of personal accomplishment (feeling of professional inefficiency in a doctor. Conclusion: Assessment of physicians by patients is reliably and significantly influenced by continuation of long-term therapy and regularity of drug taking.

Long-term impact of perfusion CT data after subarachnoid hemorrhage

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Mathys, Christian; Martens, Daniel; Reichelt, Dorothea C.; Caspers, Julian; Aissa, Joel; May, Rebecca; Antoch, Gerald; Turowski, Bernd [University Duesseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany); Haenggi, Daniel [University Duesseldorf, Medical Faculty, Department of Neurosurgery, Duesseldorf (Germany)

2013-11-15

Dynamic perfusion computed tomography (PCT) has been established as a diagnostic instrument for the detection of vasospasm after subarachnoid hemorrhage (SAH). The purpose of this study was to assess the prognostic impact of PCT parameters after SAH on the long-term outcome of patients. Three hundred twelve patients were retrospectively interrogated with a questionnaire 23.06 {+-} 14.33 months after spontaneous subarachnoid hemorrhage. The modified Rankin scale (mRS) was determined, respectively. Scheduled PCT data sets from the first days after ictus were available for all patients. The maximum mean transit time over several examinations per hemisphere (MTT{sub PEAK}) values were significantly correlated (p {<=} 0.001, r = 0.422) with the clinical long-term outcome (mRS). Corresponding to our linear regression analysis, MTT{sub PEAK} is the second most important regressor (behind clinical severity of the initial hemorrhage) for the prediction of long-term mRS. An MTT{sub PEAK} threshold of 3.98 s (identified by receiver operating characteristic analysis, area under the curve = 0.75) predicted an unfavorable long-term outcome (mRS {>=} 2) with a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 67.3, 74.3, 84.5, 52.1, and 69.6 %, respectively. The presented data corroborate the relevance of PCT data for the clinical long-term outcome of SAH patients. By identification of patients who are at risk for a bad outcome and may need escalation of therapy, risk-benefit analysis is supported. (orig.)

Long-term management of GERD in the elderly with pantoprazole

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Carlo Calabrese

2007-04-01

Full Text Available Carlo Calabrese, Anna Fabbri, Giulio Di FeboDepartment of Internal Medicine and Gastroenterology, University of Bologna, ItalyAbstract: The prevalence of gastroesophageal reflux disease (GERD increases with age and elderly are more likely to develop severe disease. Older patients often complain of less severe or frequent heartburn than younger patients and they may present with atypical symptoms such as dysphagia, weight loss, or extraesophageal symptoms. Proton pump inhibitors (PPIs are central in the management of GERD and are unchallenged with regards to their efficacy. They are considered safe and more effective than histamine receptor antagonists for healing esophagitis and for preventing its recurrence using a long term maintenance treatment. PPI have minimal side effects and few slight drug interactions and are considered safe for long term treatment. Pantoprazole is significantly effective both for acute and long-term treatment with excellent control of relapse and symptoms. It is well tolerated even for long-term therapy and its tolerability is optimal. Pantoprazole shows to have minimal interactions with other drugs because of a lower affinity for cytocrome P450 than older PPIs. Although the majority of elderly has concomitant illnesses and receive other drugs, this does not adversely effect the efficacy of pantoprazole because of its pharmacokinetics, which are independent of patient age. Clinical practice suggests that a low dose maintenance of PPIs should be used in older patients with GERD.Keywords: GERD, long-term management, pantoprazole, safety, efficacy, tolerability

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

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Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo; Ema, Akira; Naito, Masanori; Watanabe, Masahiko, E-mail: midoris@med.kitasato-u.ac.jp

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.

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Lee, Young Mok; Conlon, Thomas J; Specht, Andrew; Coleman, Kirsten E; Brown, Laurie M; Estrella, Ana M; Dambska, Monika; Dahlberg, Kathryn R; Weinstein, David A

2018-05-25

Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy. A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed. Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2-4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose. rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.

THE LIS STUDY (LYUBERTSY STUDY ON MORTALITY RATE IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION. EVALUATION OF DRUG THERAPY. PART 2. INFLUENCE OF PREVIOUS DRUG TREATMENT ON LONG-TERM LIFE PROGNOSIS

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S. Yu. Martsevich

2015-12-01

Full Text Available Aim. To evaluate drug therapy received by patients who had survived acute myocardial infarction (AMI in the framework of the AMI register (the “LIS” study and estimate this therapy influence on long-term outcomes of the disease. Material and methods. The total of 961 patients of 1133 enrolled in the “LIS” study , were discharged from hospital. 191 patients had died during follow-up. 632 patients (who had survived and consented to visit out-patient clinic underwent repeated examination (median of follow-up 1.6 [1.0; 2.4] years. Data about treatment before and during AMI were received from patient’s charts; data about treatment after AMI were obtained from out-patient medical records. Results. Before reference AMI only a small number of the patients received the main drug groups (antiplatelet agents, β-blockers, ACE inhibitors, statins, at that ACE inhibitors were prescribed more often than the others. Use of β-blockers and ACE inhibitors before reference AMI significantly improved long-term life prognosis [relative risk (RR 0.70 and 0.66, respectively]. Rate of the main drug groups prescribed in hospital was rather high with the exception of thrombolytics (less than 10%. Thrombolytics, β-blockers and antiplatelet agents prescribed in hospital significantly improved long-term life prognosis of patients (RR 0.42, 0.65 and 0.58 respectively. At the second visit (according to data of out-patient medical records rate of antiplatelet agents, ACE inhibitors, β-blockers and statins prescription exceeded 60%. Conclusion. Very low prevalence of adequate drug therapy preceding AMI determines high mortality rate among survived acute stage of myocardial infarction patients in long-term period.

Magnesium therapy after aneurysmal subarachnoid haemorrhage a dose-finding study for long term treatment