Hubbard Alan E; Dorsey Grant; Gupta Vinay; Rosenthal Philip J; Greenhouse Bryan
Abstract Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary elec...
The counterfeiting of anti-malarials represents a form of attack on global public health in which fake and substandard anti-malarials serve as de facto weapons of mass destruction, particularly in resource-constrained endemic settings, where malaria causes nearly 660,000 preventable deaths and threatens millions of lives annually. It has been estimated that fake anti-malarials contribute to nearly 450,000 preventable deaths every year. This crime against humanity is often underestimated or ignored. This study attempts to describe and characterize the direct and indirect effects of counterfeit anti-malarials on public health, clinical care and socio-economic conditions. A search was performed using key databases, WHO documents, and English language search engines. Of 262 potential articles that were identified using a fixed set of criteria, a convenience sample of 105 appropriate articles was selected for this review. Artemisinin-based combination therapy (ACT) is an important tool in the fight against malaria, but a sizable number of patients are unable to afford to this first-line treatment. Consequently, patients tend to procure cheaper anti-malarials, which may be fake or substandard. Forensic palynology reveals that counterfeits originate in Asia. Fragile drug regulations, ineffective law-enforcement agencies and corruption further burden ailing healthcare facilities. Substandard/fake anti-malarials can cause (a) economic sabotage; (b) therapeutic failure; (c) increased risk of the emergence and spread of resistant strains of Plasmodium falciparum and Plasmodium vivax; (d) an undermining of trust/confidence in healthcare stakeholders/systems; and, (e) serious side effects or death. Combating counterfeit anti-malarials is a complex task due to limited resources and poor techniques for the detection and identification of fake anti-malarials. This situation calls for sustainable, global, scientific research and policy change. Further, responsible stakeholders in
Full Text Available Abstract Background National malaria control programmes must deal with the complex process of changing national malaria treatment guidelines, often without guidance on the process of change. Selecting a replacement drug is only one issue in this process. There is a paucity of literature describing successful malaria treatment policy changes to help guide control programs through this process. Objectives To understand the wider context in which national malaria treatment guidelines were formulated in a specific country (Peru. Methods Using qualitative methods (individual and focus group interviews, stakeholder analysis and a review of documents, a retrospective analysis of the process of change in Peru's anti-malarial treatment policy from the early 1990's to 2003 was completed. Results The decision to change Peru's policies resulted from increasing levels of anti-malarial drug resistance, as well as complaints from providers that the drugs were no longer working. The context of the change occurred in a time in which Peru was changing national governments, which created extreme challenges in moving the change process forward. Peru utilized a number of key strategies successfully to ensure that policy change would occur. This included a having the process directed by a group who shared a common interest in malaria and who had long-established social and professional networks among themselves, b engaging in collaborative teamwork among nationals and between nationals and international collaborators, c respect for and inclusion of district-level staff in all phases of the process, d reliance on high levels of technical and scientific knowledge, e use of standardized protocols to collect data, and f transparency. Conclusion Although not perfectly or fully implemented by 2003, the change in malaria treatment policy in Peru occurred very quickly, as compared to other countries. They identified a problem, collected the data necessary to justify the
Hubbard Alan E
Full Text Available Abstract Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary electrophoresis from randomized trials of artemether-lumefantrine (AL vs. dihydroartemisinin-piperaquine (DP performed in two areas of Uganda: Kanungu, where transmission is moderate, and Apac, where transmission is very high. Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes. Results Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites. There was only moderate agreement between classification of outcomes with the two methods in Kanungu (kappa = 0.66 and poor agreement in Apac (kappa = 0.24. Overall efficacy results were similar when using gel vs. capillary methods in Kanungu (42-day risk of treatment failure for AL: 6.9% vs. 5.5%, p = 0.4; DP 2.4% vs. 2.9%, p = 0.5. However, the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac (risk of treatment failure for AL: 17.0% vs. 10.7%, p = 0.02; DP: 8.5% vs. 3.4%, p = 0.03. Risk differences between AL and DP were not significantly different whether gel or capillary methods were used. Conclusions Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity. Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible. In areas of moderate transmission
Gupta, Vinay; Dorsey, Grant; Hubbard, Alan E; Rosenthal, Philip J; Greenhouse, Bryan
Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Samples were genotyped using both gel and capillary electrophoresis from randomized trials of artemether-lumefantrine (AL) vs. dihydroartemisinin-piperaquine (DP) performed in two areas of Uganda: Kanungu, where transmission is moderate, and Apac, where transmission is very high. Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes. Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites. There was only moderate agreement between classification of outcomes with the two methods in Kanungu (kappa = 0.66) and poor agreement in Apac (kappa = 0.24). Overall efficacy results were similar when using gel vs. capillary methods in Kanungu (42-day risk of treatment failure for AL: 6.9% vs. 5.5%, p = 0.4; DP 2.4% vs. 2.9%, p = 0.5). However, the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac (risk of treatment failure for AL: 17.0% vs. 10.7%, p = 0.02; DP: 8.5% vs. 3.4%, p = 0.03). Risk differences between AL and DP were not significantly different whether gel or capillary methods were used. Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity. Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible. In areas of moderate transmission, gel electrophoresis appears adequate to estimate comparative
market shows favourable progress towards replacing artemisinin monotherapies with ACT, the widespread use of drug cocktails to treat malaria is a barrier to effective case management. Significant achievements have been made in availability of diagnostic testing and effective treatment in the public and private sectors. However, interventions to improve case management are urgently required, particularly in the private sector. Evidence-based interventions that target provider and consumer behaviour are needed to support uptake of diagnostic testing and treatment with full-course first-line anti-malarials.
Shewchuk, Tanya; O'Connell, Kathryn A; Goodman, Catherine; Hanson, Kara; Chapman, Steven; Chavasse, Desmond
Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012.ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate findings widely for decision
Full Text Available Abstract Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT and malaria diagnostics including rapid diagnostic tests (RDTs. To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the
Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate
Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug
Full Text Available Abstract Background Intermittent preventive treatment in infants (IPTi with sulphadoxine-pyrimethamine (SP reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials. Methods Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests. Results Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort. Conclusion The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low. Trial registration Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial and NCT ID # 00167843 (Lambaréné Trial, http://www.clinicaltrials.gov.
had taken chloroquine: no other anti-malarial drugs were involved . ... and angio-oedema have been described. Itching without a ... 15mg/L the risk of permanent visual damage and cardiac dysrhythmias is ... to use an alternative method.
O'Connell Kathryn A
Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC, Madagascar, Nigeria, Uganda and Zambia. Methods Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. Results 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets as compared to first-line quality-assured ACT ( Conclusions These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria.
Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial. Methods To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of the Webuye Health and Demographic Surveillance Site in the Bungoma East District of western Kenya. Results Most of the medicine retailers surveyed (65% were able to identify artemether-lumefantrine (AL as the Kenyan Ministry of Health recommended first-line anti-malarial therapy for uncomplicated malaria. Retailers who correctly identified this treatment were also more likely to recommend AL to adult and paediatric customers. However, the proportion of medicine retailers who recommend the correct treatment is disappointingly low. Only 48% would recommend AL to adults, and 37% would recommend it to children. It was discovered that customer demand has an influence on retailer behaviour. Retailer training and education were found to be correlated with anti-malarial drug knowledge, which in turn is correlated with dispensing practices. Medicine retailer behaviour, including patient referral practice and dispensing practices, are also correlated with knowledge of the first-line anti-malarial medication. The Kenya Ministry of Health guidelines were found to influence retailer drug stocking and dispensing behaviours. Conclusion Most medicine retailers could identify the recommended first-line treatment for uncomplicated malaria, but the percentage that could
Full Text Available Abstract Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers and illicit (market and street vendors, shops sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50% chloroquine, 10/77 (13% pyrimethamine-sulphadoxine, 9/77 (12% quinine, 6/77 (8% amodiaquine, 9/77 (12% artesunate, and 4/77 (5% artemether-lumefantrine. 32/77 (42% drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6% and 27/30 (90.0% samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the
Amuasi, John H; Diap, Graciela; Blay-Nguah, Samuel; Boakye, Isaac; Karikari, Patrick E; Dismas, Baza; Karenzo, Jeanne; Nsabiyumva, Lievin; Louie, Karly S; Kiechel, Jean-René
Malaria is the leading cause of morbidity and mortality in post-conflict Burundi. To counter the increasing challenge of anti-malarial drug resistance and improve highly effective treatment Burundi adopted artesunate-amodiaquine (AS-AQ) as first-line treatment for uncomplicated Plasmodium falciparum malaria and oral quinine as second-line treatment in its national treatment policy in 2003. Uptake of this policy in the public, private and non-governmental (NGO) retail market sectors of Burundi is relatively unknown. This study was conducted to evaluate access to national policy recommended anti-malarials. Adapting a standardized methodology developed by Health Action International/World Health Organization (HAI/WHO), a cross-sectional survey of 70 (24 public, 36 private, and 10 NGO) medicine outlets was conducted in three regions of Burundi, representing different levels of transmission of malaria. The availability on day of the survey, the median prices, and affordability (in terms of number of days' wages to purchase treatment) of AS-AQ, quinine and other anti-malarials were calculated. Anti-malarials were stocked in all outlets surveyed. AS-AQ was available in 87.5%, 33.3%, and 90% of public, private, and NGO retail outlets, respectively. Quinine was the most common anti-malarial found in all outlet types. Non-policy recommended anti-malarials were mainly found in the private outlets (38.9%) compared to public (4.2%) and NGO (0%) outlets. The median price of a course of AS-AQ was US$0.16 (200 Burundi Francs, FBu) for the public and NGO markets, and 3.5-fold higher in the private sector (US$0.56 or 700 FBu). Quinine tablets were similarly priced in the public (US$1.53 or 1,892.50 FBu), private and NGO sectors (both US$1.61 or 2,000 FBu). Non-policy anti-malarials were priced 50-fold higher than the price of AS-AQ in the public sector. A course of AS-AQ was affordable at 0.4 of a day's wage in the public and NGO sectors, whereas, it was equivalent to 1.5 days worth
Eberlin Marcos N
Full Text Available Abstract Background To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Methods Crude extract (CE was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7 and -resistant (S20 strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. Results At non-toxic concentrations, the 100% ethanolic (F4 and 50% methanolic (F5 fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. Conclusions The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.
Full Text Available Abstract Background The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance. Methods We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance. Results In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population. Conclusions The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.
Pell, Christopher; Tripura, Rupam; Nguon, Chea; Cheah, Phaikyeong; Davoeung, Chan; Heng, Chhouen; Dara, Lim; Sareth, Ma; Dondorp, Arjen; von Seidlein, Lorenz; Peto, Thomas J
Mass anti-malarial administration has been proposed as a key component of the Plasmodium falciparum malaria elimination strategy in the Greater Mekong sub-Region. Its effectiveness depends on high levels of coverage in the target population. This article explores the factors that influenced mass anti-malarial administration coverage within a clinical trial in Battambang Province, western Cambodia. Qualitative data were collected through semi-structured interviews and focus group discussions with villagers, in-depth interviews with study staff, trial drop-outs and refusers, and observations in the communities. Interviews were audio-recorded, transcribed and translated from Khmer to English for qualitative content analysis using QSR NVivo. Malaria was an important health concern and villagers reported a demand for malaria treatment. This was in spite of a fall in incidence over the previous decade and a lack of familiarity with asymptomatic malaria. Participants generally understood the overall study aim and were familiar with study activities. Comprehension of the study rationale was however limited. After the first mass anti-malarial administration, seasonal health complaints that participants attributed to the anti-malarial as "side effects" contributed to a decrease of coverage in round two. Staff therefore adapted the community engagement approach, bringing to prominence local leaders in village meetings. This contributed to a subsequent increase in coverage. Future mass anti-malarial administration must consider seasonal disease patterns and the importance of local leaders taking prominent roles in community engagement. Further research is needed to investigate coverage in scenarios that more closely resemble implementation i.e. without participation incentives, blood sampling and free healthcare.
Linares, María; Viera, Sara; Crespo, Benigno; Franco, Virginia; Gómez-Lorenzo, María G; Jiménez-Díaz, María Belén; Angulo-Barturen, Íñigo; Sanz, Laura María; Gamo, Francisco-Javier
The emergence of Plasmodium falciparum resistance to artemisinins threatens to undermine the effectiveness of artemisinin-based combination anti-malarial therapy. Developing suitable drugs to replace artemisinins requires the identification of new compounds that display rapid parasite killing kinetics. However, no current methods fully meet the requirements to screen large compound libraries for candidates with such properties. This study describes the development and validation of an in vitro parasite viability fast assay for identifying rapidly parasiticidal anti-malarial drugs. Parasite killing kinetics were determined by first culturing unlabelled erythrocytes with P. falciparum in the presence of anti-malarial drugs for 24 or 48 h. After removing the drug, samples were added to erythrocytes pre-labelled with intracellular dye to allow their subsequent identification. The ability of viable parasites to re-establish infection in labelled erythrocytes could then be detected by two-colour flow cytometry after tagging of parasite DNA. Thus, double-stained erythrocytes (with the pre-labelled intracellular dye and the parasite DNA dye) result only after establishment of new infections by surviving parasites. The capacity of the test anti-malarial drugs to eliminate viable parasites within 24 or 48 h could, therefore, be determined. The parasite viability fast assay could be completed within 48 h following drug treatment and distinguished between rapidly parasiticidal anti-malarial drugs versus those acting more slowly. The assay was validated against ten standard anti-malarial agents with known properties and results correlated well with established methods. An abbreviated assay, suitable for adaption to medium-high throughput screening, was validated and applied against a set of 20 compounds retrieved from the publically available Medicines for Malaria Venture 'Malaria Box'. The quantification of new infections to determine parasite viability offers important
Duah, Nancy O; Matrevi, Sena A; de Souza, Dziedzom K; Binnah, Daniel D; Tamakloe, Mary M; Opoku, Vera S; Onwona, Christiana O; Narh, Charles A; Quashie, Neils B; Abuaku, Benjamin; Duplessis, Christopher; Kronmann, Karl C; Koram, Kwadwo A
With the introduction of artemisinin-based combination therapy (ACT) in 2005, monitoring of anti-malarial drug efficacy, which includes the use of molecular tools to detect known genetic markers of parasite resistance, is important for first-hand information on the changes in parasite susceptibility to drugs in Ghana. This study investigated the Plasmodium falciparum multidrug resistance gene (pfmdr1) copy number, mutations and the chloroquine resistance transporter gene (pfcrt) mutations in Ghanaian isolates collected in seven years to detect the trends in prevalence of mutations. Archived filter paper blood blots collected from children aged below five years with uncomplicated malaria in 2003-2010 at sentinel sites were used. Using quantitative real-time polymerase chain reaction (qRT-PCR), 756 samples were assessed for pfmdr1 gene copy number. PCR and restriction fragment length polymorphism (RFLP) were used to detect alleles of pfmdr1 86 in 1,102 samples, pfmdr1 184, 1034, 1042 and 1246 in 832 samples and pfcrt 76 in 1,063 samples. Merozoite surface protein 2 (msp2) genotyping was done to select monoclonal infections for copy number analysis. The percentage of isolates with increased pfmdr1 copy number were 4, 27, 9, and 18% for 2003-04, 2005-06, 2007-08 and 2010, respectively. Significant increasing trends for prevalence of pfmdr1 N86 (×(2) = 96.31, p resistance has been reported. The decreasing trend in the prevalence of chloroquine resistance markers after change of treatment policy presents the possibility for future introduction of chloroquine as prophylaxis for malaria risk groups such as children and pregnant women in Ghana.
O'Connell, Kathryn A; Gatakaa, Hellen; Poyer, Stephen; Njogu, Julius; Evance, Illah; Munroe, Erik; Solomon, Tsione; Goodman, Catherine; Hanson, Kara; Zinsou, Cyprien; Akulayi, Louis; Raharinjatovo, Jacky; Arogundade, Ekundayo; Buyungo, Peter; Mpasela, Felton; Adjibabi, Chérifatou Bello; Agbango, Jean Angbalu; Ramarosandratana, Benjamin Fanomezana; Coker, Babajide; Rubahika, Denis; Hamainza, Busiku; Chapman, Steven; Shewchuk, Tanya; Chavasse, Desmond
Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector
Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu
Rogers William O
Full Text Available Abstract Background Chloroquine-resistant Plasmodium falciparum was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated P. falciparum infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for Plasmodium vivax. Methods In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for P. vivax and chloroquine/sulphadoxine-pyrimethamine for P. falciparum infections. Results The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between P. falciparum and P. vivax. Twenty percent and 23% of participants with patent P. vivax and P. falciparum parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with P. vivax predominating. Among individuals participating in the clinical trial, the 28-day chloroquine P. vivax cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine P. falciparum cure rate was 97%. The single treatment failure, confirmed by merozoite surface protein-2 genotyping, was classified as a day 28 late parasitological treatment failure. All P. falciparum isolates carried the Thr-76 pfcrt mutant allele and the double Asn-108 + Arg-59 dhfr mutant alleles. Dhps mutant alleles were not detected in the study sample. Conclusion Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study
Lussiana, Cristina; Floridia, Marco; Martinho do Rosário, Joana; Fortes, Filomeno; Allan, Richard
Artemisinin-based combination therapies (ACTs) against malaria are subsidized in many African countries, but the impact of subsidy programs in reducing the sales of concomitantly available antimalarial monotherapies is poorly defined. Data from The MENTOR initiative, that introduced subsidized artemether-lumefantrine (sAL) in the private sector of Huambo province, Angola, were used. The main response variable was represented by sales of sAL and of monotherapies, measured as number of treatment courses. Sales in private pharmacies of sAL and four antimalarial monotherapies between 2009 and 2013 were organized in four time-periods, and analyzed using generalized linear models for repeated measures. A secondary analysis evaluated changes in relative market share. We analyzed data from 34 pharmacies at four time points, taken from a larger survey that involved 165 pharmacies between June 2009 and March 2013. The sAL, following its introduction, became the dominant antimalarial treatment in the private sector, usually exceeding the total sales of all antimalarial monotherapies combined (1480/2800 total treatment courses, 52.8% of all sales in March 2013). Sales of monotherapies decreased significantly, but did not stop, representing 36.7% (1028/2800) of sales at the end of the survey. Subsidized ACTs can attain rapidly a high relative market share. Their introduction reduced, but did not eliminate the demand for less effective monotherapies, that might favor parasite resistance. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: email@example.com.
Full Text Available Abstract Background The aim of this study was to evaluate the clinical outcome after seven-day artesunate monotherapy for uncomplicated Plasmodium falciparum malaria in Yingjiang County along the China-Myanmar border and investigate genetic polymorphisms in the P. falciparum chloroquine-resistance transporter (pfcrt, multidrug resistance 1 (pfmdr1, dihydrofolate reductase (pfdhfr, dihydropteroate synthase (pfdhps and ATPase (pfatp6 genes. Methods Patients ≥ one year of age with fever (axillary temperature ≥37.5°C or history of fever and P. falciparum mono-infection were included. Patients received anti-malarial treatment with artesunate (total dose of 16 mg/kg over seven days by directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed based on clinical and parasitological outcomes. Treatment failure was defined as recrudescence of the original parasite and distinguished with new infection confirmed by PCR. Analysis of gene mutation and amplification were performed by nested polymerase chain reaction. Results Sixty-five patients were enrolled; 10 withdrew from the study, and six were lost to follow-up. All but two patients demonstrated adequate clinical and parasitological response; 12 had detectable parasitaemia on day 3. These two patients were confirmed to be new infection by PCR. The efficacy of artesunate was 95.9%. The pfcrt mutation in codon 76 was found in all isolates (100%, and mutations in codons 71 and 72 were found in 4.8% of parasite isolates. No mutation of pfmdr1 (codons 86 or 1246 was found. Among all samples, 5.1% were wild type for pfdhfr, whereas the other samples had mutations in four codons (51, 59, 108 and 164, and mutations in pfdhps (codons 436, 437, 540 and 581 were found in all isolates. No samples had mutations in pfatp6 codons 623 or 769, but two new mutations (N683K and R756K were found in 4.6% and 9.2% of parasite isolates, respectively. Conclusion Plasmodium
Dondorp Arjen M
Full Text Available Abstract Background Most malaria-endemic countries are implementing a change in anti-malarial drug policy to artemisinin-based combination therapy (ACT. The impact of different drug choices and implementation strategies is uncertain. Data from many epidemiological studies in different levels of malaria endemicity and in areas with the highest prevalence of drug resistance like borders of Thailand are certainly valuable. Formulating an appropriate dynamic data-driven model is a powerful predictive tool for exploring the impact of these strategies quantitatively. Methods A comprehensive model was constructed incorporating important epidemiological and biological factors of human, mosquito, parasite and treatment. The iterative process of developing the model, identifying data needed, and parameterization has been taken to strongly link the model to the empirical evidence. The model provides quantitative measures of outcomes, such as malaria prevalence/incidence and treatment failure, and illustrates the spread of resistance in low and high transmission settings. The model was used to evaluate different anti-malarial policy options focusing on ACT deployment. Results The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and treatment failure is the main force driving the spread of drug resistance. In low transmission settings, ACT slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. In the high transmission settings, however, drug resistance is driven by the proportion of the human population with a residual drug level, which gives resistant parasites some survival advantage. The spread of drug resistance could be slowed down by controlling presumptive drug use and avoiding the use of combination therapies containing drugs with
Amuasi, John H; Diap, Graciela; Nguah, Samuel Blay; Karikari, Patrick; Boakye, Isaac; Jambai, Amara; Lahai, Wani Kumba; Louie, Karly S; Kiechel, Jean-Rene
Malaria remains the leading burden of disease in post-conflict Sierra Leone. To overcome the challenge of anti-malarial drug resistance and improve effective treatment, Sierra Leone adopted artemisinin-combination therapy artesunate-amodiaquine (AS+AQ) as first-line treatment for uncomplicated P. falciparum malaria. Other national policy anti-malarials include artemether-lumefantrine (AL) as an alternative to AS+AQ, quinine and artemether for treatment of complicated malaria; and sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment (IPTp). This study was conducted to evaluate access to national policy recommended anti-malarials. A cross-sectional survey of 127 medicine outlets (public, private and NGO) was conducted in urban and rural areas. The availability on the day of the survey, median prices, and affordability policy and available non-policy anti-malarials were calculated. Anti-malarials were stocked in 79% of all outlets surveyed. AS+AQ was widely available in public medicine outlets; AL was only available in the private and NGO sectors. Quinine was available in nearly two-thirds of public and NGO outlets and over one-third of private outlets. SP was widely available in all outlets. Non-policy anti-malarials were predominantly available in the private outlets. AS+AQ in the public sector was widely offered for free. Among the anti-malarials sold at a cost, the same median price of a course of AS+AQ (US$1.56), quinine tablets (US$0.63), were found in both the public and private sectors. Quinine injection had a median cost of US$0.31 in the public sector and US$0.47 in the private sector, while SP had a median cost of US$0.31 in the public sector compared to US$ 0.63 in the private sector. Non-policy anti-malarials were more affordable than first-line AS+AQ in all sectors. A course of AS+AQ was affordable at nearly two days' worth of wages in both the public and private sectors.
Swain Bijay K
Full Text Available Abstract Background Herbal extracts of Andrographis paniculata (AP and Hedyotis corymbosa (HC are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20 and resistant (MRC-pf-303 strains of Plasmodium falciparum for their anti-malarial activity. Methods Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. Results The 50% inhibitory concentration (IC50 of AP (7.2 μg/ml was found better than HC (10.8 μg/ml. Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC and their individual synergism with curcumin (AP+CUR, HC+CUR were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. Conclusion Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.
Mishra, Kirti; Dash, Aditya P; Swain, Bijay K; Dey, Nrisingha
Background Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity. Methods Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. Results The 50% inhibitory concentration (IC50) of AP (7.2 μg/ml) was found better than HC (10.8 μg/ml). Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC) and their individual synergism with curcumin (AP+CUR, HC+CUR) were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. Conclusion Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs. PMID:19216765
Masand, Vijay H; Toropov, Andrey A; Toropova, Alla P; Mahajan, Devidas T
In the present study, predictive quantitative structure - activity relationship (QSAR) models for anti-malarial activity of 4-aminoquinolines have been developed. CORAL, which is freely available on internet (http://www.insilico.eu/coral), has been used as a tool of QSAR analysis to establish statistically robust QSAR model of anti-malarial activity of 4-aminoquinolines. Six random splits into the visible sub-system of the training and invisible subsystem of validation were examined. Statistical qualities for these splits vary, but in all these cases, statistical quality of prediction for anti-malarial activity was quite good. The optimal SMILES-based descriptor was used to derive the single descriptor based QSAR model for a data set of 112 aminoquinolones. All the splits had r(2)> 0.85 and r(2)> 0.78 for subtraining and validation sets, respectively. The three parametric multilinear regression (MLR) QSAR model has Q(2) = 0.83, R(2) = 0.84 and F = 190.39. The anti-malarial activity has strong correlation with presence/absence of nitrogen and oxygen at a topological distance of six.
Ringsted, Frank M; Massawe, Isolide S; Lemnge, Martha M
women depend on SP for Intermittent Preventive Treatment (IPTp) during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform...... practice, the saleability of ACT was negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated in the national anti-malarial policy. It is a major reason for concern that such drug-pressure in the community equals de facto intermittent presumptive treatment. In an area where SP drug...
Full Text Available Abstract Background Despite a significant reduction in the number of malaria cases in Guyana and Suriname, this disease remains a major problem in the interior of both countries, especially in areas with gold mining and logging operations, where malaria is endemic. National malaria control programmes in these countries provide treatment to patients with medicines that are procured and distributed through regulated processes in the public sector. However, availability to medicines in licensed facilities (private sector and unlicensed facilities (informal sector is common, posing the risk of access to and use of non-recommended treatments and/or poor quality products. Methods To assess the quality of circulating anti-malarial medicines, samples were purchased in the private and informal sectors of Guyana and Suriname in 2009. The sampling sites were selected based on epidemiological data and/or distance from health facilities. Samples were analysed for identity, content, dissolution or disintegration, impurities, and uniformity of dosage units or weight variation according to manufacturer, pharmacopeial, or other validated method. Results Quality issues were observed in 45 of 77 (58% anti-malarial medicines sampled in Guyana of which 30 failed visual & physical inspection and 18 failed quality control tests. The proportion of monotherapy and ACT medicines failing quality control tests was 43% (13/30 and 11% (5/47 respectively. A higher proportion of medicines sampled from the private sector 34% (11/32 failed quality control tests versus 16% (7/45 in the informal sector. In Suriname, 58 medicines were sampled, of which 50 (86% were Artecom®, the fixed-dose combination of piperaquine-dihydroartemisinin-trimethoprim co-blistered with a primaquine phosphate tablet. All Artecom samples were found to lack a label claim for primaquine, thus failing visual and physical inspection. Conclusions The findings of the studies in both countries point to
Evans, Lawrence; Coignez, Veerle; Barojas, Adrian; Bempong, Daniel; Bradby, Sanford; Dijiba, Yanga; James, Makeida; Bretas, Gustavo; Adhin, Malti; Ceron, Nicolas; Hinds-Semple, Alison; Chibwe, Kennedy; Lukulay, Patrick; Pribluda, Victor
Despite a significant reduction in the number of malaria cases in Guyana and Suriname, this disease remains a major problem in the interior of both countries, especially in areas with gold mining and logging operations, where malaria is endemic. National malaria control programmes in these countries provide treatment to patients with medicines that are procured and distributed through regulated processes in the public sector. However, availability to medicines in licensed facilities (private sector) and unlicensed facilities (informal sector) is common, posing the risk of access to and use of non-recommended treatments and/or poor quality products. To assess the quality of circulating anti-malarial medicines, samples were purchased in the private and informal sectors of Guyana and Suriname in 2009. The sampling sites were selected based on epidemiological data and/or distance from health facilities. Samples were analysed for identity, content, dissolution or disintegration, impurities, and uniformity of dosage units or weight variation according to manufacturer, pharmacopeial, or other validated method. Quality issues were observed in 45 of 77 (58%) anti-malarial medicines sampled in Guyana of which 30 failed visual & physical inspection and 18 failed quality control tests. The proportion of monotherapy and ACT medicines failing quality control tests was 43% (13/30) and 11% (5/47) respectively. A higher proportion of medicines sampled from the private sector 34% (11/32) failed quality control tests versus 16% (7/45) in the informal sector. In Suriname, 58 medicines were sampled, of which 50 (86%) were Artecom®, the fixed-dose combination of piperaquine-dihydroartemisinin-trimethoprim co-blistered with a primaquine phosphate tablet. All Artecom samples were found to lack a label claim for primaquine, thus failing visual and physical inspection. The findings of the studies in both countries point to significant problems with the quality of anti-malarial medicines
Full Text Available Abstract Background Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment. The aim was to assess the effect of implementing malaria rapid diagnostic tests (mRDTs on prescription of anti-malarials in urban Tanzania. Methods The design was a prospective collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in randomly selected health facilities (HF in Dar es Salaam, Tanzania. The participants were all clinicians and their patients in the above health facilities. The intervention consisted of training and introduction of mRDTs in all three hospitals and in six HF. Three HF without mRDTs were selected as matched controls. The use of routine mRDT and treatment upon result was advised for all patients complaining of fever, including children under five years of age. The main outcome measures were: (1 anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention; (2 anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after mRDT implementation. Results Based on routine statistics, the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68% (95%CI 57-80 in intervention and 32% (9-54 in control HF. For quinine vials, the reduction was 63% (54-72 in intervention and an increase of 2.49 times (1.62-3.35 in control HF. Before-and-after cross-sectional surveys showed a similar decrease from 75% to 20% in the proportion of patients receiving anti-malarial treatment (Risk ratio 0.23, 95%CI 0.20-0.26. The cluster randomized analysis showed a considerable difference of anti-malarial prescription between intervention HF (22% and control HF (60% (Risk ratio 0.30, 95%CI 0.14-0.70. Adherence to test result was excellent since only 7% of negative patients received an anti-malarial. However, antibiotic
Alebie, Getachew; Urga, Befikadu; Worku, Amha
Ethiopia is endowed with abundant medicinal plant resources and traditional medicinal practices. However, available research evidence on indigenous anti-malarial plants is highly fragmented in the country. The present systematic review attempted to explore, synthesize and compile ethno-medicinal research evidence on anti-malarial medicinal plants in Ethiopia. A systematic web search analysis and review was conducted on research literature pertaining to medicinal plants used for traditional malaria treatment in Ethiopia. Data were collected from a total of 82 Ethiopian studies meeting specific inclusion criteria including published research articles and unpublished thesis reports. SPSS Version 16 was used to summarize relevant ethno-botanical/medicinal information using descriptive statistics, frequency, percentage, tables, and bar graphs. A total of 200 different plant species (from 71 families) used for traditional malaria treatment were identified in different parts of Ethiopia. Distribution and usage pattern of anti-malarial plants showed substantial variability across different geographic settings. A higher diversity of anti-malarial plants was reported from western and southwestern parts of the country. Analysis of ethno-medicinal recipes indicated that mainly fresh leaves were used for preparation of remedies. Decoction, concoction and eating/chewing were found to be the most frequently employed herbal remedy preparation methods. Notably, anti-malarial herbal remedies were administered by oral route. Information on potential side effects of anti-malarial herbal preparations was patchy. However, some anti-malarial plants were reported to have potentially serious side effects using different local antidotes and some specific contra-indications. The study highlighted a rich diversity of indigenous anti-malarial medicinal plants with equally divergent herbal remedy preparation and use pattern in Ethiopia. Baseline information gaps were observed in key geographic
Arise Rotimi Olusanya
Full Text Available So far, some prospective metal-based anti-malarial drugs have been developed. The mechanochemical synthesis and characterization of Zn (II complex with amodiaquine and its anti-malarial efficacy on Plasmodium berghei-infected mice and safety evaluation were described in this study.
Huang, Yangmu; Pan, Ke; Peng, Danlu; Stergachis, Andy
While China is a major manufacturer of artemisinin and its derivatives, it lags as a global leader in terms of the total export value of anti-malarial drugs as finished pharmaceutical products ready for marketing and use by patients. This may be due to the limited number of World Health Organization (WHO) prequalified anti-malarial drugs from China. Understanding the reasons for the slow progress of WHO prequalification (PQ) in China can help improve the current situation and may lead to greater efforts in malaria eradication by Chinese manufacturers. In-depth interviews were conducted in China between November 2014 and December 2016. A total of 26 key informants from central government agencies, pharmaceutical companies, universities, and research institutes were interviewed, all of which had current or previous experience overseeing or implementing anti-malarial research and development in China. Chinese anti-malarial drugs that lack WHO PQ are mainly exported for use in the African private market. High upfront costs with unpredictable benefits, as well as limited information and limited technical support on WHO PQ, were reported as the main barriers to obtain WHO PQ for anti-malarial drugs by respondents from Chinese pharmaceutical companies. Potential incentives identified by respondents included tax relief, human resource training and consultation, as well as other incentives related to drug approval, such as China's Fast Track Channel. Government support, as well as innovative incentives and collaboration mechanisms are needed for further adoption of WHO PQ for anti-malarial drugs in China.
Ringsted Frank M
Full Text Available Abstract Background Artemether-lumefantrine (ALu replaced sulphadoxine-pymimethamine (SP as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant women depend on SP for Intermittent Preventive Treatment (IPTp during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform a baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. Methods All drug shops selling prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. Results All surveyed drug shops illicitly sold SP and quinine (QN, and legally amodiaquine (AQ. Calculated monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local brands of SP accounted for 74% of sales volume, compared to AQ (13%, QN (11% and ACT (2%. Conclusions In community practice, the saleability of ACT was negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated in the national anti-malarial policy. It is a major reason for concern that such drug-pressure in the community equals de facto intermittent presumptive treatment. In an area where SP drug resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp
Full Text Available Abstract Background Mechanistic within-host models relating blood anti-malarial drug concentrations with the parasite-time profile help in assessing dosing schedules and partner drugs for new anti-malarial treatments. A comprehensive simulation study to assess the utility of a stage-specific pharmacokinetic-pharmacodynamic (PK-PD model for predicting within-host parasite response was performed. Methods Three anti-malarial combination therapies were selected: artesunate-mefloquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine. The PK-PD model included parameters to represent the concentration-time profiles of both drugs, the initial parasite burden and distribution across the parasite life cycle, and the parasite multiplication factor due to asexual reproduction. The model also included the maximal killing rate of each drug, and the blood drug concentration associated with half of that killing effect (in vivo EC50, derived from the in vitro IC50, the extent of binding to 0.5% Albumax present in the in vitro testing media, and the drugs plasma protein binding and whole blood to plasma partitioning ratio. All stochastic simulations were performed using a Latin-Hypercube-Sampling approach. Results The simulations demonstrated that the proportion of patients cured was highly sensitive to the in vivo EC50 and the maximal killing rate of the partner drug co-administered with the artemisinin derivative. The in vivo EC50 values that corresponded to on average 95% of patients cured were much higher than the adjusted values derived from the in vitro IC50. The proportion clinically cured was not strongly influenced by changes in the parameters defining the age distribution of the initial parasite burden (mean age of 4 to 16 hours and the parasite multiplication factor every life cycle (ranging from 8 to 12 fold/cycle. The median parasite clearance times, however, lengthened as the standard deviation of the initial parasite burden increased (i
Chance Michael L
Full Text Available Abstract Background This is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (CQ against falciparum malaria in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at assessment of therapeutic response to CQ and elucidation of baseline information on molecular markers for Plasmodium falciparum resistance against CQ and sulphadoxine/pyrimethamine (SP. Methods Between 2002 and 2003 the field test was conducted according to the standard WHO protocol to evaluate the therapeutic efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj Governorate in Yemen. Blood samples collected during this study were analysed for P. falciparum chloroquine resistance transporter gene (pfcrt-76 polymorphisms, mutation pfcrt-S163R and the antifolate resistance-associated mutations dihydrofolate reductase (dhfr-C59R and dihydropteroate synthase (dhps-K540E. Direct DNA sequencing of the pfcrt gene from three representative field samples was carried out after DNA amplification of the 13 exons of the pfcrt gene. Results Treatment failure was detected in 61% of the 122 cases that completed the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9. The prevalence of dhfr Arg-59 mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni CQ resistant P. falciparum carry the old world (Asian and African CQ resistant haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. Conclusion This is the first study to report baseline information on the characteristics and implications of anti-malarial drug resistance markers in Yemen. It is also the first report of the haplotype associated with CQR P. falciparum
Mubjer, Reem A; Adeel, Ahmed A; Chance, Michael L; Hassan, Amir A
This is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (CQ) against falciparum malaria in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at assessment of therapeutic response to CQ and elucidation of baseline information on molecular markers for Plasmodium falciparum resistance against CQ and sulphadoxine/pyrimethamine (SP). Between 2002 and 2003 the field test was conducted according to the standard WHO protocol to evaluate the therapeutic efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj Governorate in Yemen. Blood samples collected during this study were analysed for P. falciparum chloroquine resistance transporter gene (pfcrt)-76 polymorphisms, mutation pfcrt-S163R and the antifolate resistance-associated mutations dihydrofolate reductase (dhfr)-C59R and dihydropteroate synthase (dhps)-K540E. Direct DNA sequencing of the pfcrt gene from three representative field samples was carried out after DNA amplification of the 13 exons of the pfcrt gene. Treatment failure was detected in 61% of the 122 cases that completed the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9). The prevalence of dhfr Arg-59 mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni CQ resistant P. falciparum carry the old world (Asian and African) CQ resistant haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. This is the first study to report baseline information on the characteristics and implications of anti-malarial drug resistance markers in Yemen. It is also the first report of the haplotype associated with CQR P. falciparum parasites from Yemen. Mutant pfcrtT76 is highly prevalent but it
Frausin, Gina; Hidalgo, Ari de Freitas; Lima, Renata Braga Souza; Kinupp, Valdely Ferreira; Ming, Lin Chau; Pohlit, Adrian Martin; Milliken, William
In this article we present the plants used for the treatment of malaria and associated symptoms in Santa Isabel do Rio Negro in the Brazilian Amazon. The region has important biological and cultural diversities including more than twenty indigenous ethnic groups and a strong history in traditional medicine. The aims of this study are to survey information in the Baniwa, Baré, Desana, Piratapuia, Tariana, Tukano, Tuyuca and Yanomami ethnic communities and among caboclos (mixed-ethnicity) on (a) plant species used for the treatment of malaria and associated symptoms, (b) dosage forms and (c) distribution of these anti-malarial plants in the Amazon. Information was obtained through classical ethnobotanical and ethnopharmacological methods from interviews with 146 informants in Santa Isabel municipality on the upper Negro River, Brazil. Fifty-five mainly native neotropical plant species from 34 families were in use. The detailed uses of these plants were documented. The result was 187 records (64.5%) of plants for the specific treatment of malaria, 51 records (17.6%) of plants used in the treatment of liver problems and 29 records (10.0%) of plants used in the control of fevers associated with malaria. Other uses described were blood fortification ('dar sangue'), headache and prophylaxis. Most of the therapeutic preparations were decoctions and infusions based on stem bark, root bark and leaves. These were administered by mouth. In some cases, remedies were prepared with up to three different plant species. Also, plants were used together with other ingredients such as insects, mammals, gunpowder and milk. This is the first study on the anti-malarial plants from this region of the Amazon. Aspidosperma spp. and Ampelozizyphus amazonicus Ducke were the most cited species in the communities surveyed. These species have experimental proof supporting their anti-malarial efficacy. The dosage of the therapeutic preparations depends on the kind of plant, quantity of plant
Background Households in sub-Saharan Africa are highly reliant on the retail sector for obtaining treatment for malaria fevers and other illnesses. As donors and governments seek to promote the use of artemisinin combination therapy in malaria-endemic areas through subsidized anti-malarials offered in the retail sector, understanding the stocking and pricing decisions of retail outlets is vital. Methods A survey of all medicine retailers serving Bungoma East District in western Kenya was conducted three months after the launch of the AMFm subsidy in Kenya. The survey obtained information on each anti-malarial in stock: brand name, price, sales volume, outlet characteristics and GPS co-ordinates. These data were matched to household-level data from the Webuye Health and Demographic Surveillance System, from which population density and fever prevalence near each shop were determined. Regression analysis was used to identify the factors associated with retailers’ likelihood of stocking subsidized artemether lumefantrine (AL) and the association between price and sales for AL, quinine and sulphadoxine-pyrimethamine (SP). Results Ninety-seven retail outlets in the study area were surveyed; 11% of outlets stocked subsidized AL. Size of the outlet and having a pharmacist on staff were associated with greater likelihood of stocking subsidized AL. In the multivariable model, total volume of anti-malarial sales was associated with greater likelihood of stocking subsidized AL and competition was important; likelihood of stocking subsidized AL was considerably higher if the nearest neighbour stocked subsidized AL. Price was a significant predictor of sales volume for all three types of anti-malarials but the relationship varied, with the largest price sensitivity found for SP drugs. Conclusion The results suggest that helping small outlets overcome the constraints to stocking subsidized AL should be a priority. Competition between retailers and prices can play an important
Visser, Benjamin J.; Meerveld-Gerrits, Janneke; Kroon, Daniëlle; Mougoula, Judith; Vingerling, Rieke; Bache, Emmanuel; Boersma, Jimmy; van Vugt, Michèle; Agnandji, Selidji T.; Kaur, Harparkash; Grobusch, Martin P.
Recent studies alluded to the alarming scale of poor anti-malarial drug quality in malaria-endemic countries, but also illustrated the major geographical gaps in data on anti-malarial drug quality from endemic countries. Data are particularly scarce from Central Africa, although it carries the
Gee, Kevin A.
Children's health is an important factor that influences their success in education--poor health, especially when induced by disease, has been linked to poorer cognitive performance, particularly among children across the developing world (Behrman, 1996; UNESCO, 2008; Jukes et al., 2008). One health concern, particularly for sub-Saharan Africa,…
Thein, Si Thu; Khin, Hnin Su Su; Thi, Aung
In 2015/2016, an ACTwatch outlet survey was implemented to assess the anti-malarial and malaria testing landscape in Myanmar across four domains (Eastern, Central, Coastal, Western regions). Indicators provide an important benchmark to guide Myanmar's new National Strategic Plan to eliminate malaria by 2030. This was a cross-sectional survey, which employed stratified cluster-random sampling across four regions in Myanmar. A census of community health workers (CHWs) and private outlets with potential to distribute malaria testing and/or treatment was conducted. An audit was completed for all anti-malarials, malaria rapid diagnostic tests. A total of 28,664 outlets were approached and 4416 met the screening criteria. The anti-malarial market composition comprised CHWs (41.5%), general retailers (27.9%), itinerant drug vendors (11.8%), pharmacies (10.9%), and private for-profit facilities (7.9%). Availability of different anti-malarials and diagnostic testing among anti-malarial-stocking CHWs was as follows: artemisinin-based combination therapy (ACT) (81.3%), chloroquine (67.0%), confirmatory malaria test (77.7%). Less than half of the anti-malarial-stocking private sector had first-line treatment in stock: ACT (41.7%) chloroquine (41.8%), and malaria diagnostic testing was rare (15.4%). Oral artemisinin monotherapy (AMT) was available in 27.7% of private sector outlets (Western, 54.1%; Central, 31.4%; Eastern; 25.0%, Coastal; 15.4%). The private-sector anti-malarial market share comprised ACT (44.0%), chloroquine (26.6%), and oral AMT (19.6%). Among CHW the market share was ACT (71.6%), chloroquine (22.3%); oral AMT (3.8%). More than half of CHWs could correctly state the national first-line treatment for uncomplicated falciparum and vivax malaria (59.2 and 56.9%, respectively) compared to the private sector (15.8 and 13.2%, respectively). Indicators on support and engagement were as follows for CHWs: reportedly received training on malaria diagnosis (60.7%) or
Mishra, Satyendra; Karmodiya, Krishanpal; Surolia, Namita; Surolia, Avadhesha
Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC(50) of approximately 3.25 microM (MIC=13.2 microM) and IC(50) 4.21 microM (MIC=14.4 microM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC(50) of 0.48, 0.87, 0.92 microM and CQ-R P. falciparum at IC(50) of 0.45 microM, 0.89, 0.75 microM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.
Full Text Available Abstract Background Poor access to prompt and effective treatment for malaria contributes to high mortality and severe morbidity. In Kenya, it is estimated that only 12% of children receive anti-malarials for their fever within 24 hours. The first point of care for many fevers is a local medicine retailer, such as a pharmacy or chemist. The role of the medicine retailer as an important distribution point for malaria medicines has been recognized and several different strategies have been used to improve the services that these retailers provide. Despite these efforts, many mothers still purchase ineffective drugs because they are less expensive than effective artemisinin combination therapy (ACT. One strategy that is being piloted in several countries is an international subsidy targeted at anti-malarials supplied through the retail sector. The goal of this strategy is to make ACT as affordable as ineffective alternatives. The programme, called the Affordable Medicines Facility - malaria was rolled out in Kenya in August 2010. Methods In December 2010, the affordability and accessibility of malaria medicines in a rural district in Kenya were evaluated using a complete census of all public and private facilities, chemists, pharmacists, and other malaria medicine retailers within the Webuye Demographic Surveillance Area. Availability, types, and prices of anti-malarials were assessed. There are 13 public or mission facilities and 97 medicine retailers (registered and unregistered. Results The average distance from a home to the nearest public health facility is 2 km, but the average distance to the nearest medicine retailer is half that. Quinine is the most frequently stocked anti-malarial (61% of retailers. More medicine retailers stocked sulphadoxine-pyramethamine (SP; 57% than ACT (44%. Eleven percent of retailers stocked AMFm subsidized artemether-lumefantrine (AL. No retailers had chloroquine in stock and only five were selling artemisinin
Newton Paul N
Full Text Available Abstract Background Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. Methods Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis and botanical investigations were performed. Results Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA containing paracetamol (acetaminophen, counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. Conclusions Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.
Thiam, Sylla; Thior, Moussa; Faye, Babacar; Ndiop, Médoune; Diouf, Mamadou Lamine; Diouf, Mame Birame; Diallo, Ibrahima; Fall, Fatou Ba; Ndiaye, Jean Louis; Albertini, Audrey; Lee, Evan; Jorgensen, Pernille; Gaye, Oumar; Bell, David
Background While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. Methods and Findings Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584873 suspect fever cases). An estimated 516576 courses of inappropriate ACT prescription were averted. Conclusions The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT
Full Text Available Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69 µg/ml anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250 mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.
Full Text Available Abstract Background Two major cities in West Africa, Accra, the capital of Ghana, and Lagos, the largest city of Nigeria, have significant problems with substandard pharmaceuticals. Both have actively combated the problem in recent years, particularly by screening products on the market using the Global Pharma Health Fund e.V. Minilab® protocol. Random sampling of medicines from the two cities at least twice over the past 30 months allows a tentative assessment of whether improvements in drug quality have occurred. Since intelligence provided by investigators indicates that some counterfeit producers may be adapting products to pass Minilab tests, the results are compared with those from a Raman spectrometer and discrepancies are discussed. Methods Between mid-2007 and early-2010, samples of anti-malarial drugs were bought covertly from pharmacies in Lagos on three different occasions (October 2007, December 2008, February 2010, and from pharmacies in Accra on two different occasions (October 2007, February 2010. All samples were tested using the Minilab® protocol, which includes disintegration and active ingredient assays as well as visual inspection, and most samples were also tested by Raman spectrometry. Results In Lagos, the failure rate in the 2010 sampling fell to 29% of the 2007 finding using the Minilab® protocol, 53% using Raman spectrometry, and 46% using visual inspection. In Accra, the failure rate in the 2010 sampling fell to 54% of the 2007 finding using the Minilab® protocol, 72% using Raman spectrometry, and 90% using visual inspection. Conclusions The evidence presented shows that drug quality is probably improving in both cities, especially Lagos, since major reductions of failure rates over time occur with all means of assessment. Many more samples failed when examined by Raman spectrometry than by Minilab® protocol. The discrepancy is most likely caused by the two techniques measuring different aspects of the medication
Asase, Alex; Oteng-Yeboah, Alfred A; Odamtten, George T; Simmonds, Monique S J
An ethnobotanical study was conducted in the Wechiau Community Hippopotamus Sanctuary area in Ghana, through interviews and quadrate studies, to investigate the range and abundance of species used in the treatment of malaria. Forty-one species belonging to 17 families were encountered during the study. Of the 17 families studied Leguminosae and Anacardiaceae predominated in terms of number of species used to treat malaria. Eight plant species namely, Afraegle paniculata (Rutaceae), Haematostaphis barteri (Anacardiaceae), Indigo era pulchra (Leguminosae), Monanthotaxis sp. (Annonaceae), Ozoroa insignis (Anacardiaceae), Strychnos innocua (Loganiaceae), Strychnos spinosa (Loganiaceae) and Xeroderris stuhlmannii (Leguminosae) have not previously been documented for the treatment of malaria in Ghana. The results are discussed and recommendations made for future research to support the conservation and sustainable harvesting of the species reported to have medicinal properties.
Full Text Available Abstract Background There is an urgent need to identify new anti-malarial drug targets for both prophylaxis and chemotherapy, due to the increasing problem of drug resistance to malaria parasites. In the present study, the aim was to discover novel, effective plant-based extracts for the activity against malaria. Methods Ten plants found in Iran were selected by ethnobotanical survey of medicinal plants. The crude ethanolic extracts were tested for in vitro anti-plasmodial activity against two strains of Plasmodium falciparum: K1 (chloroquine-resistant strain and CY27 (chloroquine-sensitive strain, using the parasite lactate dehydrogenase (pLDH assay. The anti-plasmodial activity of the extracts was also assessed in the 4-day suppressive anti-malarial assay in mice inoculated with Plasmodium berghei (ANKA strain. Crude ethanolic extracts showed good anti-plasmodial activity were further fractionated by partitioning in water and dichloromethane. Results Of 10 plant species assayed, three species: Boerhavia elegans (Choisy, Solanum surattense (Burm.f. and Prosopis juliflora (Sw. showed promising anti-plasmodial activity in vitro (IC50 ≤ 50 μg/ml and in vivo with no toxicity. The dichloromethane fraction of three extracts revealed stronger anti-plasmodial activity than the total extracts. Conclusion Anti-plasmodial activities of extracts of B. elegans and S. surattense are reported for the first time.
Background There is an urgent need to identify new anti-malarial drug targets for both prophylaxis and chemotherapy, due to the increasing problem of drug resistance to malaria parasites. In the present study, the aim was to discover novel, effective plant-based extracts for the activity against malaria. Methods Ten plants found in Iran were selected by ethnobotanical survey of medicinal plants. The crude ethanolic extracts were tested for in vitro anti-plasmodial activity against two strains of Plasmodium falciparum: K1 (chloroquine-resistant strain) and CY27 (chloroquine-sensitive strain), using the parasite lactate dehydrogenase (pLDH) assay. The anti-plasmodial activity of the extracts was also assessed in the 4-day suppressive anti-malarial assay in mice inoculated with Plasmodium berghei (ANKA strain). Crude ethanolic extracts showed good anti-plasmodial activity were further fractionated by partitioning in water and dichloromethane. Results Of 10 plant species assayed, three species: Boerhavia elegans (Choisy), Solanum surattense (Burm.f.) and Prosopis juliflora (Sw.) showed promising anti-plasmodial activity in vitro (IC50 ≤ 50 μg/ml) and in vivo with no toxicity. The dichloromethane fraction of three extracts revealed stronger anti-plasmodial activity than the total extracts. Conclusion Anti-plasmodial activities of extracts of B. elegans and S. surattense are reported for the first time. PMID:20462416
Marrelli, Mauro Toledo; Brotto, Marco
Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country. Among the several complications, the effects of malaria seem to target the skeletal muscle system, leading to symptoms, such as muscle aches, muscle contractures, muscle fatigue, muscle pain, and muscle weakness. Malaria cause also parasitic coronary artery occlusion. This article reviews the current knowledge regarding the effect of malaria disease and the anti-malarial drugs on skeletal and cardiac muscles. Research articles and case report publications that addressed aspects that are important for understanding the involvement of malaria parasites and anti-malarial therapies affecting skeletal and cardiac muscles were analysed and their findings summarized. Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles. These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage.
Khin, Hnin Su Su; Chen, Ingrid; White, Chris; Sudhinaraset, May; McFarland, Willi; Littrell, Megan; Montagu, Dominic; Aung, Tin
Global malaria control efforts are threatened by the spread and emergence of artemisinin-resistant Plasmodium falciparum parasites. In 2012, the widespread sale of partial courses of artemisinin-based monotherapy was suspected to take place in the highly accessed, weakly regulated private sector in Myanmar, posing potentially major threats to drug resistance. This study investigated the presence of artemisinin-based monotherapies in the Myanmar private sector, particularly as partial courses of therapy, to inform the targeting of future interventions to stop artemisinin resistance. A large cross-sectional survey comprised of a screening questionnaire was conducted across 26 townships in Myanmar between March and May, 2012. For outlets that stocked anti-malarials at the time of survey, a stock audit was conducted, and for outlets that stocked anti-malarials within 3 months of the survey, a provider survey was conducted. A total of 3,658 outlets were screened, 83% were retailers (pharmacies, itinerant drug vendors and general retailers) and 17% were healthcare providers (private facilities and health workers). Of the 3,658 outlets screened, 1,359 outlets (32%) stocked at least one anti-malarial at the time of study. Oral artemisinin-based monotherapy comprised of 33% of self-reported anti-malarials dispensing volumes found. The vast majority of artemisinin-based monotherapy was sold by retailers, where 63% confirmed that they sold partial courses of therapy by cutting blister packets. Very few retailers (5%) had malaria rapid diagnostic tests available, and quality-assured artemisinin-based combination therapy was virtually nonexistent among retailers. Informal private pharmacies, itinerant drug vendors and general retailers should be targeted for interventions to improve malaria treatment practices in Myanmar, particularly those that threaten the emergence and spread of artemisinin resistance.
Wells Timothy NC
Full Text Available Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal
Talisuna, Ambrose O; Daumerie, Penny Grewal; Balyeku, Andrew; Egan, Timothy; Piot, Bram; Coghlan, Renia; Lugand, Maud; Bwire, Godfrey; Rwakimari, John Bosco; Ndyomugyenyi, Richard; Kato, Fred; Byangire, Maria; Kagwa, Paul; Sebisubi, Fred; Nahamya, David; Bonabana, Angela; Mpanga-Mukasa, Susan; Buyungo, Peter; Lukwago, Julius; Batte, Allan; Nakanwagi, Grace; Tibenderana, James; Nayer, Kinny; Reddy, Kishore; Dokwal, Nilesh; Rugumambaju, Sylvester; Kidde, Saul; Banerji, Jaya; Jagoe, George
Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Four intervention districts were purposefully selected to receive branded subsidized medicines - "ACT with a leaf", while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention's impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, "ACT with a leaf" accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4) at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, psupply-side subsidy and an intensive communications campaign significantly increased the uptake and use of ACT in the private sector in Uganda.
Talisuna Ambrose O
Full Text Available Abstract Background Artemisinin-based combination therapy (ACT, the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Methods Four intervention districts were purposefully selected to receive branded subsidized medicines - “ACT with a leaf”, while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention’s impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. Results At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, “ACT with a leaf” accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2% at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%. The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4 at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p Conclusions These data demonstrate that a supply-side subsidy and an intensive communications campaign
Bahamontes-Rosa, Noemí; Alejandre, Ane Rodriguez; Gomez, Vanesa; Viera, Sara; Gomez-Lorenzo, María G; Sanz-Alonso, Laura María; Mendoza-Losana, Alfonso
Quantitative real-time PCR (qPCR) is now commonly used as a method to confirm diagnosis of malaria and to differentiate recrudescence from re-infection, especially in clinical trials and in reference laboratories where precise quantification is critical. Although anti-malarial drug discovery is based on in vivo murine efficacy models, use of molecular analysis has been limited. The aim of this study was to develop qPCR as a valid methodology to support pre-clinical anti-malarial models by using filter papers to maintain material for qPCR and to compare this with traditional methods. FTA technology (Whatman) is a rapid and safe method for extracting nucleic acids from blood. Peripheral blood samples from mice infected with Plasmodium berghei, P. yoelii, or P. falciparum were kept as frozen samples or as spots on FTA cards. The extracted genetic material from both types of samples was assessed for quantification by qPCR using sets of specific primers specifically designed for Plasmodium 18S rRNA, LDH, and CytB genes. The optimal conditions for nucleic acid extraction from FTA cards and qPCR amplification were set up, and were confirmed to be suitable for parasite quantification using DNA as template after storage at room temperature for as long as 26 months in the case of P. berghei samples and 52 months for P. falciparum and P. yoelii. The quality of DNA extracted from the FTA cards for gene sequencing and microsatellite amplification was also assessed. This is the first study to report the suitability of FTA cards and qPCR assay to quantify parasite load in samples from in vivo efficacy models to support the drug discovery process.
Full Text Available Abstract Background A better anti-malarial efficiency and lower neurotoxicity have been reported for mefloquine (MQ (+- enantiomer. However, the importance of stereoselectivity remains poorly understood as the anti-malarial activity of pure enantiomer MQ analogues has never been described. Building on these observations, a series of enantiopure 4-aminoalcohol quinoline derivatives has previously been synthesized to optimize the efficiency and reduce possible adverse effects. Their in vitro activity on Plasmodium falciparum W2 and 3D7 strains is reported here along with their inhibition of β-haematin formation and peroxidative degradation of haemin, two possible mechanisms of action of anti-malarial drugs. Results The (S-enantiomers of this series of 4-aminoalcohol quinoline derivatives were found to be at least as effective as both chloroquine (CQ and MQ. The derivative with a 5-carbon side-chain length was the more efficient on both P. falciparum strains. (R -enantiomers displayed an activity decreased by 2 to 15-fold as compared to their (S counterparts. The inhibition of β-haematin formation was significantly stronger with all tested compounds than with MQ, irrespective of the stereochemistry. Similarly, the inhibition of haemin peroxidation was significantly higher for both (S and (R-enantiomers of derivatives with a side-chain length of five or six carbons than for MQ and CQ. Conclusions The prominence of stereochemistry in the anti-malarial activity of 4-aminoalcohol quinoline derivatives is confirmed. The inhibition of β-haematin formation and haemin peroxidation can be put forward as presumed mechanisms of action but do not account for the stereoselectivity of action witnessed in vitro.
Cochrane, Rachel V. K.; Sanichar, Randy; Lambkin, Gareth R.; Reiz, Béla; Xu, Wei; Tang, Yi; Vederas, John C.
The anti-malarial agent cladosporin is a nanomolar inhibitor of Plasmodium falciparum lysyl-tRNA synthetase, and exhibits activity against both blood and liver stage infection. Cladosporin can be isolated from the fungus Cladosporium cladosporioides, where it was believed to be biosynthesized by a highly reducing (HR) and non-reducing (NR) iterative type I polyketide synthase (PKS) pair. Genome sequencing of the host organism, and subsequent heterologous expression of these enzymes in Sacchar...
Full Text Available Abstract Background Anti-malarial drug resistance poses a threat to current global efforts towards control and elimination of malaria. Several methods are used in monitoring anti-malarial drug resistance. Molecular markers such as single nucleotide polymorphism (SNP for example are increasingly being used to identify genetic mutations related to anti-malarial drug resistance. Several methods are currently being used in analysis of SNP associated with anti-malarial drug resistance and although each one of these methods has unique strengths and shortcoming, there is still need to improve and/or develop new methods that will close the gap found in the current methods. Methods TaqMan Allelic Discrimination assays for detection of SNPs associated with anti-malarial drug resistance were designed for analysis on Applied Biosystems PCR platform. These assays were designed by submitting SNP sequences associated with anti-malarial drug resistance to Applied Biosystems website. Eleven SNPs associated with resistance to anti-malarial drugs were selected and tested. The performance of each SNP assay was tested by creating plasmid DNAs carrying codons of interests and analysing them for analysis. To test the sensitivity and specificity of each SNP assay, 12 clinical samples were sequenced at codons of interest and used in the analysis. Plasmid DNAs were used to establish the Limit of Detection (LoD for each assay. Results Data from genetic profiles of the Plasmodium falciparum laboratory strains and sequence data from 12 clinical samples was used as the reference method with which the performance of the SNP assays were compared to. The sensitivity and specificity of each SNP assay was establish at 100%. LoD for each assay was established at 2 GE, equivalent to less than 1 parasite/μL. SNP assays performed well in detecting mixed infection and analysis of clinical samples. Conclusion TaqMan Allelic Discrimination assay provides a good alternative tool in
Olasehinde, Grace I; Ojurongbe, Olusola; Adeyeba, Adegboyega O; Fagade, Obasola E; Valecha, Neena; Ayanda, Isaac O; Ajayi, Adesola A; Egwari, Louis O
The resistance of human malaria parasites to anti-malarial compounds has become considerable concern, particularly in view of the shortage of novel classes of anti-malarial drugs. One way to prevent resistance is by using new compounds that are not based on existing synthetic antimicrobial agents. Sensitivity of 100 Plasmodium falciparum isolates to chloroquine, quinine, amodiaquine, mefloquine, sulphadoxine/pyrimethamine, artemisinin, Momordica charantia ('Ejirin') Diospyros monbuttensis ('Egun eja') and Morinda lucida ('Oruwo') was determined using the in vitro microtest (Mark III) technique to determine the IC50 of the drugs. All the isolates tested were sensitive to quinine, mefloquine and artesunate. Fifty-one percent of the isolates were resistant to chloroquine, 13% to amodiaquine and 5% to sulphadoxine/pyrimethamine. Highest resistance to chloroquine (68.9%) was recorded among isolates from Yewa zone while highest resistance to amodiaquine (30%) was observed in Ijebu zone. Highest resistance to sulphadoxine/pyrimethamine was recorded in Yewa and Egba zones, respectively. A positive correlation was observed between the responses to artemisinin and mefloquine (P0.05). Highest anti-plasmodial activity was obtained with the ethanolic extract of D. monbuttensis (IC50 = 3.2 nM) while the lowest was obtained from M. lucida (IC50 = 25 nM). Natural products isolated from plants used in traditional medicine, which have potent anti-plasmodial action in vitro, represent potential sources of new anti-malarial drugs.
Full Text Available Abstract Background Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. Methods Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. Results IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP. Conclusion Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease.
"Every drug goes to treat its own disease…" - a qualitative study of perceptions and experiences of taking anti-retrovirals concomitantly with anti-malarials among those affected by HIV and malaria in Tanzania
Mangesho, Peter E; Reynolds, Joanna; Lemnge, Martha
BACKGROUND: Little is known about how people living with human immunodeficiency virus (HIV) experience malaria and the concomitant use of anti-malarial treatments with anti-retrovirals (ARVs). An understanding of how patients make sense of these experiences is important to consider in planning......, perceptions of drug strength appeared to compel some people not enrolled in the clinical study to take the drugs at separate times to avoid anticipated harm to the body. CONCLUSIONS: Management of HIV and malaria concurrently often requires individuals to cross the domains of different disease programmes...
Full Text Available Abstract Background Maintaining adequate supplies of anti-malarial medicines at the health facility level in rural sub-Saharan Africa is a major barrier to effective management of the disease. Lack of visibility of anti-malarial stock levels at the health facility level is an important contributor to this problem. Methods A 21-week pilot study, 'SMS for Life', was undertaken during 2009-2010 in three districts of rural Tanzania, involving 129 health facilities. Undertaken through a collaborative partnership of public and private institutions, SMS for Life used mobile telephones, SMS messages and electronic mapping technology to facilitate provision of comprehensive and accurate stock counts from all health facilities to each district management team on a weekly basis. The system covered stocks of the four different dosage packs of artemether-lumefantrine (AL and quinine injectable. Results Stock count data was provided in 95% of cases, on average. A high response rate (≥ 93% was maintained throughout the pilot. The error rate for composition of SMS responses averaged 7.5% throughout the study; almost all errors were corrected and messages re-sent. Data accuracy, based on surveillance visits to health facilities, was 94%. District stock reports were accessed on average once a day. The proportion of health facilities with no stock of one or more anti-malarial medicine (i.e. any of the four dosages of AL or quinine injectable fell from 78% at week 1 to 26% at week 21. In Lindi Rural district, stock-outs were eliminated by week 8 with virtually no stock-outs thereafter. During the study, AL stocks increased by 64% and quinine stock increased 36% across the three districts. Conclusions The SMS for Life pilot provided visibility of anti-malarial stock levels to support more efficient stock management using simple and widely available SMS technology, via a public-private partnership model that worked highly effectively. The SMS for Life system has
Background Maintaining adequate supplies of anti-malarial medicines at the health facility level in rural sub-Saharan Africa is a major barrier to effective management of the disease. Lack of visibility of anti-malarial stock levels at the health facility level is an important contributor to this problem. Methods A 21-week pilot study, 'SMS for Life', was undertaken during 2009-2010 in three districts of rural Tanzania, involving 129 health facilities. Undertaken through a collaborative partnership of public and private institutions, SMS for Life used mobile telephones, SMS messages and electronic mapping technology to facilitate provision of comprehensive and accurate stock counts from all health facilities to each district management team on a weekly basis. The system covered stocks of the four different dosage packs of artemether-lumefantrine (AL) and quinine injectable. Results Stock count data was provided in 95% of cases, on average. A high response rate (≥ 93%) was maintained throughout the pilot. The error rate for composition of SMS responses averaged 7.5% throughout the study; almost all errors were corrected and messages re-sent. Data accuracy, based on surveillance visits to health facilities, was 94%. District stock reports were accessed on average once a day. The proportion of health facilities with no stock of one or more anti-malarial medicine (i.e. any of the four dosages of AL or quinine injectable) fell from 78% at week 1 to 26% at week 21. In Lindi Rural district, stock-outs were eliminated by week 8 with virtually no stock-outs thereafter. During the study, AL stocks increased by 64% and quinine stock increased 36% across the three districts. Conclusions The SMS for Life pilot provided visibility of anti-malarial stock levels to support more efficient stock management using simple and widely available SMS technology, via a public-private partnership model that worked highly effectively. The SMS for Life system has the potential to alleviate
Reeder John C
Full Text Available Abstract Background Molecular monitoring of parasite resistance has become an important complementary tool in establishing rational anti-malarial drug policies. Community surveys provide a representative sample of the parasite population and can be carried out more rapidly than accrual of samples from clinical cases, but it is not known whether the frequencies of genetic resistance markers in clinical cases differ from those in the overall population, or whether such community surveys can provide good predictions of treatment failure rates. Methods Between 2003 and 2005, in vivo drug efficacy of amodiaquine or chloroquine plus sulphadoxine-pyrimethamine was determined at three sites in Papua New Guinea. The genetic drug resistance profile (i.e., 33 single nucleotide polymorphisms in Plasmodium falciparum crt, mdr1, dhfr, dhps, and ATPase6 was concurrently assessed in 639 community samples collected in the catchment areas of the respective health facilities by using a DNA microarray-based method. Mutant allele and haplotype frequencies were determined and their relationship with treatment failure rates at each site in each year was investigated. Results PCR-corrected in vivo treatment failure rates were between 12% and 28% and varied by site and year with variable longitudinal trends. In the community samples, the frequencies of mutations in pfcrt and pfmdr1 were high and did not show significant changes over time. Mutant allele frequencies in pfdhfr were moderate and those in pfdhps were low. No mutations were detected in pfATPase6. There was much more variation between sites than temporal, within-site, variation in allele and haplotype frequencies. This variation did not correlate well with treatment failure rates. Allele and haplotype frequencies were very similar in clinical and community samples from the same site. Conclusions The relationship between parasite genetics and in vivo treatment failure rate is not straightforward. The
Nguetse, Christian N.; Adegnika, Ayola Akim; Agbenyega, Tsiri; Ogutu, Bernhards R.; Krishna, Sanjeev; Kremsner, Peter G.; Velavan, Thirumalaisamy P.
BACKGROUND: The Plasmodium falciparum multidrug resistance 1 (PfMDR1), P. falciparum Ca(2+)-ATPase (PfATP6) and Kelch-13 propeller domain (PfK13) loci are molecular markers of parasite susceptibility to anti-malarial drugs. Their frequency distributions were determined in the isolates collected from children with severe malaria originating from three African countries. METHODS: Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped fo...
Full Text Available Abstract Background Knowing the safety profile of anti-malarial treatments in routine use is essential; millions of patients receive now artemisinin combination therapy (ACT annually, but the return on information through current systems is as yet inadequate. Cohort event monitoring (CEM is a WHO (World Health Organization-recommended practice; testing its performance and feasibility in routine practice in malaria-endemic is important. Methods A nine-year CEM-based study of the safety of artesunate-amodiaquine (ASAQ at five peripheral health facilities in a rural district of South-western Senegal. Staff (nurses, health workers were trained to collect actively and systematically information on the patient, treatment and events on a purposely designed questionnaire. The occurrence and severity of events was collected before, during and after treatment up to 28 days in order to generate information on all adverse events (AEs as well as treatment-emerging signs/symptoms (TESS. Laboratory tests (haematology, liver and renal was planned for at least 10% of cases. Results During 2001–2009, 3,708 parasitologically-confirmed malaria cases (mean age = 16.0 ± 12.7 years were enrolled (26% and 52% of all and parasitologically-confirmed ASAQ treatments, respectively. Treatment was supervised in 96% of cases. Products changed over time: 49% were a loose combination of individually-packaged products (available 2001–03, 42% co-blistered products (2004–09 and 9% a fixed-dose co-formulation (2006–09; dosing was age-based for 42%, weight-based for 58%. AS and AQ were correctly dosed in 97% and 82% of cases with the loose and 93% and 86% with the fixed combination, but only 50% and 42% with the co-blistered product. Thirty-three per cent (33% of patients had at least one sign/symptom pre-treatment, 12% had at least one AE and 9% a TESS (total events 3,914, 1,144 and 693, respectively. AEs overestimated TESS by 1.2-2 fold (average 1.7. Changes in
Full Text Available Abstract Background Petroleum ether extracts of Viola websteri Hemsl (Violaceae were reported to have anti-plasmodial activity against Plasmodium falciparum in vitro, with this activity being largely attributable to 6-(8'Z-pentadecenyl-salicylic acid (6-SA. Methods The schizontocidal activity of 6-SA on early Plasmodium berghei infections was evaluated in a four-day test. The possible 'repository' activity of 6-SA was assessed using the method described by Peters. The median lethal dose (LD50 of 6-SA, when given intraperitoneally, was also determined using uninfected ICR mice and the method of Lorke. Results In the present study, 6-SA was found to have anti-malarial activity in vivo, when tested against P. berghei in mice. 6-SA at 5, 10 and 25 mg/kg·day exhibited a significant blood schizontocidal activity in four-day early infections, repository evaluations and established infections with a significant mean survival time comparable to that of the standard drug, chloroquine (5 mg/kg·day. Conclusion 6-SA possesses a moderate anti-malarial activity that could be exploited for malaria therapy.
Patouillard, Edith; Hanson, Kara; Kleinschmidt, Immo; Palafox, Benjamin; Tougher, Sarah; Pok, Sochea; O?Connell, Kate; Goodman, Catherine
Background In many low-income countries, the private commercial sector plays an important role in the provision of malaria treatment. However, the quality of care it provides is often poor, with artemisinin combination therapy (ACT) generally being too costly for consumers. Decreasing ACT prices is critical for improving private sector treatment outcomes and reducing the spread of artemisinin resistance. Yet limited evidence exists on the factors influencing retailers? pricing decisions. This...
Musuva, Anne; Ejersa, Waqo; Kiptui, Rebecca; Memusi, Dorothy; Abwao, Edward
Since 2004, Kenya's national malaria treatment guidelines have stipulated artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria, and since 2014, confirmatory diagnosis of malaria in all cases before treatment has been recommended. A number of strategies to support national guidelines have been implemented in the public and private sectors in recent years. A nationally-representative malaria outlet survey, implemented across four epidemiological zones, was conducted between June and August 2016 to provide practical evidence to inform strategies and policies in Kenya towards achieving national malaria control goals. A total of 17,852 outlets were screened and 2271 outlets were eligible and interviewed. 78.3% of all screened public health facilities stocked both malaria diagnostic testing and quality-assured ACT (QAACT). Sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy was available in 70% of public health facilities in endemic areas where it is recommended for treatment. SP was rarely found in the public sector outside of the endemic areas (private sector had lower levels of QAACT (46.7%) and malaria blood testing (20.8%) availability but accounted for majority of anti-malarial distribution (70.6% of the national market share). More than 40% of anti-malarials were distributed by unregistered pharmacies (37.3%) and general retailers (7.1%). QAACT accounted for 58.2% of the total anti-malarial market share, while market share for non-QAACT was 15.8% and for SP, 24.8%. In endemic areas, 74.9% of anti-malarials distributed were QAACT. Elsewhere, QAACT market share was 49.4% in the endemic-prone areas, 33.2% in seasonal-transmission areas and 37.9% in low-risk areas. Although public sector availability of QAACT and malaria diagnosis is relatively high, there is a gap in availability of both testing and treatment that must be addressed. The private sector in Kenya, where the majority of anti-malarials
Olugbenga O. Oluwagbemi
Full Text Available Malaria is one of the infectious diseases consistently inherent in many Sub-Sahara African countries. Among the issues of concern are the consequences of wrong diagnosis and dosage administration of anti-malarial drugs on sick patients; these have resulted into various degrees of complications ranging from severe headaches, stomach and body discomfort, blurred vision, dizziness, hallucinations, and in extreme cases, death. Many expert systems have been developed to support different infectious disease diagnoses, but not sure of any yet, that have been specifically designed as a voice-based application to diagnose and translate malaria patients’ symptomatic data for pre-laboratory screening and correct prescription of proper dosage of the appropriate medication. We developed Malavefes, (a malaria voice-enabled computational fuzzy expert system for correct dosage prescription of anti-malarial drugs using Visual Basic.NET., and Java programming languages. Data collation for this research was conducted by survey from existing literature and interview from public health experts. The database for this malaria drug informatics system was implemented using Microsoft Access. The Root Sum Square (RSS was implemented as the inference engine of Malavefes to make inferences from rules, while Centre of Gravity (CoG was implemented as the defuzzification engine. The drug recommendation module was voice-enabled. Additional anti-malaria drug expiration validation software was developed using Java programming language. We conducted a user-evaluation of the performance and user-experience of the Malavefes software. Keywords: Informatics, Bioinformatics, Fuzzy, Anti-malaria, Voice computing, Dosage prescription
Full Text Available Abstract Background Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties. Therapeutic activity, as well as toxicity and other essential properties can be analysed and optimized simultaneously, independently of one another. Such methodology is suitable for a search of novel, non-toxic, active anti-malarial compounds. Methods A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and de novo molecular design. Results Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were discovered and experimentally validated. Twelve compounds were identified in silico and tested in vitro; eight of them showed anti-malarial activity (IC50 ≤ 10 μM, with six being very effective (IC50 ≤ 1 μM, and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a
Diarra, Amidou; Nebie, Issa; Tiono, Alfred
ABSTRACT: BACKGROUND: Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment...... of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. METHODS: Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child...... to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. RESULTS: IgG levels to MSP3 were always higher in the successfully treated...
Full Text Available Abstract Background Patterns of decreasing malaria transmission intensity make presumptive treatment of malaria an unjustifiable approach in many African settings. The controlled use of anti-malarials after laboratory confirmed diagnosis is preferable in low endemic areas. Diagnosis may be facilitated by malaria rapid diagnostic tests (RDTs. In this study, the impact of a government policy change, comprising the provision of RDTs and advice to restrict anti-malarial treatment to RDT-positive individuals, was assessed by describing diagnostic behaviour and treatment decision-making in febrile outpatients Methods Prospective data from Biharamulo and Rubya Designated District Hospital (DDH were collected before and after policy change, in Sumve DDH no new policy was implemented. Diagnosis of malaria was confirmed by RDT; transmission intensity was evaluated by a serological marker of malaria exposure in hospital attendees. Results Prior to policy change, there was no evident association between the actual level of transmission intensity and drug-prescribing behaviour. After policy change, there was a substantial decrease in anti-malarial prescription and an increase in prescription of antibiotics. The proportion of parasite-negative individuals who received anti-malarials decreased from 89.1% (244/274 to 38.7% (46/119 in Biharamulo and from 76.9% (190/247 to 10.0% (48/479 in Rubya after policy change. Conclusion This study shows that an official policy change, where RDTs were provided and healthcare providers were advised to adhere to RDT results in prescribing drugs can be followed by more rational drug-prescribing behaviour. The current findings are promising for improving treatment policy in Tanzanian hospitals.
Gopalan, Rajendran C; Emerce, Esra; Wright, Colin W; Karahalil, Bensu; Karakaya, Ali E; Anderson, Diana
Malaria is a mosquito-borne infectious disease caused by the genus Plasmodium. It causes one million deaths per year in African children under the age of 5 years. There is an increasing development of resistance of malarial parasites to chloroquine and other currently used anti-malarial drugs. Some plant products such as the indoloquinoline alkaloid cryptolepine have been shown to have potent activity against P. falciparum in vitro. On account of its toxicity, cryptolepine is not suitable for use as an antimalarial drug but a number of analogues of cryptolepine have been synthesised in an attempt to find compounds that have reduced cytotoxicity and these have been investigated in the present study in human sperm and lymphocytes using the Comet assay. The results suggest that cryptolepine and the analogues cause DNA damage in lymphocytes, but appear to have no effect on human sperm at the assessed doses. In the context of antimalarial drug development, the data suggest that all cryptolepine compounds and in particular 2,7-dibromocryptolepine cause DNA damage and therefore may not be suitable for pre clinical development as antimalarial agents. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Full Text Available Abstract Background In the past many regions of Bangladesh were hyperendemic for malaria. Malaria control in the 1960s to 1970s eliminated malaria from the plains but in the Chittagong Hill Tracts remained a difficult to control reservoir. The Chittagong Hill Tracts have areas with between 1 and 10% annual malaria rates, predominately 90-95% Plasmodium falciparum. In Southeast Asia, multiplicity of infection for hypo-endemic regions has been approximately 1.5. Few studies on the genetic diversity of P. falciparum have been performed in Bangladesh. Anderson et al. performed a study in Khagrachari, northern Chittagong Hill Tracts in 2002 on 203 patients and found that parasites had a multiplicity of infection of 1.3 by MSP-1, MSP-2 and GLURP genotyping. A total of 94% of the isolates had the K76T Pfcrt chloroquine resistant genotype, and 70% showed the N86Y Pfmdr1 genotype. Antifolate drug resistant genotypes were high with 99% and 73% of parasites having two or more mutations at the dhfr or dhps loci. Methods Nested and real-time polymerase chain reaction (PCR methods were used to genotype P. falciparum using antigenic polymorphic markers and to study anti-malarial drug resistance markers in malaria endemic areas of Bangladesh. Results The analysis of polymorphic and drug resistant genotype on 33 paired recrudescent infections after drug treatment in the period 2004 to 2008 in the Chittagong Hill Tracts, which is just prior to countrywide provision of artemisinin combination therapy. Overall the multiplicity of infection for MSP-1 was 2.7 with a slightly smaller parasite diversity post-treatment. The 13 monoclonal infections by both GLURP and MSP-1 were evenly divided between pre- and post-treatment. The MSP-1 MAD block was most frequent in 66 of the samples. The prevalence of the K76T PfCRT chloroquine resistant allele was approximately 82% of the samples, while the resistant Pfmdr1 N86Y was present in 33% of the samples. Interestingly, the post-treatment
Venous blood and masturbation specimens of semen were obtained from the subjects before treatment, immediately post-treatment and by the 65th day from commencement of treatment. Blood levels of follicle stimulating hormones, leutinizing hormone and testosterone were determined by Enzyme Linked Imuno Assay.
Full Text Available Abstract Background The introduction of new anti-malarial treatment that is effective, but more expensive, raises questions about whether the high level of effectiveness observed in clinical trials can be found in a context of family use. The objective of this study was to determine the factors related to adherence, when using the amodiaquine/sulphadoxine-pyrimethamine (AQ/SP association, a transitory strategy before ACT implementation in Senegal. Methods The study was conducted in five rural dispensaries. Children, between two and 10 years of age, who presented mild malaria were recruited at the time of the consultation and were prescribed AQ/SP. The child's primary caretaker was questioned at home on D3 about treatment compliance and factors that could have influenced his or her adherence to treatment. A logistic regression model was used for the analyses. Results The study sample included 289 children. The adherence rate was 64.7%. Two risks factors for non-adherence were identified: the children's age (8–10 years (ORa = 3.07 [1.49–6.29]; p = 0.004; and the profession of the head of household (retailer/employee versus farmer (ORa = 2.71 [1.34–5.48]; p = 0.006. Previously seeking care (ORa = 0.28 [0.105–0.736], p=0.001] satisfaction with received information (ORa = 0.45 [0.24–0.84]; p = 0.013, and the quality of history taking (ORa = 0.38 [0.21–0.69]; p = 0.001 were significantly associated with good compliance. Conclusion The results of the study show the importance of information and communication between caregivers and health center staff. The experience gained from this therapeutic transition emphasizes the importance of information given to the patients at the time of the consultation and drug delivery in order to improve drug use and thus prevent the emergence of rapid drug resistance.
Verbeken, Mathieu; Suleman, Sultan; Baert, Bram; Vangheluwe, Elien; Van Dorpe, Sylvia; Burvenich, Christian; Duchateau, Luc; Jansen, Frans H; De Spiegeleer, Bart
Lumefantrine (benflumetol) is a fluorene derivative belonging to the aryl amino alcohol class of anti-malarial drugs and is commercially available in fixed combination products with β-artemether. Impurity characterization of such drugs, which are widely consumed in tropical countries for malaria control programmes, is of paramount importance. However, until now, no exhaustive impurity profile of lumefantrine has been established, encompassing process-related and degradation impurities in active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs). Using HPLC-DAD/UV-ESI/ion trap/MS, a comprehensive impurity profile was established based upon analysis of market samples as well as stress, accelerated and long-term stability results. In-silico toxicological predictions for these lumefantrine related impurities were made using Toxtree® and Derek®. Several new impurities are identified, of which the desbenzylketo derivative (DBK) is proposed as a new specified degradant. DBK and the remaining unspecified lumefantrine related impurities are predicted, using Toxtree® and Derek®, to have a toxicity risk comparable to the toxicity risk of the API lumefantrine itself. From unstressed, stressed and accelerated stability samples of lumefantrine API and FPPs, nine compounds were detected and characterized to be lumefantrine related impurities. One new lumefantrine related compound, DBK, was identified and characterized as a specified degradation impurity of lumefantrine in real market samples (FPPs). The in-silico toxicological investigation (Toxtree® and Derek®) indicated overall a toxicity risk for lumefantrine related impurities comparable to that of the API lumefantrine itself.
Full Text Available Background and objectives: This investigation was performed in order to analyze the composition of the essential oil (EO of Anthriscus nemorosa and evaluation of its anti-oxidant and anti-malarial activity of its extracts and determination of the total phenolics content (TPC and total flavonoid content (TFC. Methods: One hundred g dried powder of Anthriscus nemorosa was submitted to hydro-distillation and also was extracted (with n-hexane, dichloromethane (DCM and methanol (MeOH, by using Clevenger and Soxhlet apparatus, respectively. Moreover, extracted essential oil (EO was analyzed by GC-MS. Furthermore, the anti-oxidant, anti- malaria, Total phenolics content (TPC and total flavonoid content (TFC of EO and the extracts were investigated by DPPH, cell free -hematin formation, Folin- Ciocalteau and colorimetric methods, respectively. Results: Fifty nine compounds, representing 94% of total oil were identified High content of terpenoids (60.02% were identified in the essential oil with isogeranol (28.86%, crystathenyl acetate (13.86% and farnesene (10.39% as the most dominant compounds.. Methanol extract demonstrated free radical scavenging activity (RC50 0.192±0.133.Total phenol contents was (325.82±2.72 mg/g. Total flavonoid content was (140.4096±2.4 mg/g. None of the extracts showed anti-malaria effect. Conclusion: Main constituents of A. nemorosa were terpenoids. In comparison with other species of Anthriscus, antioxidant activity of A. nemorosa essential oil was less noticeable.
Pybus Brandon S
Full Text Available Abstract Background The 8-aminoquinoline (8AQ drug primaquine (PQ is currently the only approved drug effective against the persistent liver stage of the hypnozoite forming strains Plasmodium vivax and Plasmodium ovale as well as Stage V gametocytes of Plasmodium falciparum. To date, several groups have investigated the toxicity observed in the 8AQ class, however, exact mechanisms and/or metabolic species responsible for PQ’s haemotoxic and anti-malarial properties are not fully understood. Methods In the present study, the metabolism of PQ was evaluated using in vitro recombinant metabolic enzymes from the cytochrome P450 (CYP and mono-amine oxidase (MAO families. Based on this information, metabolite identification experiments were performed using nominal and accurate mass measurements. Results Relative activity factor (RAF-weighted intrinsic clearance values show the relative role of each enzyme to be MAO-A, 2C19, 3A4, and 2D6, with 76.1, 17.0, 5.2, and 1.7% contributions to PQ metabolism, respectively. CYP 2D6 was shown to produce at least six different oxidative metabolites along with demethylations, while MAO-A products derived from the PQ aldehyde, a pre-cursor to carboxy PQ. CYPs 2C19 and 3A4 produced only trace levels of hydroxylated species. Conclusions As a result of this work, CYP 2D6 and MAO-A have been implicated as the key enzymes associated with PQ metabolism, and metabolites previously identified as potentially playing a role in efficacy and haemolytic toxicity have been attributed to production via CYP 2D6 mediated pathways.
Five medicinal plants, Acacia nilotica (Fabaceae), Citrus aurantifolia (Rutaceae), Mangifera indica (Anacardiaceae) Carica papaya (Caricaceae), and Psidium guajava (Myrtaceae) used for the treatment of malaria/ fever by the Hausa people of Kano-Nigeria were selected based on their traditional claims. These were ...
Kovacs, Stephanie D; Mills, Brianna M; Stergachis, Andy
Malaria control efforts have been strengthened by funding from donor groups and government agencies. The Global Fund to Fight AIDS, Tuberculosis and the Malaria (Global Fund), the US President's Malaria Initiative (PMI) account for the majority of donor support for malaria control and prevention efforts. Pharmacovigilance (PV), which encompasses all activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem, is a necessary part of efforts to reduce drug resistance and improve treatment outcomes. This paper reports on an analysis of PV plans in the Global Fund and PMI and World Bank's grants for malaria prevention and control. All active malaria grants as of September 2015 funded by the Global Fund and World Bank, and fiscal year 2015 and 2016 PMI Malaria Operational Plans (MOP) were identified. The total amount awarded for PV-related activities and drug quality assurance was abstracted. A Key-Word-in-Context (KWIC) analysis was conducted for the content of each grant. Specific search terms consisted of pharmacovigilance, pregn*, registry, safety, adverse drug, mass drug administration, primaquine, counterfeit, sub-standard, and falsified. Grants that mentioned PV activities identified in the KWIC search, listed PV in their budgets, or included the keywords: counterfeit, sub-standard, falsified, mass drug administration, or adverse event were thematically coded using Dedoose software version 7.0. The search identified 159 active malaria grants including 107 Global Fund grants, 39 fiscal year 2015 and 2016 PMI grants and 13 World Bank grants. These grants were primarily awarded to low-income countries (57.2%) and in sub-Saharan Africa (SSA) (70.4%). Thirty-seven (23.3%) grants included a budget line for PV- or drug quality assurance-related activities, including 21 PMI grants and 16 Global Fund grants. Only 23 (14.5%) grants directly mentioned PV. The primary focus area was improving drug
Corran, Patrick H; Cook, Jackie; Lynch, Caroline; Leendertse, Heleen; Manjurano, Alphaxard; Griffin, Jamie; Cox, Jonathan; Abeku, Tarekegn; Bousema, Teun; Ghani, Azra C; Drakeley, Chris; Riley, Eleanor
at ambient humidity and temperature showed severe loss of recoveries. Estimates of malaria transmission intensity obtained from serum and from blood spots were similar, and values obtained using blood spots agreed well with entomologically determined values. Conclusion This study has demonstrated the suitability of filter paper blood spots paper for collection of serum antibodies, and provided clear guidelines for the treatment and storage of filter papers which emphasize the importance of desiccation and minimisation of time spent at ambient temperatures. A recommended protocol for collecting, storing and assaying blood spots is provided. PMID:18826573
Stuckey, Erin M; Miller, John M; Littrell, Megan; Chitnis, Nakul; Steketee, Rick
Malaria elimination requires reducing both the potential of mosquitoes to transmit parasites to humans and humans to transmit parasites to mosquitoes. To achieve this goal in Southern province, Zambia a mass test and treat (MTAT) campaign was conducted from 2011-2013 to complement high coverage of long-lasting insecticide-treated nets (LLIN). To identify factors likely to increase campaign effectiveness, a modelling approach was applied to investigate the simulated effect of alternative operational strategies for parasite clearance in southern province. OpenMalaria, a discrete-time, individual-based stochastic model of malaria, was parameterized for the study area to simulate anti-malarial drug administration for interruption of transmission. Simulations were run for scenarios with a range of artemisinin-combination therapies, proportion of the population reached by the campaign, targeted age groups, time between campaign rounds, Plasmodium falciparum test protocols, and the addition of drugs aimed at preventing onward transmission. A sensitivity analysis was conducted to assess uncertainty of simulation results. Scenarios were evaluated based on the reduction in all-age parasite prevalence during the peak transmission month one year following the campaign, compared to the currently-implemented strategy of MTAT 19 % population coverage at pilot and 40 % coverage during the first year of implementation in the presence of 56 % LLIN use and 18 % indoor residual spray coverage. Simulation results suggest the most important determinant of success in reducing prevalence is the population coverage achieved in the campaign, which would require more than 1 year of campaign implementation for elimination. The inclusion of single low-dose primaquine, which acts as a gametocytocide, or ivermectin, which acts as an endectocide, to the drug regimen did not further reduce parasite prevalence one year following the campaign compared to the currently-implemented strategy
Asare, Aquisman Ebenezer
The availability of numerous brands of artesunate in our drug market today places clinicians and pharmacists in a difficult situation of choice of a suitable brand or the possibility of alternative use. Fake artesunate could compromise the hope that ACT (artemisinin combination therapy) offers for malaria control in Africa. In this study, quality of some selected brands of anti - malarial drugs used in the communities of Agona west Municipality, Ghana was determined. Blister or packs of anti – malarial tablets were randomly sampled. The Protocols of the International Pharmacopeia and Global Pharma Health Fund Minilab were used to assess the quality of anti – malarial tablets per blister pack manufactured by Bliss Gvs Pharma Ltd. India, Letap Pharmaceutical Company Ltd. Ghana and Guilin Pharmaceutical Company Ltd. China and sold in chemical sales outlets at the farming communities of Agona West Municipality, Ghana. The identification test was used to confirm the presence of active ingredients in the tablets. A confirmatory test for the active ingredient was achieved with artesunate (ICRS 1302) reference standards and Gsunate reference standard (ICRS4061). The friability test was used to confirm the hardness of the tablets to determine the drug ability to withstand abrasion in packaging, handling and shipping. The disintegration test was used to confirm the time required for the tablets to disintegrate into particles. Titrimetric analysis confirmed the amount of artesunate found in tablets.The results of the study are as follows for Artesunate by GPCL, LPL and Gsunate by BGPL; the identification test confirmed the presence of the active ingredient in all the brands. Based on the International Pharmacopoeia acceptable range of 1 to 15 min for genuine artesunate per tablet, 93.75 % of field selected artesunate blister pack tablets manufactured by GPCL passed the disintegration test and 6.25% failed. Also 85.57% of the sampled artesunate blister pack manufactured by
Conclusions: CM1 would be effective per se and synergize with PYR in inhibiting growth of murine malaria parasites, possibly by limiting iron supply from plasma transferrin and host PRBC cytoplasm, and chelating catalytic iron cstitutive in parasites’ mitochondrial cytochromes and cytoplasmic ribonucleotide reductase. CM1 would be a promising adjuvant to enhance PYR anti-malarial activity and minimize the drug resistance.
Bhattacharya, Debopam; Dupas, Pascaline; Kanaya, Shin
and its neighbors. Using experimental data from Kenya where subsidies were randomized, coupled with GPS-based location information, we show how to estimate aggregate ITN use resulting from means-tested subsidies in the presence of such spatial spillovers. Accounting for spillovers introduces infinite......-dimensional estimated regressors corresponding to continuously distributed location coordinates and makes the inference problem novel. We show that even if individual ITN use unambiguously increases with increasing incidence of subsidy in the neighborhood, ignoring spillovers may over- or under-predict overall ITN use...... resulting from a specific targeting rule, depending on the resulting aggregate incidence of subsidy. Applying our method to the Kenyan data, we find that (i) individual ITN use rises with neighborhood subsidy-rates, (ii) under means-testing, predicted ITN use is a convex increasing function of the subsidy...
Mikkelsen-Lopez, Inez; Shango, Winna; Barrington, Jim; Ziegler, Rene; Smith, Tom; deSavigny, Don
Between 2007 and 2013, the Tanzanian public sector received 93.1 million doses of first-line anti-malarial artemisinin-based combination therapy (ACT) in the form of artemether-lumefantrine entirely supplied by funding partners. The introduction of a health facility ACT stock monitoring system using SMS technology by the National Malaria Control Programme in mid 2011 revealed a high frequency of stock-outs of ACT in primary care public health facilities. The objective of this study was to determine the pattern of availability of ACT and possible causes of observed stock-outs across public health facilities in Tanzania since mid-2011. Data were collected weekly by the mobile phone reporting tool SMS for Life on ACT availability from over 5,000 public health facilities in Tanzania starting from September 2011 to December 2012. Stock data for all four age-dose levels of ACT across health facilities were summarized and supply of ACT at the national level was also documented. Over the period of 15 months, on average 29% of health facilities in Tanzania were completely stocked out of all four-age dose levels of the first-line anti-malarial with a median duration of total stock-out of six weeks. Patterns of total stock-out by region ranged from a low of 9% to a high of 52%. The ACT stock-outs were most likely caused by: a) insufficient ACT supplies entering Tanzania (e.g. in 2012 Tanzania received 10.9 million ACT doses compared with a forecast demand of 14.4 million doses); and b) irregular pattern of ACT supply (several months with no ACT stock). The reduced ACT availability and irregular pattern of supply were due to cumbersome bureaucratic processes and delays both within the country and from the main donor, the Global Fund to Fight AIDS, Tuberculosis and Malaria. Tanzania should invest in strengthening both the supply system and the health information system using mHealth solutions such as SMS for Life. This will continue to assist in tracking ACT availability across
Oyoo George O
Full Text Available Abstract Background Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. Methods Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. Results The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product were reported. The maximum concentration (Cmax was 160-200 nM and after 6 hours, the effective concentration (Ceff was Conclusion Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.
Lall Varinder K
Full Text Available Abstract Background Mefloquine is an anti-malarial drug that can have neurological side effects. This study examines how mefloquine (MF influences central nervous control of autonomic and respiratory systems using the arterially perfused working heart brainstem preparation (WHBP of the rat. Recordings of nerve activity were made from the thoracic sympathetic chain and phrenic nerve, while heart rate (HR and perfusion pressure were also monitored in the arterially perfused, decerebrate, rat WHBP. MF was added to the perfusate at 1 μM to examine its effects on baseline parameters as well as baroreceptor and chemoreceptor reflexes. Results MF caused a significant, atropine resistant, bradycardia and increased phrenic nerve discharge frequency. Chemoreceptor mediated sympathoexcitation (elicited by addition of 0.1 ml of 0.03% sodium cyanide to the aortic cannula was significantly attenuated by the application of MF to the perfusate. Furthermore MF significantly decreased rate of return to resting HR following chemoreceptor induced bradycardia. An increase in respiratory frequency and attenuated respiratory-related sympathetic nerve discharge during chemoreceptor stimulation was also elicited with MF compared to control. However, MF did not significantly alter baroreceptor reflex sensitivity. Conclusions These studies indicate that in the WHBP, MF causes profound alterations in autonomic and respiratory control. The possibility that these effects may be mediated through actions on connexin 36 containing gap junctions in central neurones controlling sympathetic nervous outflow is discussed.
Ogunwande Isiaka A
Full Text Available Abstract Background Adverse drug reactions (ADRs contribute to ill-health or life-threatening outcomes of therapy during management of infectious diseases. The exposure to anti-malarial and use of mobile phone technology to report ADRs following drug exposures were investigated in Sagamu - a peri-urban community in Southwest Nigeria. Methods Purchase of medicines was actively monitored for 28 days in three Community Pharmacies (CP and four Patent and Proprietary Medicine Stores (PPMS in the community. Information on experience of ADRs was obtained by telephone from 100 volunteers who purchased anti-malarials during the 28-day period. Results and Discussion A total of 12,093 purchases were recorded during the period. Antibiotics, analgesics, vitamins and anti-malarials were the most frequently purchased medicines. A total of 1,500 complete courses of anti-malarials were purchased (12.4% of total purchases; of this number, purchases of sulphadoxine-pyrimethamine (SP and chloroquine (CQ were highest (39.3 and 25.2% respectiuvely. Other anti-malarials purchased were artesunate monotherapy (AS - 16.1%, artemether-lumefantrine (AL 10.0%, amodiaquine (AQ - 6.6%, quinine (QNN - 1.9%, halofantrine (HF - 0.2% and proguanil (PR - 0.2%. CQ was the cheapest (USD 0.3 and halofantrine the most expensive (USD 7.7. AL was 15.6 times ($4.68 more expensive than CQ. The response to mobile phone monitoring of ADRs was 57% in the first 24 hours (day 1 after purchase and decreased to 33% by day 4. Participants in this monitoring exercise were mostly with low level of education (54%. Conclusion The findings from this study indicate that ineffective anti-malaria medicines including monotherapies remain widely available and are frequently purchased in the study area. Cost may be a factor in the continued use of ineffective monotherapies. Availability of a toll-free telephone line may facilitate pharmacovigilance and follow up of response to medicines in a resource
What happened to anti-malarial markets after the Affordable Medicines Facility-malaria pilot? Trends in ACT availability, price and market share from five African countries under continuation of the private sector co-payment mechanism.
Tougher, Sarah; Hanson, Kara; Goodman, Catherine
The private sector supplies anti-malarial treatment for large proportions of patients in sub-Saharan Africa. Following the large-scale piloting of the Affordable Medicines Facility-malaria (AMFm) from 2010 to 2011, a private sector co-payment mechanism (CPM) provided continuation of private sector subsidies for quality-assured artemisinin combination therapies (QAACT). This article analyses for the first time the extent to which improvements in private sector QAACT supply and distribution observed during the AMFm were maintained or intensified during continuation of the CPM through 2015 in Kenya, Madagascar, Nigeria, Tanzania and Uganda using repeat cross-sectional outlet survey data. QAACT market share in all five countries increased during the AMFm period (p private sector QAACT availability were maintained or improved. In 2014/15, private sector QAACT availability was greater than 70% in Nigeria (84.3%), Kenya (70.5%), Tanzania (83.0%) and Uganda (77.1%), but only 11.2% in Madagascar. QAACT market share was maintained or improved post-AMFm in Nigeria, Tanzania and Uganda, but statistically significant declines were observed in Kenya and Madagascar. In 2014/5, QAACT market share was highest in Kenya and Uganda (48.2 and 47.5%, respectively) followed by Tanzania (39.2%), Nigeria (35.0%), and Madagascar (7.0%). Four of the five countries experienced significant decreases in median QAACT price during the AMFm period. Private sector QAACT prices were maintained or further reduced in Tanzania, Nigeria and Uganda, but prices increased significantly in Kenya and Madagascar. SP prices were consistently lower than those of QAACT in the AMFm period, with the exception of Kenya and Tanzania in 2011, where they were equal. In 2014/5 QAACT remained two to three times more expensive than the most popular non-artemisinin therapy in all countries except Tanzania. Results suggest that a private sector co-payment mechanism for QAACT implemented at national scale for 5 years was
Alam, Mohammad Shafiul; Ley, Benedikt; Nima, Maisha Khair; Johora, Fatema Tuj; Hossain, Mohammad Enayet; Thriemer, Kamala; Auburn, Sarah; Marfurt, Jutta; Price, Ric N; Khan, Wasif A
Artemisinin resistance is present in the Greater Mekong region and poses a significant threat for current anti-malarial treatment guidelines in Bangladesh. The aim of this molecular study was to assess the current status of drug resistance in the Chittagong Hill Tracts of Bangladesh near the Myanmar border. Samples were obtained from patients enrolled into a Clinical Trial (NCT02389374) conducted in Alikadam, Bandarban between August 2014 and January 2015. Plasmodium falciparum infections were confirmed by PCR and all P. falciparum positive isolates genotyped for the pfcrt K76T and pfmdr1 N86Y markers. The propeller region of the kelch 13 (k13) gene was sequenced from isolates from patients with delayed parasite clearance. In total, 130 P. falciparum isolates were available for analysis. The pfcrt mutation K76T, associated with chloroquine resistance was found in 81.5% (106/130) of cases and the pfmdr1 mutation N86Y in 13.9% (18/130) cases. No single nucleotide polymorphisms were observed in the k13 propeller region. This study provides molecular evidence for the ongoing presence of chloroquine resistant P. falciparum in Bangladesh, but no evidence of mutations in the k13 propeller domain associated with artemisinin resistance. Monitoring for artemisinin susceptibility in Bangladesh is needed to ensure early detection and containment emerging anti-malarial resistance.
Khalil, Insaf F; Alifrangis, Michael; Recke, Camilla
In Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ) remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1...... therapeutic agent. There is a dire need to continue monitoring quality of CQ as there is a major influx of substandard and fake formulations into malaria-endemic countries. The use of fake/substandard drugs will result in sub-therapeutic levels endangering the patient and possibly select for parasite...
Full Text Available Abstract Background In Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1 therapeutic agent. There is a dire need to continue monitoring quality of CQ as there is a major influx of substandard and fake formulations into malaria-endemic countries. The use of fake/substandard drugs will result in sub-therapeutic levels endangering the patient and possibly select for parasite resistance. The aim of this study was to develop an inexpensive, simple antibody-based ELISA to measure CQ concentrations in tablets and in plasma. Methods A monoclonal antibody (MAb that reacts with the N-side chain of the CQ molecule was prepared by use of a CQ analogue. A specific and reliable ELISA for detection of CQ was developed. The developed assay was validated by measuring CQ in tablets sold in Denmark, India and Sudan. Furthermore, kinetics of CQ concentrations in plasma of four volunteers, who ingested two tablets of Malarex® containing, 250 mg CQ base, were measured before drug intake, three hours later and thereafter at days 1, 3, 7, 14, 21 and 28. The same plasma samples were simultaneously measured by high performance liquid chromatography (HPLC. Results The ELISA proved an easy-to-handle and very sensitive tool for the detection of CQ with a lower limit of detection at 3.9 ng/ml. ELISA levels of CQ in plasma showed high agreement with the levels obtained by HPLC (r = 0.98. The specificity in the negative control group was 100%. Conclusion The developed ELISA can be used for quality screening of CQ in pharmaceutical formulations and for drug monitoring in malaria and in other infectious diseases, such as HIV, where CQ proved to be an effective therapeutic agent. The methodology has been exploited to develop monoclonal
Duffy, Sandra; Avery, Vicky M
The continuous culture of Plasmodium falciparum is often seen as a means to an end, that end being to probe the biology of the parasite in question, and ultimately for many in the malaria drug discovery arena, to identify means of killing the parasite in order to treat malaria. In vitro continuous culture of Plasmodium falciparum is a fundamental requirement when undertaking malaria research where the primary objectives utilise viable parasites of a desired lifecycle stage. This investigation, and resulting data, compared the impact culturing Plasmodium falciparum long term (4 months) in different environmental conditions had on experimental outcomes and thus conclusions. The example presented here focused specifically on the effect culture conditions had on the in vitro tolerance of Plasmodium falciparum to standard anti-malarial drugs, including artemisinin and lumefantrine. Historical data from an independent experiment for 3D7-ALB (5% O 2 ) was also compared with that obtained from this study. We concluded that parasites cultured for several months in media supplemented with a serum substitute such as Albumax II ® or within hyperoxic conditions (21% O 2 ), demonstrate highly variable responses to artemisinin and lumefantrine but not all anti-malarial drugs, when compared to those cultured in human serum in combination with Albumax II ® under normoxic conditions (5% O 2 ) for the parasite. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Nanyunja, Miriam; Nabyonga Orem, Juliet; Kato, Frederick; Kaggwa, Mugagga; Katureebe, Charles; Saweka, Joaquim
Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ) was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.
Full Text Available Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.
Full Text Available Abstract Background WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT. However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa. Methods Children 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days. Results Over the course of one year, 965 children were enrolled; 158 (16.4% were RDT-positive and treated with artemether-lumefantrine and 807 (83.4% were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6% children became RDT-positive after enrolment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrolment. In addition, 12 (1.2% children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9% children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95%CI 96.9-98.7 and specificity of 96.3% (95%CI 96.3-98.4. Conclusions Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive
Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot
BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone
Jensen, Kasper; Plichta, Damian Rafal; Panagiotou, Gianni
, in order to uncover the weak links in the proteome of the parasite. We predicted 293 proteins of P. falciparum, including the six out of the seven verified targets for P. falciparum malaria treatment, as targets of 4645 GSK active compounds. Furthermore, we prioritized druggable targets, based on a number...... of factors, such as essentiality for growth, lack of homology with human proteins, and availability of experimental data on ligand activity with a non-human homologue of a parasite protein. We have additionally prioritized predicted ligands based on their polypharmacology profile, with focus on validated...
Massaquoi, Moses B F; Kennedy, Stephen B
Chloroquine-resistant plasmodium falciparum malaria is a serious public health threat that is spreading rapidly across Sub-Saharan Africa. It affects over three quarters (80%) of malarial endemic countries. Of the estimated 300-500 million cases of malaria reported annually, the vast majority of malarial-related morbidities occur among young children in Africa, especially those concentrated in the remote rural areas with inadequate access to appropriate health care services. In Liberia, in vivo studies conducted between 1993 and 2000 observed varying degrees of plasmodium falciparum malaria infections that were resistant to chloroquine, including sulfadiazine-pyrimethamine. As the country emerges from a prolonged civil war, the health care delivery system may not be adequately prepared to implement an effective nation-wide malarial control strategy. As a result, the management of uncomplicated malaria in Liberia poses a significant public health challenge for the government-financed health care delivery system. Therefore, based on extensive literature review, we report the failure of chloroquine as an effective first-line drug for the treatment of uncomplicated plasmodium falciparum malaria in Liberia and recommend that national health efforts be directed at identifying alternative drug(s) to replace it.
Newton, Paul N; Hanson, Kara; Goodman, Catherine
Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector. In 2014/15, non-QAACT were most commonly available in Kinshasa (83%), followed by Katanga (53%), Nigeria (48%), Kenya (42%), and Uganda (33%). Non-QAACT accounted for 20% of the market share in the private sector in Kenya, followed by Benin and Uganda (19%), Nigeria (12%) and Zambia (8%); this figure was 27% in Katanga and 40% in Kinshasa. Public sector non-QAACT availability and distribution was much lower, with the exception of Zambia (availability, 85%; market share, 32%). Diverse generics and formulations were available, but non-QAACT were most commonly artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA PPQ), in tablet formulation, imported, and distributed in urban areas at either pharmacies or drug stores. The number of unique manufacturers supplying non-QAACT to each country ranged from 9 in Uganda to 92 in Nigeria. Addressing the availability and distribution of non-QAACT will require effective private sector engagement and evidence-based strategies to address provider and consumer demand for these products. Given the variation in non-QAACT markets observed across the eight study countries, active efforts to limit registration, importation and distribution of non-QAACT must be tailored to the country context
Ranque, S; Marchou, B; Malvy, D; Adehossi, E; Laganier, R; Tissot-Dupont, H; Lotte, A; Dydymsky, S; Durant, J; Stahl, J-P; Bosseray, A; Gaillat, J; Sotto, A; Cazorla, C; Ragneau, J-M; Brouqui, P; Delmont, J
Data about anti-malarial drugs prescription practices in Europe and the safety of imported malaria treatments are scanty. In 1999, a French consensus development conference published guidelines for the prevention and treatment of imported P. falciparum malaria. The impact of these guidelines has not been evaluated. To investigate the impact of these guidelines on the prescription of anti-malarials, and to evaluate the incidence of acute drug events (ADEs) leading to discontinuation of treatment. Cross-sectional survey. Members of the medical staff in 14 French infectious and tropical disease wards completed a standardized form for each patient treated for imported malaria in 2001. A propensity score matching technique was used to estimate the risk of ADEs leading to discontinuation of the regimen. In the 474 patients studied, quinine was the first-line anti-malarial most often prescribed. Only 3% of patients received halofantrine. Mefloquine was associated with a RR of 4.9 (95%CI 3.2-7.4, p guidelines have been taken into account. Mefloquine was associated with a substantial risk of discontinuing the treatment because of ADEs. This is a serious limitation for the use of mefloquine in the treatment of out-patients with imported malaria.
Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot
BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone and pyrimethamine in Plasmodium yoelii was examined in such a model. METHODS: Treatment of P. yoelii infected mice, with atovaquone or pyrimethamine, was started at parasitaemia level of 3-5%, inter...
Ould Ahmedou Salem, Mohamed Salem; Mohamed Lemine, Yeslim Ould; Deida, Jemila Mint; Lemrabott, Mohamed Aly Ould; Ouldabdallahi, Mohamed; Ba, Mamadou dit Dialaw; Boukhary, Ali Ould Mohamed Salem; Khairy, Mohamed Lemine Ould; Abdel Aziz, Mohamed Boubacar; Ringwald, Pascal; Basco, Leonardo K; Niang, Saidou Doro; Lebatt, Sidi Mohamed
Background: In 2006, the Mauritanian Ministry of Health adopted a new therapeutic strategy based on the systematic use of artemisinin-based combination therapy (ACT), artesunate-amodiaquine and artemether-lumefantrine, for the first-and second-line treatment of uncomplicated malaria, respectively, regardless of Plasmodium spp. In the Saharan zone of the country, recent studies have shown that Plasmodium vivax largely predominates over Plasmodium falciparum. Anti-malarial drug response of P. v...
Full Text Available Abstract Background Effective case management is central to reducing malaria mortality and morbidity worldwide, but only a minority of those affected by malaria, have access to prompt effective treatment. In Kenya, the Division of Malaria Control is committed to ensuring that 80 percent of childhood fevers are treated with effective anti-malarial medicines within 24 hours of fever onset, but this target is largely unmet. This review aimed to document evidence on access to effective malaria treatment in Kenya, identify factors that influence access, and make recommendations on how to improve prompt access to effective malaria treatment. Since treatment-seeking patterns for malaria are similar in many settings in sub-Saharan Africa, the findings presented in this review have important lessons for other malaria endemic countries. Methods Internet searches were conducted in PUBMED (MEDLINE and HINARI databases using specific search terms and strategies. Grey literature was obtained by soliciting reports from individual researchers working in the treatment-seeking field, from websites of major organizations involved in malaria control and from international reports. Results The review indicated that malaria treatment-seeking occurs mostly in the informal sector; that most fevers are treated, but treatment is often ineffective. Irrational drug use was identified as a problem in most studies, but determinants of this behaviour were not documented. Availability of non-recommended medicines over-the-counter and the presence of substandard anti-malarials in the market are well documented. Demand side determinants of access include perception of illness causes, severity and timing of treatment, perceptions of treatment efficacy, simplicity of regimens and ability to pay. Supply side determinants include distance to health facilities, availability of medicines, prescribing and dispensing practices and quality of medicines. Policy level factors are around
Hanson Kara G
Full Text Available Abstract Background In many low-income countries, the retail sector plays an important role in the treatment of malaria and is increasingly being considered as a channel for improving medicine availability. Retailers are the last link in a distribution chain and their supply sources are likely to have an important influence on the availability, quality and price of malaria treatment. This article presents the findings of a systematic literature review on the retail sector distribution chain for malaria treatment in low and middle-income countries. Methods Publication databases were searched using key terms relevant to the distribution chain serving all types of anti-malarial retailers. Organizations involved in malaria treatment and distribution chain related activities were contacted to identify unpublished studies. Results A total of 32 references distributed across 12 developing countries were identified. The distribution chain had a pyramid shape with numerous suppliers at the bottom and fewer at the top. The chain supplying rural and less-formal outlets was made of more levels than that serving urban and more formal outlets. Wholesale markets tended to be relatively concentrated, especially at the top of the chain where few importers accounted for most of the anti-malarial volumes sold. Wholesale price mark-ups varied across chain levels, ranging from 27% to 99% at the top of the chain, 8% at intermediate level (one study only and 2% to 67% at the level supplying retailers directly. Retail mark-ups tended to be higher, and varied across outlet types, ranging from 3% to 566% in pharmacies, 29% to 669% in drug shops and 100% to 233% in general shops. Information on pricing determinants was very limited. Conclusions Evidence on the distribution chain for retail sector malaria treatment was mainly descriptive and lacked representative data on a national scale. These are important limitations in the advent of the Affordable Medicine Facility for
Patouillard, Edith; Hanson, Kara G; Goodman, Catherine A
In many low-income countries, the retail sector plays an important role in the treatment of malaria and is increasingly being considered as a channel for improving medicine availability. Retailers are the last link in a distribution chain and their supply sources are likely to have an important influence on the availability, quality and price of malaria treatment. This article presents the findings of a systematic literature review on the retail sector distribution chain for malaria treatment in low and middle-income countries. Publication databases were searched using key terms relevant to the distribution chain serving all types of anti-malarial retailers. Organizations involved in malaria treatment and distribution chain related activities were contacted to identify unpublished studies. A total of 32 references distributed across 12 developing countries were identified. The distribution chain had a pyramid shape with numerous suppliers at the bottom and fewer at the top. The chain supplying rural and less-formal outlets was made of more levels than that serving urban and more formal outlets. Wholesale markets tended to be relatively concentrated, especially at the top of the chain where few importers accounted for most of the anti-malarial volumes sold. Wholesale price mark-ups varied across chain levels, ranging from 27% to 99% at the top of the chain, 8% at intermediate level (one study only) and 2% to 67% at the level supplying retailers directly. Retail mark-ups tended to be higher, and varied across outlet types, ranging from 3% to 566% in pharmacies, 29% to 669% in drug shops and 100% to 233% in general shops. Information on pricing determinants was very limited. Evidence on the distribution chain for retail sector malaria treatment was mainly descriptive and lacked representative data on a national scale. These are important limitations in the advent of the Affordable Medicine Facility for Malaria, which aims to increase consumer access to artemisinin
Ye, Yazoume; Madise, Nyovani; Ndugwa, Robert; Ochola, Sam; Snow, Robert W
In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya. In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT) and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour. Of the 1,069 participants visited, 983 (92%) consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%-20.5%) and higher among children below five years (20.1%, 95%CI:13.8%-27.8%). Of the fever episodes with treatment information 54.3% (95%CI:46.3%-62.2%) were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine. The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies, including testing for malaria parasites to reduce the inappropriate
Full Text Available Abstract Background In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya. Methods In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour. Results Of the 1,069 participants visited, 983 (92% consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%–20.5% and higher among children below five years (20.1%, 95%CI:13.8%–27.8%. Of the fever episodes with treatment information 54.3% (95%CI:46.3%–62.2% were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine. Conclusion The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies
Nicole M Fett
Morphea is a rare fibrosing disorder of the skin. Evidence-based treatment strategies in morphea are lacking. This review summarizes the available data on morphea treatment and provides therapeutic strategies based on morphea subtypes. The Cochrane Library, Medline and Embase from inception until May of 2011 were searched using the key words "morphea" and "morphea treatment." Reference lists of the resultant articles, as well as relevant reviews, were also searched. This review focuses on ran...
Famenini, Shannon; Goh, Carolyn
Currently, topical minoxidil and finasteride are the only treatments that have been FDA approved for the treatment of female pattern hair loss and androgenetic alopecia. Given the incomplete efficacy and sife effect profile of these medications, some patients utilize alternative treatments to help improve this condition. In this review, we illustrate the scientific evidence underlying the efficacy of these alternative approaches, including biotin, caffeine, melatonin, a marine extract, and zinc.
Nicole M Fett
Full Text Available Morphea is a rare fibrosing disorder of the skin. Evidence-based treatment strategies in morphea are lacking. This review summarizes the available data on morphea treatment and provides therapeutic strategies based on morphea subtypes. The Cochrane Library, Medline and Embase from inception until May of 2011 were searched using the key words "morphea" and "morphea treatment." Reference lists of the resultant articles, as well as relevant reviews, were also searched. This review focuses on randomized controlled trials, prospective interventional trials without controls and retrospective reviews with greater than five subjects.
Vaughan-Williams Charles H; Raman Jaishree; Raswiswi Eric; Immelman Etienne; Reichel Holger; Gate Kelly; Knight Steve
Abstract Background Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine w...
Khin, Hnin Su Su; Aung, Tin; Aung, Moe; Thi, Aung; Boxshall, Matt; White, Chris
In 2012, alarmingly high rates of oral artemisinin monotherapy availability and use were detected along Eastern Myanmar, threatening efforts to halt the spread of artemisinin resistance in the Greater Mekong Subregion (GMS), and globally. The aim of this paper is to exemplify how the use of supply side evidence generated through the ACTwatch project shaped the artemisinin monotherapy replacement malaria (AMTR) project's design and interventions to rapidly displace oral artemisinin monotherapy with subsidized, quality-assured ACT in the private sector. The AMTR project was implemented as part of the Myanmar artemisinin resistance containment (MARC) framework along Eastern Myanmar. Guided by outlet survey and supply chain evidence, the project implemented a high-level subsidy, including negotiations with a main anti-malarial distributor, with the aim of squeezing oral artemisinin monotherapy out of the market through price competition and increased availability of quality-assured artemisinin-based combinations. This was complemented with a plethora of demand-creation activities targeting anti-malarial providers and consumers. Priority outlet types responsible for the distribution of oral artemisinin monotherapy were identified by the outlet survey, and this evidence was used to target the AMTR project's supporting interventions. The widespread availability and use of oral artemisinin monotherapy in Myanmar has been a serious threat to malaria control and elimination in the country and across the region. Practical anti-malarial market evidence was rapidly generated and used to inform private sector approaches to address these threats. The program design approach outlined in this paper is illustrative of the type of evidence generation and use that will be required to ensure effective containment of artemisinin drug resistance and progress toward regional and global malaria elimination goals.
Full Text Available Abstract Background Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. Methods In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. Results SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. Conclusion These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed.
Full Text Available Objective To evaluate the current treatments and possible adverse reactions of metabolic myopathy, and to develop the best solution for evidence-based treatment. Methods Taking metabolic myopathy, mitochondrial myopathy, lipid storage myopathy, glycogen storage diseases, endocrine myopathy, drug toxicity myopathy and treatment as search terms, retrieve in databases such as PubMed, Cochrane Library, ClinicalKey database, National Science and Technology Library (NSTL, in order to collect the relevant literature database including clinical guidelines, systematic reviews (SR, randomized controlled trials (RCT, controlled clinical trials, retrospective case analysis and case study. Jadad Scale was used to evaluate the quality of literature. Results Twenty-eight related articles were selected, including 6 clinical guidelines, 5 systematic reviews, 10 randomized controlled trials and 7 clinical controlled trials. According to Jadad Scale, 23 articles were evaluated as high-quality literature (≥ 4, and the remaining 5 were evaluated as low-quality literature (< 4. Treatment principles of these clinical trials, efficacy of different therapies and drug safety evaluation suggest that: 1 Acid α-glycosidase (GAA enzyme replacement therapy (ERT is the main treatment for glycogen storage diseases, with taking a high-protein diet, exercising before taking a small amount of fructose orally and reducing the patient's physical activity gradually. 2 Carnitine supplementation is used in the treatment of lipid storage myopathy, with carbohydrate and low fat diet provided before exercise or sports. 3 Patients with mitochondrial myopathy can take coenzyme Q10, vitamin B, vitamin K, vitamin C, etc. Proper aerobic exercise combined with strength training is safe, and it can also enhance the exercise tolerance of patients effectively. 4 The first choice to treat the endocrine myopathy is treating primary affection. 5 Myopathies due to drugs and toxins should
Full Text Available Abstract Background After adoption of artesunate-amodiaquine (AS/AQ as first-line therapy for the treatment of uncomplicated malaria by the malaria control programme, this study was designed to assess the availability of anti-malarial drugs, treatment practices and acceptability of the new protocol by health professionals, in the urban health facilities and drugstores of Yaoundé city, Cameroon. Methods Between April and August 2005, retrospective and current information was collected by consulting registers and interviewing health practitioners in urban health facilities using a structured questionnaire. Results In 2005, twenty-seven trade-named drugs have been identified in drugstores; quinine tablets (300 mg were the most affordable anti-malarial drugs. Chloroquine was restricted to food market places and no generic artemisinin derivative was available in public health centres. In public health facilities, 13.6% of health professionals were informed about the new guidelines; 73.5% supported the use of AS-AQ as first-line therapy. However, 38.6% apprehended its use due to adverse events attributed to amodiaquine. Malaria treatment was mainly based on the diagnosis of fever. Quinine (300 mg tablets was the most commonly prescribed first-line anti-malarial drug in adults (44.5% and pregnant women (52.5%. Artequin® was the most cited artemsinin-based combination therapy (ACT (9.9%. Medical sales representatives were the main sources of information on anti-malarials. Conclusion The use of AS/AQ was not implemented in 2005 in Yaoundé, despite the wide range of anti-malarials and trade-named artemisinin derivatives available. Nevertheless, medical practitioners will support the use of this combination, when it is available in a paediatric formulation, at an affordable price. Training, information and participation of health professionals in decision-making is one of the key elements to improve adherence to new protocol guidelines. This baseline
Full Text Available Rubesh Gooriah, Alina Buture, Fayyaz Ahmed Department of Neurology, Hull Royal Infirmary, Kingston upon Hull, UK Abstract: Cluster headache (CH, one of the most painful syndromes known to man, is managed with acute and preventive medications. The brief duration and severity of the attacks command the use of rapid-acting pain relievers. Inhalation of oxygen and subcutaneous sumatriptan are the two most effective acute therapeutic options for sufferers of CH. Several preventive medications are available, the most effective of which is verapamil. However, most of these agents are not backed by strong clinical evidence. In some patients, these options can be ineffective, especially in those who develop chronic CH. Surgical procedures for the chronic refractory form of the disorder should then be contemplated, the most promising of which is hypothalamic deep brain stimulation. We hereby review the pathogenesis of CH and the evidence behind the treatment options for this debilitating condition. Keywords: cluster headache, pathogenesis, vasoactive intestinal peptide, suprachiasmatic nucleus
Spelman, Kevin; Depoix, Delphine; McCray, Megan; Mouray, Elisabeth; Grellier, Philippe
Spilanthes spp. are used as traditional herbal medicines in Africa and India to treat malaria. Yet, to date, there is no data on active constituents or most effective extraction methods for this indication. The isolated alkylamides, spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide, found in S. acmella Murr., were shown to have IC50s of 16.5 μg/mL and 41.4 μg/mL on Plasmodium falciparum strain PFB and IC50s of 5.8 μg/mL and 16.3 μg/mL for the chloroquine resistant P. falciparum K1 strain, respectively. Further investigations revealed that at relatively low concentrations, spilanthol and the water extract of S. acmella reduced the parasitemia 59% and 53% in mice infected with P. yoelii yoelii 17XNL at 5 mg/kg and 50 mg/kg, respectively. Unexpectedly, the 95% ethanol extract of S. acmella was less effective (36% reduction in parasitemia) at 50 mg/kg. These results provide the first evidence supporting S. acmella against malaria and demonstrating active constituents in S. acmella against P. falciparum. PMID:22692989
Ranjitkar, Samir; Schousboe, Mette L; Thomsen, Thomas
ABSTRACT: BACKGROUND: Sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) have been used in treatment of falciparum and vivax malaria in Nepal. Recently, resistance to both drugs have necessitated a change towards artemisinin combination therapy (ACT) against Plasmodium falciparum in highly...... endemic areas. However, SP is still used against P. falciparum infections in low endemic areas while CQ is used in suspected cases in areas with lack of diagnostic facilities. This study examines the prevalence of molecular markers of P. falciparum and Plasmodium vivax CQ and SP resistance to determine...... and P. vivax for CQ (Pfcrt, Pfmdr1, Pvmdr1) and SP (Pfdhfr, Pfdhps, Pvdhfr), using various PCR-based methods. RESULTS AND DISCUSSION: Positive P. vivax and P. falciparum infections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based...
Ndyomugyenyi, Richard; Magnussen, Pascal; Clarke, Siân
assessed in an area of low transmission in south-western Uganda. Methods The study had two components: 1) passive case detection where all patients attending the out patient clininc with a febrile illness were included and 2) a longitudinal active malaria case detection survey was conducted in selected...... negative cases received alternative treatment. Conclusion In low-transmission areas, more attention needs to be paid to differential diagnosis of febrile illnesses In view of suggested changes in anti-malarial drug policy, introducing costly artemisinin combination therapy accurate, rapid diagnostic tools...
Recent reviews of evidence-based treatment for depression did not identify behavioral activation as an evidence-based practice. Therefore, this article conducted a systematic review of behavioral activation treatment of depression, which identified three meta-analyses, one recent randomized controlled trial and one recent follow-up of an earlier…
Full Text Available Oral phenobarbital and imepitoin in particular, followed by potassium bromide and levetiracetam are likely to be effective for the treatment of canine idiopathic epilepsy. There is strong evidence supporting the use of oral phenobarbital and imepitoin as ‘first line’ medications. However, there remains a lack of evidence for targeted treatment for the various individual epileptic phenotypes and quite limited evidence on direct comparisons of the efficacy between various anti-epileptic drugs.
There is, thus, the need to initiate further in-depth investigation by using different experimental ... antiprotozoal compounds, a sapogenin (muzanzagenin) and lignan ((+) .... The microscope had an. Ehrlich's ... 100 red blood cells per field.
Lowes, David; Pradhan, Anupam; Iyer, Lalitha V.; Parman, Toufan; Gow, Jason; Zhu, Fangyi; Furimsky, Anna; Lemoff, Andrew; Guiguemde, W. Armand; Sigal, Martina; Clark, Julie A.; Wilson, Emily; Tang, Liang; Connelly, Michele C.; DeRisi, Joseph L.; Kyle, Dennis E.; Mirsalis, Jon; Guy, R. Kiplin
Previously reported studies identified analogs of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are non-toxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges. PMID:22708838
MATERIALS AND METHODS. Study Design. The study was a cross ... Muhammadu Sanusi General Hospital (SMSGH) and ... regimens, guided focus group presentations and one .... to the optimal theoretical value of 17.2% proposed in.
Artemisinin is a naturally occurring antimalarial showing anticancer properties. ..... Artemisinins usually promote apoptosis rather than necrosis in most cases ... artemisinin-mediated inhibition of vascular endothelial growth factor C (VEGF-C).
A PubMed search of about 127 papers on anti‑cancer effects of antimalarials has revealed that this class of drug, including other antimalarials, have several biological characteristics that include anticancer properties. ... Keywords: Anticancer agents, Antimalarials, Antitumor activity, Artemisinins, Novel chemotherapy ...
Lin, Chung-Wei Christine; Hiller, Claire E; de Bie, Rob A
The most common ankle injuries are ankle sprain and ankle fracture. This review discusses treatments for ankle sprain (including the management of the acute sprain and chronic instability) and ankle fracture, using evidence from recent systematic reviews and randomized controlled trials. After ankle sprain, there is evidence for the use of functional support and non-steroidal anti-inflammatory drugs. There is weak evidence suggesting that the use of manual therapy may lead to positive short-t...
Gaillard, Tiphaine; Briolant, Sébastien; Madamet, Marylin; Pradines, Bruno
Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. However, doxycycline is not used in young children under 8 years of age due to its contraindication due to the risk of yellow tooth discolouration and dental enamel hypoplasia. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines. However, recent studies report little or no effects of doxycycline on tooth staining or dental enamel hypoplasia in children under 8 years of age. In the United States, the Centers for Disease Control and Prevention have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age.
Plucinski, Mateusz M; Dimbu, Pedro Rafael; Macaia, Aleixo Panzo; Ferreira, Carolina Miguel; Samutondo, Claudete; Quivinja, Joltim; Afonso, Marília; Kiniffo, Richard; Mbounga, Eliane; Kelley, Julia S; Patel, Dhruviben S; He, Yun; Talundzic, Eldin; Garrett, Denise O; Halsey, Eric S; Udhayakumar, Venkatachalam; Ringwald, Pascal; Fortes, Filomeno
Recent anti-malarial resistance monitoring in Angola has shown efficacy of artemether-lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013. During January-June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate-amodiaquine (ASAQ), or dihydroartemisinin-piperaquine (DP). The study comprised two treatment arms in each of three provinces: Benguela (AL, ASAQ), Zaire (AL, DP), and Lunda Sul (ASAQ, DP). Samples from treatment failures were analysed for molecular markers of resistance for artemisinin (K13) and lumefantrine (pfmdr1). A total of 467 children reached a study endpoint. Fifty-four treatment failures were observed: four early treatment failures, 40 re-infections and ten recrudescences. Excluding re-infections, the 28-day microsatellite-corrected efficacy was 96.3% (95% CI 91-100) for AL in Benguela, 99.9% (95-100) for ASAQ in Benguela, 88.1% (81-95) for AL in Zaire, and 100% for ASAQ in Lunda Sul. For DP, the 42-day corrected efficacy was 98.8% (96-100) in Zaire and 100% in Lunda Sul. All treatment failures were wild type for K13, but all AL treatment failures had pfmdr1 haplotypes associated with decreased lumefantrine susceptibility. No evidence was found to corroborate the specific allegation of artemisinin resistance in Lunda Sul. The efficacy below 90% of AL in Zaire matches findings from 2013 from the same site. Further monitoring, particularly including measurement of lumefantrine blood levels, is recommended.
Schaffner, Angela D.; Buchanan, Linda Paulk
This study examined the current issues relevant to implementing evidence-based practices in the context of outpatient treatment for eating disorders. The study also examined the effectiveness of an outpatient treatment program for eating disorders among a group of 196 patients presenting with anorexia nervosa, bulimia nervosa, or eating disorder…
Evidence-based medicine is an approach to medical treatment intended to optimize patient-oriented decision-making on the basis of empirically proven effectiveness. For this purpose, a classification system has been established to categorize studies – and hence therapy options – in respect of associated evidence according to defined criteria. The Eustachian tube connects the nasopharynx with the middle ear cavity. Its key function is to ensure middle ear ventilation. Compromised ventilation results in inflammatory middle ear disorders. Numerous evidence-based therapy options are available for the treatment of impaired middle ear ventilation and otitis media, the main therapeutic approach being antibiotic treatment. More recent procedures such as balloon dilation of the Eustachian tube have also shown initial success but must undergo further evaluation with regard to evidence. There is, as yet, no evidence for some of the other long-established procedures. Owing to the multitude of variables, the classification of evidence levels for various treatment approaches calls for highly diversified assessment. Numerous evidence-based studies are therefore necessary in order to evaluate the evidence pertaining to existing and future therapy solutions for impaired middle ear ventilation and otitis media. If this need is addressed, a wealth of implications can be expected for therapeutic approaches in the years to come. PMID:28025605
Findling, Robert L
Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes. © Copyright 2016 Physicians Postgraduate Press, Inc.
Sienaert, P.; Lambrichts, L.; Dols, A.; De Fruyt, J.
Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment-resistant bipolar
Full Text Available Abstract Background Intermittent Preventive Treatment for malaria control in infants (IPTi consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204]. Methods After baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12 or not (n = 12. Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived. Results Survival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P P = 0.31. Conclusion The lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.
Lunt, Neil; Horsfall, Daniel; Hanefeld, Johanna
The scoping review focuses on medical tourism, whereby consumers elect to travel across borders or to overseas destinations to receive their treatment. Such treatments include: cosmetic and dental surgery; cardio, orthopaedic and bariatric surgery; IVF; and organ and tissue transplantation. The review assesses the emerging focus of research evidence post-2010. The narrative review traverses discussion on medical tourism definitions and flows, consumer choice, clinical quality and outcomes, and health systems implications. Attention is drawn to gaps in the research evidence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Bettany-Saltikov, Josette; Turnbull, Deborah; Ng, Shu Yan; Webb, Richard
Introduction: The review evaluates the up-to-date evidence for the treatment of spinal deformities, including scoliosis and hyperkyphosis in adolescents and adults. Material and Methods: The PubMed database was searched for review articles, prospective controlled trials and randomized controlled trials related to the treatment of spinal deformities. Articles on syndromic scoliosis were excluded and so were the articles on hyperkyphosis of the spine with causes other than Scheuermann’s disease and osteoporosis. Articles on conservative and surgical treatments of idiopathic scoliosis, adult scoliosis and hyperkyphosis were also included. For retrospective papers, only studies with a follow up period exceeding 10 years were included. Results: The review showed that early-onset idiopathic scoliosis has a worse outcome than late-onset idiopathic scoliosis, which is rather benign. Patients with AIS function well as adults; they have no more health problems when compared to patients without scoliosis, other than a slight increase in back pain and aesthetic concern. Conservative treatment of adolescent idiopathic scoliosis (AIS) using physiotherapeutic scoliosis-specific exercises (PSSE), specifically PSSR and rigid bracing was supported by level I evidence. Yet to date, there is no high quality evidence (RCT`s) demonstrating that surgical treatment is superior to conservative treatment for the management of AIS. For adult scoliosis, there are only a few studies on the effectiveness of PSSEs and a conclusion cannot as yet be drawn. For hyperkyphosis, there is no high-quality evidence for physiotherapy, bracing or surgery for the treatment of adolescents and adults. However, bracing has been found to reduce thoracic hyperkyphosis, ranging from 55 to 80° in adolescents. In patients over the age of 60, bracing improves the balance score, and reduces spinal deformity and pain. Surgery is indicated in adolescents and adults in the presence of progression of kyphosis
Full Text Available Objective. To perform an evidence-based review of treatments for Toxoplasma retinochoroiditis (TRC. Methods. A systematic literature search was performed using the PubMed database and the key phrase “ocular toxoplasmosis treatment” and the filter for “controlled clinical trial” and “randomized clinical trial” as well as OVID medline (1946 to May week 2 2014 using the keyword ‘‘ocular toxoplasmosis’’. The included studies were used to evaluate the various treatment modalities of TRC. Results. The electronic search yielded a total of 974 publications of which 44 reported on the treatment of ocular toxoplasmosis. There were 9 randomized controlled studies and an additional 3 comparative studies on the treatment of acute TRC with systemic or intravitreous antibiotics or on reducing the recurrences of TRC. Endpoints of studies included visual acuity improvement, inflammatory response, lesion size changes, recurrences of lesions, and adverse effects of medications. Conclusions. There was conflicting evidence as to the effectiveness of systemic antibiotics for TRC. There is no evidence to support that one antibiotic regimen is superior to another so choice needs to be informed by the safety profile. Intravitreous clindamycin with dexamethasone seems to be as effective as systemic treatments. There is currently level I evidence that intermittent trimethoprim-sulfamethoxazole prevents recurrence of the disease.
Meroni, Pier Luigi
Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions. AMs display a pleiotropic activity spanning from immunomodulation effect to anti-inflammatory and anti-thrombotic activities, all of which potentially useful in APS. The well-known safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune rheumatic disorders including APS and observational reports suggested a protective effect on obstetrical recurrences. Since thrombosis does not seem to be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment with HCQ should be related to other pharmacological effects rather than to the anti-platelet or anti-thrombotic activity of the molecule. Experimental models showed that HCQ may restore some defective biological functions induced by anti-phospholipid antibodies (aPL) on trophoblasts and a recent study reported a protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental abnormalities. Although the rational behind the use of HCQ in obstetric APS is sound, the evidence from the real life is not conclusive and a critical appraisal through clinical trials is mandatory. Copyright © 2016. Published by Elsevier Ltd.
Toma, Alemayehu; Deyno, Serawit; Fikru, Abrham; Eyado, Amalework; Beale, Andrew
Medicinal plants have contributed significantly to current malaria treatment. Emergence of resistance to currently available drugs has necessitated the search for new plant-based anti-malarial agents and several plant-based, pharmacologically active anti-malarial compounds have been isolated. This study was conducted to validate the traditional usage of Echinops kebericho for treating malaria in the traditional health care system of Ethiopia. The roots of E. kebericho were collected from Masha Woreda, Sheka Zone. After collection, the plant materials were identified by a taxonomist, dried under shade and crushed to powder for extraction. The powdered roots were extracted by maceration using 70 % ethanol. Acute toxicity study of the crude extract was carried out in Swiss albino mice. The in vivo anti-malarial activity of plant extract (200, 350 and 500 mg/kg) of E. kebericho roots against a chloroquine (CQ) sensitive strain of Plasmodium berghei strain ANKA was assessed using the four-day suppressive test procedure. Parameters such as parasitaemia, packed cell volume, body weight and survival time were then determined using standard tests. Oral administration of the ethanol extract showed significant (P<0.001) parasitaemia suppression at dose levels of 350 and 500 mg/kg in dose-related manner compared with the negative control. Five hundred mg/kg showed the highest (57.29±1.76 %) parasitaemia suppression. The survival times of P. berghei-infected mice were also increased in a dose-dependent manner but the test material did not prevent weight loss associated with increased parasitaemia. The result also showed the plant material prevented the loss in packed cell volume associated with increased parasitaemia. Its oral LD50 was found to be greater than 5,000 mg/kg, indicating its wider safety margin in mice. The result revealed the ethanol extract of E. kebericho roots has anti-malarial activity against P. berghei in an animal model and lends support to the use of the
Currently there are three well-established treatment options for hyperthyroid Graves' disease (GD): antithyroid drug therapy with thionamides (ATD), radioactive iodine treatment with (131)I, and thyroid surgery. This article reviews the current evidence so the reader can evaluate advantages...... and disadvantages of these treatment modalities. Surgery is rarely used, except for patients who have a large goiter or ophthalmopathy. Fewer than 50% of patients treated with ATD remain in long-term remission. Therefore, radioactive iodine is used increasingly. No data as yet support the routine use of biologic...
Christiansen, Ole B; Nybo Andersen, Anne-Marie; Bosch, Ernesto
OBJECTIVE: To give an overview of currently used investigations and treatments offered to women with recurrent pregnancy loss (RPL) and, from an evidence-based point of view, to evaluate the usefulness of these interventions. DESIGN: Ten experts on epidemiologic, genetic, anatomic, endocrinologic......, thrombophilic, immunologic, and immunogenetic aspects of RPL discussed methodologic problems threatening the validity of research in RPL during and after an international workshop on the evidence-based management of RPL. CONCLUSION(S): Most RPL patients have several risk factors for miscarriage...
Full Text Available Objective To formulate the best treatment plan for multiple sclerosis (MS patients by evaluating the therapeutic efficacy and side effect of various evidence-based programs. Methods Key words were defined as multiple sclerosis, immunomodulatory therapy and therapy, etc. We searched MEDLINE, Cochrane Library, Wanfang data bases for Scientific Journals in China and National Knowledge Infrastructure for Chinese Scientific Journals Database. Additionally, we applied manual searching and screened out conference paper and academic dissertation, etc, from various references. After that we obtained and evaluated by Jadad scales on systematic reviews, randomized controlled trials, controlled clinical trials and observational study cases about glucocorticoids, plasmapheresis, intravenous immunoglobulin, IFN-β, glatiramer acetate, mitoxantrone, natalizumab, fingolimod. Results After screening, all seventeen selected resources included systematic reviews 6 articles, randomized controlled trials 7 articles, controlled clinical trials 2 articles, observational study cases 2 articles, among which fifteen articles were proved to be high quality (according to Jadad scoring system, five score 4, six score 5, four score 7, two chapters were judged to be low quality scoring 3. Finally, we summerize that: 1 The first choice of treatment for acute relapses is glucocorticoids and we suggest that plasmapheresis or intravenous immunoglobulin may be tried as an alternative therapy in acute MS relapse, especially in case of contraindications to intravenous methylprednisolone. 2 Immunomodulatory or immunosuppressive treatment (IFN-β, glatiramer acetate, mitoxantrone, natalizumab can be an option to prevent new relapses and progression of disability. 3 Fingolimod is an oral treatment for multiple sclerosis to improve treatment adherence. Conclusion Using evidence-based medicine methods can provide us best clinical evidence on MS treatment.
Finnerup, Nanna Brix; Sindrup, Søren Hein; Jensen, Troels Staehelin
Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids are the drug classes for which there is the best evidence for a clinical relevant effect. Despite a 66% increase in published trials only a limited improvement of neuropathic pain treatment has been obtained. A large proportion of neuropathic pain patients are left with insufficient pain relief. This fact calls for other treatment options to target chronic neuropathic pain. Large-scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism-based classification may help improve treatment of the individual patients. Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Hinshaw, Stephen P; Arnold, L Eugene
Given major increases in the diagnosis of attention-deficit hyperactivity disorder (ADHD) and in rates of medication for this condition, we carefully examine evidence for effects of single versus multimodal (i.e., combined medication and psychosocial/behavioral) interventions for ADHD. Our primary data source is the Multimodal Treatment Study of Children with ADHD (MTA), a 14-month, randomized clinical trial in which intensive behavioral, medication, and multimodal treatment arms were contrasted with one another and with community intervention (treatment-as-usual), regarding outcome domains of ADHD symptoms, comorbidities, and core functional impairments. Although initial reports emphasized the superiority of well-monitored medication for symptomatic improvement, reanalyses and reappraisals have highlighted (a) the superiority of combination treatment for composite outcomes and for domains of functional impairment (e.g., academic achievement, social skills, parenting practices); (b) the importance of considering moderator and mediator processes underlying differential patterns of outcome, including comorbid subgroups and improvements in family discipline style during the intervention period; (c) the emergence of side effects (e.g., mild growth suppression) in youth treated with long-term medication; and (d) the diminution of medication's initial superiority once the randomly assigned treatment phase turned into naturalistic follow-up. The key paradox is that whereas ADHD clearly responds to medication and behavioral treatment in the short term, evidence for long-term effectiveness remains elusive. We close with discussion of future directions and a call for greater understanding of relevant developmental processes in the attempt to promote optimal, generalized, and lasting treatments for this important and impairing neurodevelopmental disorder.
Breitbart, William; Alici, Yesne
Delirium is the most common neuropsychiatric complication seen in patients with cancer, and it is associated with significant morbidity and mortality. Increased health care costs, prolonged hospital stays, and long-term cognitive decline are other well-recognized adverse outcomes of delirium. Improved recognition of delirium and early treatment are important in diminishing such morbidity. There has been an increasing number of studies published in the literature over the last 10 years regarding delirium treatment as well as prevention. Antipsychotics, cholinesterase inhibitors, and alpha-2 agonists are the three groups of medications that have been studied in randomized controlled trials in different patient populations. In patients with cancer, the evidence is most clearly supportive of short-term, low-dose use of antipsychotics for controlling the symptoms of delirium, with close monitoring for possible adverse effects, especially in older patients with multiple medical comorbidities. Nonpharmacologic interventions also appear to have a beneficial role in the treatment of patients with cancer who have or are at risk for delirium. This article presents evidence-based recommendations based on the results of pharmacologic and nonpharmacologic studies of the treatment and prevention of delirium. PMID:22412123
Mansion-de Vries, E M; Hoedemaker, M; Krömker, V
Mastitis is one of the most common and expensive diseases in dairy cattle. The decision to treat clinical mastitis is usually made without any knowledge of the etiology, and can therefore only be evidence-based to a limited extent. Evidence-based medicine relies essentially on a combination of one's own clinical competence and scientific findings. In mastitis therapy, those insights depend mostly on pathogen-specific factors. Therefore, in evidence-based therapeutic decision making the pathogen identification should serve as a basis for the consideration of scientifically validated therapeutic concepts. The present paper considers evidence-based treatment of clinical mastitis based on a literature review. The authors conclude that an anti-inflammatory treatment using an NSAID should be conducted regardless of the pathogen. However, the choice of an antibiotic therapy depends on the mastitis causative pathogen, clinical symptoms and the animal itself. In principle, a local antibiotic treatment should be chosen for mild and moderate mastitis. It should be noted, that the benefit of an antibiotic therapy for coliform infections is questionable. With knowledge concerning the pathogen, it appears entirely reasonable to refrain from an antibiotic therapy. For severe (i. e. feverish) mastitis, a parenteral antibiotic therapy should be selected. An extension of the antibiotic therapy beyond the manufacturer's information is only reasonable for streptococcal infections. It is important to make the decision on a prolonged antibiotic therapy only with the knowledge of the mastitis-causative pathogen. In terms of the therapy of a staphylococcus or streptococcus infection, a narrow-spectrum antibiotic from the penicillin family should be adopted when selecting the active agents.
Full Text Available Objective To formulate the best treatment plan for Alzheimer's disease patients by evaluating the therapeutic efficacy and side effect of various evidence-based programs. Methods Alzheimer's disease, donepezil, rivastigmine, galantamine, memantine, rosiglitazone, etc. were defined as retrieval words. PubMed, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases were used with applying of manual searching. Systematic reviews, randomized controlled trials (RCT, controlled clinical trials and case-observation studies were collected and evaluated by Jadad Scale. Results After screening, 33 selected resources included 14 systematic reviews, 14 randomized controlled trials, 4 controlled clinical trials and 1 case-observation study. According to Jadad Scale, total 28 articles were evaluated to be high quality (12 with score 4, 10 score 5, 6 score 7, and 5 were low quality with score 3. It was summarized as follows: 1 Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. To date, only symptomatic treatments with cholinesterase inhibitors (donepezil, rivastigmine, galantamine and an N-methyl-D-aspartate (NMDA receptor noncompetitive antagonist (memantine, are effective and well tolerated to counterbalance the neurotransmitter disturbance, but cannot limit or impact on disease progression. 2 Disease modifying drug is an potential agent, with persistent effect on slowing the progression of structural damage, and can be detected even after withdrawing the treatment. Many types of disease modifying drugs are undergoing clinical trials. Conclusions Using evidence-based medicine methods can provide best clinical evidence on Alzheimer's disease treatment. doi: 10.3969/j.issn.1672-6731.2014.03.009
Full Text Available Over the last decade, investigators have paid increasing attention to the effects of resistance training (RT on several metabolic syndrome variables. Evidence suggests that skeletal muscle is responsible for up to 40% of individuals' total body weight and may be influential in modifying metabolic risk factors via muscle mass development. Due to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. The purpose of this review is to (1 evaluate the potential clinical effectiveness and biological mechanisms of RT in the treatment of obesity and (2 provide up-to-date evidence relating to the impact of RT in reducing major cardiovascular disease risk factors (including dyslipidaemia and type 2 diabetes. A further aim of this paper is to provide clinicians with recommendations for facilitating the use of RT as therapy in obesity and obesity-related metabolic disorders.
Full Text Available Abstract Background Prompt access to effective malaria treatment is central to the success of malaria control worldwide, but few fevers are treated with effective anti-malarials within 24 hours of symptoms onset. The last two decades saw an upsurge of initiatives to improve access to effective malaria treatment in many parts of sub-Saharan Africa. Evidence suggests that the poorest populations remain least likely to seek prompt and effective treatment, but the factors that prevent them from accessing interventions are not well understood. With plans under way to subsidize ACT heavily in Kenya and other parts of Africa, there is urgent need to identify policy actions to promote access among the poor. This paper explores access barriers to effective malaria treatment among the poorest population in four malaria endemic districts in Kenya. Methods The study was conducted in the poorest areas of four malaria endemic districts in Kenya. Multiple data collection methods were applied including: a cross-sectional survey (n = 708 households; 24 focus group discussions; semi-structured interviews with health workers (n = 34; and patient exit interviews (n = 359. Results Multiple factors related to affordability, acceptability and availability interact to influence access to prompt and effective treatment. Regarding affordability, about 40 percent of individuals who self-treated using shop-bought drugs and 42 percent who visited a formal health facility reported not having enough money to pay for treatment, and having to adopt coping strategies including borrowing money and getting treatment on credit in order to access care. Other factors influencing affordability were seasonality of illness and income sources, transport costs, and unofficial payments. Regarding acceptability, the major interrelated factors identified were provider patient relationship, patient expectations, beliefs on illness causation, perceived effectiveness of treatment, distrust in
Finnerup, Nanna Brix; Sindrup, Søren Hein; Jensen, Troels Staehelin
to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes......Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used......) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids...
To be an autonomous agent is to determine one's own path in life. However, this cannot plausibly be seen as a one-off affair. An autonomous agent does not merely set herself on a particular course and then lock the steering wheel in place, so to speak, but must maintain some form of ongoing control over her direction in life-must keep her eyes on the road and her hands on the wheel. Circumstances often change in important and unexpected ways, after all, and it is reasonable to think that a crucial part of autonomy consists of the ability and disposition to recognize and properly respond to such changes. This implies, I contend, that a patient whose initial decision to undergo a given treatment satisfied plausible requirements of autonomy, but who is now unable to recognize that available evidence indicates the need to reconsider her medical situation and options has come to lack autonomy with respect to her desire to continue that treatment. However, and despite its importance with respect to both theoretical understandings of autonomy and applications of the concept to clinical ethics, this ongoing aspect of autonomy has received little attention. This paper aims to go some way toward remedying that. I first critically review two of the few theories of autonomy that do address "evidence-responsiveness" so as to identify and elaborate what I take to be the most promising way in which to account for this aspect of autonomy. After considering and responding to a possible objection to the evidence-responsiveness condition I propose, I conclude by discussing its clinical implications. That condition, I argue, is not merely theoretically sound, but can and should be applied to clinical practice.
Liu, Jenny X; Modrek, Sepideh
In Nigeria, access to malaria diagnostics may be expanded if drug retailers were allowed to administer malaria rapid diagnostic tests (RDTs). A 2012 pilot intervention showed that short message service (SMS) reminder messages could boost treatment adherence to RDT results by 10-14% points. This study aimed to replicate the SMS intervention in a different population, and additionally test the effect of an expanded message about anticipated RDT access policy change on customers' acceptability for drug retailers' administration of RDTs. One day after being tested with an RDT, participants who purchased malaria treatment from drug shops were randomized to receive (1) a basic SMS reminder repeating the RDT result and appropriate treatment actions, (2) an expanded SMS reminder additionally saying that the 'government might allow pharmacists/chemists to do RDTs' or (3) no SMS reminders (i.e. control). Using regression analysis, we estimate intent-to-treat (ITT) and treatment effects on the treated for 686 study participants. Results corroborate previous findings that a basic SMS reminder increased treatment adherence [odds ratio (OR) = 1.53, 95% CI 0.96-2.44] and decreased use of unnecessary anti-malarials for RDT-negative adults [OR = 0.63, 95% CI 0.39-1.00]. The expanded SMS also increased adherence for adults [OR = 1.42, 95% CI 0.97-2.07], but the effects for sick children differed-the basic SMS did not have any measurable impact on treatment adherence [OR = 0.87, 95% CI 0.24-3.09] or use of unnecessary anti-malarials [OR = 1.27, 95% CI 0.32-1.93], and the expanded SMS actually led to poorer treatment adherence [OR = 0.26, 95% CI 0.10-0.66] and increased use of unnecessary anti-malarials [OR = 4.67, 95% CI 1.76-12.43]. Further, the targeted but neutral message in the expanded SMS lowered acceptance for drug retailers' administration of RDTs [OR = 0.55, 95% CI 0.10-2.93], counter to what we hypothesized. Future SMS interventions should
Jacobsen, Iben Brock; Henriksen, J E; Hother-Nielsen, O
AIM: Evaluation of the evidence base for recommending different insulin treatment regimens in type 1 diabetes. METHODS: A computerised literature survey was conducted using The Cochrane Controlled Trials Register and the Pub Med database for the period of 1982-2007. RESULTS: A meta-analysis on only...... 49 out of 1295 references showed that CSII compared with conventional or multiple insulin injections therapy demonstrated a significant reduction in mean HbA1c (primary outcome) of 1.2% CI [0.73; 1.59] (P... daily insulin injections was based on only one publication demonstrating an improved quality of life but no significant reduction in HbA1c or hypoglycaemia. A comparison of rapid-acting insulin analogues and human soluble insulin demonstrated a statistically significant reduction in HbA1c of 0.1% CI: [0...
Kam Lun Hon
Full Text Available Aim: To review current classes of emollients in the market, their clinical efficacy in atopic dermatitis (AD and considerations for choice of an emollient. Methods: PubMed Clinical Queries under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow and Systematic Reviews were used as the search engine. Keywords of ‘emollient or moisturizer’ and ‘atopic dermatitis’ were used. Overview of findings: Using the keywords of ‘emollient’ and ‘atopic dermatitis’, there were 105 and 36 hits under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow and Systematic Reviews, respectively. Plant-derived products, animal products and special ingredients were discussed. Selected proprietary products were tabulated. Conclusions: A number of proprietary emollients have undergone trials with clinical data available on PubMed-indexed journals. Most moisturizers showed some beneficial effects, but there was generally no evidence that one moisturizer is superior to another. Choosing an appropriate emollient for AD patients would improve acceptability and adherence for emollient treatment. Physician’s recommendation is the primary consideration for patients when selecting a moisturizer/ emollient; therefore, doctors should provide evidence-based information about these emollients.
Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS, and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.
Watsierah Carren A
Full Text Available Abstract Background Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers’ knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers’ knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. Methods A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription, was collected. Results Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100% in public and majority (98.4% in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039 and severe malaria (P P = 0.002 in children and adults
Kabaghe, Alinune N; Phiri, Mphatso D; Phiri, Kamija S; van Vugt, Michèle
Prompt and effective malaria treatment are key in reducing transmission, disease severity and mortality. With the current scale-up of artemisinin-based combination therapy (ACT) coverage, there is need to focus on challenges affecting implementation of the intervention. Routine indicators focus on utilization and coverage, neglecting implementation quality. A health system in rural Malawi was assessed for uncomplicated malaria treatment implementation in children. A cross-sectional health facility survey was conducted in six health centres around the Majete Wildlife Reserve in Chikwawa district using a health system effectiveness approach to assess uncomplicated malaria treatment implementation. Interviews with health facility personnel and exit interviews with guardians of 120 children under 5 years were conducted. Health workers appropriately prescribed an ACT and did not prescribe an ACT to 73% (95% CI 63-84%) of malaria rapid diagnostic test (RDT) positive and 98% (95% CI 96-100%) RDT negative children, respectively. However, 24% (95% CI 13-37%) of children receiving artemisinin-lumefantrine had an inappropriate dose by weight. Health facility findings included inadequate number of personnel (average: 2.1 health workers per 10,000 population), anti-malarial drug stock-outs or not supplied, and inconsistent health information records. Guardians of 59% (95% CI 51-69%) of children presented within 24 h of onset of child's symptoms. The survey presents an approach for assessing treatment effectiveness, highlighting bottlenecks which coverage indicators are incapable of detecting, and which may reduce quality and effectiveness of malaria treatment. Health service provider practices in prescribing and dosing anti-malarial drugs, due to drug stock-outs or high patient load, risk development of drug resistance, treatment failure and exposure to adverse effects.
Kleeff, Jörg; Stöß, Christian; Mayerle, Julia; Stecher, Lynne; Maak, Matthias; Simon, Peter; Nitsche, Ulrich; Friess, Helmut
If conservative treatment of chronic pancreatitis is unsuccessful, surgery is an option. The choice of the most suitable surgical method can be difficult, as the indications, advantages, and disadvantages of the available methods have not yet been fully documented with scientific evidence. In April 2015, we carried out a temporally unlimited systematic search for publications on surgery for chronic pancreatitis. The target parameters were morbidity, mortality, pain, endocrine and exocrine insuffi - ciency, weight gain, quality of life, length of hospital stay, and duration of urgery. Differences between surgical methods were studied with network meta-analysis, and duodenum-preserving operations were compared with partial duodenopancreatectomy with standard meta-analysis. Among the 326 articles initially identified, 8 randomized controlled trials on a total of 423 patients were included in the meta-analysis. The trials were markedly heterogeneous in some respects. There was no significant difference among surgical methods with respect to perioperative morbidity, pain, endocrine and exocrine insufficiency, or quality of life. Duodenumpreserving procedures, compared to duodenopancreatectomy, were associated with a long-term weight gain that was 3 kg higher (p chronic pancreatitis is superior to partial duodenopancreatectomy in multiple respects. Only limited recommendations can be given, however, on the basis of present data. The question of the best surgical method for the individual patient, in view of the clinical manifestations, anatomy, and diagnostic criteria, remains open.
Hamed, Sherifa A
Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements. It also highlights the mechanisms of diabetes-induced brain injury. It seems that the pathogenesis of hyperglycemia-induced brain injury is complex and includes combination of vascular disease, oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, reduction of neurotrophic factors, acetylcholinesterase (AChE) activation, neurotransmitters' changes, impairment of brain repair processes, impairment of brain glymphatic system, accumulation of amyloid β and tau phosphorylation and neurodegeneration. The potentials for prevention and treatment are also discussed. Expert commentary: We summarize the risks and the possible mechanisms of DM-induced brain injury and recommend strategies for neuroprotection and neurorestoration. Recently, a number of drugs and substances [in addition to insulin and its mimics] have shown promising potentials against diabetes-induced brain injury. These include: antioxidants, neuroinflammation inhibitors, anti-apoptotics, neurotrophic factors, AChE inhibitors, mitochondrial function modifiers and cell based therapies.
Stone, Beth Pionek; Kratochwill, Thomas R.; Sladezcek, Ingrid; Serlin, Ronald C.
Presents systematic analysis of the major treatment approaches used for selective mutism. Based on nonparametric statistical tests of effect sizes, major findings include the following: treatment of selective mutism is more effective than no treatment; behaviorally oriented treatment approaches are more effective than no treatment; and no…
Suleman, Sultan; Beyene Tufa, Takele; Kebebe, Dereje; Belew, Sileshi; Mekonnen, Yimer; Gashe, Fanta; Mussa, Seid; Wynendaele, Evelien; Duchateau, Luc; De Spiegeleer, Bart
Medicinal plants have always been an integral part of different cultures in Ethiopia in the treatment of different illnesses including malaria and related symptoms. However, due to lack of proper documentation, urbanization, drought, acculturation and deforestation, there is an increased risk of losing this traditional knowledge. Hence, the use of the indigenous knowledge should be well documented and validated for potential future use. To gather and document information on medicinal plants which are used in the traditional treatment of malaria and related symptoms in Ethiopia. First, an ethnomedicinal survey of plants was conducted in 17 districts of Jimma zone, the Oromia national regional state of Ethiopia. Jimma zone is malarious and rich in natural flora. A total of 115 traditional healers were interviewed using a semi-structured questionnaire containing personal data of the respondents, and information on medicinal plants used to treat malaria and related symptoms. In addition, a literature search using Medline/PubMed, Google Scholar, ScienceDirect and HINARI was conducted on the indigenous use, in-vitro/in-vivo anti-malarial activity reports, and the chemical characterization of medicinal plants of Ethiopia used against malaria. From ethnomedicinal survey, a total of 28 species of plants used in the traditional treatment of malaria and related symptoms in Jimma Zone were collected, identified and documented. In addition, the literature search revealed that 124 medicinal plant species were reported to be traditionally used in the treatment of malaria in Ethiopia. From both ethnomedicinal survey and the literature search, Asteraceae and Fabaceae were the most represented families and Allium sativum L., Carica papaya L., Vernonia amygdalina Del., Lepidium sativum L. and Croton macrostachyus Del. were the most frequently reported plant species for their anti-malarial use. The dominant plant parts used in the preparation of remedies were leaves. About 54% of the
Awad El Karim, M A; Collins, K J; Sukkar, M Y; Omer, A H; Amin, M A; Doré, C
Acting as their own controls, village subjects from the Gezira are of the Sudan with relatively high levels of schistosomiasis infection were first tested in an exercise laboratory in Khartoum and the tests were then repeated after a period of about 1 yr during which time the subjects were treated with hycanthone and periodically monitored to ensure that they had remained free of the disease. In the meantime they were also given anti-malarial prophylaxis. Laboratory tests showed a significant improvement in physiological work capacity of up to 20% after treatment compared with untreated controls. An overall improvement in pulmonary function, particularly forced vital capacity, was observed as well as a significant increase in mean haemoglobin concentration by 1.1 g/100 ml of blood in the treated group. Apart from these improvements in physical working capacity, the treated subjects subjectively felt better after the exercise tests, as expressed by the disappearance of fatiguability.
Axelsson, Paul Bryde; Bjerrum, Flemming; Løkkegaard, Ellen Christine Leth
INTRODUCTION: Breast milk has many advantages over formula for infants in developed and developing countries alike. Despite intentions of breastfeeding, some women develop insufficient lactation. Treatment options traditionally include breastfeeding education and pharmacotherapy. MATERIAL AND MET...... be initiated by counselling and education. Only when these treatment options are exhausted should pharmacotherapy with a suitable medication be considered. FUNDING: not relevant. TRIAL REGISTRATION: not relevant....
Shepard, Jaclyn A; Poler, Joseph E; Grabman, Jesse H
Pediatric elimination disorders are common in childhood, yet psychosocial correlates are generally unclear. Given the physiological concomitants of both enuresis and encopresis, and the fact that many children with elimination disorders are initially brought to their primary care physician for treatment, medical evaluation and management are crucial and may serve as the first-line treatment approach. Scientific investigation on psychological and behavioral interventions has progressed over the past couple of decades, resulting in the identification of effective treatments for enuresis and encopresis. However, the body of literature has inherent challenges, particularly given the multicomponent nature of many of the treatment packages. This review identified 25 intervention studies-18 for nocturnal enuresis and 7 for encopresis-over the past 15 years and classified them according to the guidelines set forth by the Task Force on the Promotion and Dissemination of Psychological Procedures. For nocturnal enuresis, the urine alarm and dry-bed training were identified as well-established treatments, Full Spectrum Home Therapy was probably efficacious, lifting was possibly efficacious, and hypnotherapy and retention control training were classified as treatments of questionable efficacy. For encopresis, only two probably efficacious treatments were identified: biofeedback and enhanced toilet training (ETT). Best practice recommendations and suggestions for future research are provided to address existing limitations, including heterogeneity and the multicomponent nature of many of the interventions for pediatric elimination disorders.
ty of the women attending antenatal clin- ics are healthy and therefore ... a decrease in the patient's risk of falling ill from opportunistic .... 10% risk in those who are tuberculin-. n e g a t i v e . In summary. • There is grade-A evidence that. HIV-positive patients who are tuberculin skin-positive benefit from anti-TB prophylaxis.
Full Text Available Abstract Background In 1999 a four-level hierarchy of evidence was promoted by the National Health and Medical Research Council in Australia. The primary purpose of this hierarchy was to assist with clinical practice guideline development, although it was co-opted for use in systematic literature reviews and health technology assessments. In this hierarchy interventional study designs were ranked according to the likelihood that bias had been eliminated and thus it was not ideal to assess studies that addressed other types of clinical questions. This paper reports on the revision and extension of this evidence hierarchy to enable broader use within existing evidence assessment systems. Methods A working party identified and assessed empirical evidence, and used a commissioned review of existing evidence assessment schema, to support decision-making regarding revision of the hierarchy. The aim was to retain the existing evidence levels I-IV but increase their relevance for assessing the quality of individual diagnostic accuracy, prognostic, aetiologic and screening studies. Comprehensive public consultation was undertaken and the revised hierarchy was piloted by individual health technology assessment agencies and clinical practice guideline developers. After two and a half years, the hierarchy was again revised and commenced a further 18 month pilot period. Results A suitable framework was identified upon which to model the revision. Consistency was maintained in the hierarchy of "levels of evidence" across all types of clinical questions; empirical evidence was used to support the relationship between study design and ranking in the hierarchy wherever possible; and systematic reviews of lower level studies were themselves ascribed a ranking. The impact of ethics on the hierarchy of study designs was acknowledged in the framework, along with a consideration of how harms should be assessed. Conclusion The revised evidence hierarchy is now widely
Background In 1999 a four-level hierarchy of evidence was promoted by the National Health and Medical Research Council in Australia. The primary purpose of this hierarchy was to assist with clinical practice guideline development, although it was co-opted for use in systematic literature reviews and health technology assessments. In this hierarchy interventional study designs were ranked according to the likelihood that bias had been eliminated and thus it was not ideal to assess studies that addressed other types of clinical questions. This paper reports on the revision and extension of this evidence hierarchy to enable broader use within existing evidence assessment systems. Methods A working party identified and assessed empirical evidence, and used a commissioned review of existing evidence assessment schema, to support decision-making regarding revision of the hierarchy. The aim was to retain the existing evidence levels I-IV but increase their relevance for assessing the quality of individual diagnostic accuracy, prognostic, aetiologic and screening studies. Comprehensive public consultation was undertaken and the revised hierarchy was piloted by individual health technology assessment agencies and clinical practice guideline developers. After two and a half years, the hierarchy was again revised and commenced a further 18 month pilot period. Results A suitable framework was identified upon which to model the revision. Consistency was maintained in the hierarchy of "levels of evidence" across all types of clinical questions; empirical evidence was used to support the relationship between study design and ranking in the hierarchy wherever possible; and systematic reviews of lower level studies were themselves ascribed a ranking. The impact of ethics on the hierarchy of study designs was acknowledged in the framework, along with a consideration of how harms should be assessed. Conclusion The revised evidence hierarchy is now widely used and provides a common
Background In vitro evidence indicates that tetrandrine (TT) can potentiate the action of chloroquine 40-fold against choloquine-resistant Plasmodium falciparum. The key question emanating from that study is “would tetrandine and chloroquine be highly effective in a live Aotus monkey model with chloroquine-resistant parasites”. This study was designed to closely mimic the pharmacological/anti-malarial activity in man. Methods The Vietnam Smith/RE strain of P. falciparum, which is chloroquine-resistant was used in this study. Previous experimental procedures were followed. Panamanian owl monkeys (Aotus) were inoculated with 5×106 erythrocytes parasitized with the CQ-resistant strain of P. falciparum. Oral drug treatment was with CQ (20 mg/kg) and/or tetrandrine at 15 mg/Kg, 30 mg/Kg or 60 mg/Kg or 25 mg/Kg depending on experimental conditions. Results and Discussion Parasitaemia was cleared rapidly with CQ and TT while CQ treatment alone was ineffective. Recrudescence of malaria occurred after seven days post-infection. However, four animals were treated orally with TT and CQ parasites were cleared. It is likely that monkeys were cured via a combination of both drug and host immune responses. A single Aotus monkey infected with P. falciparum and untreated with drugs, died. No side effects were observed with these drug treatments. Conclusions This combination of chloroquine and tetrandrine forms the basis of a new attack on chloroquine-resistant malaria - one based upon inhibition of the basis of chloroquine resistance, the multiple drug resistance pump. Previous studies demonstrated that the parasite MDR pump was found on parasite membranes using 3H azidopine photoaffinity labelling. Since MDR-based choloroquine resistance is induced by chloroquine, the basis of the action of tetrandrine is the following: 1) tetrandrine inhibits the MDR pump by stimulating MDR ATPase which limits the energy of the pump by depletion of parasite ATP, 2) tetrandrine blocks the
Inoue, Juliana; Lopes, Dinora; do Rosário, Virgílio; Machado, Marta; Hristov, Angélica D; Lima, Giselle Fmc; Costa-Nascimento, Maria J; Segurado, Aluísio C; Di Santi, Silvia M
Anti-malarial resistance in Plasmodium falciparum remains an obstacle for malaria control. Resistance-associated genes were analysed in Brazilian samples over four decades to evaluate the impact of different treatment regimens on the parasite genetic profile. Samples were collected on filter paper from patients infected in the Amazon region from 1984 to 2011. DNA was extracted with Chelex® 100 and monoinfection confirmed by PCR. SNPs in the pfcrt, pfmdr1, pfdhfr and pfdhps genes were assessed by PCR-RFLP. The pfmdr1 copy number was estimated using real time quantitative PCR with SYBR® Green. Parasite response was assessed ex vivo with seven concentrations of each anti-malarial. Patients were treated according to Brazilian guidelines: quinine plus tetracycline or mefloquine in period 1 and ACT in period 2. All 96 samples presented the pfcrt 76T mutant throughout the assessed periods. In addition, all isolates showed ex vivo chloroquine resistance. The pfmdr1 86Y was detected in 1.5% of samples in period 1, and in 25% in period 2. All samples presented the pfmdr1 1246Y. The analysis of pfmdr1 copy number showed amplification in 37.3% in period 1 and in 42% in period 2. Mutations in pfdhfr were shown as follows: 51I in all samples in period 1 and in 81.2% in period 2; 59R in 6.4% in period 2. The pfdhfr 108N and the pfdhps 437G were seen in all samples along time; the pfdhps 540E in 93.7% in period 1 and in 75% in period 2. The 76T mutation associated to chloroquine resistance is still present in the parasite population, although this anti-malarial was withdrawn from the chemotherapy of P. falciparum in Brazil in the mid-1980s. All isolates assayed ex vivo for chloroquine showed resistant phenotype and 76T. No association was observed between pfmdr1 mutations and resistance to quinine, mefloquine and artemisinin derivatives. Additionally, the pfdhfr 108N mutation was detected in all samples throughout the evaluated periods, demonstrating fixation of the mutant
Jann, Michael W.
Background Patients with bipolar disorder are exceptionally challenging to manage because of the dynamic, chronic, and fluctuating nature of their disease. Typically, the symptoms of bipolar disorder first appear in adolescence or early adulthood, and are repeated over the patient's lifetime, expressed as unpredictable recurrences of hypomanic/manic or depressive episodes. The lifetime prevalence of bipolar disorder in adults is reported to be approximately 4%, and its management was estimated to cost the US healthcare system in 2009 $150 billion in combined direct and indirect costs. Objective To review the published literature and describe the personal and societal burdens associated with bipolar disorder, the impact of delays in accurate diagnosis, and the evidence for the clinical effectiveness of available pharmacologic therapies. Methods The studies in this comprehensive review were selected for inclusion based on clinical relevance, importance, and robustness of data related to diagnosis and treatment of bipolar disorder. The search terms that were initially used on MEDLINE/PubMed and Google Scholar were restricted to 1994 through 2014 and included “bipolar disorder,” “mania,” “bipolar depression,” “mood stabilizer,” “atypical antipsychotics,” and “antidepressants.” High-quality, recent reviews of major relevant topics were included to supplement the primary studies. Discussion Substantial challenges facing patients with bipolar disorder, in addition to their severe mood symptoms, include frequent incidence of psychiatric (eg, anxiety disorders, alcohol or drug dependence) and general medical comorbidities (eg, diabetes, cardiovascular disease, obesity, migraine, and hepatitis C virus infection). It has been reported that more than 75% of patients take their medication less than 75% of the time, and the rate of suicide (0.4%) among patients with bipolar disorder is more than 20 times greater than in the general US population. Mood
Birgden, Astrid; Cucolo, Heather
Public policy is necessarily a political process with the law and order issue high on the political agenda. Consequently, working with sex offenders is fraught with legal and ethical minefields, including the mandate that community protection automatically outweighs offender rights. In addressing community protection, contemporary sex offender treatment is based on management rather than rehabilitation. We argue that treatment-as-management violates offender rights because it is ineffective and unethical. The suggested alternative is to deliver treatment-as-rehabilitation underpinned by international human rights law and universal professional ethics. An effective and ethical community-offender balance is more likely when sex offenders are treated with respect and dignity that, as human beings, they have a right to claim.
Di Pietro, Nina C.; Whiteley, Louise; Mizgalewicz, Ania; Illes, Judy
The Internet is a major source of health-related information for parents of sick children despite concerns surrounding quality. For neurodevelopmental disorders, the websites of advocacy groups are a largely unexamined source of information. We evaluated treatment information posted on nine highly-trafficked advocacy websites for autism, cerebral…
Newborn sepsis is managed with a wide range of antibiotics in different parts of the world depending on the spectrum of bacterial aetiologies. Although, there are standard guidelines for the treatment of neonatal sepsis in most parts of the developed world, the situation is a lot different in most parts of the developing world.
Bay, Vahid; Tabarsi, Payam; Rezapour, Aziz; Marzban, Sima; Zarei, Ehsan
This study aimed to estimate the cost of smear-positive drug-susceptible pulmonary tuberculosis (TB) treatment of the patients in the Azadshahr district, Golestan Province, Iran. In this retrospective study, all new smear positive pulmonary TB patients who had been registered at the district's health network between April, 2013 and December, 2015 and had successfully completed their treatment were entered into the study (45 patients). Treatment costs were estimated from the provider's perspective using an activity-based costing (ABC) method. The cost of treating a new smear-positive pulmonary TB patient was US dollar (USD) 1,409.00 (Iranian Rial, 39,438,260), which can be divided into direct and indirect costs (USD 1,226.00 [87%] and USD 183.00 [13%], respectively). The highest cost (58.1%) was related to care and management of TB patients (including 46.1% human resources costs and 12% directly-observed treatment, short course implementation) and then respectively related to hospitalization (12.1%), supportive activity centers (11.4%), transportation (6.5%), medicines (5.3%), and laboratory tests and radiography (3.2%). Using disease-specific cost studies can help the healthcare system management to have correct insight into the financial burden created by the disease. This can subsequently be used in prioritization, planning, operational budgeting, economic evaluation of programs, interventions, and ultimately in disease management.
Odoh, Uchenna E; Uzor, Philip F; Eze, Chidimma L; Akunne, Theophine C; Onyegbulam, Chukwuma M; Osadebe, Patience O
Malaria is a serious public health problem especially in sub-Saharan African countries such as Nigeria. The causative parasite is increasingly developing resistance to the existing drugs. There is urgent need for alternative and affordable therapy from medicinal plants which have been used by the indigenous people for many years. This study was conducted to document the medicinal plant species traditionally used by the people of Nsukka Local Government Area in south-eastern Nigeria for the treatment of malaria. A total of 213 respondents, represented by women (59.2%) and men (40.8%), were interviewed using a semi-structured questionnaire. The results were analysed and discussed in the context of previously published information on anti-malarial and phytochemical studies of the identified plants. The survey revealed that 50 plant species belonging to 30 botanical families were used in this region for the treatment of malaria. The most cited families were Apocynaceae (13.3%), Annonaceae (10.0%), Asteraceae (10.0%), Lamiaceae (10.0%), Poaceae (10.0%), Rubiaceae (10.0%) and Rutaceae (10.0%). The most cited plant species were Azadirachta indica (11.3%), Mangifera indica (9.1%), Carica papaya (8.5%), Cymbopogon citratus (8.5%) and Psidium guajava (8.5%). The present findings showed that the people of Nsukka use a large variety of plants for the treatment of malaria. The identified plants are currently undergoing screening for anti-malarial, toxicity and chemical studies in our laboratory. Copyright © 2018 Elsevier B.V. All rights reserved.
Schmidt, Frank P; Schmitt, Claus; Hochadel, Matthias; Giannitsis, Evangelos; Darius, Harald; Maier, Lars S; Schmitt, Claus; Heusch, Gerd; Voigtländer, Thomas; Mudra, Harald; Gori, Tommaso; Senges, Jochen; Münzel, Thomas
Patients with non ST-segment elevation myocardial infarction (NSTEMI) represent the largest fraction of patients with acute coronary syndrome in German Chest Pain units. Recent evidence on early vs. selective percutaneous coronary intervention (PCI) is ambiguous with respect to effects on mortality, myocardial infarction (MI) and recurrent angina. With the present study we sought to investigate the prognostic impact of PCI and its timing in German Chest Pain Unit (CPU) NSTEMI patients. Data from 1549 patients whose leading diagnosis was NSTEMI were retrieved from the German CPU registry for the interval between 3/2010 and 3/2014. Follow-up was available at median of 167days after discharge. The patients were grouped into a higher (Group A) and lower risk group (Group B) according to GRACE score and additional criteria on admission. Group A had higher Killip classes, higher BNP levels, reduced EF and significant more triple vessel disease (pGerman Chest Pain Units. This treatment paradox may worsen prognosis in patients who could derive the largest benefit from early revascularization. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Sahan, Kate; Pell, Christopher; Smithuis, Frank; Phyo, Aung Kyaw; Maung, Sai Maung; Indrasuta, Chanida; Dondorp, Arjen M; White, Nicholas J; Day, Nicholas P J; von Seidlein, Lorenz; Cheah, Phaik Yeong
The spread of artemisinin-resistance in Plasmodium falciparum is a threat to current global malaria control initiatives. Targeted malaria treatment (TMT), which combines mass anti-malarial administration with conventional malaria prevention and control measures, has been proposed as a strategy to tackle this problem. The effectiveness of TMT depends on high levels of population coverage and is influenced by accompanying community engagement activities and the local social context. The article explores how these factors influenced attitudes and behaviours towards TMT in Kayin (Karen) State, Myanmar. Semi-structured interviews were conducted with villagers from study villages (N = 31) and TMT project staff (N = 14) between March and July 2015. Community engagement consisted of a range of activities to communicate the local malaria situation (including anti-malarial drug resistance and asymptomatic malaria), the aims of the TMT project, and its potential benefits. Community engagement was seen by staff as integral to the TMT project as a whole and not a sub-set of activities. Attitudes towards TMT (including towards community engagement) showed that developing trusting relationships helped foster participation. After initial wariness, staff received hospitality and acceptance among villagers. Offering healthcare alongside TMT proved mutually beneficial for the study and villagers. A handful of more socially-mobile and wealthy community members were reluctant to participate. The challenges of community engagement included time constraints and the isolation of the community with its limited infrastructure and a history of conflict. Community engagement had to be responsive to the local community even though staff faced time constraints. Understanding the social context of engagement helped TMT to foster respectful and trusting relationships. The complex relationship between the local context and community engagement complicated evaluation of the community strategy
Mahlich, Jörg; Kamae, Isao; Sruamsiri, Rosarin
Drug price setting is one of the key challenges faced by the Japanese health care system. This study aims to identify the determinants of drug price in Japan using the example of the rheumatoid arthritis (RA) treatment market. In order to compare prices across different products, we calculated prices per defined daily dose using WHO methodology. Price determinants were calculated both at launch and over time using IMS quarterly data on medicines approved for RA treatment in Japan from 2012 to 2015. Pharmaceutical pricing was modeled as a function of clinical and economic variables using regression analysis. For prices at the launch we found that differences in efficacy are not reflected in price differentials. We also report that the number of products within a molecule class had a negative effect on prices while originator drugs maintained higher prices. Although the existing pricing rules in Japan are very comprehensive they do not necessarily capture differences in product characteristics. The findings here support the notion that competitive forces are weak in highly regulated markets such as Japan.
Full Text Available Several domains of cognitive function, e.g., verbal memory, information processing, fluency, attention, and executive function are impaired in patients with schizophrenia. Cognitive impairments in schizophrenia have attracted interests as a treatment target, because they are considered to greatly affect functional outcome. Electrophysiological markers, including electroencephalogram (EEG, particularly, event-related potentials, have contributed to psychiatric research and clinical practice. In this review, we provide a summary of studies relating electrophysiological findings to cognitive performance in schizophrenia. Electrophysiological indices may provide an objective marker of cognitive processes, contributing to the development of effective interventions to improve cognitive and social outcomes. Further efforts to understand biological mechanisms of cognitive disturbances, and develop effective therapeutics are warranted.
Ethan R. Stewart
Full Text Available Aspergillus spp. are a group of filamentous molds that were first described due to a perceived similarity to an aspergillum, or liturgical device used to sprinkle holy water, when viewed under a microscope. Although commonly inhaled due to their ubiquitous nature within the environment, an invasive fungal infection (IFI is a rare outcome that is often reserved for those patients who are immunocompromised. Given the potential for significant morbidity and mortality within this patient population from IFI due to Aspergillus spp., along with the rise in the use of therapies that confer immunosuppression, there is an increasing need for appropriate initial clinical suspicion leading to accurate diagnosis and effective treatment. Voriconazole remains the first line agent for therapy; however, the use of polyenes, novel triazole agents, or voriconazole in combination with an echinocandin may also be utilized. Consideration as to which particular agent and for what duration should be made in the individual context for each patient based upon underlying immunosuppression, comorbidities, and overall tolerance of therapy.
Full Text Available Agnieszka Blum, Despina Bazou, Peter O’Gorman Department of Hematology, Mater Misericordiae University Hospital, Dublin, UK Abstract: Smoldering multiple myeloma (SMM is an asymptomatic plasma cell proliferative disorder associated with risk of progression to symptomatic multiple myeloma (MM or amyloidosis. In comparison to monoclonal gammopathy of undetermined significance (MGUS, SMM has a much higher risk of progression to MM. Thanks to advances in our understanding of the risk factors, the subset of patients with ultra-high risk of progression to MM (80%–90% at 2 years has been identified. The revision of the diagnostic criteria resulted in changes in the management of this cohort of patients. In contrast to the management guidelines for MGUS patients, SMM patients need to be studied more intensively in order to identify biomarkers necessary for accurate risk stratification. In this review, we focus on the risk of progression from SMM to MM, as well as the influence of early treatment on overall survival, time to progression and quality of life. Keywords: smoldering multiple myeloma, risk factor, biomarker, genomic aberrations, glycan analysis
Horigian, Viviana E.; Espinal, Paula S.; Alonso, Elizabeth; Verdeja, Rosa E.; Duan, Rui; Usaga, Ingrid M.; Pérez-López, Alejandro; Marín-Navarrete, Rodrigo; Feaster, Daniel J.
ABSTRACT: Introduction: Evidence shows a lag in adoption of evidence-based practices (EBPs) for substance abuse treatment and supports the need for studying the factors involved in this worldwide problem. Objective: This study aimed to assess the readiness and barriers to adopt EBPs for substance abuse in a sample of outpatient treatment centers of a newly created Mexican Clinical Trials Network. Method: An online survey was administered to directors (n = 8) and clinicians (n = 40) from se...
Bhaumik, Sabyasachi; Gangadharan, Satheesh; Hiremath, Avinash; Russell, Paul Swamidhas Sudhakar
Psychological treatments are widely used for the management of mental health and behavioural problems in people with intellectual disabilities. The evidence base, including the cost-effectiveness of such interventions, is limited. This editorial explores the current evidence base and analyses its strengths and limitations. The editorial also highlights current problems in conducting randomised controlled trials in this area and suggests a way forward.
Muttiah, Nimisha; Georges, Katie; Brackenbury, Tim
Purpose: Evidence-based practice (EBP) involves the incorporation of research evidence, clinical expertise, and client values in clinical decision making. One case in which these factors conflict is the use of nonspeech oral motor treatments (NSOMTs) for children with developmental speech sound disorders. Critical reviews of the research evidence…
DiMeo, Michelle A.; Moore, G. Kurt; Lichtenstein, Carolyn
Evidence-based treatments (EBTs) are "interventions" that have been proven effective through rigorous research methodologies. Evidence-based practice (EBP), however, refers to a "decision-making process" that integrates the best available research, clinician expertise, and client characteristics. This study examined community mental health service…
Quality assurance and evidence in career guidance in Europe are often seen as self-evident approaches, but particular interests lie behind......Quality assurance and evidence in career guidance in Europe are often seen as self-evident approaches, but particular interests lie behind...
Full Text Available Context Scoliosis is a three-dimensional deformity of the spine and trunk which includes lateral deviation, rotation, and a disturbance of the sagittal profile. Treatment is indicated for scoliosis because it may lead to negative consequences with regard to the quality of life and other health issues for some patients. The purpose of this review was to gather current, up-to-date information, and to search the recent articles on scoliosis for evidence of the different modes of treatment. Evidence Acquisition A PubMed search for review articles, prospective controlled trials (PCT, and randomized controlled trials (RCT was performed. The search terms were: 1 scoliosis, treatment (12,045 items found; 2 scoliosis, physiotherapy (776 items found; 3 scoliosis, brace treatment (1,447 items found; and 4 scoliosis, surgery (10,485 items found. Results When looking at the current literature, high quality evidence (level I was found to support physical rehabilitation and brace treatments, while no evidence was found to support spinal fusion surgery. The numerous long-term complications that patients may face post-operation, and the lack of evidence for spinal fusion surgery indicate that there is no clear medical indication for this kind of treatment. Conclusions There is a high level of evidence for the conservative treatment of scoliosis, but there are varying levels of success in the different approaches. The better the correction of the curve, the better the end result and outcome for the patient. This is supported by the current evidence reviewed in this paper. Physiotherapy and bracing should be used and, specifically, those approaches using high corrective methods. Spinal fusion surgery is not supported by the current evidence. According to the literature, the long-term complications of surgery for scoliosis far outweigh the consequences of untreated scoliosis.
Blake, Margaret Lehman; Frymark, Tobi; Venedictov, Rebecca
Purpose: The purpose of this review is to evaluate and summarize the research evidence related to the treatment of individuals with right hemisphere communication disorders. Method: A comprehensive search of the literature using key words related to right hemisphere brain damage and communication treatment was conducted in 27 databases (e.g.,…
Weiss, H-R; Goodall, D
Traditionally, the treatment options for adolescent idiopathic scoliosis (AIS), the most common form of scoliosis, are exercises; in-patient rehabilitation; braces and surgery. The outcomes of treatments are usually compared with the natural history or observation (non-intervention). The aim of this paper was to provide a synopsis of all treatment options in the light of evidence based practice (EBP). A systematic review was carried out using the most encompassing databases available. Literature has been searched for the outcome parameter ''rate of progression'' and only prospective controlled studies that have considered the treatment versus the natural history have been included. The search strategy included the following terms: ''adolescent idiopathic scoliosis''; ''idiopathic scoliosis''; ''natural history''; ''observation''; ''physiotherapy''; ''physical therapy''; ''rehabilitation''; ''bracing''; ''orthotics'' and ''surgery''. Prospective short-term studies have been found to support outpatient physiotherapy. One prospective controlled study was found to support scoliosis in-patient rehabilitation (SIR). One prospective multi-centre study, a long-term prospective controlled study and a meta-analysis have been found to support bracing. No controlled study, neither short, mid nor long-term, was found to reveal any substantial evidence to support surgery as a treatment for this condition. There is some evidence supporting the conservative treatment for AIS. No substantial evidence has been found in terms of prospective controlled studies to support surgical intervention. In light of the unknown long-term effects of surgery, a randomised controlled trial (RCT) seems necessary. Due to the presence of evidence to support conservative treatments, a plan to compose a RCT for conservative treatment options seems unethical. But it is also important to conclude that the evidence for conservative treatments is weak in number and length.
Hill, Jonathan C.; Foster, Nadine E.; Protheroe, Joanne
Background & aims Musculoskeletal pain, the most common cause of disability globally, is most frequently managed in primary care. People with musculoskeletal pain in different body regions share similar characteristics, prognosis, and may respond to similar treatments. This overview aims to summarise current best evidence on currently available treatment options for the five most common musculoskeletal pain presentations (back, neck, shoulder, knee and multi-site pain) in primary care. Methods A systematic search was conducted. Initial searches identified clinical guidelines, clinical pathways and systematic reviews. Additional searches found recently published trials and those addressing gaps in the evidence base. Data on study populations, interventions, and outcomes of intervention on pain and function were extracted. Quality of systematic reviews was assessed using AMSTAR, and strength of evidence rated using a modified GRADE approach. Results Moderate to strong evidence suggests that exercise therapy and psychosocial interventions are effective for relieving pain and improving function for musculoskeletal pain. NSAIDs and opioids reduce pain in the short-term, but the effect size is modest and the potential for adverse effects need careful consideration. Corticosteroid injections were found to be beneficial for short-term pain relief among patients with knee and shoulder pain. However, current evidence remains equivocal on optimal dose, intensity and frequency, or mode of application for most treatment options. Conclusion This review presents a comprehensive summary and critical assessment of current evidence for the treatment of pain presentations in primary care. The evidence synthesis of interventions for common musculoskeletal pain presentations shows moderate-strong evidence for exercise therapy and psychosocial interventions, with short-term benefits only from pharmacological treatments. Future research into optimal dose and application of the most
König, Jochem; Krahn, Ulrike; Binder, Harald
Network meta-analysis techniques allow for pooling evidence from different studies with only partially overlapping designs for getting a broader basis for decision support. The results are network-based effect estimates that take indirect evidence into account for all pairs of treatments. The results critically depend on homogeneity and consistency assumptions, which are sometimes difficult to investigate. To support such evaluation, we propose a display of the flow of evidence and introduce new measures that characterize the structure of a mixed treatment comparison. Specifically, a linear fixed effects model for network meta-analysis is considered, where the network estimates for two treatments are linear combinations of direct effect estimates comparing these or other treatments. The linear coefficients can be seen as the generalization of weights known from classical meta-analysis. We summarize properties of these coefficients and display them as a weighted directed acyclic graph, representing the flow of evidence. Furthermore, measures are introduced that quantify the direct evidence proportion, the mean path length, and the minimal parallelism of mixed treatment comparisons. The graphical display and the measures are illustrated for two published network meta-analyses. In these applications, the proposed methods are seen to render transparent the process of data pooling in mixed treatment comparisons. They can be expected to be more generally useful for guiding and facilitating the validity assessment in network meta-analysis. Copyright © 2013 John Wiley & Sons, Ltd.
Williams, Nathaniel J
Intentions play a central role in numerous empirically supported theories of behavior and behavior change and have been identified as a potentially important antecedent to successful evidence-based treatment (EBT) implementation. Despite this, few measures of mental health clinicians' EBT intentions exist and available measures have not been subject to thorough psychometric evaluation or testing. This paper evaluates the psychometric properties of the evidence-based treatment intentions (EBTI) scale, a new measure of mental health clinicians' intentions to adopt EBTs. The study evaluates the reliability and validity of inferences made with the EBTI using multi-method, multi-informant criterion variables collected over 12 months from a sample of 197 mental health clinicians delivering services in 13 mental health agencies. Structural, predictive, and discriminant validity evidence is assessed. Findings support the EBTI's factor structure (χ (2) = 3.96, df = 5, p = .556) and internal consistency reliability (α = .80). Predictive validity evidence was provided by robust and significant associations between EBTI scores and clinicians' observer-reported attendance at a voluntary EBT workshop at a 1-month follow-up (OR = 1.92, p adoption at a 12-month follow-up (R (2) = .17, p adopt EBTs. Discussion focuses on research and practice applications.
Juliana Saboia Fontenele e Silva
Full Text Available We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed, EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine, patients with renal disease (amphotericin B or miltefosine, patients with heart disease (amphotericin B, miltefosine or pentamidine, immunosuppressed patients (liposomal amphotericin, the elderly (meglumine antimoniate, pregnant women (amphotericin B and patients with liver disease (no evidence available. The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.
Ssewanyana, Isaac; Arinaitwe, Emmanuel; Nankabirwa, Joaniter I; Yeka, Adoke; Sullivan, Richard; Kamya, Moses R; Rosenthal, Philip J; Dorsey, Grant; Mayanja-Kizza, Harriet; Drakeley, Chris; Greenhouse, Bryan; Tetteh, Kevin K A
People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection. Cross-sectional surveys were performed in children and adults at three sites in Uganda with varied P. falciparum transmission intensity (entomological inoculation rates; 3.8, 26.6, and 125 infectious bites per person per year). Sandwich ELISA was used to measure antibody responses to two P. falciparum merozoite surface antigens: merozoite surface protein 1-19 (MSP1-19) and apical membrane antigen 1 (AMA1). In individuals with detectable antibody levels, guanidine hydrochloride (GuHCl) was added to measure the relative avidity of antibody responses by ELISA. Within a site, there were no significant differences in median antibody levels between the three age groups. Between sites, median antibody levels were generally higher in the higher transmission sites, with differences more apparent for AMA-1 and in ≥5 year group. Similarly, median avidity index (proportion of high avidity antibodies) showed no significant increase with increasing age but was significantly lower at sites of higher transmission amongst participants ≥5 years of age. Using 5 M GuHCl, the median avidity indices in the ≥5 year group at the highest and lowest transmission sites were 19.9 and 26.8, respectively (p = 0.0002) for MSP1-19 and 12.2 and 17.2 (p = 0.0007) for AMA1. Avidity to two different P. falciparum antigens was lower in areas of high transmission intensity compared to areas with lower transmission. Appreciation of the mechanisms behind these findings as well as their clinical consequences will require additional investigation, ideally utilizing longitudinal data and investigation of a broader array of responses.
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Oct 6, 2008 ... Malaria is caused by any of the four protozoan species of the genus plasmodium. ... intervention for malaria therapy in patients living in areas of high level of resistance. ..... need for assisted conception. The observation that ...
Full Text Available Abstract Background The ACCESS programme aims at understanding and improving access to prompt and effective malaria treatment. Between 2004 and 2008 the programme implemented a social marketing campaign for improved treatment-seeking. To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO was created in Tanzania in 2006. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP to artemether-lumefantrine (ALu in 2007 and subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on understanding and treatment of malaria was studied in rural Tanzania. The data also enabled an investigation of the determinants of access to treatment. Methods Three treatment-seeking surveys were conducted in 2004, 2006 and 2008 in the rural areas of the Ifakara demographic surveillance system (DSS and in Ifakara town. Each survey included approximately 150 people who had suffered a fever case in the previous 14 days. Results Treatment-seeking and awareness of malaria was already high at baseline, but various improvements were seen between 2004 and 2008, namely: better understanding causes of malaria (from 62% to 84%; an increase in health facility attendance as first treatment option for patients older than five years (27% to 52%; higher treatment coverage with anti-malarials (86% to 96% and more timely use of anti-malarials (80% to 93-97% treatments taken within 24 hrs. Unfortunately, the change of treatment policy led to a low availability of ALu in the private sector and, therefore, to a drop in the proportion of patients taking a recommended malaria treatment (85% to 53%. The availability of outlets (health facilities or drug shops is the most important determinant of whether patients receive prompt and effective treatment, whereas affordability and accessibility contribute to a lesser extent. Conclusions An
Dorsey, Shannon; McLaughlin, Katie A.; Kerns, Suzanne E. U.; Harrison, Julie P.; Lambert, Hilary K.; Briggs, Ernestine C.; Cox, Julia Revillion; Amaya-Jackson, Lisa
Child and adolescent trauma exposure is prevalent, with trauma exposure-related symptoms, including posttraumatic stress, depressive, and anxiety symptoms often causing substantial impairment. This article updates the evidence base on psychosocial treatments for child and adolescent trauma exposure completed for this journal by Silverman et al. (2008). For this review, we focus on 37 studies conducted during the seven years since the last review. Treatments are grouped by overall treatment family (e.g., cognitive behavioral therapy), treatment modality (e.g., individual vs. group), and treatment participants (e.g., child only vs. child and parent). All studies were evaluated for methodological rigor according to Journal of Clinical Child & Adolescent Psychology evidence-based treatment evaluation criteria (Southam-Gerow & Prinstein, 2014), with cumulative designations for level of support for each treatment family. Individual CBT with parent involvement, individual CBT, and group CBT were deemed well-established; group CBT with parent involvement and eye movement desensitization and reprocessing (EMDR) were deemed probably efficacious; individual integrated therapy for complex trauma and group mind–body skills were deemed possibly efficacious; individual client-centered play therapy, individual mind–body skills, and individual psychoanalysis were deemed experimental; and group creative expressive + CBT was deemed questionable efficacy. Advances in the evidence base, with comparisons to the state of the science at the time of the Silverman et al. (2008) review, are discussed. Finally, we present dissemination and implementation challenges and areas for future research. PMID:27759442
McConnell, V.D.; Schwarz, G.E.
This paper analyzes the determination of pollution control from wastewater treatment plants as an economic decision facing local or regional regulators. Pollution control is measured by plant design effluent concentration levels and is fully endogenous in a supply- and-demand model of treatment choice. On the supply side, plant costs are a function of the design treatment level of the plant, and on the demand side, treatment level is a function of both the costs of control and the regional or regulatory preferences for control. We find evidence that the economic model of effluent choice by local regulators has a good deal of explanatory power. We find evidence that wastewater treatment plant removal of biological oxygen demand (BOD) is sensitive to many local factors including the size of the treatment plant, the flow rate of the receiving water, the population density of the surrounding area, regional growth, state sensitivity to environmental issues, state income, and the extent to which the damages from pollution fall on other states. We find strong evidence that regulators are sensitive to capital costs in determining the design level of BOD effluent reduction at a plant. Thus, proposed reductions in federal subsidies for wastewater treatment plant construction are likely to have significant adverse effects on water quality. ?? 1992.
Treuer, Tamás; Liu, Chia-Yih; Salazar, Gerardo; Kongsakon, Ronnachai; Jia, Fujun; Habil, Hussain; Lee, Min-Soo; Lowry, Amanda; Dueñas, Héctor
Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients. Copyright © 2013 Wiley Publishing Asia Pty Ltd.
Nabyonga-Orem, Juliet; Ssengooba, Freddie; Macq, Jean; Criel, Bart
Although increasing attention is being paid to knowledge translation (KT), research findings are not being utilized to the desired extent. The present study explores the role of evidence, barriers, and factors facilitating the uptake of evidence in the change in malaria treatment policy in Uganda, building on previous work in Uganda that led to the development of a middle range theory (MRT) outlining the main facilitatory factors for KT. Application of the MRT to a health policy case will contribute to refining it. Using a case study approach and mixed methods, perceptions of respondents on whether evidence was available, had been considered and barriers and facilitatory factors to the uptake of evidence were explored. In addition, the respondents' rating of the degree of consistency between the policy decision and available evidence was assessed. Data collection methods included key informant interviews and document review. Qualitative data were analysed using content thematic analysis, whereas quantitative data were analysed using Excel spreadsheets. The two data sets were eventually triangulated. Evidence was used to change the malaria treatment policy, though the consistency between evidence and policy decisions varied along the policy development cycle. The availability of high-quality and contextualized evidence, including effective dissemination, Ministry of Health institutional capacity to lead the KT process, intervention of the WHO and a regional professional network, the existence of partnerships for KT with mutual trust and availability of funding, tools, and inputs to implement evidence, were the most important facilitatory factors that enhanced the uptake of evidence. Among the barriers that had to be overcome were resistance from implementers, the health system capacity to implement evidence, and financial sustainability. The results agree with facilitatory factors identified in the earlier developed MRT, though additional factors emerged. These
Full Text Available Introduction. Depression in adolescents and young people is associated with reduced social, occupational, and interpersonal functioning, increases in suicide and self-harm behaviours, and problematic substance use. Age-appropriate, evidence-based treatments are required to provide optimal care. Methods. “Evidence mapping” methodology was used to quantify the nature and distribution of the extant high-quality research into the prevention and treatment of depression in young people across psychological, medical, and other treatment domains. Results. Prevention research is dominated by cognitive-behavioral- (CBT- based interventions. Treatment studies predominantly consist of CBT and SSRI medication trials, with few trials of other psychological interventions or complementary/alternative treatments. Quality studies on relapse prevention and treatment for persistent depression are distinctly lacking. Conclusions. This map demonstrates opportunities for future research to address the numerous evidence gaps for interventions to prevent or treat depression in young people, which are of interest to clinical researchers, policy makers, and funding bodies.
Groot, Noortje; de Graeff, Nienke; Avcin, Tadej; Bader-Meunier, Brigitte; Dolezalova, Pavla; Feldman, Brian; Kenet, Gili; Koné-Paut, Isabelle; Lahdenne, Pekka; Marks, Stephen D; McCann, Liza; Pilkington, Clarissa A; Ravelli, Angelo; van Royen-Kerkhof, Annet; Uziel, Yosef; Vastert, Sebastiaan J; Wulffraat, Nico M; Ozen, Seza; Brogan, Paul; Kamphuis, Sylvia; Beresford, Michael W
Antiphospholipid syndrome (APS) is rare in children, and evidence-based guidelines are sparse. Consequently, management is mostly based on observational studies and physician's experience, and treatment regimens differ widely. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative was launched to develop diagnostic and management regimens for children and young adults with rheumatic diseases. Here, we developed evidence-based recommendations for diagnosis and treatment of paediatric APS. Evidence-based recommendations were developed using the European League Against Rheumatism standard operating procedure. Following a detailed systematic review of the literature, a committee of paediatric rheumatologists and representation of paediatric haematology with expertise in paediatric APS developed recommendations. The literature review yielded 1473 articles, of which 15 were valid and relevant. In total, four recommendations for diagnosis and eight for treatment of paediatric APS (including paediatric Catastrophic Antiphospholipid Syndrome) were accepted. Additionally, two recommendations for children born to mothers with APS were accepted. It was agreed that new classification criteria for paediatric APS are necessary, and APS in association with childhood-onset systemic lupus erythematosus should be identified by performing antiphospholipid antibody screening. Treatment recommendations included prevention of thrombotic events, and treatment recommendations for venous and/or arterial thrombotic events. Notably, due to the paucity of studies on paediatric APS, level of evidence and strength of the recommendations is relatively low. The SHARE initiative provides international, evidence-based recommendations for diagnosis and treatment for paediatric APS, facilitating improvement and uniformity of care. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use
Arnold P Oranje
Full Text Available Atopic dermatitis (AD is one of the most common skin diseases with a complex multifactorial background. The clinical presentation, the aggravating factors and the complications vary according to the age of the patients. Most cases, approximately 60-80%, present for the 1 st time before the age of 12 months. Adult-onset AD has been observed as a special variant. Pruritus is the worst sign of AD, which also often indicates an exacerbation and is considered to be the most annoying symptom of AD. Treatment is preferably started based on the severity of AD. In only 10% of the cases, AD is so severe that systemic treatment is necessary. Systemic treatment including topical wet-wrap treatment is indicated in the worst and recalcitrant cases of AD. Systemic treatment of AD is discussed with regards to the evidence-based efficacy and safety aspects. I prefer wet-wraps as a crisis intervention in severe childhood cases, whereas UV and systemic treatments are the choices in patients older than 10 years. Probiotics are not useful in the treatment. If they have any effect at all it may only be in food-allergic children with AD. Finally, anti-histamines are not effective against pruritus in AD. They are only effective against urticarial flares and in cases with food-allergy. This article consists of an expert opinion on evidence-based pharmacological treatment of AD, but it is not a systemic review.
Marsch, Lisa A; Dallery, Jesse
The clinical community has a growing array of psychosocial interventions with a strong evidence base available for the treatment of SUDs. Considerable opportunity exists for leveraging technology in the delivery of evidence-based interventions to promote widespread reach and impact of evidence-based care. Data from this line of research to date are promising, and underscore the potential public health impact of technology-based therapeutic tools. To fully realize the potential of technology-delivered interventions, several areas of inquiry remain important. First, scientifically sound strategies should be explored to ensure technology-based interventions are optimally designed to produce maximal behavior change. Second, efficient and effective methods should be identified to integrate technology-based interventions into systems of care in a manner that is most responsive to the needs of individual users. Third, payment, privacy, and regulatory systems should be refined and extended to go beyond electronic medical records and telehealth/distance care models, and support the deployment of technology-based systems to enhance the quality, efficiency and cost-effectiveness of care. Fourth, the mechanisms underlying behavior change derived from technology-based treatments should be explicated, including new mechanisms that may be tapped via novel, technology-based tools. Such work will be critical in isolating mechanisms that are useful in predicting treatment response, and in ensuring that key ingredients are present in technology-based interventions as they are made widely available.
Bouter, L M
The Dutch Health Council recently published a report on the efficacy of electrotherapy, laser therapy and ultrasound treatment for musculoskeletal disorders. The assessment was based on three systematic reviews, including 169 randomized clinical trials, and focused on a best-evidence synthesis.
Sytema, Sjoerd; Jörg, Frederike; Nieboer, Roeline; Wunderink, Lex
OBJECTIVE: This 24-month study, conducted in The Netherlands, examined the feasibility of enhancing the effectiveness of assertive community treatment (ACT) by adding evidence-based interventions. METHODS: A total of 159 patients were randomly assigned to two ACT teams, one providing standard ACT
Southam-Gerow, Michael A.; Hourigan, Shannon E.; Allin, Robert B., Jr.
This article describes the application of a university-community partnership model to the problem of adapting evidence-based treatment approaches in a community mental health setting. Background on partnership research is presented, with consideration of methodological and practical issues related to this kind of research. Then, a rationale for…
Sheidow, Ashli J.; Jayawardhana, Jayani; Bradford, W. David; Henggeler, Scott W.; Shapiro, Steven B.
The 12-month cost-effectiveness of juvenile drug court and evidence-based treatments within court were compared with traditional Family Court for 128 substance-abusing/dependent juvenile offenders participating in a 4-condition randomized trial. Intervention conditions included Family Court with community services (FC), Drug Court with community…
Evidence-based treatments are increasingly important and necessary parts of many disciplines when working with very young children and their families. In using them, it is advantageous to be grounded in the principles and practices that research has shown are critical to children's healthy development, particularly the importance of supporting the…
Yon, Adriana; Scogin, Forrest
The authors describe the methods used to identify evidence-based psychological treatments for older adults in this contribution to the special section. Coding teams were assembled to review the literature on several problems relevant to mental health and aging. These teams used the manual developed by the Committee on Science and Practice of the Society for Clinical Psychology (Division 12) of the American Psychological Association that provided definitions of key constructs used in coding. The authors provide an overview of the process followed by the review teams and of some of the issues that emerged to illustrate the steps involved in the coding procedure. Identifying evidence-based treatments is a fundamental aspect of promoting evidence-based practice with older adults; such practice is advocated by most health care disciplines, including psychology. ((c) 2007 APA, all rights reserved).
Afrashtehfar, K I; Eimar, H; Yassine, R; Abi-Nader, S; Tamimi, F
Evidence-based dentistry (EBD) can help provide the best treatment option for every patient, however, its implementation in restorative dentistry is very limited. This study aimed at assessing the barriers preventing the implementation of EBD among dental undergraduate and graduate students in Montreal, and explore possible solutions to overcome these barriers. A cross-sectional survey was conducted by means of a paper format self-administrated questionnaire distributed among dental students. The survey assessed the barriers and potential solutions for implementation of an evidence-based practice. Sixty-one students completed the questionnaire. Forty-one percent of respondents found evidence-based literature to be the most reliable source of information for restorative treatment planning, however, only 16% used it. They considered that finding reliable information was difficult and they sometimes encountered conflicting information when consulting different sources. Dental students had positive attitudes towards the need for better access to evidence-based literature to assist learning and decision making in restorative treatment planning and to improve treatment outcomes. Even for dentists trained in EBD, online searching takes too much time, and even though it can provide information of better quality than personal intuition, it might not be enough to identify the best available evidence. Even though dental students are aware of the importance of EBD in restorative dentistry they rarely apply the concept, mainly due to time constraints. For this reason, implementation of EBD would probably require faster access to evidence-based knowledge. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Ulrich, Martina; Pellacani, Giovanni; Ferrandiz, Carlos; Lear, John T
Actinic keratosis (AK) is a common skin disease seen in daily practice. It is associated with a risk of progression to invasive squamous cell carcinoma and can be regarded as a marker of increased risk for non-melanoma skin cancer. The use of a field-directed treatment approach reflects the need to initiate early treatment over an affected area to prevent tumour development and local recurrence. Candidate field-directed treatments require a mechanism of action compatible with an effect on field cancerisation, immediate and long-term efficacy against visible lesions and efficacy against subclinical AK. Applicability to large treatment areas, tolerability compatible with long-term use, utility in organ transplant patients and, ideally, evidence of extended long-term activity may also be desirable. We review the evidence of a role for topical diclofenac sodium 3% administered in a 2.5% hyaluronic acid gel (diclofenac/HA) as field-directed treatment. Diclofenac/HA directly targets AK pathophysiology through multiple mechanisms, including induction of apoptosis, inhibition of angiogenesis and reduced inflammation. Clearance of visible field cancerisation is safely and rapidly achieved with a 90-day treatment course in patients with affected areas of up to 50 cm(2) and is associated with a ≥75% reduction in target lesion number score in 85% and 91% of patients, respectively, at 30 days and 1 year post-treatment. Following treatment of AK in high-risk transplant patients, 45% remained free of lesions in the treatment area at 2 years post-treatment. We conclude that diclofenac/HA fulfils most criteria necessary to be considered an appropriate candidate for a field-directed treatment in AK.
Moriana, Juan Antonio; Gálvez-Lara, Mario; Corpas, Jorge
Most mental health services throughout the world currently regard evidence-based psychological treatments as best practice for the treatment of mental disorders. The aim of this study was to analyze evidence-based treatments drawn from RCTs, reviews, meta-analyses, guides, and lists provided by the National Institute for Health and Care Excellence (NICE), Division 12 (Clinical Psychology) of the American Psychological Association (APA), Cochrane and the Australian Psychological Society (APS) in relation to mental disorders in adults. A total of 135 treatments were analyzed for 23 mental disorders and compared to determine the level of agreement among the organizations. The results indicate that, in most cases, there is little agreement among organizations and that there are several discrepancies within certain disorders. These results require reflection on the meaning attributed to evidence-based practice with regard to psychological treatments. The possible reasons for these differences are discussed. Based on these findings, proposals to unify the criteria that reconcile the realities of clinical practice with a scientific perspective were analyzed. Copyright © 2017 Elsevier Ltd. All rights reserved.
Pourat, Nadereh; Choi, Moonkyung Kate; Chen, Xiao
Preventive dental health services are intended to reduce the likelihood of development of tooth decay and the need for more intensive treatment overtime. The evidence on the effectiveness of preventive dental care in reducing treatment services and expenditures is lagging for adults, particularly those with lower incomes and chronic conditions. We assessed the impact of preventive dental services on dental treatment service use and expenditures overall and by category of service. We calculated the annual numbers of preventive (periodic diagnostic and prophylactic procedures) and treatment (restorative, surgery, prosthodontic, endodontic, and periodontic) services per beneficiary using Medicaid enrollment and claims data for beneficiaries with three categories of conditions (diabetes, heart disease, and respiratory disease) from 10 largest California counties. We used Cragg hurdle exponential regression models controlling for past service use, demographics, length of enrollment, and county. We found that using preventive services in 2005-2007 was associated with higher likelihood and number of treatment dental services used, but associated with lower treatment expenditures in 2008. The reduction in expenditures was noted only in restorative, prosthodontics, and periodontic services. The findings provide much needed evidence of the contribution of preventive dental care in maintaining oral health of low-income adults with chronic conditions and potential for savings to the Medicaid program. Providing lower cost preventive dental care to the individuals with chronic conditions would achieve better oral health and lower treatment expenditures. © 2018 American Association of Public Health Dentistry.
Full Text Available Angela Dunsford1, Saravana Kumar1,2, Sarah Clarke1 1International Centre for Allied Health Evidence, 2School of Health Sciences, University of South Australia, Adelaide, South Australia, Australia Abstract: Low back pain (LBP is a major health issue with significant socioeconomic implications in most Western countries. Many forms of treatment have been proposed and investigated in the past, with exercise being a commonly prescribed intervention. Within allied health, in particular physiotherapy, there has been a growing movement that recognizes the role of the McKenzie method in treating LBP. Within the McKenzie framework, directional preference (DP exercises are one such intervention, with preliminary data demonstrating its effectiveness in the management of LBP. In this paper, we aim to integrate the evidence from current research, identified using a systematic review, and utilize a practical real-life case scenario to outline how evidence from the literature can be implemented in clinical practice. The findings from the systematic review indicate that DP exercises may have positive effects in the management of LBP. While the body of evidence to support this is limited (only four studies and therefore modest at best, it does provide some emerging evidence to support the use of DP exercises in clinical practice. Despite this, gaps also persist in the literature on DP exercises, and this relates to the exercise parameters and the compliance rates. Recognizing this dichotomy (modest evidence in some areas and evidence gaps in other areas, which is likely to confront health practitioners, using a practical approach with a real-life clinical scenario, we outline how the evidence from the systematic review can be implemented in clinical practice. This approach builds on the philosophy of evidence-based practice of integrating research evidence with clinical expertise and patient values. Keywords: low back pain, McKenzie method, directional
Suojala, L; Kaartinen, L; Pyörälä, S
Bovine mastitis caused by Escherichia coli can range from being a subclinical infection of the mammary gland to a severe systemic disease. Cow-dependent factors such as lactation stage and age affect the severity of coliform mastitis. Evidence for the efficacy of antimicrobial treatment for E. coli mastitis is very limited. Antimicrobial resistance is generally not a limiting factor for treatment, but it should be monitored to detect changes in resistance profiles. The only antimicrobials for which there is some scientific evidence of beneficial effects in the treatment for E. coli mastitis are fluoroquinolones and cephalosporins. Both are critically important drugs, the use of which in animals destined for food should be limited to specific indications and should be based on bacteriological diagnosis. The suggested routine protocol in dairy herds could target the primary antimicrobial treatment for mastitis, specifically infections caused by gram-positive bacteria. In E. coli mastitis with mild to moderate clinical signs, a non-antimicrobial approach (anti-inflammatory treatment, frequent milking and fluid therapy) should be the first option. In cases of severe E. coli mastitis, parenteral administration of fluoroquinolones, or third- or fourth-generation cephalosporins, is recommended due to the risk of unlimited growth of bacteria in the mammary gland and ensuing bacteremia. Evidence for the efficacy of intramammary-administered antimicrobial treatment for E. coli mastitis is so limited that it cannot be recommended. Nonsteroidal anti-inflammatory drugs have documented the efficacy in the treatment for E. coli mastitis and are recommended for supportive treatment for clinical mastitis. © 2013 John Wiley & Sons Ltd.
Bredow, J; Bloess, K; Oppermann, J; Boese, C K; Löhrer, L; Eysel, P
Non-specific chronic low back pain (NSCLBP): Which conservative therapy shows an evident effectiveness - A review of the current literature. Our results are based on literature reviews of current randomised control studies, reviews and meta-analysis drawn from the Cochrane Library and Medline-Database between the years 2004 until 2015. German and English Studies were included. We focused on different conservative Treatments of NSCLBP, which are listed at, the NVL-Guidelines. Based on the given evidence we evaluated their effectiveness. As part of the review we identified 4657 Publications, 85 were included in this study. Therapeutic options such as bed rest, TENS, Massage, Spine Supports, Back Schools and Antidepressants showed no evident effectiveness. Injections, NSAR analgesic therapy, Thermotherapy and Opioid analgesic therapy indicated a short-time effectiveness. A long term success (> 6 weeks) however, can not be shown. Only the Movement therapy can, in the summation of the included studies, postulate an evident (Evidence Level I) long-term effect treating NSCLBP. Only a few therapy options indicate a significant evident effectiveness for treating NSCLBP conservatively. At short notice methods such as injection therapy, thermo-therapy and analgesic therapies with NSAR and/or opioids help coping the acute phase. In the long term only movement therapy seems to provide an evident effectiveness. In the case of therapy-refractory NSCLBP a multimodal therapy should be considered.
Full Text Available Acute ankle injuries are among the most common injuries in emergency departments. However, a standardized examination and an evidence-based treatment are missing. Therefore, aim of this study was to systematically search the current literature, classify the evidence and develop an algorithm for diagnosis and treatment of acute ankle injuries. We systematically searched PubMed and the Cochrane Database for randomized controlled trials, meta-analysis, systematic reviews, or if applicable observational studies and classified them according to their level of evidence. According to the currently available literature, the following recommendations are given. The Ottawa Ankle/Foot Rule should be applied in order to rule out fractures, Physical examination is sufficient for diagnosing injuries to the lateral ligament complex. Classification into stable and unstable injuries is applicable and of clinical importance. The squeeze-, crossed leg- and external rotation test are indicative for injuries of the syndesmosis. Magnetic resonance imaging is recommended to verify such injuries. Stable ankle sprains have a good prognosis, while for unstable ankle sprains conservative treatment is at least as effective as operative treatment without carrying possible complications. Early functional treatment leads to the fastest recovery and the least rate of re-injury. Supervised rehabilitation reduces residual symptoms and re-injuries. Taken these recommendations into account, we here present an applicable and evidence-based step by step decision pathway for the diagnosis and treatment of acute ankle injuries, which can be implemented in any emergency department or doctor’s practice. It provides quality assurance for the patient and confidence for the attending physician.
Gainsbury, Sally M
Culturally and linguistically diverse (CALD) populations often have high rates of addictive disorders, but lower rates of treatment seeking and completion than the mainstream population. A significant barrier to treatment is the lack of culturally relevant and appropriate treatment. A literature review was conducted to identify relevant literature related to cultural competence in mental health services delivery and specifically treatment for addictive disorders. Several theoretical models of cultural competence in therapy have been developed, but the lack of rigorous research limits the empirical evidence available. Research indicates that culturally competent treatment practices including providing therapy and materials in the client's language, knowledge, understanding and appreciation for cultural perspectives and nuances, involving the wider family and community and training therapists can enhance client engagement, retention and treatment outcomes for substance use and gambling. Further methodologically rigorous research is needed to isolate the impact of cultural competence for the treatment of addictions and guide research to determine treatment efficacy within specific CALD populations. Training therapists and recruiting therapists and researchers from CALD communities is important to ensure an ongoing focus and improved outcomes for CALD populations due to the importance of engaging these populations with addiction treatment. Copyright © 2016 John Wiley & Sons, Ltd. Key Practitioner Message: The treatment needs of culturally diverse individuals with addictions are often not met. Theoretical models can guide therapists in incorporating cultural competence. Culturally targeted treatments increase recruitment, retention and treatment outcomes. Cultural competence includes matching clinicians and clients on linguistic and cultural backgrounds as well as being mindful of the impact of culture on client's experience of addiction problems. Few methodologically
Abstract Eating disorders often develop during adolescence and young adulthood, and are associated with significant psychological and physical burden. Identifying evidence-based interventions is critical and there is need to take stock of the extant literature, to inform clinical practice regarding well-researched interventions and to direct future research agendas by identifying gaps in the evidence base. Aim To investigate and quantify the nature and distribution of existing high-quality research on the prevention and treatment of eating disorders in young people using evidence mapping methodology. Method A systematic search for prevention and treatment intervention studies in adolescents and young adults (12–25 years) was conducted using EMBASE, PSYCINFO and MEDLINE. Studies were screened and mapped according to disorder, intervention modality, stage of eating disorder and study design. Included studies were restricted to controlled trials and systematic reviews published since 1980. Results The eating disorders evidence map included 197 trials and 22 systematic reviews. Prevention research was dominated by trials of psychoeducation (PE). Bulimia nervosa (BN) received the most attention in the treatment literature, with cognitive behavioural therapy (CBT) and antidepressants the most common interventions. For anorexia nervosa (AN), family based therapy (FBT) was the most studied. Lacking were trials exploring treatments for binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS). Relapse prevention strategies were notably absent across the eating disorders. Conclusions Despite substantial literature devoted to the prevention and treatment of eating disorders in young people, the evidence base is not well established and significant gaps remain. For those identified as being at-risk, there is need for prevention research exploring strategies other than passive PE. Treatment interventions targeting BED and EDNOS are required, as are
VINÍCIUS ZOLEZI DA SILVA
Full Text Available SUMMARY Introduction Since the 1980s, the use of autologous fat grafting has been growing in plastic surgery. Recently, this procedure has come to be used as a treatment for keloids and hypertrophic scars mainly due to the lack of satisfactory results with other techniques. So far, however, it lacks more consistent scientific evidence to recommend its use. The aim of this study was to review the current state of autologous fat grafting for the treatment of keloids and hypertrophic scars, their benefits and scientific evidences in the literature. Method A review in the Pubmed database was performed using the keywords “fat grafting and scar”, “fat grafting and keloid scar” and “fat grafting and hypertrophic scar.” Inclusion criteria were articles written in English and published in the last 10 years, resulting in 15 studies. Results These articles indicate that autologous fat grafting carried out at sites with pathological scars leads to a reduction of the fibrosis and pain, an increased range of movement in areas of scar contraction, an increase in their flexibility, resulting in a better quality of scars. Conclusion So far, evidences suggest that autologous fat grafting for the treatment of keloids and hypertrophic scars is associated with a better quality of scars, leading to esthetic and functional benefits. However, this review has limitations and these findings should be treated with reservations, since they mostly came from studies with low levels of evidence.
Full Text Available Abstract Background To analyze the characteristics and outcomes of women with breast cancer in the Northern Alberta Health Region (NAHR who declined recommended primary standard treatments. Methods A chart review was performed of breast cancer patients who refused recommended treatments during the period 1980 to 2006. A matched pair analysis was performed to compare the survival data between those who refused or received standard treatments. Results A total of 185 (1.2% patients refused standard treatment. Eighty-seven (47% were below the age of 75 at diagnosis. The majority of those who refused standard treatments were married (50.6%, 50 years or older (60.9%, and from the urban area (65.5%. The 5-year overall survival rates were 43.2% (95% CI: 32.0 to 54.4% for those who refused standard treatments and 81.9% (95% CI: 76.9 to 86.9% for those who received them. The corresponding values for the disease-specific survival were 46.2% (95% CI: 34.9 to 57.6% vs. 84.7% (95% CI: 80.0 to 89.4%. Conclusions Women who declined primary standard treatment had significantly worse survival than those who received standard treatments. There is no evidence to support using Complementary and Alternative Medicine (CAM as primary cancer treatment.
Abdul-Wahab, Taiceer A.; Betancourt, Jean P.; Hassan, Fadi; Thani, Saeed Al.; Choueiri, Hened; Jain, Nitin B.; Malanga, Gerard A.; Murrell, William D.; Prasad, Anil; Verborgt, Olivier
Summary Background rotator cuff tear affects many people. Natural history, and evidence for non-operative treatment remains limited. Our objective is to assess evidence available for the efficacy and morbidity of commonly used systemic medications, physiotherapy, and injections alongside evaluating any negative long-term effects. Methods a systematic search was performed of PubMed, Cochrane, EMBASE and CINAHL dates (1 January 1960 – 1 December 2014), search terms: ‘rotator cuff tear’, ‘natural history’, ‘atraumatic’, ‘injection’, ‘physiotherapy’ or ‘physical therapy’, ‘injection’, ‘corticosteroid’, ‘PRP‘, ‘MSC’, risk of conservative treatment’, and ‘surgical indication’. Results eleven studies were included. The mean Coleman Methodology Score modified for conservative therapy is 69.21 (range 88–44) (SD 12.31). This included 2 RCTs, 7 prospective, and 2 retrospective studies. Evidence suggests it is safe to monitor symptomatic rotator cuff tears, as tear size and symptoms are not correlated with pain, function, and/or ultimate outcome. Conclusions complete rotator cuff tears may be effectively treated with injections, exercise in the short and intermediate terms respectively. Negative effect of corticosteroids on rotator cuff tissue has not been demonstrated. Timing to end conservative treatment is unknown, but likely indicated when a patient demonstrates increased weakness and loss of function not recoverable by physiotherapy. PMID:27331030
Lovell, Karina; Bee, Penny
Obsessive-compulsive disorder (OCD) is a chronic and disabling mental health problem. Only a minority of people receive evidence-based psychological treatments, and this deficit has prompted an increasing focus on delivering cognitive behaviour therapy (CBT) in new and innovative ways. To conduct a scoping review of the published evidence base for CBT-based interventions incorporating a health technology in the treatment of OCD. The questions posed by the review were (a) are technology-assisted treatments clinically effective, (b) are patient outcomes durable and (c) are more innovative services deemed acceptable by those individuals who engage in them? Scoping review of published studies using any study design examining CBT interventions incorporating a health technology for OCD. Electronic databases searched included MEDLINE (1966-2010), PsycInfo (1967-2010), EMBASE (1980-2010) and CINAHL databases (1982-2010). Thirteen studies were identified, of these, five used bibliotherapy, five examined computerised CBT (cCBT), two investigated telephone delivered CBT and one evaluated video conferencing. Overall studies were small and methodologically flawed, which precludes definitive conclusions of clinical effectiveness, durability or stakeholder satisfaction. To date the evidence base for technology-enhanced OCD treatments has undergone limited development. Future research should seek to overcome the methodological shortcomings of published work by conducting large-scale trials that incorporate clinical, cost and acceptability outcomes.
Rainsford, K D; Parke, Ann L; Clifford-Rashotte, Matthew; Kean, W F
This review examines the pharmacokinetics, modes of action and therapeutic properties of the anti-malarial drugs, hydroxychloroquine (HCQ) and chloroquine (CQ), in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and related conditions, as well as osteoarthritis (OA). Both HCQ and CQ have historically been employed successfully for the treatment of SLE and RA for over 70 years. HCQ has been used extensively for SLE where it has a good reputation for controlling the dermatological complications in SLE. It has also been reported to effectively control the symptoms of Sjøgren's syndrome, as well as preventing thrombosis in phospholipid antibody (aPL) syndrome. In RA and SLE, HCQ is preferred because of the lower incidence of gastrointestinal adverse reactions compared with CQ and it might have a lower risk of ocular adverse reactions. There is increasing evidence that HCQ may reduce atherosclerosis and risks of cardiovascular disease in rheumatic patients. Both HCQ and CQ have been shown to improve glycaemia and reduce the risks of type II diabetes mellitus. Although both HCQ and CQ are effective in low-moderate RA, HCQ is now preferred as part of combination therapy for more severe disease. The advantages of combination therapy are that the doses of the individual drugs may be lowered so reducing adverse reactions. Both HCQ and CQ are diastereoisomers, have basic properties and are given as the sulphate and phosphate salts. While being relatively well absorbed orally and with good bioavailability, they have long and variable plasma terminal elimination half-lives (approximately 40-60 days). This reflects their high volume of distribution, V D (HCQ 44,000L; CQ 65,000L) which extends into aqueous compartments, long mean residence time (HCQ 1300 h; CQ 900 h) and with about half the drugs (metabolites) undergoing renal clearance. The strong binding to melanin reflects the ocular injury and dermatological properties of these drugs. The
Thilini N Jayasinghe
Full Text Available Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an endocrine organ, whose composition and functionality may contribute to the development of obesity. Therefore, faecal/gut microbiome transplantation (GMT, which involves the transfer of faeces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity.
Haug, Nancy A.; Shopshire, Michael; Tajima, Barbara; Gruber, Valerie; Guydish, Joseph
This research was conducted at a Substance Abuse Forum designed to address local community needs by focusing on Evidence-Based Practices (EBPs) in addiction treatment. The purpose of the study was to assess substance abuse treatment professionals’ readiness to adopt EBPs, experience with EBPs, and attitudes toward EBPs, as well as agency support for EBPs. A total of 119 addiction treatment providers completed pre-test measures, and 82% completed a post-test. Eighty-three percent of participants reported using some EBPs in the past year, and 75% reported currently using EBPs. Participants who were currently licensed or certified in addictions had less negative attitudes toward EBPs than those without credentials. While respondents reported agency support for EBPs, most expressed interest in further training. This study underscores the movement toward EBPs in addiction treatment and the need for effective dissemination and training in this area. PMID:18724657
Proffen, B; von Keudell, A; Vavken, P
The treatment of cartilage defects has seen a shift from replacement to regeneration in the last few years. The rationale behind this development is the improvement in the quality-of-care for the growing segment of young patients who are prone to arthroplasty complications because of their specific characteristics - young age, high level of activity, high demand for functionality. These days, two of the most popular regenerative treatments are microfracture and autologous chondrocyte implantation (ACI). Although these new options show promising results, no final algorithm for the treatment of cartilage lesions has been established as yet. The objective of this review is to describe and compare these two treatment options and to present an evidence-based treatment algorithm for focal cartilage defects. Microfracture is a cost-effective, arthroscopic one-stage procedure, in which by drilling of the subchondral plate, mesenchymal stem cells from the bone marrow migrate into the defect and rebuild the cartilage. ACI is a two-stage procedure in which first chondrocytes are harvested, expanded in cell culture and in a second open procedure reimplanted into the cartilage defect. Microfracture is usually used for focal cartilage defects osteophyte, and for the ACI patient, periosteal hypertrophy and the need for two procedures in ACI. Only a few studies provide detailed and evidence-based information on a comparative assessment. These studies, however, are showing widely similar clinical outcomes but better histological results for ACI, which are likely to translate into better long-term outcomes. Although evidence-based studies comparing microfracture and ACI have not found significant differences in the clinical outcome, the literature does show that choosing the treatment based on the size and characteristics of the osteochondral lesion might be beneficial. The American Association of Orthopedic Surgeons suggest that contained lesions < 4 cm2 should be treated by
Sørensen, Camilla Birgitte; Debes, Nanette Mol; Skov, Liselotte; Miranda, Maria J
Chronic tic disorder and Tourette syndrome are both chronic and impairing neurobiological disorders starting in childhood with a prevalence between 0.4 and 1.6%. Traditionally, pharmacological therapies have been first-line treatment but are often associated with adverse effects. Recently behavioural therapy has shown to be effective in treating tics and today both habit reversal (HR) and exposure and response prevention (ERP) are recommended as first-line treatments. HR and ERP are now available for Danish patients. This article describes the evidence and recommendations for both therapies.
INTRODUCTION: Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases with childhood onset. It comprises different subtypes of which the systemic onset subtype is often resistant to treatment. With the advent of biological treatment with tumor necrosis factor-alpha (TNFalpha......)-inhibitors, the clinical outcome of JIA has improved considerably, but only for subtypes other than systemic JIA. Substantial evidence shows that the proinflammatory cytokine interleukin-6 (IL-6) plays a pivotal role in systemic JIA. The blockage of IL-6 action by tocilizumab, a humanized anti-IL-6-receptor monoclonal...
Parker, Jacqui A; Barroso, Filipa; Stanworth, Simon J; Spiby, Helen; Hopewell, Sally; Doree, Carolyn J; Renfrew, Mary J; Allard, Shubha
Anaemia, in particular due to iron deficiency, is common in pregnancy with associated negative outcomes for mother and infant. However, there is evidence of significant variation in management. The objectives of this review of systematic reviews were to analyse and summarise the evidence base, identify gaps in the evidence and develop a research agenda for this important component of maternity care. Multiple databases were searched, including MEDLINE, EMBASE and The Cochrane Library. All systematic reviews relating to interventions to prevent and treat anaemia in the antenatal and postnatal period were eligible. Two reviewers independently assessed data inclusion, extraction and quality of methodology. 27 reviews were included, all reporting on the prevention and treatment of anaemia in the antenatal (n = 24) and postnatal periods (n = 3). Using AMSTAR as the assessment tool for methodological quality, only 12 of the 27 were rated as high quality reviews. The greatest number of reviews covered antenatal nutritional supplementation for the prevention of anaemia (n = 19). Iron supplementation was the most extensively researched, but with ongoing uncertainty about optimal dose and regimen. Few identified reviews addressed anaemia management post-partum or correlations between laboratory and clinical outcomes, and no reviews reported on clinical symptoms of anaemia. The review highlights evidence gaps including the management of anaemia in the postnatal period, screening for anaemia, and optimal interventions for treatment. Research priorities include developing standardised approaches to reporting of laboratory outcomes, and information on clinical outcomes relevant to the experiences of pregnant women.
Raza, A.; Beg, M.A.
Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, particularly Sulphadoxine-Pyrimethamine (SP) is threatening to make this form of control defunct. Therefore, studies on drug resistance are necessary so that anti-malarial treatment strategies can be structured and implemented accordingly by the Malaria Control Program, Pakistan. This review aims to provide information on genetic markers of P. vivax population structure and drug resistance and comment on their usefulness in molecular surveillance and control. (author)
McPherson, Sterling; Orr, Michael; Lederhos, Crystal; McDonell, Michael; Leickly, Emily; Hirchak, Katherine; Oluwoye, Oladunni A; Murphy, Sean M; Layton, Matthew; Roll, John M
Despite high rates of smoking (70-90%) and the severely negative impact of smoking on physical and mental health, only 12% of individuals receiving stimulant-use disorder treatment also receive smoking-cessation treatment. The aim of this investigation was to examine the effect of a contingency management (CM) intervention targeting methamphetamine (MA) use on cigarette smoking. Sixty-one adults with MA-use disorders who were smokers were assigned to CM or standard psychosocial treatment. Rates of smoking-negative breath samples (carbon monoxide <3 ppm) were compared between the two groups while controlling for baseline carbon monoxide level, marijuana use, MA use, and time. This subgroup of mostly male (59%) participants included 44 participants in the CM group and 17 participants in the standard psychosocial treatment. Tobacco smoking participants who received CM targeting MA use were 140% (odds ratio: 2.395; 95% confidence interval: 1.073-5.346) more likely to submit a smoking-negative breath sample relative to standard psychosocial treatment during the treatment period, holding constant several other prespecified covariates. This study provides evidence that a behavioral treatment for MA use results in reductions in cigarette smoking in adults with MA-use disorder.
Hinshaw, Stephen P; Arnold, L Eugene
Given major increases in the diagnosis of attention-deficit hyperactivity disorder (ADHD) and in rates of medication for this condition, we carefully examine evidence for effects of single versus multimodal (i.e., combined medication and psychosocial/behavioral) interventions for ADHD. Our primary data source is the Multimodal Treatment Study of Children with ADHD (MTA), a 14-month, randomized clinical trial in which intensive behavioral, medication, and multimodal treatment arms were contrasted with one another and with community intervention (treatment-as-usual), regarding outcome domains of ADHD symptoms, comorbidities, and core functional impairments. Although initial reports emphasized the superiority of well-monitored medication for symptomatic improvement, reanalyses and reappraisals have highlighted (1) the superiority of combination treatment for composite outcomes and for domains of functional impairment (e.g., academic achievement, social skills, parenting practices); (2) the importance of considering moderator and mediator processes underlying differential patterns of outcome, including comorbid subgroups and improvements in family discipline style during the intervention period; (3) the emergence of side effects (e.g., mild growth suppression) in youth treated with long-term medication; and (4) the diminution of medication's initial superiority once the randomly assigned treatment phase turned into naturalistic follow-up. The key paradox is that while ADHD clearly responds to medication and behavioral treatment in the short term, evidence for long-term effectiveness remains elusive. We close with discussion of future directions and a call for greater understanding of relevant developmental processes in the attempt to promote optimal, generalized, and lasting treatments for this important and impairing neurodevelopmental disorder. © 2014 John Wiley & Sons, Ltd.
Bergstrand, Fredrik; Twetman, Svante
The aim of this paper was to update the evidence for primary and secondary prevention (treatment) of white spot lesions (WSL) adjacent to fixed orthodontic appliances.......The aim of this paper was to update the evidence for primary and secondary prevention (treatment) of white spot lesions (WSL) adjacent to fixed orthodontic appliances....
Marcotte, Anne K
The purpose of this clinical focus article is to summarize 1 possible process that a clinician might follow in designing and conducting a treatment program with John, a 14-year-old male individual who stutters. The available research evidence, practitioner experience, and consideration of individual preferences are combined to address goals, treatment procedures, and outcomes for John. The stuttering treatment research literature includes multiple well-designed reviews and individual studies that have shown the effectiveness of prolonged speech (and smooth speech and related variations) for improving stuttered speech and for improving social, emotional, cognitive, and related variables in adolescents who stutter. Based on that evidence, and incorporating the additional elements of practitioner experience and client preferences, this clinical focus article suggests that John would be likely to benefit from a treatment program based on prolonged speech. The basic structure of 1 possible such program is also described, with an emphasis on the goals and outcomes that John could be expected to achieve.
Patel, Nupur U; Felix, Kayla; Reimer, Danielle; Feldman, Steven R
While topical medications remain the cornerstone of the psoriasis treatment paradigm, they also come with the risk of multiple side effects. An alternative topical treatment option, calcipotriene or calcipotriol, is a vitamin D derivative that is thought to work by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. Multiple studies have demonstrated its efficacy and safety in improving psoriasis when used in combination with topical corticosteroids. Given the effectiveness and side effect profile seen with this combination of topical steroid and calcipotriene, the US Food and Drug Administration approved a calcipotriene/betamethasone dipropionate product for use in psoriasis patients over the age of 12 in 2006. Our paper seeks to review clinical trial evidence of this combination medication and its use in the treatment of psoriasis vulgaris. While assessment of available evidence indicates that the topical medication is both safe and effective for the treatment of psoriasis vulgaris, addressing limitations of what is known, such as tolerability, adherence, and patient preference, of this combination drug in future high-impact studies is needed. PMID:29033598
Avraham, Ronen; Schanzenbach, Max
This paper analyzes the effect of non-economic damage caps on the treatment intensity of heart attack victims. We focus on whether a patient receives a major intervention in the form of either a coronary artery by-pass or angioplasty. We find strong evidence that treatment intensity declines after a cap on non-economic damages. The probability of receiving a major intervention in the form of either an angioplasty or bypass declines by 1.25-2 percentage points after non-economic damage caps are enacted, and this effect is larger a year or two after reform. However, we also find clear evidence of substitution between major interventions. When doctors have discretion to perform a by-pass and patients have insurance coverage, caps on non-economic damages increase the probability that a by-pass is performed. The effect of non-economic damage caps on costs is not always statistically significant, but in models with state-specific trends, total costs decline by as much as four percent. We conclude that tort reform reduces treatment intensity overall, even though it changes the mix of treatments. Using the Center for Disease Control's Vital Statistics data, we find that tort reform is not associated with an increase in mortality from coronary heart disease; if anything, mortality declines. Copyright © 2014 Elsevier B.V. All rights reserved.
Kaula, Henry; Buyungo, Peter; Opigo, Jimmy
Several interventions have been put in place to promote access to quality malaria case management services in Uganda's private sector, where most people seek treatment. This paper describes evidence using a mixed-method approach to examine the role, readiness and performance of private providers at a national level in Uganda. These data will be useful to inform strategies and policies for improving malaria case management in the private sector. The ACTwatch national anti-malarial outlet survey was conducted concurrently with a fever case management study. The ACTwatch nationally representative anti-malarial outlet survey was conducted in Uganda between May 18th 2015 and July 2nd 2015. A representative sample of sub-counties was selected in 14 urban and 13 rural clusters with probability proportional to size and a census approach was used to identify outlets. Outlets eligible for the survey met at least one of three criteria: (1) one or more anti-malarials were in stock on the day of the survey; (2) one or more anti-malarials were in stock in the 3 months preceding the survey; and/or (3) malaria blood testing (microscopy or RDT) was available. The fever case management study included observations of provider-patient interactions and patient exit interviews. Data were collected between May 20th and August 3rd, 2015. The fever case management study was implemented in the private sector. Potential outlets were identified during the main outlet survey and included in this sub-sample if they had both artemisinin-based combination therapy (ACT) [artemether-lumefantrine (AL)], in stock on the day of survey as well as diagnostic testing available. A total of 9438 outlets were screened for eligibility in the ACTwatch outlet survey and 4328 outlets were found to be stocking anti-malarials and were interviewed. A total of 9330 patients were screened for the fever case management study and 1273 had a complete patient observation and exit interview. Results from the outlet
Sach, Tracey Helen; McManus, Emma; Mcmonagle, Christopher; Levell, Nick
Eczema, synonymous with atopic eczema or atopic dermatitis, is a chronic skin disease that has a similar impact on health-related quality of life as other chronic diseases. The proposed research aims to provide a comprehensive systematic assessment of the economic evidence base available to inform economic modelling and decision making on interventions to prevent and treat eczema at any stage of the life course. Whilst the Global Resource of Eczema Trials (GREAT) database collects together the effectiveness evidence for eczema, there is currently no such systematic resource on the economics of eczema. It is important to gain an overview of the current state of the art of economic methods in the field of eczema in order to strengthen the economic evidence base further. The proposed study is a systematic review of the economic evidence surrounding interventions for the prevention and treatment of eczema. Relevant search terms will be used to search MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, National Health Service (NHS) Economic Evaluation Database, Health Technology Assessment, Cumulative Index to Nursing and Allied Health Literature, EconLit, Scopus, Cost-Effectiveness Analysis Registry and Web of Science in order to identify relevant evidence. To be eligible for inclusion studies will be primary empirical studies evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema. Two reviewers will independently assess studies for eligibility and perform data abstraction. Evidence tables will be produced presenting details of study characteristics, costing methods, outcome methods and quality assessment. The methodological quality of studies will be assessed using accepted checklists. The systematic review is being undertaken to identify the type of economic evidence available, summarise the results of the available
Beatrice I. Amboko
Full Text Available Abstract Background Up to 90 % of the global burden of malaria morbidity and mortality occurs in sub-Saharan Africa and children under-five bear a disproportionately high malaria burden. Effective inpatient case management can reduce severe malaria mortality and morbidity, but there are few reports of how successfully international and national recommendations are adopted in management of inpatient childhood malaria. Methods A descriptive cross-sectional study of inpatient malaria case management practices was conducted using data collected over 24 months in five hospitals from high malaria risk areas participating in the Clinical Information Network (CIN in Kenya. This study describes documented clinical features, laboratory investigations and treatment of malaria in children (2–59 months and adherence to national guidelines. Results A total of 13,014 children had a malaria diagnosis on admission to the five hospitals between March, 2014 and February, 2016. Their median age was 24 months (IQR 12–36 months. The proportion with a diagnostic test for malaria requested was 11,981 (92.1 %. Of 10,388 patients with malaria test results documented, 8050 (77.5 % were positive and anti-malarials were prescribed in 6745 (83.8 %. Malaria treatment was prescribed in 1613/2338 (69.0 % children with a negative malaria result out of which only 52 (3.2 % had a repeat malaria test done as recommended in national guidelines. Documentation of clinical features was good across all hospitals, but quinine remained the most prescribed malaria drug (47.2 % of positive cases although a transition to artesunate (46.1 % was observed. Although documented clinical features suggested approximately half of positive malaria patients were not severe cases artemether-lumefantrine was prescribed on admission in only 3.7 % cases. Conclusions Despite improvements in inpatient malaria care, high rates of presumptive treatment for test negative children and likely
Linkov, Faina; Valappil, Benita; McAfee, Jacob; Goughnour, Sharon L; Hildrew, Douglas M; McCall, Andrew A; Linkov, Igor; Hirsch, Barry; Snyderman, Carl
To integrate multiple sources of clinical information with patient feedback to build evidence-based decision support model to facilitate treatment selection for patients suffering from vestibular schwannomas (VS). This was a mixed methods study utilizing focus group and survey methodology to solicit feedback on factors important for making treatment decisions among patients. Two 90-minute focus groups were conducted by an experienced facilitator. Previously diagnosed VS patients were recruited by clinical investigators at the University of Pittsburgh Medical Center (UPMC). Classical content analysis was used for focus group data analysis. Providers were recruited from practices within the UPMC system and were surveyed using Delphi methods. This information can provide a basis for multi-criteria decision analysis (MCDA) framework to develop a treatment decision support system for patients with VS. Eight themes were derived from these data (focus group + surveys): doctor/health care system, side effects, effectiveness of treatment, anxiety, mortality, family/other people, quality of life, and post-operative symptoms. These data, as well as feedback from physicians were utilized in building a multi-criteria decision model. The study illustrated steps involved in the development of a decision support model that integrates evidence-based data and patient values to select treatment alternatives. Studies focusing on the actual development of the decision support technology for this group of patients are needed, as decisions are highly multifactorial. Such tools have the potential to improve decision making for complex medical problems with alternate treatment pathways. Copyright © 2016 Elsevier Inc. All rights reserved.
Akpek, Esen Karamursel; Lindsley, Kristina B; Adyanthaya, Rohit S; Swamy, Ramya; Baer, Alan N; McDonnell, Peter J
Outcomes-based review of reported treatment options for patients with dry eye secondary to Sjögren's syndrome (SS). Dry eye affects many individuals worldwide. Significant proportion of patients with dry eye has underlying SS, a progressive autoimmune condition. The few suggested guidelines for the treatment of dry eye are mostly based on severity of symptoms and/or clinical findings rather than on outcomes analysis, and do not differentiate SS from other causes of dry eye. METHODS AND LITERATURE REVIEW: A search strategy was developed to identify prospective, interventional studies of treatments for SS-associated dry eye from electronic databases. Eligible references were restricted to English-language articles published after 1975. These sources were augmented by hand searches of reference lists from accessed articles. Study selection, data extraction, and grading of evidence were completed independently by ≥4 review authors. The searches identified 3559 references as of August 10, 2010. After duplicate review of the titles and abstracts, 245 full-text papers were assessed, 62 of which were relevant for inclusion in the review. In the current literature on SS-associated dry eye, there is a paucity of rigorous clinical trials to support therapy recommendations. Nonetheless, the recommended treatments include topical lubricants, topical anti-inflammatory therapy, and tear-conserving strategies. The efficacy of oral secretagogues seems greater in the treatment of oral dryness than ocular dryness. Although oral hydroxychloroquine is commonly prescribed to patients with SS to alleviate fatigue and arthralgias, the literature lacks strong evidence for the efficacy of this treatment for dry eye. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Younker, D.R.; Daniels, V.R.; Boyd, J.L.; Putcha, L.
An objective of this data compilation and analysis project is to examine incidence and treatment efficacy of common patho-physiological disturbances during spaceflight. Analysis of medical debriefs data indicated that astronauts used medications to alleviate symptoms of four major ailments for which astronauts received treatment for sleep disturbances, space motion sickness (SMS), pain (headache, back pain) and sinus congestion. In the present data compilation and analysis project on SMS treatment during space missions, subject demographics (gender, age, first-time or repeat flyer), incidence and severity of SMS symptoms and subjective treatment efficacy from 317 crewmember debrief records were examined from STS-1 through STS-89. Preliminary analysis of data revealed that 50% of crew members reported SMS symptoms on at least one flight and 22% never experienced it. In addition, there were 387 medication dosing episodes reported, and promethazine was the most commonly used medication. Results of analysis of symptom check lists, medication use/efficacy and gender and flight record differences in incidence and treatment efficacy will be presented. Evidence gaps for treatment efficacy along with medication use trend analysis will be identified.
Weersing, V. Robin; Jeffreys, Megan; Do, Minh-Chau T.; Schwartz, Karen T. G.; Bolano, Carl
Depression in youth is prevalent and disabling and tends to presage a chronic and recurrent course of illness and impairment in adulthood. Clinical trial research in youth depression has a 30 year history, and evidence-based treatment reviews appeared in 1998 and 2008. The current review of 42 randomized controlled trials (RCTs) updates these reviews to include RCTs published between 2008 and 2014 (N = 14) and re-evaluates previously reviewed literature. Given the growing maturity of the field, this review utilized a stringent set of methodological criteria for trial inclusion, most notable for excluding trials based in sub-clinical samples of youth that had been included in previous reviews (N = 12) and including well-designed RCTs with null and negative findings (N = 8). Findings from the current review suggest that evidence for child treatments is notably weaker than for adolescent interventions, with no child treatments achieving well-established status and the evidentiary basis of treatments downgraded from previous reports. Cognitive behavioral therapy (CBT) for clinically depressed children appears to be possibly efficacious, with mixed findings across trials. For depressed adolescents, both CBT and Interpersonal Psychotherapy (IPT) are well-established interventions, with evidence of efficacy in multiple trials by independent investigative teams. This positive conclusion is tempered by the small size of the IPT literature (N = 6) and concern that CBT effects may be attenuated in clinically complicated samples and when compared against active control conditions. In conclusion, data on predictors, moderators, and mediators are examined and priorities for future research discussed. PMID:27870579
Weersing, V Robin; Jeffreys, Megan; Do, Minh-Chau T; Schwartz, Karen T G; Bolano, Carl
Depression in youth is prevalent and disabling and tends to presage a chronic and recurrent course of illness and impairment in adulthood. Clinical trial research in youth depression has a 30-year history, and evidence-based treatment reviews appeared in 1998 and 2008. The current review of 42 randomized controlled trials (RCTs) updates these reviews to include RCTs published between 2008 and 2014 (N = 14) and reevaluates previously reviewed literature. Given the growing maturity of the field, this review utilized a stringent set of methodological criteria for trial inclusion, most notable for excluding trials based in subclinical samples of youth that had been included in previous reviews (N = 12) and including well-designed RCTs with null and negative findings (N = 8). Findings from the current review suggest that evidence for child treatments is notably weaker than for adolescent interventions, with no child treatments achieving well-established status and the evidentiary basis of treatments downgraded from previous reports. Cognitive behavioral therapy (CBT) for clinically depressed children appears to be possibly efficacious, with mixed findings across trials. For depressed adolescents, both CBT and interpersonal psychotherapy are well-established interventions, with evidence of efficacy in multiple trials by independent investigative teams. This positive conclusion is tempered by the small size of the interpersonal psychotherapy literature (N = 6) and concern that CBT effects may be attenuated in clinically complicated samples and when compared against active control conditions. Data on predictors, moderators, and mediators are examined and priorities for future research discussed.
Wilkinson, C P
To assess the quality of information in the literature regarding the benefits of prophylactic treatment of asymptomatic retinal tears and lattice degeneration. Asymptomatic retinal breaks occur in approximately 7% of patients over age 40, and lattice degeneration is present in approximately 8% of the general population. Because retinal breaks cause retinal detachment and lattice degeneration is associated with approximately 30% of retinal detachments, prophylactic treatment of these lesions has sometimes been recommended. A panel of vitreoretinal experts performed a literature review of all publications regarding prevention of retinal detachment that have been published in English. These articles were then used to prepare recommendations for patient care in an American Academy of Ophthalmology Preferred Practice Pattern (PPP). Each recommendation was rated according to: (1) its importance in the care process and (2) the strength of evidence supporting the given recommendation. Most recommendations were rated as A (most important to patient care). Only a single publication was graded as I (providing strong evidence in support of a recommendation), and this was not a prospective trial. Of the few publications rated as II (substantial evidence), most were studies documenting a lack of treatment benefit. Because of an absence of level I and level II studies in the literature, level III (consensus of expert opinion) was the basis for most recommendations in the PPP. The current literature regarding prevention of retinal detachment does not provide sufficient information to support strongly prophylactic treatment of lesions other than symptomatic flap tears. Prospective randomized trials of prophylactic therapy are indicated. Eyes highly predisposed to retinal detachment should be considered for such studies.
Castro, Carlos; Cardona, Andres Felipe; Reveiz, Ludovic; Serrano, Silvia Juliana; Carranza, Hernan; Vargas, Carlos Alberto; Reguart, Noemi; Campo, Felipe; Ospina, Edgar Guillermo; Sanchez, Oswaldo; Torres, Diana; Otero, Jorge Miguel
to perform a review of evidence about the treatment of non-small cell lung cancer (NSCLC). Source of data: the information was obtained from searches conducted in Medline, CCTR, Biosis, Embase, Lilacs and CINHAL. We also collected the most representative references presented during the last five years at Asco, ESMO and IASLC. Data extraction: data were extracted by associate members to the ONCOL Group. The collection of information did not follow a uniform strategy. Results of data synthesis: therapy for NSCLC can prolong survival and improve quality of life, but the majority of advanced stage patients dies due to disease progression within 2 years, meaning that there is room for improvement. The standard chemotherapy for NSCLC involves one of a number of platinum-based doublets that have been shown to improve survival when compared with single agents or best supportive care. These doublets are generally comparable in terms of efficacy, differing primarily in their toxicity profiles. However, encouraging new options may be approaching, including therapies targeted to specific patient subpopulations, and the use of combinations of current and new drugs to produce synergistic effects. This review present a detailed analysis of current evidence regarding the treatment of NSCLC based on a representative case series. This review didn't conduct a systematic evaluation of the evidence. Conclusion: medical therapy for NSCLC produces positive changes in main outcomes, including quality of life
WHO malaria expert, Dr. Charlotte Rasmussen, discusses anti-malarial drug resistance in Vietnam. Created: 6/5/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID). Date Released: 6/5/2017.
Wallon, Martine; Liou, Christiane; Garner, Paul; Peyron, François
Objective To summarise the evidence that treating toxoplasmosis in pregnancy reduces the risk of congenital toxoplasma infection and improves infant outcomes. Design Systematic review of studies comparing at least two concurrent groups of pregnant women with proved or likely acute toxoplasma infection in which treatments were compared with no treatment and outcomes in the children were reported. Subjects Studies were identified from Medline (1966-97), Pascal (1990-7), Embase (1993-7), and Biological abstracts (1993-5) plus contact with experts in the field, including the European Research Network on Congenital Toxoplasmosis. Main outcome measure Proportion of infected children at 1 year born to infected pregnant women who were or were not treated. Results Out of 2591 papers identified, nine met the inclusion criteria. There were no randomised comparisons, and control groups were generally not directly comparable with the treatment groups. Congenital infection was common in treated groups. five studies showed that treatment was effective and four that it was not. Conclusion It is unclear whether antenatal treatment in women with presumed toxoplasmosis reduces congenital transmission of Toxoplasma gondii. Screening is expensive, so the effects of treatment and impact of screening programmes need to be evaluated. In countries where screening or treatment is not routine, these technologies should not be introduced outside carefully controlled trials. Key messagesPregnant women in France and Austria are routinely screened for toxoplasmosis, and women negative for antibodies are followed up at regular intervalsThe value of antenatal toxoplasmosis screening programmes depends on safe treatments that reduce the risk of congenital diseaseThis systematic review found no good comparative data measuring the potential harms and benefits of antiparasitic drugs used for presumed antenatal toxoplasma infectionMost control groups were not comparable, and incidence of congenital
Pedro Leonel Almeida
Full Text Available Background. Advances in technological, laboratorial, and imaging studies and new treatments available in the last decades significantly improved prostate cancer survival rates. However, this did not occur in metastatic prostate cancer (mPCa at diagnosis which, in young and fit patients, will become invariably resistant to the established treatments. Progression will lead to an impairment in patients’ quality of life and disease-related death. Methods. The authors intend to perform a literature review of the advantages of primary treatment of mPCa. Articles were retrieved and filtered for relevance from PubMed, SciELO, and ScienceDirect until March 2017. Results. Primary treatment is currently indicated only in cases of nonmetastatic PCa. Nonetheless, there might be some benefits in doing local treatment in mPCa in order to control local disease, prevent new metastasis, and improve the efficacy of chemotherapy and hormonotherapy with similar complications rate when compared to locally confined cancer. Independent factors that have a negative influence are age above 70 years, cT4 stage or high-grade disease, PSA≥20 ng/ml, and pelvic lymphadenopathies. The presence of 3 or more of these factors conditions CSS and OS is the same between patients who performed local treatment and those who did not. Metastasis degree and location number can also influence outcome. Meanwhile, patients with visceral metastases have worse results. Conclusions. There is growing evidence supporting local treatment in cases of metastatic prostate cancer at diagnosis in the context of a multimodal approach. However, it should be kept in mind that most of the existing studies are retrospective and it would be important to make consistent prospective studies with well-defined patient selection criteria in order to sustain the existing data and understand the main indications to select patients and perform primary treatment in mPCa.
Leonel Almeida, Pedro; Jorge Pereira, Bruno
Advances in technological, laboratorial, and imaging studies and new treatments available in the last decades significantly improved prostate cancer survival rates. However, this did not occur in metastatic prostate cancer (mPCa) at diagnosis which, in young and fit patients, will become invariably resistant to the established treatments. Progression will lead to an impairment in patients' quality of life and disease-related death. The authors intend to perform a literature review of the advantages of primary treatment of mPCa. Articles were retrieved and filtered for relevance from PubMed, SciELO, and ScienceDirect until March 2017. Primary treatment is currently indicated only in cases of nonmetastatic PCa. Nonetheless, there might be some benefits in doing local treatment in mPCa in order to control local disease, prevent new metastasis, and improve the efficacy of chemotherapy and hormonotherapy with similar complications rate when compared to locally confined cancer. Independent factors that have a negative influence are age above 70 years, cT4 stage or high-grade disease, PSA ≥ 20 ng/ml, and pelvic lymphadenopathies. The presence of 3 or more of these factors conditions CSS and OS is the same between patients who performed local treatment and those who did not. Metastasis degree and location number can also influence outcome. Meanwhile, patients with visceral metastases have worse results. There is growing evidence supporting local treatment in cases of metastatic prostate cancer at diagnosis in the context of a multimodal approach. However, it should be kept in mind that most of the existing studies are retrospective and it would be important to make consistent prospective studies with well-defined patient selection criteria in order to sustain the existing data and understand the main indications to select patients and perform primary treatment in mPCa.
Timko, Christine; Below, Maureen; Schultz, Nicole R; Brief, Deborah; Cucciare, Michael A
Although completion of detoxification (detox) and a successful transition from detox to substance use disorder (SUD) treatment and/or mutual-help groups are associated with better SUD outcomes, many patients do not complete detox or do not receive SUD care following detox. The purpose of this structured evidence review, summarizing data extraction on a yield of 26 articles, is to identify patient, program, and system factors associated with the outcomes of completion of alcohol detox and successful transitions from alcohol detox to SUD treatment and mutual-help group participation. The review found wide variability among studies in the rates at which patients complete a detox episode (45 to 95%) and enter SUD treatment or mutual-help groups after detox (14 to 92%). Within program factors, behavioral practices that contribute to both detox completion and transitioning to SUD care after detox entail involving the patient's family and utilizing motivational-based approaches. Such practices should be targeted at younger patients, who are less likely to complete detox. Although more studies using a randomized controlled trial design are needed, the evidence suggests that barriers to detox completion and transition to SUD care can be overcome to improve patient outcomes. Published by Elsevier Inc.
Tomé-Carneiro, Joao; Visioli, Francesco
In addition to prescription drugs, nutraceuticals/functional foods/medical foods are being increasingly added as adjunct treatment of cardiovascular disease (CVD), even though most of them have been exclusively studied in vitro. We review the available evidence (focusing on when the amount of polyphenols' intake was measured) coming from randomized controlled trials (RCTs) of (poly)phenol-based supplements. We conclude that (poly)phenol-based nutraceuticals and functional foods might be indeed used as adjunct therapy of CVD, but additional long-term RCTs with adequate numerosity and with clinically relevant end points are needed to provide unequivocal evidence of their clinical usefulness. Copyright © 2015. Published by Elsevier GmbH.
Simó, Rafael; Ballarini, Stefania; Cunha-Vaz, José; Ji, Linong; Haller, Hermann; Zimmet, Paul; Wong, Tien Y.
The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising. This up-to-date critical review of non-traditional systemic treatments for DR is based on the published evidence in MEDLINE spanning 1980-December 2014. It discusses a number of therapeutic options, paying particular attention to the mechanisms of action and the clinical evidence for the use of renin-angiotensin system blockade, fenofibrate and calcium dobesilate monohydrate in DR. PMID:25989912
Nasri, Hamid; Bahmani, Mahmoud; Shahinfard, Najmeh; Moradi Nafchi, Atefeh; Saberianpour, Shirin; Rafieian Kopaei, Mahmoud
Acne vulgaris affects about 85% of teenagers and may continue to adulthood. There are about two million visits to physicians per year for teenagers and the direct cost of acne treatment in the US exceeds $1 billion per year. A wide variety of treatment regimens exist for acne vulgaris including benzoil peroxide, retinoids, isotretinoids, keratolytic soaps, alpha hydroxy acids, azelaic acid, salicilic acid as well as hormonal, anti-androgen or antiseborrheic treatments. However, none of these methods is free of side effects and their exact role in therapy is not clear. In this paper apart from presenting the possible causes of acne vulgaris and its available drugs, recently published papers about medicinal plants used in the treatment of acne vulgaris were reviewed. Consumption of alternative and complementary medicine, including medicinal plants, is increasing and is common amongst patients affected by acne and infectious skin diseases. Medicinal plants have a long history of use and have been shown to possess low side effects. These plants are a reliable source for preparation of new drugs. Many plants seem to have inhibitory effects on the growth of bacteria, fungi and viruses in vitro. However, there are a few clinical evidences about the effectiveness and safety of these plants in the treatment of acne and other skin infections.
Neumeister, Alexander; Seidel, Jordan; Ragen, Benjamin J.; Pietrzak, Robert H.
Introduction Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and disabling anxiety disorder that may develop following exposure to a traumatic event. Despite the public health significance of PTSD, relatively little is known about the etiology or pathophysiology of this disorder, and pharmacotherapy development to date has been largely opportunistic instead of mechanism-based. Recently, an accumulating body of evidence has implicated the endocannabinoid system in the etiology of PTSD, and targets within this system are believed to be suitable for treatment development. Methods Herein, we describe evidence from translational studies arguing for the relevance of the endocannabinoid system in the etiology of PTSD. We also show mechanisms relevant for treatment development. Results There is convincing evidence from multiple studies for reduced endocannabinoid availability in PTSD. Brain imaging studies show molecular adaptations with elevated cannabinoid type 1 (CB1) receptor availability in PTSD which is linked to abnormal threat processing and anxious arousal symptoms. Conclusion Of particular relevance is evidence showing reduced levels of the endocannabinoid anandamide and compensatory increase of CB1 receptor availability in PTSD, and an association between increased CB1 receptor availability in the amygdala and abnormal threat processing, as well as increased severity of hyperarousal, but not dysphoric symptomatology, in trauma survivors. Given that hyperarousal symptoms are the key drivers of more disabling aspects of PTSD such as emotional numbing or suicidality, novel, mechanism-based pharmacotherapies that target this particular symptom cluster in patients with PTSD may have utility in mitigating the chronicity and morbidity of the disorder. PMID:25456347
Parker Jacqui A
Full Text Available Abstract Background Anaemia, in particular due to iron deficiency, is common in pregnancy with associated negative outcomes for mother and infant. However, there is evidence of significant variation in management. The objectives of this review of systematic reviews were to analyse and summarise the evidence base, identify gaps in the evidence and develop a research agenda for this important component of maternity care. Methods Multiple databases were searched, including MEDLINE, EMBASE and The Cochrane Library. All systematic reviews relating to interventions to prevent and treat anaemia in the antenatal and postnatal period were eligible. Two reviewers independently assessed data inclusion, extraction and quality of methodology. Results 27 reviews were included, all reporting on the prevention and treatment of anaemia in the antenatal (n = 24 and postnatal periods (n = 3. Using AMSTAR as the assessment tool for methodological quality, only 12 of the 27 were rated as high quality reviews. The greatest number of reviews covered antenatal nutritional supplementation for the prevention of anaemia (n = 19. Iron supplementation was the most extensively researched, but with ongoing uncertainty about optimal dose and regimen. Few identified reviews addressed anaemia management post-partum or correlations between laboratory and clinical outcomes, and no reviews reported on clinical symptoms of anaemia. Conclusions The review highlights evidence gaps including the management of anaemia in the postnatal period, screening for anaemia, and optimal interventions for treatment. Research priorities include developing standardised approaches to reporting of laboratory outcomes, and information on clinical outcomes relevant to the experiences of pregnant women.
Aesthetic improvement and psychological enhancement have been cited as justifications for orthodontic treatment. This paper reviews the evidence that relates malocclusion to psychological health and quality of life and explores whether this evidence supports the most commonly used aesthetic Orthodontic Treatment Need Indices (OTNI). The relevant cited material from the MEDLINE, Web of Science, Scopus, Cochrane databases, and scientific textbooks were used. The citation rate was confirmed by using the Google Scholar. The subjective nature of aesthetic indices and the variable perception of attractiveness between clinicians and patients, and among various cultures or countries are a few limitations of aesthetic OTNI. The available evidence of mainly cross-sectional studies on the link between malocclusion and either psychosocial well-being or quality of life is not conclusive, and sometimes contradictory, to suggest these characteristics are affected by malocclusions. Further, the long-term longitudinal studies did not suggest that people with malocclusion are disadvantaged psychologically, or their quality of life would be worse off, which challenges using aesthetic OTNI to assess the social and psychological implications of malocclusion. The subjective nature of aesthetic OTNI and the minor contributory role of malocclusion in psychosocial health or quality of life undermine using aesthetic indices to assess the likely social and psychological implications of malocclusion. Consequently, using aesthetic OTNI, as a method to quantify malocclusion remains open to debate. Various soft and hard-tissue analyses are used before formulating a treatment plan (i.e., assessment of sagittal and vertical skeletal relationships). The addition of a shortened version of these analyses to the aesthetic OTNI can be a good substitute for the aesthetic components of OTNI, if an assessment of the aesthetic aspects of malocclusion is intended. This reduces subjectivity and improves the
Moore, R Andrew; Derry, Sheena; Wiffen, Philip J; Straube, Sebastian; Bendtsen, Lars
The International Headache Society (IHS) provides guidance on the conduct of trials for acute treatment of episodic tension-type headache (TTH), a common disorder with considerable disability. Electronic and other searches identified randomised, double-blind trials of oral drugs treating episodic TTH with moderate or severe pain at baseline, or that tested drugs at first pain onset. The aims were to review methods, quality, and outcomes reported (in particular the IHS-recommended primary efficacy parameter pain-free after 2 hours), and to assess efficacy by meta-analysis. We identified 58 reports: 55 from previous reviews and searches, 2 unpublished reports, and 1 clinical trial report with results. We included 40 reports of 55 randomised trials involving 12,143 patients. Reporting quality was generally good, with potential risk of bias from incomplete outcome reporting and small size; the 23 largest trials involved 82% of patients. Few trials reported IHS outcomes. The number needed to treat values for being pain-free at 2 hours compared with placebo were 8.7 (95% confidence interval [CI] 6.2 to 15) for paracetamol 1000 mg, 8.9 (95% CI 5.9 to 18) for ibuprofen 400mg, and 9.8 (95% CI 5.1 to 146) for ketoprofen 25mg. Lower (better) number needed to treat values were calculated for outcomes of mild or no pain at 2 hours, and patient global assessment. These were similar to values for these drugs in migraine. No other drugs had evaluable results for these patient-centred outcomes. There was no evidence that any one outcome was better than others. The evidence available for treatment efficacy is small in comparison to the size of the clinical problem. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Kanayama, Gen; Brower, Kirk J.; Wood, Ruth I.; Hudson, James I.; Pope, Harrison G.
Currently, few users of anabolic-androgenic steroids (AAS) seek substance-abuse treatment. But this picture may soon change substantially, because illicit AAS use did not become widespread until the 1980s, and consequently the older members of this AAS-using population—those who initiated AAS as youths in the 1980s—are only now reaching middle age. Members of this group, especially those who have developed AAS dependence, may therefore be entering the age of risk for cardiac and psychoneuroendocrine complications sufficient to motivate them for substance-abuse treatment. We suggest that this treatment should address at least three etiologic mechanisms by which AAS dependence might develop. First, individuals with body-image disorders such as “muscle dysmorphia” may become dependent on AAS for their anabolic effects; these body-image disorders may respond to psychological therapies or pharmacologic treatments. Second, AAS suppress the male hypothalamic-pituitary-gonadal axis via their androgenic effects, potentially causing hypogonadism during AAS withdrawal. Men experiencing prolonged dysphoric effects or frank major depression from hypogonadism may desire to resume AAS, thus contributing to AAS dependence. AAS-induced hypogonadism may require treatment with human chorionic gonadotropin or clomiphene to reactivate neuroendocrine function, and may necessitate antidepressant treatments in cases of depression inadequately responsive to endocrine therapies alone. Third, human and animal evidence indicates that AAS also possess hedonic effects, which likely promote dependence via mechanisms shared with classical addictive drugs, especially opioids. Indeed, the opioid antagonist naltrexone blocks AAS dependence in animals. By inference, pharmacological and psychosocial treatments for human opioid dependence might also benefit AAS-dependent individuals. PMID:20188494
Kanayama, Gen; Brower, Kirk J; Wood, Ruth I; Hudson, James I; Pope, Harrison G
Currently, few users of anabolic-androgenic steroids (AAS) seek substance abuse treatment. But this picture may soon change substantially, because illicit AAS use did not become widespread until the 1980s, and consequently the older members of this AAS-using population - those who initiated AAS as youths in the 1980s - are only now reaching middle age. Members of this group, especially those who have developed AAS dependence, may therefore be entering the age of risk for cardiac and psychoneuroendocrine complications sufficient to motivate them for substance abuse treatment. We suggest that this treatment should address at least three etiologic mechanisms by which AAS dependence might develop. First, individuals with body image disorders such as "muscle dysmorphia" may become dependent on AAS for their anabolic effects; these body image disorders may respond to psychological therapies or pharmacological treatments. Second, AAS suppress the male hypothalamic-pituitary-gonadal axis via their androgenic effects, potentially causing hypogonadism during AAS withdrawal. Men experiencing prolonged dysphoric effects or frank major depression from hypogonadism may desire to resume AAS, thus contributing to AAS dependence. AAS-induced hypogonadism may require treatment with human chorionic gonadotropin or clomiphene to reactivate neuroendocrine function, and may necessitate antidepressant treatments in cases of depression inadequately responsive to endocrine therapies alone. Third, human and animal evidence indicates that AAS also possess hedonic effects, which likely promote dependence via mechanisms shared with classical addictive drugs, especially opioids. Indeed, the opioid antagonist naltrexone blocks AAS dependence in animals. By inference, pharmacological and psychosocial treatments for human opioid dependence might also benefit AAS-dependent individuals. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
Dorsey, Shannon; Pullmann, Michael D; Kerns, Suzanne E U; Jungbluth, Nathaniel; Meza, Rosemary; Thompson, Kelly; Berliner, Lucy
Supervisors are an underutilized resource for supporting evidence-based treatments (EBTs) in community mental health. Little is known about how EBT-trained supervisors use supervision time. Primary aims were to describe supervision (e.g., modality, frequency), examine functions of individual supervision, and examine factors associated with time allocation to supervision functions. Results from 56 supervisors and 207 clinicians from 25 organizations indicate high prevalence of individual supervision, often alongside group and informal supervision. Individual supervision serves a wide range of functions, with substantial variation at the supervisor-level. Implementation climate was the strongest predictor of time allocation to clinical and EBT-relevant functions.
El-Mallakh, Peggy; Howard, Patricia B; Rayens, Mary Kay; Roque, Autumn P; Adkins, Sarah
Organizational support is essential for successful implementation of evidence-based practice (EBP) in clinical settings. This 3-year study used a mixed qualitative and quantitative design to implement a medication management EBP in the treatment of schizophrenia in six community mental health clinics in a south-central state of the United States. Findings from organizational fidelity assessments indicate that support for EBP implementation was moderate. Organizational support was highest for prescriber access to relevant patient information at each medication visit, scheduling flexibility for patients' urgent problems, and availability of medication guidelines. Organizational support was lowest for medication availability and identification of treatment refractory patients. Findings suggest that leadership is essential to support successful implementation. Nurse educators can incorporate implementation research and leadership training into graduate nursing programs to facilitate successful EBP implementation in practice settings. Copyright 2013, SLACK Incorporated.
Santiago, Catherine Decarlo; Pears, Gillian; Baweja, Shilpa; Vona, Pamela; Tang, Jennifer; Kataoka, Sheryl H
This study explored parent engagement in an evidence-based treatment, the Cognitive Behavioral Intervention for Trauma in Schools (CBITS), which was delivered in a school setting. To examine the successes and challenges in engaging parents in this school-based program, we conducted qualitative interviews by phone to obtain data from clinicians, parents, and other school personnel across eleven schools from 3 different regions of the United States. Almost all of these schools served low-income and ethnically diverse communities. We describe general impressions of parent engagement, parent reactions and preferences with regard to CBITS, barriers to parent engagement, and how to overcome barriers from multiple perspectives. Parent engagement across schools varied, with extensive outreach and relatively good parent engagement in CBITS described in some schools, while in other schools, efforts to engage parents were not as consistent. Implications for future efforts to engage parents in school-based treatments are discussed.
Full Text Available Ross Leighton,1 Jane Fitzpatrick,2,3 Helen Smith,4 Daniela Crandall,4 Carl R Flannery,4 Thierry Conrozier5 1Department of Surgery, Dalhousie University, Halifax, NS, Canada; 2Sports Medicine Professionals Pty Ltd, Richmond, VIC, Australia; 3University of Western Australia, Perth, WA, Australia; 4Bioventus LLC, Durham, NC, USA; 5Department of Rheumatology, Hospital Nord Franche-Comte, Belfort, France Background: Pain and limitations in joint mobility associated with knee osteoarthritis (OA are clinically challenging to manage, and advanced progression of disease can often lead to total knee arthroplasty. Intra-articular injection of hyaluronic acid (HA, also referred to as viscosupplementation, is a non-surgical treatment approach for OA, the effectiveness of which may depend on the HA composition, and the length of time over which it resides in the joint. One of the available options for such therapies includes NASHA (Durolane HA, a non-animal, biofermentation-derived product, which is manufactured using a process that stabilizes the HA molecules to slow down their rate of degradation and produce a unique formulation with a terminal half-life of ~1 month. The objectives of the current review were to assess, in patients with OA of the knee, the efficacy and safety of intra-articular treatment with NASHA relative to control (saline injections, other HA products, and other injectables (corticosteroids, platelet-rich plasma, mesenchymal stem cells.Methods: This systematic evidence review examines patient outcomes following NASHA treatment as described in published data from studies conducted in subjects with knee OA. A Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant literature search strategy yielded 11 eligible clinical studies with a variety of comparator arms. Outcomes assessed at various time points following intra-articular treatment included measures of pain, function, quality of life, and incidence of treatment
Ruud A. Jongedijk
Full Text Available Narrative exposure therapy (NET is a recently developed, short-term treatment for patients with a posttraumatic stress disorder (PTSD as a result of multiple trauma. NET can be applied very successfully in patients with complex trauma complaints (Jongedijk, 2014; Schauer, Neuner, & Elbert, 2011.An important feature of NET is that trauma processing is never an isolated event but is always embedded in the context of a traumatic event and in the life history as a whole. At the start, the lifeline is laid. The lifeline is made up of a rope, with flowers (happy events, stones (traumatic events, sometimes candles (grief, or recently also sticks for aggressive acts (NET for offenders; see Stenmark, Cuneyt Guzey, Elbert, & Holen, 2014. These symbols are laid down along the rope, in chronological order. Subsequently, in the subsequent therapy sessions the lifeline is processed in chronological order, giving attention to all the important events a person has experienced in his or her life, both the adverse as well as the pleasurable ones. The narration ends with a written testimony.To date, there is good evidence NET is effective in the treatment of PTSD patients, with support from 18 RCTs (N=950. For culturally diverse populations, NET is recommended as the most evidence-based trauma treatment, besides culturally adapted CBT. NET has been investigated in different populations in Africa, Europe, and Asia. In Asia, research has been carried out in Sri Lanka as well as in China. In China, NET was conducted and investigated with survivors of the Sichuan earthquake (Zang, Hunt, & Cox, 2013, 2014. NET is understandable, even appealing and also supportive for patients with multiple trauma. In this presentation, the treatment principles and the practice of NET will be explained.
Lorenc, Z; Gökçe, Ö
The combination of tribenoside+lidocaine (Procto-Glyvenol®) is a medical preparation for the local treatment of hemorrhoids, delivered as a suppository or rectal cream. This product has been used for decades in the therapy of hemorrhoids. This review discusses available evidence on the use of tribenoside/lidocaine in clinical practice. Papers were retrieved by a PubMed search, using different combinations of pertinent keywords (e.g. tribenoside AND hemorrhoids), without any limitations in terms of publication date and language. Documents from Authors' personal collection of literature could also be considered. Papers were selected for inclusion according to their relevance for the topic, as judged by the Authors. The efficacy of the combination of tribenoside+lidocaine in relieving symptoms caused by hemorrhoids and its safety have been assessed in several clinical studies on patients of either gender, either versus its two individual components (tribenoside and lidocaine) or versus steroids in the same setting. Five studies compared the combination treatment with each of its single components, and of these, three studies compared tribenoside+ lidocaine with a tribenoside-free semi-placebo preparation containing only lidocaine, and two studies compared this combination with lidocaine-free preparations containing only tribenoside. Tribenoside+lidocaine was compared with steroid-containing preparations in six studies. Last, two studies evaluated the efficacy and tolerability of the tribenoside+lidocaine combination in women with hemorrhoids as a consequence of pregnancy or delivery. All the above-mentioned studies were well-conducted and can provide a comprehensive evaluation of tribenoside+lidocaine in the treatment of hemorrhoids. Enough evidence exists to recommend the use of this combination therapy as a fast, effective and safe option for the local treatment of low-grade hemorrhoids.
Phok, Sochea; Phanalasy, Saysana; Thein, Si Thu; Likhitsup, Asawin
The aim of this paper is to review multi-country evidence of private sector adherence to national regulations, guidelines, and quality-assurance standards for malaria case management and to document current coverage of private sector engagement and support through ACTwatch outlet surveys implemented in 2015 and 2016. Over 76,168 outlets were screened, and approximately 6500 interviews were conducted (Cambodia, N = 1303; the Lao People's Democratic Republic (PDR), N = 724; Myanmar, N = 4395; and Thailand, N = 74). There was diversity in the types of private sector outlets providing malaria treatment across countries, and the extent to which they were authorized to test and treat for malaria differed. Among outlets stocking at least one anti-malarial, public sector availability of the first-line treatment for uncomplicated Plasmodium falciparum or Plasmodium vivax malaria was >75%. In the anti-malarial stocking private sector, first-line treatment availability was variable (Cambodia, 70.9%; the Lao PDR, 40.8%; Myanmar P. falciparum = 42.7%, P. vivax = 19.6%; Thailand P. falciparum = 19.6%, P. vivax = 73.3%), as was availability of second-line treatment (the Lao PDR, 74.9%; Thailand, 39.1%; Myanmar, 19.8%; and Cambodia, 0.7%). Treatment not in the National Treatment Guidelines (NTGs) was most common in Myanmar (35.8%) and Cambodia (34.0%), and was typically stocked by the informal sector. The majority of anti-malarials distributed in Cambodia and Myanmar were first-line P. falciparum or P. vivax treatments (90.3% and 77.1%, respectively), however, 8.8% of the market share in Cambodia was treatment not in the NTGs (namely chloroquine) and 17.6% in Myanmar (namely oral artemisinin monotherapy). In the Lao PDR, approximately 9 in 10 anti-malarials distributed in the private sector were second-line treatments-typically locally manufactured chloroquine. In Cambodia, 90% of anti-malarials were distributed through outlets that had confirmatory testing
Palsson, Olafur S
Hypnotherapy has been investigated for 30 years as a treatment for gastrointestinal (GI) disorders. There are presently 35 studies in the published empirical literature, including 17 randomized controlled trials (RCTs) that have assessed clinical outcomes of such treatment. This body of research is reviewed comprehensively in this article. Twenty-four of the studies have tested hypnotherapy for adult irritable bowel syndrome (IBS) and 5 have focused on IBS or abdominal pain in children. All IBS hypnotherapy studies have reported significant improvement in gastrointestinal symptoms, and 7 out of 10 RCTs in adults and all 3 RCTs in pediatric patient samples found superior outcomes for hypnosis compared to control groups. Collectively this body of research shows unequivocally that for both adults and children with IBS, hypnosis treatment is highly efficacious in reducing bowel symptoms and can offer lasting and substantial symptom relief for a large proportion of patients who do not respond adequately to usual medical treatment approaches. For other GI disorders the evidence is more limited, but preliminary indications of therapeutic potential can be seen in the single randomized controlled trials published to date on hypnotherapy for functional dyspepsia, functional chest pain, and ulcerative colitis. Further controlled hypnotherapy trials in those three disorders should be a high priority. The mechanisms underlying the impact of hypnosis on GI problems are still unclear, but findings from a number of studies suggest that they involve both modulation of gut functioning and changes in the brain's handling of sensory signals from the GI tract.
Yára Dadalti Fragoso
Full Text Available Multiple sclerosis (MS is a chronic neurological disease that typically affects young adults. A recent publication suggested that MS might originate from insufficient blood drainage in certain areas of the central nervous system. The condition was named chronic cerebrospinal venous insufficiency (CCSVI. Other papers have not confirmed these findings and, therefore, the matter remains controversial. Nineteen months after the original publication on CCSVI and MS, another 22 papers have been published addressing the matter. No clinical trials have been carried out on the subject and there is no evidence-based indication to perform surgical vascular procedures in MS patients. However, over the same nineteen-month period, the internet discussion on the subject of CCSVI and MS has led to countless websites advertising treatment using vascular surgery for patients with MS all over the world. The treatment based on the CCSVI theory has appealingly been called "liberation treatment", thus making it difficult to explain to patients why a treatment that has been highly praised (on the internet cannot be recommended based on partial medical results that await confirmation.
Pérez Atamoros, Francisco M; Alcalá Pérez, Daniel; Asz Sigall, Daniel; Ávila Romay, Alfonsina A; Barba Gastelum, José A; de la Peña Salcedo, José A; Escalante Salgado, Pablo E; Gallardo Palacios, Guillermo J; Guerrero-Gonzalez, Guillermo A; Morales De la Cerda, Rodrigo; Ponce Olivera, Rosa María; Rossano Soriano, Fabiola; Solís Tinoco, Eduardo; Welsh Hernández, Esperanza C
Gynoid lipodystrophy (GLD) is a structural, inflammatory, and biochemical disorder of the subcutaneous tissue causing alterations in the topography of the skin. Commonly known as "cellulite," GLD affects up to 90% of women, practically in all stages of the life cycle, beginning in puberty. It is a clinical condition that considerably affects the patients' quality of life. It is a frequent reason for consultation, although the patients resort to empirical, improvised, nonevidence-based treatments which discourage and can be a source of frustration not only because of the lack of results but also due to the complications derived from those treatments. In this article, a panel of experts from different specialties involved in the management of this clinical skin disorder presents the results of a systematic literature search and of the consensus discussion of the evidence obtained from different treatments currently available. The analysis was divided into topical, systemic, noninvasive, and minimally invasive treatments. © 2018 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.
Full Text Available Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze, a recombinant C1 inhibitor (Ruconest/Conestat alpha, a kallikrein inhibitor (Ecallantide, and a bradykinin B2 receptor inhibitor (Icatibant are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose–response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment.
Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients' quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose-response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment.
Goetz, Christopher G; Poewe, Werner; Rascol, Olivier; Sampaio, Cristina
The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001-January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non-Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Non- efficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner. Copyright 2005 Movement Disorder Society.
Donaldson, Sandra; Chundamala, Josie; Yandow, Suzanne; Wright, James G
The purpose of this paper is to perform an evidence based review for treatment of unicameral bone cysts. A search of MEDLINE (1966 to 2009) was conducted and the studies were classified according to levels of evidence. This review includes only comparative Level I-III studies. The systematic review identified 16 studies. There is one level I study, one level II study and the remaining 14 studies are level III. Seven of the sixteen studies had statistically different results: three studies indicated that steroid injection was superior to bone marrow injection or curettage and bone grafting; one study indicated that cannulated screws were superior to steroid injections; one study indicated resection and myoplasty was superior to steroid injection; one study indicated a combination of steroid, demineralized bone matrix and bone marrow aspirate, and curettage and bone grafting were superior to steroid injection; and one study indicated that curettage and bone grafting was superior to non-operative immobilization. Based on one Level I study, including a limited number of individuals, steroid injection seems to be superior to bone marrow injection. As steroid injections have already demonstrated superiority over bone marrow injections in a randomized clinical trial, the next step would be a prospective trial comparing steroid injections with other treatments.
Sandra E. Donaldson
Full Text Available The purpose of this paper is to perform an evidence based review for treatment of unicameral bone cysts. A search of MEDLINE (1966 to 2009 was conducted and the studies were classified according to levels of evidence. This review includes only comparative Level I-III studies. The systematic review identified 16 studies. There is one level I study, one level II study and the remaining 14 studies are level III. Seven of the sixteen studies had statistically different results: three studies indicated that steroid injection was superior to bone marrow injection or curettage and bone grafting; one study indicated that cannulated screws were superior to steroid injections; one study indicated resection and myoplasty was superior to steroid injection; one study indicated a combination of steroid, demineralized bone matrix and bone marrow aspirate, and curettage and bone grafting were superior to steroid injection; and one study indicated that curettage and bone grafting was superior to non-operative immobilization. Based on one Level I study, including a limited number of individuals, steroid injection seems to be superior to bone marrow injection. As steroid injections have already demonstrated superiority over bone marrow injections in a randomized clinical trial, the next step would be a prospective trial comparing steroid injections with other treatments.
Full Text Available Abstract Background Malaria treatment-seeking practices vary worldwide and Bangladesh is no exception. Individuals from 88 villages in Rajasthali were asked about their treatment-seeking practices. A portion of these households preferred malaria treatment from the National Control Programme, but still a large number of households continued to use drug vendors and approximately one fourth of the individuals surveyed relied exclusively on non-control programme treatments. The risks of low-control programme usage include incomplete malaria treatment, possible misuse of anti-malarial drugs, and an increased potential for drug resistance. Methods The spatial patterns of treatment-seeking practices were first examined using hot-spot analysis (Local Getis-Ord Gi statistic and then modelled using regression. Ordinary least squares (OLS regression identified key factors explaining more than 80% of the variation in control programme and vendor treatment preferences. Geographically weighted regression (GWR was then used to assess where each factor was a strong predictor of treatment-seeking preferences. Results Several factors including tribal affiliation, housing materials, household densities, education levels, and proximity to the regional urban centre, were found to be effective predictors of malaria treatment-seeking preferences. The predictive strength of each of these factors, however, varied across the study area. While education, for example, was a strong predictor in some villages, it was less important for predicting treatment-seeking outcomes in other villages. Conclusion Understanding where each factor is a strong predictor of treatment-seeking outcomes may help in planning targeted interventions aimed at increasing control programme usage. Suggested strategies include providing additional training for the Building Resources across Communities (BRAC health workers, implementing educational programmes, and addressing economic factors.
Full Text Available Abstract Background This review analyses and summarises the recent advances in understanding the neurobiology of violence and empathy, taxonomical issues on defining personality disorders characterised by disregard for social norms, evidence for efficacy of different treatment modalities and ethical implications in defining 'at-risk' individuals for preventive interventions. Methods PubMed was searched with the keywords 'antisocial personality disorder', 'dissocial personality disorder' and 'psychopathy'. The search was limited to articles published in English over the last 10 years (1999 to 2009 Results Both diagnostic manuals used in modern psychiatry, the Diagnostic and Statistical Manual published by the American Psychiatric Association and the International Classification of Diseases published by the World Health Organization, identify a personality disorder sharing similar traits. It is termed antisocial personality disorder in the diagnostic and statistical manual and dissocial personality disorder in the International Classification of Diseases. However, some authors query the ability of the existing manuals to identify a special category termed 'psychopathy', which in their opinion deserves special attention. On treatment-related issues, many psychological and behavioural therapies have shown success rates ranging from 25% to 62% in different cohorts. Multisystemic therapy and cognitive behaviour therapy have been proven efficacious in many trials. There is no substantial evidence for the efficacy of pharmacological therapy. Currently, the emphasis is on early identification and prevention of antisocial behaviour despite the ethical implications of defining at-risk children. Conclusions Further research is needed in the areas of neuroendocrinological associations of violent behaviour, taxonomic existence of psychopathy and efficacy of treatment modalities.
Wing, R R
The purpose of this paper is to review the evidence on the role of physical activity in the treatment of adult overweight and obesity. Three specific questions are addressed: (1) Does exercise alone produce weight loss? (2) Does exercise in combination with diet produce greater weight loss than diet only? and (3) Does exercise in combination with diet produce better maintenance of weight loss than diet alone? The literature initially identified by the Expert Panel on Clinical Guidelines for the Treatment of Obesity, three key meta analyses, and additional literature searches were used to identify randomized trials related to the three aforementioned topics. These articles were reviewed and tabulated. Six of 10 randomized studies found significantly greater weight loss in exercise alone versus no treatment controls. The magnitude of the effect averaged 1-2 kg. Only 2 of 13 studies found significant differences in initial weight loss for diet plus exercise versus diet only, although almost all studies pointed in this direction. Six studies were identified with maintenance periods of at least 1 yr. In two of the six there were significant long term differences favoring diet plus exercise, but in every study considered the direction of the difference favored diet plus exercise. Other strong evidence showing benefits of exercise for long-term weight loss comes from correlational analyses which consistently find that those individuals who report the greatest exercise have the best maintenance of weight loss. Randomized trials consistently show benefits of exercise for weight loss, but the effects are often modest. This may result from small sample sizes, short study duration, and poor adherence to the exercise prescriptions. To better define the doses and types of exercise that will promote long-term weight loss, it is necessary to develop better ways to measure exercise and promote adherence to exercise.
Prochaska, Judith J.; Fromont, Sebastien C.; Leek, Desiree; Hudmon, Karen Suchanek; Louie, Alan K.; Jacobs, Marc H.; Hall, Sharon M.
Objective Smokers with mental illness and addictive disorders account for nearly one in two cigarettes sold in the United States and are at high risk for smoking-related deaths and disability. Psychiatry residency programs provide a unique arena for disseminating tobacco treatment guidelines, influencing professional norms, and increasing access to tobacco cessation services among smokers with mental illness. The current study evaluated the Rx for Change in Psychiatry curriculum, developed for psychiatry residency programs and focused on identifying and treating tobacco dependence among individuals with mental illness. Methods The 4-hour curriculum emphasized evidence-based, patient-oriented cessation treatments relevant for all tobacco users, including those not yet ready to quit. The curriculum was informed by comprehensive literature review, consultation with an expert advisory group, faculty interviews, and a focus group with psychiatry residents. This study reports on evaluation of the curriculum in 2005–2006, using a quasi-experimental design, with 55 residents in three psychiatry residency training programs in Northern California. Results The curriculum was associated with improvements in psychiatry residents’ knowledge, attitudes, confidence, and counseling behaviors for treating tobacco use among their patients, with initial changes from pre- to posttraining sustained at 3-months’ follow-up. Residents’ self-reported changes in treating patients’ tobacco use were substantiated through systematic chart review. Conclusion The evidence-based Rx for Change in Psychiatry curriculum is offered as a model tobacco treatment curriculum that can be implemented in psychiatry residency training programs and disseminated widely, thereby effectively reaching a vulnerable and costly population of smokers. PMID:19190293
Ruzek, Josef I; Rosen, Raymond C
Dissemination of evidence-based treatments for PTSD has become an important focus of activity in the aftermath of recent terrorist attacks (e.g., London underground and U.S. 9/11 attacks), natural disasters (e.g., Indian Ocean tsunami and Hurricane Katrina), and wars (e.g., in Iraq and Afghanistan). This has become a high priority need for all mental health training and service delivery organizations. Researchers and educators have begun to examine clinician and client perceptions and preferences regarding PTSD treatment processes, and health care systems are organizing more comprehensive efforts at training and system change. As this evolution of services moves forward, effective dissemination should be a major focus of health policy research for the next decade or more. This review critically evaluates the PTSD-related research and emerging theory related to four major sets of variables that affect dissemination: (1) Practitioner factors, (2) Training methods, (3) The practice innovation(s) being disseminated; and (4) Organization or system factors. We evaluate findings from recent studies in light of emerging models of dissemination, and in the final section of the paper, we consider five broad topics with particular implications for dissemination of PTSD-specific treatments. They are: (1) The content of dissemination (i.e., which treatment protocols or intervention methods should be prioritized); (2) Strict adherence versus flexibility in the use of treatment manuals and the role of fidelity assessment; (3) The need for collaboration with user audiences; (4) The potential role of web-based technologies in increasing the effectiveness and efficiency of dissemination; and (5) Development of dissemination infrastructures within organizations.
Lundgren, Lena; Krull, Ivy; Zerden, Lisa de Saxe; McCarty, Dennis
This national study of community-based addiction-treatment organizations' (CBOs) implementation of evidence-based practices explored CBO Program Directors' (n = 296) and clinical staff (n = 518) attitudes about the usefulness of science-based addiction treatment. Through multivariable regression modeling, the study identified that identical…
This review was conducted to assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). rTMS is a noninvasive way to stimulate nerve cells in areas of the brain. During rTMS, an electrical current passes through a wire coil placed over the scalp. The current induces a magnetic field that produces an electrical field in the brain that then causes nerve cells to depolarize, resulting in the stimulation or disruption of brain activity. Researchers have investigated rTMS as an option to treat MDD, as an add-on to drug therapy, and, in particular, as an alternative to electroconvulsive therapy (ECT) for patients with treatment-resistant depression. The advantages of rTMS over ECT for patients with severe refractory depression are that general anesthesia is not needed, it is an outpatient procedure, it requires less energy, the simulation is specific and targeted, and convulsion is not required. The advantages of rTMS as an add-on treatment to drug therapy may include hastening of the clinical response when used with antidepressant drugs. The Medical Advisory Secretariat used its standard search strategy to locate international health technology assessments and English-language journal articles published from January 1996 to March 2004. Some early meta-analyses suggested rTMS might be effective for the treatment of MDD (for treatment-resistant MDD and as an add-on treatment to drug therapy for patients not specifically defined as treatment resistant). There were, however, several crucial methodological limitations in the included studies that were not critically assessed. These are discussed below. Recent meta-analyses (including 2 international health technology assessments) have done evidence-based critical analyses of studies that have assessed rTMS for MDD. The 2 most recent health technology assessments (from the Oxford Cochrane Collaboration and the Norwegian Centre for Health Technology
Saxena, Amol; Fullem, Brian; Gerdesmeyer, Ludger
Two case reports of high-level athletes with medial tibial stress syndrome (MTSS), 1 an Olympian with an actual stress fracture, are presented. Successful treatment included radial soundwave therapy, pneumatic leg braces, relative rest using an antigravity treadmill, and temporary foot orthoses. Radial soundwave therapy has a high level of evidence for treatment of MTSS. We also present recent evidence of the value of vitamin D assessment. Both patients had a successful outcome with minimal downtime. Finally, a suggested treatment regimen for MTSS is presented. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.
Law, Zhe Kang; Meretoja, Atte; Engelter, Stefan T
Purpose Haematoma expansion is a devastating complication of intracerebral haemorrhage (ICH) with no established treatment. Tranexamic acid had been an effective haemostatic agent in reducing post-operative and traumatic bleeding. We review current evidence examining the efficacy of tranexamic acid...... in improving clinical outcome after ICH. Method We searched MEDLINE, EMBASE, CENTRAL and clinical trial registers for studies using search strategies incorporating the terms ‘intracerebral haemorrhage’, ‘tranexamic acid’ and ‘antifibrinolytic’. Authors of ongoing clinical trials were contacted for further...... details. Findings We screened 268 publications and retrieved 17 articles after screening. Unpublished information from three ongoing clinical trials was obtained. We found five completed studies. Of these, two randomised controlled trials (RCTs) comparing intravenous tranexamic acid to placebo (n = 54...
Full Text Available Treatment of melasma is known to be less satisfactory, often incomplete, and relapse is frequent. Although many treatment options are available, they are either known to be unsafe on long-term use or their long-term safety profile is unknown. Patients often use various drugs, even topical steroid-based preparation without any medical supervision for long period of time, making the skin unsuitable for many of the drugs available. Thus, there has been gross disparity among the treating physician about what drugs and what regimen are best suitable for various categories of melasma patients and in different situations. With this background, numerous newer drugs, mostly combinations of some proprietary molecules or even unknown plant extracts, have flooded the market for the management of melasma. Information on efficacy or safety of these products are almost unknown. Studies on Asian people, especially Indian population, are far less commonly available. Therapeutic guideline for use on Indian patients with melasma is almost missing. Extrapolation of data from Caucasian people for use on Asian people may not be scientifically justifiable because Caucasian and Asian people are known to have inherent difference in their response as well as tolerance to the drugs used for melasma. With this background, we have extensively evaluated, following a strict, scientifically designed protocol, all the available studies on melasma management till May 2016 and prepared this document on level of evidence, grade of recommendation and suggested therapeutic guideline for melasma as per the method proposed by Oxford Centre of Evidence-Based Medicine. Various ethical, social, logical, regional, and economic issues in the context of Indian and similar populations were given due importance while preparing the suggested therapeutic recommendation.
Mihcin, Senay; Strehlow, Jan; Demedts, Daniel; Schwenke, Michael; Levy, Yoav; Melzer, Andreas
The novel Trans-Fusimo Treatment System (TTS) is designed to control Magnetic Resonance guided Focused Ultrasound (MRgFUS) therapy to ablate liver tumours under respiratory motion. It is crucial to deliver the acoustic power within tolerance limits for effective liver tumour treatment via MRgFUS. Before application in a clinical setting, evidence of reproducibility and reliability is a must for safe practice. The TTS software delivers the acoustic power via ExAblate-2100 Conformal Bone System (CBS) transducer. A built-in quality assurance application was developed to measure the force values, using a novel protocol to measure the efficiency for the electrical power values of 100 and 150W for 6s of sonication. This procedure was repeated 30 times by two independent users against the clinically approved ExAblate-2100 CBS for cross-validation. Both systems proved to deliver the power within the accepted efficiency levels (70-90%). Two sample t-tests were used to assess the differences in force values between the ExAblate-2100 CBS and the TTS (p > 0.05). Bland-Altman plots were used to demonstrate the limits of agreement between the two systems falling within the 10% limits of agreement. Two sample t-tests indicated that TTS does not have user dependency (p > 0.05). The TTS software proved to deliver the acoustic power without exceeding the safety levels. Results provide evidence as a part of ISO13485 regulations for CE marking purposes. The developed methodology could be utilised as a part of quality assurance system in clinical settings; when the TTS is used in clinical practice.
Shy Cian Khor
Full Text Available Sarcopenia is a geriatric syndrome that is characterized by gradual loss of muscle mass and strength with increasing age. Although the underlying mechanism is still unknown, the contribution of increased oxidative stress in advanced age has been recognized as one of the risk factors of sarcopenia. Thus, eliminating reactive oxygen species (ROS can be a strategy to combat sarcopenia. In this review, we discuss the potential role of vitamin E in the prevention and treatment of sarcopenia. Vitamin E is a lipid soluble vitamin, with potent antioxidant properties and current evidence suggesting a role in the modulation of signaling pathways. Previous studies have shown its possible beneficial effects on aging and age-related diseases. Although there are evidences suggesting an association between vitamin E and muscle health, they are still inconclusive compared to other more extensively studied chronic diseases such as neurodegenerative diseases and cardiovascular diseases. Therefore, we reviewed the role of vitamin E and its potential protective mechanisms on muscle health based on previous and current in vitro and in vivo studies.
Loeb, Katharine L.; Walsh, B. Timothy; Lock, James; Le Grange, Daniel; Jones, Jennifer; Marcus, Sue; Weaver, James; Dobrow, Ilyse
Objective: There is a paucity of evidence-based interventions for anorexia nervosa (AN). An innovative family-based treatment (FBT), developed at the Maudsley Hospital and recently put in manual form, has shown great promise for adolescents with AN. Unlike traditional treatment approaches, which promote sustained autonomy around food, FBT…
Increased access to any treatment sensibly follows the clinical and cost benefit being established. For many treatments this requires multiple, high-quality clinical trials and supporting cost analysis. Cost analysis may be applied to a single treatment or used to compare two or more treatments. Clinical efficacy and cost benefit are best scrutinised and validated by publication in the peer-reviewed literature. True peer review is most effectively achieved 'after publication' by the wider scientific community, i.e., the journal readers. However, initially an editor, usually advised by referees, is asked to make a judgment on a paper's suitability for publication. It follows that medical journals are in a position of power and responsibility. Researchers and editors know publications are currency; effectively they are the equivalent of academic bitcoins. Regarding the paper in this issue by Santema et al., the same authors, in designing a prospective randomised controlled trial (RCT) of the role of hyperbaric oxygen treatment (HBOT) in diabetic wounds, included the name "Damocles" in that trial's title. Readers will perhaps appreciate from my comments below as a referee for the Santema et al. paper, that behind the scenes "the Sword of Damocles" (an allusion to the imminent and ever-present peril faced by those in positions of power) hangs over researchers, treating physician, journal editors and referees alike. Whilst positive about its content, upon reflection, my concern was the anticipated reception of this paper by the journal readership. This is, of course, a matter for the Editor; however, herewith is my reasoning. Further to the body of published work by Bennett et al., and others that has focused attention on the lack of good quality evidence for the use of HBOT for most indications, I think this regrettable state of affairs is now both known and accepted by mainstream healthcare purchasers and providers. I speculate that all these bodies already
Hague, Ben; Hall, Jo; Kellett, Stephen
Background and aims This review appraises the progression and status of the evidence base for the treatment of compulsive buying disorder (CBD), in order to highlight what currently works and to prompt useful future research. Methods Online databases ISI Web of Knowledge, PsycINFO, and PubMed via Ovid were searched at two time points. Two quality checklists and an established model of therapy evaluation (hourglass model) evaluated the quality and progression of both psychotherapy and pharmacotherapy treatments for CBD. Uncontrolled effect sizes were calculated and meta-regression analyses were performed regarding treatment duration. Results A total of 29 articles met the inclusion criteria, which were divided into psychotherapy (n = 17) and pharmacotherapy treatments (n = 12). Of the 29 studies, only 5 studies have been tested under conditions of high methodological quality. Both forms of treatment had been evaluated in a haphazard manner across the stages of the hourglass model. Although large effects were demonstrated for group psychotherapy and pharmacotherapy, such evidence of effectiveness was undermined by poor study quality and risk of publication bias. Long-term CBD treatment was associated with improved outcome with pharmacotherapy, but not when delivering psychotherapy. Discussion Group psychotherapy currently appears the most promising treatment option for CBD. Poor methodological control and sporadic evaluation of specific treatments have slowed the generation of a convincing evidence base for CBD treatment. Defining the active ingredients of effective CBD treatment is a key research goal.
Full Text Available OBJETIVO: Este artigo tem por objetivo analisar a situação do tratamento farmacológico da gagueira, mostrando a eficácia de diferentes abordagens baseadas em drogas psiquiátricas, além de evidenciar a utilização de outros fármacos no tratamento dessa enfermidade. MÉTODOS: Revisão de literatura em base de dados Medline, utilizando os termos stuttering treatment, disfluency, disfluency treatments, botulinum toxin and stuttering treatment, botulinum toxin and disfluency treatment. RESULTADOS: Foram encontrados estudos envolvendo as seguintes drogas: citalopram + clomipramina, paroxetina, olanzapina, citalopram + alprazolam, pimozida, risperidona, tiaprida, clomipramina e desipramina, levetiracetam, divalproato de sódio, clonidina e betanecol, além de ensaios clínicos com a utilização de toxina botulínica tipo A e anestésicos. Os estudos envolvendo citalopram + clomipramina, paroxetina, olanzapina, citalopram + alprazolam, risperidona, clomipramina e desipramina, levetiracetam, divalproato de sódio, lidocaína e toxina botulínica tipo A demonstraram resultados positivos. A maioria das pesquisas relativas ao tratamento farmacológico da gagueira se restringe a estudos de caso e ensaios clínicos com pequenas amostras. CONCLUSÃO: Não existem evidências suficientes que justifiquem a utilização de um tratamento específico para a gagueira. Os estudos apresentados indicam a necessidade da realização de mais ensaios clínicos duplo-cegos e controlados com placebo envolvendo amostras maiores.OBJECTIVE: This article analyzes the pharmacologic treatment of stuttering, assessing the effectiveness of different treatments using psychiatric drugs and further evidences of other drugs in the treatment of this disorder. METHODS: Search in Medline database, using the terms stuttering treatment, disfluency, disfluency treatments, botulinum toxin and stuttering treatment, botulinum toxin and disfluency treatment. RESULTS: Studies involving
Gálvez-Lara, Mario; Corpas, Jorge; Moreno, Eliana; Venceslá, José F; Sánchez-Raya, Araceli; Moriana, Juan A
In recent decades, the evidence on psychological treatments for children and adolescents has increased considerably. Several organizations have proposed different criteria to evaluate the evidence of psychological treatment in this age group. The aim of this study was to analyze evidence-based treatments drawn from RCTs, reviews, meta-analyses, guides and lists provided by four leading international organizations. The institutions reviewed were the National Institute for Health and Care Excellence, the Society of Clinical Child and Adolescent Psychology (Division 53) of the American Psychological Association, Cochrane Collaboration and the Australian Psychological Society in relation to mental disorders in children and adolescents. A total of 137 treatments were analyzed for 17 mental disorders and compared to determine the level of agreement among the organizations. The results indicate that, in most cases, there is little agreement among organizations and that there are several discrepancies within certain disorders. These results require reflection on the meaning attributed to evidence-based treatments with regard to psychological treatments in children and adolescents. The possible reasons for these differences could be explained by a combination of different issues: the procedures or committees may be biased, different studies were reviewed, different criteria are used by the organizations or the reviews of existing evidence were conducted in different time periods.
Whiteneck, Gale G; Gassaway, Julie
To describe the application of practice-based evidence (PBE) methodology to spinal cord injury (SCI) rehabilitation in the SCIRehab study, and to summarize associations of patient characteristics and treatment interventions to outcomes. Prospective observational study. Six SCI rehabilitation centers. Patients with traumatic SCI (N=1376) admitted for first rehabilitation. Not applicable. FIM and residence at discharge, and FIM, residence, Craig Handicap Assessment and Reporting Technique, work/school status, Patient Health Questionnaire-9, Diener Satisfaction with Life Scale, rehospitalization, and presence of pressure ulcers at 1 year postinjury. Patient demographic and injury characteristics explained significant variation in rehabilitation outcomes, particularly functional outcomes. Regression modeling also identified a large number of significant associations with outcomes when total time in each discipline was modeled and when models were developed for each discipline, examining time spent in the many specific interventions provided by each discipline. The application of PBE methodology in the SCIRehab study provided extensive information about the process of inpatient SCI rehabilitation. While patient demographic and injury characteristics explain substantial variation in rehabilitation outcomes, particularly functional outcomes, significant relations also were found between the type and quantity of treatment interventions delivered by each rehabilitation discipline and a broad range of outcomes. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Full Text Available Abstract Background Little is known about the factors influencing treatment choice in psychosis, the majority of this work being conducted with specialists (consultant in psychiatry. We sought to examine trainees' choices of treatment for psychosis if they had to prescribe it for themselves, their patients, and factors influencing decision-making. Methods Cross-sectional, semi-structured questionnaire-based study. Results Of the 726 respondents (response rate = 66%, the majority chose second-generation antipsychotics (SGAs if they had to prescribe it for themselves (n = 530, 93% or for their patients (n = 546, 94%. The main factor influencing choice was perceived efficacy, 84.8% (n = 475 of trainees stating this was the most important factor for the patient, and 77.8% (n = 404 stating this was the most important factor for their own treatment. Trainees with knowledge of trials questioning use of SGAs (CATIE, CUtLASS, TEOSS were more likely to choose second-generation antipsychotics than those without knowledge of these trials (χ2 = 3.943; p = 0.047; O.R. = 2.11; 95% C.I. = 1.0-4.48. Regarding psychotherapy, cognitive behavioural therapy (CBT was the most popular choice for self (33.1%; n = 240 and patient (30.9%; n = 224. Trainees were significantly more likely to prefer some form of psychotherapy for themselves rather than patients (χ2 = 9.98; p Conclusions Trainees are more likely to choose second-generation antipsychotic medication for patients and themselves. Despite being aware of evidence that suggests otherwise, they predominantly base these choices on perceived efficacy.
Sacroiliac joint (SIJ) pain refers to the pain arising from the SIJ joint structures. SIJ dysfunction generally refers to aberrant position or movement of SIJ structures that may or may not result in pain. This paper aims to clarify the difference between these clinical concepts and present current available evidence regarding diagnosis and treatment of SIJ disorders. Tests for SIJ dysfunction generally have poor inter-examiner reliability. A reference standard for SIJ dysfunction is not readily available, so validity of the tests for this disorder is unknown. Tests that stress the SIJ in order to provoke familiar pain have acceptable inter-examiner reliability and have clinically useful validity against an acceptable reference standard. It is unknown if provocation tests can reliably identify extra-articular SIJ sources of pain. Three or more positive pain provocation SIJ tests have sensitivity and specificity of 91% and 78%, respectively. Specificity of three or more positive tests increases to 87% in patients whose symptoms cannot be made to move towards the spinal midline, i.e., centralize. In chronic back pain populations, patients who have three or more positive provocation SIJ tests and whose symptoms cannot be made to centralize have a probability of having SIJ pain of 77%, and in pregnant populations with back pain, a probability of 89%. This combination of test findings could be used in research to evaluate the efficacy of specific treatments for SIJ pain. Treatments most likely to be effective are specific lumbopelvic stabilization training and injections of corticosteroid into the intra-articular space. PMID:19119403
Andrews, Gavin; Simonella, Leonardo; Lapsley, Helen; Sanderson, Kristy; March, Lyn
To determine the cost-effectiveness of averting the burden of disease. We used secondary population data and metaanalyses of various government-funded services and interventions to investigate the costs and benefits of various levels of treatment for rheumatoid arthritis (RA) and osteoarthritis (OA) in adults using a burden of disease framework. Population burden was calculated for both diseases in the absence of any treatment as years lived with disability (YLD), ignoring the years of life lost. We then estimated the proportion of burden averted with current interventions, the proportion that could be averted with optimally implemented current evidence-based guidelines, and the direct treatment cost-effectiveness ratio in dollars per YLD averted for both treatment levels. The majority of people with arthritis sought medical treatment. Current treatment for RA averted 26% of the burden, with a cost-effectiveness ratio of dollar 19,000 per YLD averted. Optimal, evidence-based treatment would avert 48% of the burden, with a cost-effectiveness ratio of dollar 12,000 per YLD averted. Current treatment of OA in Australia averted 27% of the burden, with a cost-effectiveness ratio of dollar 25,000 per YLD averted. Optimal, evidence-based treatment would avert 39% of the burden, with an unchanged cost-effectiveness ratio of dollar 25,000 per YLD averted. While the precise dollar costs in each country will differ, the relativities at this level of coverage should remain the same. There is no evidence that closing the gap between evidence and practice would result in a drop in efficiency.
Wade, Ros; Hodgson, Robert; Biswas, Mousumi; Harden, Melissa; Woolacott, Nerys
As part of the National Institute for Health and Care Excellence's (NICE) Single Technology Appraisal (STA) process, ruxolitinib was assessed to determine the clinical and cost effectiveness of its use in the treatment of disease-related splenomegaly or symptoms in adults with myelofibrosis. Ruxolitinib had previously been assessed as part of the STA process and was not recommended in NICE guidance issued in June 2013 (TA289). A review of TA289 was commissioned following the availability of new longer-term survival data; a price discount patient access scheme (PAS) was also introduced. The Centre for Reviews and Dissemination (CRD) and Centre for Health Economics (CHE) Technology Appraisal Group at the University of York was commissioned to act as the independent Evidence Review Group (ERG). This article provides a summary of the manufacturer or sponsor of the technology's (referred to as the company) submission, the ERG review and the resulting NICE guidance issued in March 2016. The main clinical effectiveness data were derived from two good-quality multicentre randomised controlled trials (RCTs): COMFORT-II compared ruxolitinib with best available therapy (BAT) and COMFORT-I compared ruxolitinib with placebo. Both RCTs demonstrated a statistically significant reduction in splenomegaly and its associated symptoms in intermediate-2 and high-risk myelofibrosis patients. Overall survival was statistically significantly improved with ruxolitinib compared with BAT at 3.5 years of follow-up in the COMFORT-II trial (hazard ratio 0.58, 95 % CI 0.36-0.93). Grade 3-4 adverse events were more frequent in the ruxolitinib group than in the BAT group; 42 % compared with 25 %. Evidence relating to patients with lower-risk disease or low platelet counts (50-100 × 10 9 /L) was less robust. The company's economic model was well-presented and had an appropriate model structure. The base-case incremental cost-effectiveness ratio (ICER) was estimated to be around £45,000 per
Full Text Available Abstract Background Management of cancer treatment-related symptoms is an important safety issue given that symptoms can become life-threatening and often occur when patients are at home. With funding from the Canadian Partnership Against Cancer, a pan-Canadian steering committee was established with representation from eight provinces to develop symptom protocols using a rigorous methodology (CAN-IMPLEMENT©. Each protocol is based on a systematic review of the literature to identify relevant clinical practice guidelines. Protocols were validated by cancer nurses from across Canada. The aim of this study is to build an effective and sustainable approach for implementing evidence-informed protocols for nurses to use when providing remote symptom assessment, triage, and guidance in self-management for patients experiencing symptoms while undergoing cancer treatments. Methods A prospective mixed-methods study design will be used. Guided by the Knowledge to Action Framework, the study will involve (a establishing an advisory knowledge user team in each of three targeted settings; (b assessing factors influencing nurses’ use of protocols using interviews/focus groups and a standardized survey instrument; (c adapting protocols for local use, ensuring fidelity of the content; (d selecting intervention strategies to overcome known barriers and implementing the protocols; (e conducting think-aloud usability testing; (f evaluating protocol use and outcomes by conducting an audit of 100 randomly selected charts at each of the three settings; and (g assessing satisfaction with remote support using symptom protocols and change in nurses’ barriers to use using survey instruments. The primary outcome is sustained use of the protocols, defined as use in 75% of the calls. Descriptive analysis will be conducted for the barriers, use of protocols, and chart audit outcomes. Content analysis will be conducted on interviews/focus groups and usability testing
Full Text Available In most countries where malaria is endemic, P. falciparum malaria is on the rise. This is primarily due to the spread of drug-resistant strains. Drug resistance is mediated by spontaneous changes in the parasite genome that allow resistant parasites to escape the action of the drugs. The spread of drug resistance increases the transmission of malaria parasites. The consequences for the populations at risk are profound both in terms of consequences for health and economy. In order to halt the progression of drug resistance, we need to change the way antimalarials are used. As in tuberculosis and HIV/AIDS, we must use a combination of drugs for the treatment of malaria. Taking into account the pharmacokinetic and pharmacodynamic properties of the various anti-malarial agents, artemisinin-based combination therapy (ACT seems to be the best option. This strategy should be used in conjunction with early diagnosis and appropriate vector control measures to achieve reduction in the emergence and spread of drug resistance.
Moll, Jennifer L; Brown, Candace S
The monoamine neurotransmitters serotonin, dopamine, and norepinephrine play an important role in many medical and psychological conditions, including sexual responsiveness and behavior. Pharmacological agents that modulate monoamines may help alleviate sexual dysfunction. To provide an overview of pharmacological agents that modulate monoamines and their use in the treatment of sexual dysfunction. EMBASE and PubMed search for articles published between 1950 and 2010 using key words "sexual dysfunction,"monoamines,"monoaminergic receptors," and "generic names for pharmacological agents." To assess the literature evaluating the efficacy of monoamine pharmacologic agents used in the treatment of sexual dysfunction. The literature primarily cites the use of monoaminergic agents to treat sexual side effects from serotonergic reuptake inhibitors (SSRIs), with bupropion, buspirone and ropinirole providing the most convincing evidence. Controlled trials have shown that bupropion improves overall sexual dysfunction, but not frequency of sexual activity in depressed and nondepressed patients. Nefazodone and apomorphine have been used to treat sexual dysfunction, but their use is limited by significant side effect and safety profiles. New research on pharmacologic agents with subtype selectivity at dopaminergic and serotonergic receptors and those that possess dual mechanisms of action are being investigated. There has been tremendous progress over the past 50 years in understanding the role of monoamines in sexual function and the effect of pharmacologic agents which stimulate or antagonize monoaminergic receptors on sexual dysfunction. Nevertheless, large, double-blind, placebo-controlled studies evaluating the efficacy of currently available agents in populations without comorbid disorders are limited, preventing adequate interpretation of data. Continued research on sexual function and specific receptor subtypes will result in the development of more selective
Hirjak, Dusan; Hochlehnert, Achim; Thomann, Philipp Arthur; Kubera, Katharina Maria; Schnell, Knut
Schizophrenia spectrum disorders result in enormous individual suffering and financial burden on patients and on society. In Germany, there are about 1,000,000 individuals suffering from schizophrenia (SZ) or schizoaffective disorder (SAD), a combination of psychotic and affective symptoms. Given the heterogeneous nature of these syndromes, one may assume that there is a difference in treatment costs among patients with paranoid SZ and SAD. However, the current the national system of cost accounting in psychiatry and psychosomatics in Germany assesses all schizophrenia spectrum disorders within one category. The study comprised a retrospective audit of data from 118 patients diagnosed with paranoid SZ (F20.0) and 71 patients with SAD (F25). We used the mean total costs as well as partial cost, i.e., mean costs for medication products, mean personal costs and mean infrastructure costs from each patient for the statistical analysis. We tested for differences in the four variables between SZ and SAD patients using ANCOVA and confirmed the results with bootstrapping. SAD patients had a longer duration of stay than patients with SZ (p = .02). Mean total costs were significantly higher for SAD patients (p = .023). Further, we found a significant difference in mean personnel costs (p = .02) between patients with SZ and SAD. However, we found no significant differences in mean pharmaceutical costs (p = .12) but a marginal difference of mean infrastructure costs (p = .05) between SZ and SAD. We found neither a common decrease of costs over time nor a differential decrease in SZ and SAD. We found evidence for a difference of case related costs of inpatient treatments for paranoid SZ and SAD. The differences in mean total costs seem to be primarily related to the mean personnel costs in patients with paranoid SZ and SAD rather than mean pharmaceutical costs, possibly due to higher personnel effort and infrastructure.
Full Text Available Schizophrenia spectrum disorders result in enormous individual suffering and financial burden on patients and on society. In Germany, there are about 1,000,000 individuals suffering from schizophrenia (SZ or schizoaffective disorder (SAD, a combination of psychotic and affective symptoms. Given the heterogeneous nature of these syndromes, one may assume that there is a difference in treatment costs among patients with paranoid SZ and SAD. However, the current the national system of cost accounting in psychiatry and psychosomatics in Germany assesses all schizophrenia spectrum disorders within one category.The study comprised a retrospective audit of data from 118 patients diagnosed with paranoid SZ (F20.0 and 71 patients with SAD (F25. We used the mean total costs as well as partial cost, i.e., mean costs for medication products, mean personal costs and mean infrastructure costs from each patient for the statistical analysis. We tested for differences in the four variables between SZ and SAD patients using ANCOVA and confirmed the results with bootstrapping.SAD patients had a longer duration of stay than patients with SZ (p = .02. Mean total costs were significantly higher for SAD patients (p = .023. Further, we found a significant difference in mean personnel costs (p = .02 between patients with SZ and SAD. However, we found no significant differences in mean pharmaceutical costs (p = .12 but a marginal difference of mean infrastructure costs (p = .05 between SZ and SAD. We found neither a common decrease of costs over time nor a differential decrease in SZ and SAD.We found evidence for a difference of case related costs of inpatient treatments for paranoid SZ and SAD. The differences in mean total costs seem to be primarily related to the mean personnel costs in patients with paranoid SZ and SAD rather than mean pharmaceutical costs, possibly due to higher personnel effort and infrastructure.
Dudenbostel, Tanja; Acelajado, Maria C.; Pisoni, Roberto; Li, Peng; Oparil, Suzanne; Calhoun, David A.
Refractory hypertension is an extreme phenotype of treatment failure defined as uncontrolled blood pressure (BP) in spite of ≥5 classes of antihypertensive agents, including chlorthalidone and a mineralocorticoid receptor antagonist. A prospective evaluation of possible mechanisms of refractory hypertension has not been done. The goal of this study was to test for evidence of heightened sympathetic tone as indicated by 24-hr urinary (U-) normetanephrine levels, clinic and ambulatory heart rate (HR), HR variability (HRV), arterial stiffness as indexed by pulse wave velocity (PWV), and systemic vascular resistance (SVR) compared to patients with controlled resistant hypertension. Forty-four consecutive patients, 15 with refractory and 29 with controlled resistant hypertension, were evaluated prospectively. Refractory hypertensive patients were younger (48±13.3 vs. 56.5±14.1 years, p=0.038) and more likely female (80.0 vs 51.9 %, p=0.047) compared to patients with controlled resistant hypertension. They also had higher U-normetanephrine levels (464.4±250.2 vs. 309.8±147.6 μg/24h, p=0.03), higher clinic HR (77.8±7.7 vs. 68.8±7.6 bpm, p=0.001) and 24-hr ambulatory HR (77.8±7.7 vs 68.8±7.6, p=0.0018), higher PWV (11.8±2.2 vs. 9.4±1.5 m/s, p=0.009), reduced HRV (4.48 vs. 6.11, p=0.03), and higher SVR (3795±1753 vs. 2382±349 dyne·sec·cm5·m2, p=0.008). These findings are consistent with heightened sympathetic tone being a major contributor to antihypertensive treatment failure and highlight the need for effective sympatholytic therapies in patients with refractory hypertension. PMID:25987662
Gődény, Sándor; Csenteri, Orsolya Karola
Polycystic ovary syndrome is the most common hormonal and metabolic disorder likely to affect women. The syndrome is often associated with obesity, hyperinsulinemia and adversely affects endocrine, metabolic, and cardiovascular health. The complex feature of the syndrome requires an interdisciplinary approach to treatment, where cooperation of paediatrician, internist, gynaecologist, endocrinologist, dermatologist, psychologist and oncologist is essential. The prevention and the treatment should be based on the best available evidence. This should include physical examination, laboratory tests for hormones, serum insulin, glucose, lipids, in addition patient's preferences should be considered, too. To maximise health gain of polycystic ovarian syndrome, adequate, effective, efficient and safe treatment is necessary. This article summarises the highest available evidence provided by meta-analyses and systematic reviews of the prevention of metabolic and cardiovascular complications of the syndrome, and discusses the relevant evidence published in the literature.
Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif
of antiresorptive treatment were included. All studies showed an increase in BMD, but there was only a nonsignificant trend in the reduction of clinical fractures. Three BMD studies of anabolic treatment with teriparatide were also included. These showed a significant mean increase in spine BMD and for vertebral...... treatment in men. Methods. This study was a systematic review of the published literature on the clinical efficacy of medical osteoporosis therapy in the reduction of fracture risk in men (age > 50 years). Studies included were randomised, placebo-controlled trials of men. Results. Five BMD studies...... fractures a non-significant trend towards a reduction was seen. Conclusion. The evidence of medical osteoporosis treatment in men is scant and inconclusive due to the lack of prospective RCT studies with fracture prevention as primary end point. So far, all evidence is based on BMD increases in small RCT...
Maiga, Amelia W.; Fofana, Bakary; Sagara, Issaka; Dembele, Demba; Dara, Antoine; Traore, Oumar Bila; Toure, Sekou; Sanogo, Kassim; Dama, Souleymane; Sidibe, Bakary; Kone, Aminatou; Thera, Mahamadou A.; Plowe, Christopher V.; Doumbo, Ogobara K.; Djimde, Abdoulaye A.
Plasmodium falciparum resistance to artemisinins by delayed parasite clearance is present in Southeast Asia. Scant data on parasite clearance after artemisinins are available from Africa, where transmission is high, burden is greatest, and artemisinin use is being scaled up. Children 1–10 years of age with uncomplicated malaria were treated with 7 days of artesunate and followed for 28 days. Blood smears were done every 8 hours until negative by light microscopy. Results were compared with a similar study conducted in the same village in 2002–2004. The polymerase chain reaction-corrected cure rate was 100%, identical to 2002–2004. By 24 hours after treatment initiation, 37.0% of participants had cleared parasitemia, compared with 31.9% in 2002–2004 (P = 0.5). The median parasite clearance time was 32 hours. Only one participant still had parasites at 48 hours and no participant presented parasitemia at 72 hours. Artesunate was highly efficacious, with no evidence of delayed parasite clearance. We provide baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa. PMID:22764287
Cottin, Vincent; Richeldi, Luca
In idiopathic pulmonary fibrosis (IPF), some facts or concepts based on substantial evidence, whilst implicit for learned subspecialists, have previously been neglected and/or not explicitly formulated or made accessible to a wider audience. IPF is strongly associated with cigarette smoking and is predominantly a disease of ageing. However, its cause(s) remain elusive and, thus, it is one of the most challenging diseases for the development of novel effective and safe therapies. With the approval of pirfenidone for patients with mild-to-moderate IPF, an earlier diagnosis of IPF is a prerequisite for earlier treatment and, potentially, improvement of the long-term clinical outcome of this progressive and ultimately fatal disease. An earlier diagnosis may be achieved in IPF by promoting thin-slice chest high-resolution computed tomography screening of interstitial lung disease as a "by-product" of large-scale lung cancer screening strategies in smokers, but other techniques, which have been neglected in the past, are now available. Lung auscultation and early identification of "velcro" crackles has been proposed as a key component of early diagnosis of IPF. An ongoing study is exploring correlations between lung sounds on auscultation obtained using electronic stethoscopes and high-resolution computed tomography patterns.
Full Text Available Background: In themanagement of stroke disease, evidences fromthe literature demonstrate that the introduction of stroke units, hospital wards with dedicated beds providing intensive care within 48 hours of symptoms’ onset, produced a real improvement in the outcome, reducing in-hospital fatality cases and increasing the proportion of patients independently living in long term follow-up. Discussion: The article focuses on stroke disease-management, suggesting a stroke integrated approach for the admission of patients on dedicated beds, in order to extend the ‘‘stroke care’’ approach outcomes to as many hospitals as possible in Italy. This approach implies the set up of a stroke network for an effective patients’ stratification according to the severity of the illness at debut; the set up of an integrated team of specialists in hospital management of the acute phase (first 48 hours and a timely rehabilitation treatment. Ultimately the hospital should be organized according to department’s semi-intensive areas in order to assure to the patients, in the early stage of the disease, a timely high intensity care aimed to improve the long term outcome.
Nammas, Wail; Koistinen, Juhani; Paana, Tuomas; Karjalainen, Pasi P
Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.
Keppel Hesselink JM
Full Text Available Jan M Keppel Hesselink,1 Michael E Schatman2,31Institute for Neuropathic Pain, Bosch en Duin, the Netherlands; 2Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 3Boston Pain Care, Waltham, MA, USAIntroductionMost review articles support carbamazepine as a first-line pharmacotherapy for idiopathic trigeminal neuralgia.1–3 However, the empirical support for this recommendation is somewhat suspect. Phenytoin, as the prototype for all anticonvulsants, was already positioned as an analgesic compound 70 years ago. Since these initial findings, the data that have been gathered have supported the use of anticonvulsants as painkillers – from phenytoin up to and including more recent anticonvulsants such as gabapentin and pregabalin. Since 1942, a number of papers supported phenytoin’s therapeutic effects in trigeminal neuralgia (Table 1. The introduction of carbamazepine in 1962 by Geigy shifted the interest of neurologists from phenytoin as a treatment for trigeminal neuralgia to carbamazepine, without sound scientific evidence. To date, no convincing randomized controlled trials (RCTs have been published supporting the role of carbamazepine in trigeminal neuralgia, and we could not identify a single study comparing the effects of phenytoin with those of carbamazepine. Accordingly, phenytoin should probably be considered more often as a viable therapy for (treatmentresistant trigeminal neuralgia.
Full Text Available Dementia is a leading cause of mental and physical disability. Vascular dementia (VaD is the second most common cause of dementia after Alzheimer’s disease (AD constituting 10–15% of the dementia population. Currently there are no approved pharmaceutical options for VaD and the conventional anti-AD therapies provide only modest, short-term relief of symptoms associated with VaD. Herbal medicines have been used for the management of dementia-like symptoms for centuries and may provide viable therapies for VaD due to their multicomponent and multitarget approach. This review is designed to provide an updated overview on the current status of herbal medicine research, with an emphasis on Chinese herbal medicine, for the treatment of VaD or dementia. A case study is also provided to demonstrate the development process of a novel standardized complex herbal formulation for VaD. The article reveals some preliminary evidence to support the use of single and complex herbal preparations for VaD and dementia. Multiple issues in relation to clinical and preclinical research have been identified and future research directions are discussed.
Bonham, Caroline A; Sommerfeld, David; Willging, Cathleen; Aarons, Gregory A
Objective. In recent years, New Mexico has prioritized integrated treatment for cooccurring mental health and substance use disorders within its public behavioral health system. This report describes factors likely to be important when implementing evidence-based practices (EBPs) in community agencies. Methods. Our mixed-method research design consisted of observations, semistructured interviews, and surveys undertaken with employees at 14 agencies at baseline and after 18 months. We developed four-agency typologies based on iterative coding and analysis of observations and interviews. We then examined survey data from employees at the four exemplar agencies to validate qualitative findings. Results. Financial resources and strong leadership impacted agency capacity to train providers and implement EBPs. Quantitative analysis of service provider survey responses from these agencies (N = 38) supported qualitative findings and demonstrated significant mean score differences in leadership, organizational climate, and attitudes toward EBPs in anticipated directions. Conclusion. The availability of strong leadership and financial resources were key components to initial implementation success in this study of community agencies in New Mexico. Reliance only on external funding poses risks for sustainment when demoralizing work climates precipitate employee turnover. Strong agency leadership does not always compensate for deficient financial resources in vulnerable communities.
Antonio Martín Morales
Full Text Available Antonio Martín Morales1, Vincenzo Mirone2, John Dean3, Pierre Costa41Department of Urology, Hospital Carlos Haya, Malaga, Spain; 2Department of Urology, University Federico II, Naples, Italy; 3St. Peter’s Sexual Medicine, The London Clinic, London, UK; 4Center Hospitalier Caremeau, Nîmes, FranceAbstract: Many men with erectile dysfunction (ED also have associated underlying cardiovascular and metabolic conditions, for which they are likely to be taking medication. Therefore, cardiovascular safety and potential drug interactions are two of the major concerns when using PDE-5 inhibitors in these patients. The PDE-5 inhibitor, vardenafil, is characterized by a rapid onset of action, increased duration of erection, high rates of first-dose success and reliable efficacy that can be maintained with continued use. In both clinical trials and real-life observational studies, vardenafil has demonstrated a favorable efficacy and safety profile in men with ED, including those with associated underlying conditions such as diabetes, hypertension and dyslipidemia. Importantly, the concomitant use of medication for these conditions is not associated with any noteworthy changes in the efficacy and safety of vardenafil. The evidence presented in this review supports the use of vardenafil as a first-line treatment for men with ED, including those with underlying conditions.Keywords: vardenafil, erectile dysfunction, efficacy, safety, underlying conditions
Caroline A. Bonham
Full Text Available Objective. In recent years, New Mexico has prioritized integrated treatment for cooccurring mental health and substance use disorders within its public behavioral health system. This report describes factors likely to be important when implementing evidence-based practices (EBPs in community agencies. Methods. Our mixed-method research design consisted of observations, semistructured interviews, and surveys undertaken with employees at 14 agencies at baseline and after 18 months. We developed four-agency typologies based on iterative coding and analysis of observations and interviews. We then examined survey data from employees at the four exemplar agencies to validate qualitative findings. Results. Financial resources and strong leadership impacted agency capacity to train providers and implement EBPs. Quantitative analysis of service provider survey responses from these agencies (N = 38 supported qualitative findings and demonstrated significant mean score differences in leadership, organizational climate, and attitudes toward EBPs in anticipated directions. Conclusion. The availability of strong leadership and financial resources were key components to initial implementation success in this study of community agencies in New Mexico. Reliance only on external funding poses risks for sustainment when demoralizing work climates precipitate employee turnover. Strong agency leadership does not always compensate for deficient financial resources in vulnerable communities.
Full Text Available Objective. Current evidence indicates that there is no single ideal treatment for fibromyalgia syndrome (FMS. First choice treatment options remain debatable, especially concerning the importance of complementary and alternative medicine (CAM treatments. Methods. Three evidence-based interdisciplinary guidelines on FMS in Canada, Germany, and Israel were compared for their first choice and CAM-recommendations. Results. All three guidelines emphasized a patient-tailored approach according to the key symptoms. Aerobic exercise, cognitive behavioral therapy, and multicomponent therapy were first choice treatments. The guidelines differed in the grade of recommendation for drug treatment. Anticonvulsants (gabapentin, pregabalin and serotonin noradrenaline reuptake inhibitors (duloxetine, milnacipran were strongly recommended by the Canadian and the Israeli guidelines. These drugs received only a weak recommendation by the German guideline. In consideration of CAM-treatments, acupuncture, hypnosis/guided imagery, and Tai Chi were recommended by the German and Israeli guidelines. The Canadian guidelines did not recommend any CAM therapy. Discussion. Recent evidence-based interdisciplinary guidelines concur on the importance of treatment tailored to the individual patient and further emphasize the need of self-management strategies (exercise, and psychological techniques.
Ablin, Jacob; Fitzcharles, Mary-Ann; Buskila, Dan; Shir, Yoram; Sommer, Claudia; Häuser, Winfried
Objective. Current evidence indicates that there is no single ideal treatment for fibromyalgia syndrome (FMS). First choice treatment options remain debatable, especially concerning the importance of complementary and alternative medicine (CAM) treatments. Methods. Three evidence-based interdisciplinary guidelines on FMS in Canada, Germany, and Israel were compared for their first choice and CAM-recommendations. Results. All three guidelines emphasized a patient-tailored approach according to the key symptoms. Aerobic exercise, cognitive behavioral therapy, and multicomponent therapy were first choice treatments. The guidelines differed in the grade of recommendation for drug treatment. Anticonvulsants (gabapentin, pregabalin) and serotonin noradrenaline reuptake inhibitors (duloxetine, milnacipran) were strongly recommended by the Canadian and the Israeli guidelines. These drugs received only a weak recommendation by the German guideline. In consideration of CAM-treatments, acupuncture, hypnosis/guided imagery, and Tai Chi were recommended by the German and Israeli guidelines. The Canadian guidelines did not recommend any CAM therapy. Discussion. Recent evidence-based interdisciplinary guidelines concur on the importance of treatment tailored to the individual patient and further emphasize the need of self-management strategies (exercise, and psychological techniques).
Full Text Available Pietro Enea Lazzerini,1 Pier Leopoldo Capecchi,1 Giacomo Maria Guidelli,1 Enrico Selvi,1 Maurizio Acampa,2 Franco Laghi-Pasini1 1Department of Medical Sciences, Surgery and Neurosciences, University of Siena, 2Stroke Unit, University Hospital of Siena, Siena, Italy Abstract: Rheumatoid arthritis (RA is a chronic autoimmune inflammatory disease primarily affecting synovial joints and is characterized by persistent high-grade systemic inflammation. Proinflammatory cytokines, particularly interleukin-6 (IL-6, are of crucial importance in the pathogenesis of the disease, driving both joint inflammation and extra-articular comorbidities. Tocilizumab, a humanized IL-6 receptor-inhibiting monoclonal antibody, has been the first, and, to date, the only, IL-6 inhibitor approved for the treatment of RA. Many studies have demonstrated the potency and effectiveness of tocilizumab in controlling disease activity and radiological progression of RA. These successful results have encouraged the development of novel IL-6 inhibitors, among which a promising agent is sirukumab (SRK, a human anti-IL-6 monoclonal antibody currently under evaluation in Phase II/III studies in patients with RA, systemic lupus erythematosus, giant-cell arteritis, and major depressive disorder. The evidence to date indicates SRK as an effective and well-tolerated new therapeutic tool for patients with active RA, with some preliminary data suggesting a specific beneficial impact on relevant systemic complications associated with the disease, such as depression and cardiovascular disease. Conversely, although pathophysiological considerations make plausible the hypothesis that IL-6 blockade with SRK may also be beneficial in the treatment of many diseases other than RA (either autoimmune or not, available clinical data in patients with systemic lupus erythematosus do not seem to support this view, also giving rise to potentially relevant concerns about drug safety. If large Phase III
Colen, Sascha; Haverkamp, Daniel; Mulier, Michiel; van den Bekerom, Michel P J
The use of intra-articular hyaluronic acid (HA) is a well known treatment in patients with knee osteoarthritis (OA). In other joints, less evidence is available about the efficacy of treatment with intra-articular HA. HA is also used intra-articularly in the metatarsophalangeal-1 joint, the ankle, the hip, the sacroiliac joint, the facet joints, the carpometacarpal-1 joint, the shoulder and the temporo-mandibular joint. In this systematic review we include all prospective studies about the effects of intra-articular HA in the above-mentioned joints. Its use in the knee joint, however, will be discussed in a separate article in this journal. A systematic review was conducted using databases including MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trial Register, and EMBASE. After performing a solid systematic review using a rigid methodology and trying to pool the outcomes of different studies, we noticed that, compared with baseline, there is statistical evidence for a positive effect of intra-articular HA. However, there is limited evidence HA is superior to placebo and no evidence that intra-articular HA is better than corticosteroids or other conservative therapies. Our recommendation for future research is that one should focus on adequately powered randomized trials comparing HA treatment with other types of intra-articular or conservative treatment. We think it is useless to further perform and publish (large) non-comparative prospective studies about the use of HA in the treatment of problems caused by OA. It is well perceived that HA exerts positive effects in the treatment of OA, but up to now there is no (strong) evidence available that HA is superior to other treatments of OA such as corticosteroids, physiotherapy or other conservative measures.
Greenlee, Heather; DuPont-Reyes, Melissa J.; Balneaves, Lynda G.; Carlson, Linda E.; Cohen, Misha R.; Deng, Gary; Johnson, Jillian A.; Mumber, Matthew; Seely, Dugald; Zick, Suzanna; Boyce, Lindsay; Tripathy, Debu
Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. PMID:28436999
Free treatment, rapid malaria diagnostic tests and malaria village workers can hasten progress toward achieving the malaria related millennium development goals: the Médecins Sans Frontières experience from Chad, Sierra-Leone and Mali
Full Text Available Halving the burden of malaria by 2015 and ensuring that 80% of people with malaria receive treatment is among the health related targets of the Millennium Development Goals (MDGs. Despite political momentum toward achieving this target, progress is slow and many with malaria (particularly in poor and rural communities in Africa are still without access to effective treatment. Finding ways to improve access to anti-malarial treatment in Africa is essential to achieve the malaria related and other MDG targets. During its work in Chad, Sierra Leone and Mali in the period 2004 to 2008, Médecins Sans Frontières showed that it was possible to significantly improve access to effective malaria treatment through: i the removal of health centre level user fees for essential healthcare for vulnerable population groups, ii the introduction of free community based treatment for children using malaria village workers to diagnose and treat simple malaria in communities where geographical and financial barriers limited access to effective malaria care, iii the improved diagnosis and treatment of malaria using rapid diagnosis tests and artemisinin based combination therapy, at both health facilities and in the community. This paper describes and discusses these strategies and their related impact.
Hædersdal, Merete; Togsverd-Bo, Katrine; Wulf, Hans Chr.
through searches in PubMed and the Cochrane Library. Results A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad-spectrum light sources...... outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments Udgivelsesdato: 2008/3...
.6 per 10,000 people in Canada have low vision. The 2001 Participation and Activity Limitation Survey (PALS) found that 594,350 (2.5%) Canadians had "difficulty seeing ordinary newsprint or clearly seeing the face of someone from 4 m," and the Canadian National Institute for the Blind (CNIB) registry classified 105,000 (.35%) Canadians as visually disabled. PHAKIC INTRAOCULAR LENSES (PIOL): A phakic intraocular lens (pIOL) is a supplementary lens that is inserted into the anterior or posterior chamber of the eye to correct refractive errors (myopia, hyperopia, and astigmatism). Unlike in cataract surgery, the eye's natural crystalline lens is not removed when the pIOL is inserted, so the eye retains its accommodative ability. In Canada and the United States, iris-fixated (anterior chamber lenses that are anchored to the iris with a claw) and posterior chamber lenses are the only types of pIOLs that are licensed by Health Canada and the Food and Drug Administration, respectively. EVIDENCE-BASED ANALYSIS METHOD: RESEARCH QUESTIONS #ENTITYSTARTX00026; What are the effectiveness, cost-effectiveness, and safety of pIOLs for the treatment of myopia, hyperopia, and astigmatism?Do certain subgroups (e.g. high myopia and low vision) benefit more from pIOLs?How do pIOLs compare with alternative surgical treatment options (LASIK, PRK, and CLE)?Using appropriate keywords, a literature search was conducted up to January 2009. Systematic reviews, meta-analyses, randomized controlled trials, and observational studies with more than 20 eyes receiving pIOLs were eligible for inclusion. The primary outcomes of interest were uncorrected visual acuity (UCVA), predictability of manifest refraction spherical equivalent (MRSE), and adverse events. The GRADE approach was used to systematically and explicitly evaluate the quality of evidence. The search identified 1,131 citations published between January 1, 2003, and January 16, 2009. Including a health technology assessment (HTA) identified in
Boyde, Constance; Linden, Ulrike; Boehm, Katja
Background: Music therapy is one of the oldest forms of creative art therapy and has been shown to have effects in different clinical and therapeutic settings, such as schizophrenia, pain, cardiovascular parameters, and dementia. This article provides an overview of some of the recent findings in this field and also reports two single case vignettes that offer insight into day-to-day applications of clinical music therapy. Material and Methods: For the collection of clinical studies of music therapy in oncology, the databases AMED, CAIRSS, EMBASE, MEDLINE, PsychINFO, and PSYNDEX were searched with the terms “Study OR Trial” AND “Music Therapy” AND “Cancer OR Oncolog$.” Studies were analyzed with respect to their design, setting and interventions, indications, patients, and outcomes. In addition, two case vignettes present the application of music therapy for a child with leukemia and an adult patient with breast cancer. Results: We found a total of 12 clinical studies conducted between 2001 and 2011 comprised of a total of 922 patients. Eight studies had a randomized controlled design, and four studies were conducted in the field of pediatric oncology. Studies reported heterogeneous results on short-term improvements in patients' mood and relaxation and reduced exhaustion and anxiety as well as in coping with the disease and cancer-related pain. Case descriptions showed similar effects in expressing emotions, opening up new goals, and turning the mind toward a healthy process and away form a disease-centered focus. Conclusion: The use of music therapy in the integrative treatment of cancer patients is a therapeutic option whose salutogenetic potential is shown in many case studies such as those presented here. Study results, however, did not draw a conclusive picture of the overall effect of music therapy. In addition to further clinical trials, the evidence mosaic should be complemented with qualitative studies, single case descriptions, and basic
Desai, A P; Guvenc, B H; Carachi, R
Primary intestinal lymphangiectasia is an uncommon congenital anomaly. It is an intrinsic abnormality of the intestinal lymphatics system. Over the years, various treatment options such as diuretics, albumin transfusions and a medium chain triglycerides (MCT) diet as well as surgical options such as resection of isolated segments and peritoneal-venous shunts have been used. An MCT diet, which is a low fat, high protein diet, is increasingly used in the management of this anomaly. The aim was to review the evidence for medium chain triglycerides as a therapeutic option in patients with primary intestinal lymphangiectasia. A literature search was performed and individual case details were extracted. We found 55 cases, of which 3 were from our own institute. The cases were divided in 2 groups: Group A (n=27) consisted of patients treated with MCT, and Group B (n=28) consisted patients not treated with MCT. Cases were analysed for symptomatic response to MCT as well as mortality. 17 of 27 cases (63%) treated with MCT had complete resolution of symptoms while only 10 of 28 (35.7%) patients in group B showed complete resolution. Mortality for Group A was 1 out of 27 (3.7%), while mortality in group B was 5 of 28 (17.85%) patients. We conclude that, although an MCT diet is not completely curative in all cases, it does improve the symptoms of primary intestinal lymphangiectasia and reduces mortality. Hence it is a valid option in the paediatric age group. Copyright Georg Thieme Verlag KG Stuttgart . New York.
Full Text Available Stigmatization is a major hindrance in adult psychiatric patients with Axis-I diagnoses, as shown consistently in most studies. Significantly fewer studies on the emergence of psychiatric stigma in adult patients with personality disorders exist, although the resulting evidence is conclusive. Some authors consider patients with personality disorders at risk for severe stigmatization because of intense difficulties during interpersonal contact, even in a psychotherapeutic relationship. The aim of this study was primarily the assessment of pre-existing stigma in patients referred for intensive treatment for personality disorders. The study enrolled 214 patients admitted to the adult department of a highly specialized mental health care institute offering psychotherapy for patients with severe and complex personality pathology. All patients underwent a standard assessment with self-report questionnaires and a semi-structured interview to measure Axis II personality disorders. The Stigma Consciousness Questionnaire (SCQ and the Perceived Devaluation-Discrimination Questionnaire (DDQ, both validated instruments, were used to measure perceived and actual experiences of stigma. Independent sample t-tests were used to investigate differences in the mean total stigma scores for patients both with and without a personality disorder. One-way ANOVA’s were performed to assess the differences between having a borderline personality disorder, another personality disorder, or no personality disorder diagnosis.Multiple regression main effect analyses were conducted in order to explore the impact of the different personality disorder diagnosis on the level of stigma. The mean scores across all patient groups were consistent with rather low stigma. No differences were found for patients with or without a personality disorder diagnosis. Level of stigma in general was not associated with an accumulating number of personality disorders.
Leenarts, L.E.W.; Diehle, J.; Doreleijers, T.A.H.; Jansma, E.P.; Lindauer, R.J.L.
This is a systematic review of evidence-based treatments for children exposed to childhood maltreatment. Because exposure to childhood maltreatment has been associated with a broad range of trauma-related psychopathology (e.g., PTSD, anxiety, suicidal ideation, substance abuse) and with aggressive
Luketina, Hrvoje; Fotopoulou, Christina; Luketina, Ruzica-Rosalia; Pilger, Adak; Sehouli, Jalid
The systemic treatment of epithelial ovarian cancer (OC) is one of the cornerstones in the multimodal management of advanced OC in both primary and recurrent stages of this disease. In most situations various treatment options are available but only few data exists about the treatment decision-making process. Therefore, we conducted a review of the current literature regarding the decision-making process concerning the systemic therapy in patients with advanced ovarian cancer. The electronic database MEDLINE (PubMed) was systematically reviewed for studies that evaluate the treatment decision-making processes in patients with advanced OC. The PubMed database was searched in detail for all titles and abstracts of potentially relevant studies published between 1995 and 2011. An initial search identified 15 potentially relevant studies, but only seven met all inclusion criteria. Factors that influence treatment decisions in patients with OC include not only rational arguments and medical reasons, but also individual attitudes, fears, existential questions, various projections resulting from the physician patient relationship and the social environment. The physician's personal experience with OC treatment seems to be an important factor, followed by previous personal experience with medical issues, and the fear of side-effects and future metastases. Family and self-support organisations also seem to play a significant role in the treatment decision-making process. This review underlines the need for more research activities to explore the treatment decision-making process to enable the best individual support for patients in treatment decision-making. It is a challenge for clinicians to determine the individual information needs of women with OC and to involve them during the decision-making process to the extent they wish.
Blum, Terry C; Davis, Carolyn D; Roman, Paul M
This paper examines the organizational adoption of medically assisted treatments (MAT) for substance use disorders (SUDs) in a representative sample of 555 US for-profit and not-for-profit treatment centers. The study examines organizational adoption of these treatments in an institutionally contested environment that traditionally has valued behavioral treatment, using sociological and resource dependence frameworks. The findings indicate that socialization of leadership, measured by formal clinical education, is related to the adoption of MAT. Funding patterns also affect innovation adoption, with greater adoption associated with higher proportions of earned income from third party fees for services, and less adoption associated with funding from criminal justice sources. These findings may generalize to other social mission-oriented organizations where innovation adoption may be linked to private and public benefit values inherent in the type of socialization of leadership and different patterns of funding support.
Wilfley, Denise E.; Staiano, Amanda E.; Altman, Myra; Lindros, Jeanne; Lima, Angela; Hassink, Sandra G.; Dietz, William H.; Cook, Stephen
Objectives To improve systems of care to advance implementation of the U.S. Preventive Services Task Force recommendations for childhood obesity treatment (i.e. clinicians offer/refer children with obesity to intensive, multicomponent behavioral interventions of >25 hours over 6–12 months to improve weight status) and to expand payment for these services. Methods In July 2015, forty-three cross-sector stakeholders attended a conference supported by the Agency for Healthcare Research and Quality, American Academy of Pediatrics Institute for Healthy Childhood Weight, and The Obesity Society. Plenary sessions presenting scientific evidence and clinical and payment practices were interspersed with breakout sessions to identify consensus recommendations. Results Consensus recommendations for childhood obesity treatment included: family-based multicomponent behavioral therapy; integrated care model; and multi-disciplinary care team. The use of evidence-based protocols, a well-trained healthcare team, medical oversight, and treatment at or above the minimum dose (e.g. >25 hours) are critical components to ensure effective delivery of high-quality care and to achieve clinically meaningful weight loss. Approaches to secure reimbursement for evidence-based obesity treatment within payment models were recommended. Conclusion Continued cross-sector collaboration is crucial to ensure a unified approach to increase payment and access for childhood obesity treatment and to scale-up training to ensure quality of care. PMID:27925451
Paiva, Sara; Carneiro, Márcia Mendonça
Chronic pelvic pain (CPP) is defined as pain of at least 6 months' duration that occurs in the lower abdomen or below the umbilicus and has resulted in functional or psychological disability or required intervention and treatment. Therapeutic interventions center around the treatment of CPP as a diagnosis in and of itself, and treatment of specific disorders that may be related to CPP. A multidisciplinary approach for diagnosis and treatment seems to be most effective for symptomatic relief. This paper reviews the evidence for such interventions as psychological treatments including the use of complementary and alternative medicine techniques for CPP in women. Unfortunately, finding the best evidence in this setting is difficult as only very few randomized controlled trials are available. A combination of treatments is usually required over time for the treatment of refractory CPP. The multifactorial nature of CPP needs to be discussed with the patient and a good rapport as well as a partnership needs to be developed to plan a management program with regular followup. Promotion of a multidisciplinary approach which includes complementary and alternative medicine techniques in managing CPP in women seems to yield the best results.
Lordick, Florian; Ricke, Jens; Mohnike, Konrad; Hacker, Ulrich
Summary Background While local treatment using more innovative technologies is increasingly applied in contemporary treatment of advanced cancer, its impact on outcomes is not well understood. Methods We reviewed the literature using PubMed and major oncology congress websites, and report here about the understanding of oligometastatic disease, about the role of primary tumor resection in metastatic disease, and about the value of cytoreduction and tumor ablation. Results The Achilless' heel ...
Madsen, Ole Rintek; Faurschou, Mikkel; Loft, Anne Gitte
The aim of this study was to develop 3E (Evidence, Expertise, Exchange) recommendations (RCs) on the use of methotrexate in rheumatic disorders and to assess the agreement among Danish rheumatologists.......The aim of this study was to develop 3E (Evidence, Expertise, Exchange) recommendations (RCs) on the use of methotrexate in rheumatic disorders and to assess the agreement among Danish rheumatologists....
Rodgers, G C; Condurache, C T
This article reviews the evidence supporting the efficacy of antidotes used or recommended for the potential chemical warfare agents of most concern. Chemical warfare agents considered include cyanide, vesicants, pulmonary irritants such as chlorine and phosgene, and nerve agents. The strength of evidence for most antidotes is weak, highlighting the need for additional research in this area.
Júlia Souza Vidal
Full Text Available AbstractLatent tuberculosis infection (LTBI and human immunodeficiency virus (HIV-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.
Bhidayasiri, Roongroj; Fahn, Stanley; Weiner, William J; Gronseth, Gary S; Sullivan, Kelly L; Zesiewicz, Theresa A
To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy? PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched (1966-2011). Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence. Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B6, selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, α-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).
Stark, Kevin D.; Arora, Prerna; Funk, Catherine L.
Cognitive behavioral therapy is an effective approach to the treatment of depressive disorders within schools, due to its demonstrated efficacy, as well as its availability in manualized treatment form. When implemented by therapists with inadequate training, the treatment is often stilted, less engaging for participants, and aimlessly guided…
Huber, Douglas; Curtis, Carolyn; Irani, Laili; Pappa, Sara; Arrington, Lauren
Worldwide 75 million women need postabortion care (PAC) services each year following safe or unsafe induced abortions and miscarriages. We reviewed more than 550 studies on PAC published between 1994 and 2013 in the peer-reviewed and gray literature, covering emergency treatment, postabortion family planning, organization of services, and related topics that impact practices and health outcomes, particularly in the Global South. In this article, we present findings from studies with strong evidence that have major implications for programs and practice. For example, vacuum aspiration reduced morbidity, costs, and time in comparison to sharp curettage. Misoprostol 400 mcg sublingually or 600 mcg orally achieved 89% to 99% complete evacuation rates within 2 weeks in multiple studies and was comparable in effectiveness, safety, and acceptability to manual vacuum aspiration. Misoprostol was safely introduced in several PAC programs through mid-level providers, extending services to secondary hospitals and primary health centers. In multiple studies, postabortion family planning uptake before discharge increased by 30-70 percentage points within 1-3 years of strengthening postabortion family planning services; in some cases, increases up to 60 percentage points in 4 months were achieved. Immediate postabortion contraceptive acceptance increased on average from 32% before the interventions to 69% post-intervention. Several studies found that women receiving immediate postabortion intrauterine devices and implants had fewer unintended pregnancies and repeat abortions than those who were offered delayed insertions. Postabortion family planning is endorsed by the professional organizations of obstetricians/gynecologists, midwives, and nurses as a standard of practice; major donors agree, and governments should be encouraged to provide universal access to postabortion family planning. Important program recommendations include offering all postabortion women family planning
Full Text Available Abstract Background Early recognition of symptoms and signs perceived as malaria are important for effective case management, as few laboratories are available at peripheral health facilities. The validity and reliability of clinical signs and symptoms used by health workers to diagnose malaria were assessed in an area of low transmission in south-western Uganda. Methods The study had two components: 1 passive case detection where all patients attending the out patient clininc with a febrile illness were included and 2 a longitudinal active malaria case detection survey was conducted in selected villages. A malaria case was defined as any slide-confirmed parasitaemia in a person with an axillary temperature ≥ 37.5°C or a history of fever within the last 24 hrs and no signs suggestive of other diseases. Results Cases of malaria were significantly more likely to report joint pains, headache, vomiting and abdominal pains. However, due to the low prevalence of malaria, the predictive values of these individual signs alone, or in combination, were poor. Only 24.8% of 1627 patients had malaria according to case definition and > 75% of patients were unnecessarily treated for malaria and few slide negative cases received alternative treatment. Conclusion In low-transmission areas, more attention needs to be paid to differential diagnosis of febrile illnesses In view of suggested changes in anti-malarial drug policy, introducing costly artemisinin combination therapy accurate, rapid diagnostic tools are necessary to target treatment to people in need.
Day, Ed; Mitcheson, Luke
Clinical guidelines from around the world recommend the delivery of psychosocial interventions as part of routine care in opiate substitution treatment (OST) programmes. However, although individual studies demonstrate benefit for structured psychosocial interventions, meta-analytical reviews find no benefit for manual-based treatments beyond 'routine counselling'. We consider the question of whether OST medication alone is sufficient to produce the required outcomes, or whether greater efforts should be made to provide high-quality psychosocial treatment alongside medication. In so doing, we consider the nuances and limitations of the evidence and the organizational barriers to transferring it into routine practice. The evidence base for psychosocial interventions in opiate substitution treatment (OST) services can be interpreted both positively and negatively. Steering a path between overly optimistic or nihilistic interpretations of the value of psychosocial treatment in OST programmes is the most pragmatic approach. Greater attention should be paid to elements common to all psychological treatments (such as therapeutic alliance), but also to the sequencing and packaging of psychosocial elements and their linkage to peer-led interventions. © 2017 Society for the Study of Addiction.
Unicomb, Rachael; Hewat, Sally; Spencer, Elizabeth; Harrison, Elisabeth
There is a paucity of evidence to guide treatment for children with co-occurring stuttering and speech sound disorder. Some guidelines suggest treating the two disorders simultaneously using indirect treatment approaches; however, the research supporting these recommendations is over 20 years old. In this clinical case series, we investigate whether these co-occurring disorders could be treated concurrently using direct treatment approaches supported by up-to-date, high-level evidence, and whether this could be done in an efficacious, safe and efficient manner. Five pre-school-aged participants received individual concurrent, direct intervention for both stuttering and speech sound disorder. All participants used the Lidcombe Program, as manualised. Direct treatment for speech sound disorder was individualised based on analysis of each child's sound system. At 12 months post commencement of treatment, all except one participant had completed the Lidcombe Program, and were less than 1.0% syllables stuttered on samples gathered within and beyond the clinic. These four participants completed Stage 1 of the Lidcombe Program in between 14 and 22 clinic visits, consistent with current benchmark data for this programme. At the same assessment point, all five participants exhibited significant increases in percentage of consonants correct and were in alignment with age-expected estimates of this measure. Further, they were treated in an average number of clinic visits that compares favourably with other research on treatment for speech sound disorder. These preliminary results indicate that young children with co-occurring stuttering and speech sound disorder may be treated concurrently using direct treatment approaches. This method of service delivery may have implications for cost and time efficiency and may also address the crucial need for early intervention in both disorders. These positive findings highlight the need for further research in the area and contribute to
French, L R M; Turner, K M; Dawson, S; Moran, P
It is unclear what the best psychological treatment is for depression and anxiety in people with co-morbid personality disorder. Trials of different psychological treatment options for this patient group have been conducted, but this evidence has not previously been systematically reviewed or critically appraised. We set out to conduct a scoping review in order to describe which psychological therapies appear most effective in treating depression and/or anxiety in patients with co-morbid personality disorder. PsycINFO, Cochrane library trials, Medline and Embase databases were searched for studies involving randomized, controlled, experimental, parallel-arm comparisons, examining any well-defined, psychotherapeutic intervention for adults, in an outpatient setting, with a clearly defined diagnosis of depression and/or anxiety, and co-morbid personality disorder. A total of 1662 papers were identified. Fifteen met criteria for inclusion and were reviewed. There was weak evidence to support the use of cognitive behavioural therapy as a psychological treatment for depression in patients with co-morbid personality disorder. However, the literature is characterized by considerable methodological heterogeneity, and further research is needed before there is sufficient evidence to indicate which psychological treatment would be most effective in treating anxiety and/or depression in this patient group. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
Gimeno, Carmen; Dorado, Marisa Luisa; Roncero, Carlos; Szerman, Nestor; Vega, Pablo; Balanzá-Martínez, Vicent; Alvarez, F. Javier
Patients with alcohol-use disorders (AUDs) have a high prevalence of anxiety disorders (AnxDs). “Co-occurring disorders” refers to the coexistence of an AUD and/or drug related disorders with another non-addictive psychiatric disorder. The aim of this study was to assess the effectiveness of psychopharmacological treatments and psychotherapy in patients with AUD and AnxD and to propose recommendations for the treatment of patients with comorbid AnxDs and AUDs. Randomized clinical trials, meta-analyses, and clinical guidelines were retrieved from PubMed, Embase, and Cochrane databases. Paroxetine was found to be effective in social anxiety patients with alcohol dependence. Selective serotonin reuptake inhibitors (SSRIs), especially sertraline, showed effective results in posttraumatic stress disorder and in comorbid AnxD–AUD. However, SSRIs should be used with caution when patients are actively drinking because they may increase alcohol consumption. Buspirone, gabapentin, and pregabalin were found to be effective in comorbid AnxD–AUD. The treatment of dual AnxDs should start as early as possible. Since AUDs and AnxDs can reinforce each other, treatments targeting both pathologies can be effective. Women suffer from higher levels of stress and AnxDs than men, and they are also more vulnerable to maintaining alcohol consumption levels. Further research is needed in this comorbid patient population, including the study of different types of patients and gender perspectives. PMID:29018367
Full Text Available Patients with alcohol-use disorders (AUDs have a high prevalence of anxiety disorders (AnxDs. “Co-occurring disorders” refers to the coexistence of an AUD and/or drug related disorders with another non-addictive psychiatric disorder. The aim of this study was to assess the effectiveness of psychopharmacological treatments and psychotherapy in patients with AUD and AnxD and to propose recommendations for the treatment of patients with comorbid AnxDs and AUDs. Randomized clinical trials, meta-analyses, and clinical guidelines were retrieved from PubMed, Embase, and Cochrane databases. Paroxetine was found to be effective in social anxiety patients with alcohol dependence. Selective serotonin reuptake inhibitors (SSRIs, especially sertraline, showed effective results in posttraumatic stress disorder and in comorbid AnxD–AUD. However, SSRIs should be used with caution when patients are actively drinking because they may increase alcohol consumption. Buspirone, gabapentin, and pregabalin were found to be effective in comorbid AnxD–AUD. The treatment of dual AnxDs should start as early as possible. Since AUDs and AnxDs can reinforce each other, treatments targeting both pathologies can be effective. Women suffer from higher levels of stress and AnxDs than men, and they are also more vulnerable to maintaining alcohol consumption levels. Further research is needed in this comorbid patient population, including the study of different types of patients and gender perspectives.
Lewis, Dorothy Otnow; And Others
Clinical and epidemiological evidence is presented indicating that many more Black delinquent children and their families fail to receive needed psychiatric and medical services than do White delinquents. (Author)
Louise Profit, Paul Chrisp, Carole NadinCore Medical Publishing, Knutsford, UKIntroduction: Type 2 diabetes is increasing in prevalence worldwide and is a leading cause of morbidity and mortality, mainly due to the development of complications. Vildagliptin is an inhibitor of dipeptidyl peptidase 4 (DPP-4), a new class of oral antidiabetic agents.Aims: To evaluate the role of vildagliptin in the management of type 2 diabetes.Evidence review: Clear evidence shows that vildagliptin improves gly...
Garner, Bryan R.; Hunter, Brooke D.; Modisette, Kathryn C.; Ihnes, Pamela C.; Godley, Susan H.
High staff turnover has been described as a problem for the substance use disorder treatment field. This assertion is based primarily on the assumption that staff turnover adversely impacts treatment delivery and effectiveness. This assumption, however, has not been empirically tested. In this study, we computed annualized rates of turnover for treatment staff (n=249) participating in an evidence-based practice implementation initiative and examined the association between organizational-level rates of staff turnover and client-level outcomes. Annualized rates of staff turnover were 31% for clinicians and 19% for clinical supervisors. Additionally, multilevel analyses did not reveal the expected relationship between staff turnover and poorer client-level outcomes. Rather, organizational-level rates of staff turnover were found to have a significant positive association with two measures of treatment effectiveness: less involvement in illegal activity and lower social risk. Possible explanations for these findings are discussed. PMID:22154040
Hald, Marianne; Arendrup, Maiken C; Svejgaard, Else L
Internationally approved guidelines for the diagnosis and management of Malassezia-related skin diseases are lacking. Therefore, a panel of experts consisting of dermatologists and a microbiologist under the auspices of the Danish Society of Dermatology undertook a data review and compiled...... guidelines for the diagnostic procedures and management of pityriasis versicolor, seborrhoeic dermatitis and Malassezia folliculitis. Main recommendations in most cases of pityriasis versicolor and seborrhoeic dermatitis include topical treatment which has been shown to be sufficient. As first choice....... Maintenance therapy is often necessary to prevent relapses. In the treatment of Malassezia folliculitis systemic antifungal treatment is probably more effective than topical treatment but a combination may be favourable....
Full Text Available Obesity is a very common global health problem, and it is known to be linked to cardiovascular and cerebrovascular diseases. Western medical treatments for obesity have many drawbacks, including effects on monoamine neurotransmitters and the potential for drug abuse and dependency. The safety of these medications requires improvement. Herbal medicine has been used for treatment of disease for more than 2000 years, and it has proven efficacy. Many studies have confirmed that herbal medicine is effective in the treatment of obesity, but the mechanisms are not clear. This article will discuss the possible effects and mechanisms of herbal medicine treatments for obesity that have been reported in the past decade.
Schrijver, E J M; de Graaf, K; de Vries, O J; Maier, A B; Nanayakkara, P W B
Haloperidol is generally considered the drug of choice for in-hospital delirium management. We conducted a systematic review to evaluate the evidence for the efficacy and safety of haloperidol for the prevention and treatment of delirium in hospitalized patients. PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Cochrane Library were systematically searched up to April 21, 2015. We included English full-text randomized controlled trials using haloperidol for the prevention or treatment of delirium in adult hospitalized patients reporting on delirium incidence, duration, or severity as primary outcome. Quality of evidence was graded. Meta-analysis was not conducted because of between-study heterogeneity. Twelve studies met our inclusion criteria, four prevention and eight treatment trials. Methodological limitations decreased the graded quality of included studies. Results from placebo-controlled prevention studies suggest a haloperidol-induced protective effect for delirium in older patients scheduled for surgery: two studies reported a significant reduction in ICU delirium incidence and one study found a significant reduction in delirium severity and duration. Although placebo-controlled trials are missing, pharmacological treatment of established delirium reduced symptom severity. Haloperidol administration was not associated with treatment-limiting side-effects, but few studies used a systematic approach to identify adverse events. Although results on haloperidol for delirium management seem promising, current prevention trials lack external validity and treatment trials did not include a placebo arm on top of standard nonpharmacological care. We therefore conclude that the current use of haloperidol for in-hospital delirium is not based on robust and generalizable evidence. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Samuels, Aaron M; Awino, Nobert; Odongo, Wycliffe; Abong'o, Benard; Gimnig, John; Otieno, Kephas; Shi, Ya Ping; Were, Vincent; Allen, Denise Roth; Were, Florence; Sang, Tony; Obor, David; Williamson, John; Hamel, Mary J; Patrick Kachur, S; Slutsker, Laurence; Lindblade, Kim A; Kariuki, Simon; Desai, Meghna
Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices.
Itziar Iruarrizaga Díez
Full Text Available In Spain, the importance and relevance of substance dependence and other addictive behaviours has generated great interest among the scientific community. Since its creation in 1992, Psychosocial Intervention. Journal on Equality and Quality of Life has transmitted the needs and training demands of psychologists, paying special attention to those aspects related to prevention, health outcomes and psychosocial factors involved in the onset and maintenance of drug addiction, psychosocial intervention and the treatment of addictive behaviours. As an introduction to this report on the Scientific evidence in the study and treatment of addictive behaviours, all topics covered by this journal throughout the years will be addressed.
David E Dawe
Full Text Available An increasing proportion of patients with advanced NSCLC are over 70 years old, raising unique challenges for treatment decision-making. While these patients are underrepresented in clinical trials, there is an emerging body of evidence associated with this group. The lesson of comprehensive geriatric assessment is that chronological age does not always correlate with physiological age and a variety of important comorbidities and geriatric syndromes can go undetected in a typical history and physical. These comorbidities and expected physiologic changes due to aging complicate decision-making around appropriate treatment. This review discusses geriatric assessment in elderly cancer patients and evaluates the current evidence for chemotherapy and targeted therapy for patients with advanced non-small cell lung cancer aged ≥70 years.
For some, community inclusion facilitates access to alcohol and drugs and, therefore, the potential for developing substance abuse disorders. However, little is known about substance abuse treatment use among people with intellectual disabilities. Using standardized performance measures, substance abuse treatment utilization was examined for…
Carvalho, Caroline Gomes; Medeiros-Filho, João Batista; Ferreira, Meire Coelho
Oncological treatment can cause changes in the oral cavity compromising oral functions. The aim of the study was, based on a systematic review, to draft a guide directed at the team of health professionals involved in the oral care of oncological patients. A systematic search of the literature was performed for articles published between 2000 and April 2017. Searches were made of electronic databases and hand search. The inclusion criteria were systematic reviews of randomized clinical trials (RCTs) and RCTs published in English, involving pediatric and adult oncological patients and focused on the prevention and treatment of oral complications as well as studies addressing the maintenance of oral health. Among the 1237 studies identified, 129 were pre-selected and 54 were selected to form the basis for the clinical guide. The studies analyzed stress the need for oral assessments as well as preventive and curative actions prior to oncological treatment. To minimize the severity of oral problems, the studies emphasize daily oral care, the treatment of xerostomia with saliva substitute and hydration, and low-level laser therapy, nystatin, acyclovir, respectively, for the prevention and treatment of oral mucositis, oral candidiasis, and infection by herpes simplex virus. Thus, the guide produced addresses oral assessments and professional and home care before, during, and after oncological treatment. The guide drafted has the function of assisting health professionals involved in the oral care of patients with cancer, enabling the prevention or treatment of oral complications stemming from oncological treatment.
Silverman, Wendy K.; Ortiz, Claudio D.; Viswesvaran, Chockalingham; Burns, Barbara J.; Kolko, David J.; Putnam, Frank W.; Amaya-Jackson, Lisa
The article reviews the current status (1993-2007) of psychosocial treatments for children and adolescents who have been exposed to traumatic events. Twenty-one treatment studies are evaluated using criteria from Nathan and Gorman (2002) along a continuum of methodological rigor ranging from Type 1 to Type 6. All studies were, at a minimum, robust…
Helen M Higgins
Full Text Available Footrot is a widespread, infectious cause of lameness in sheep, with major economic and welfare costs. The aims of this research were: (i to quantify how veterinary surgeons' beliefs regarding the efficacy of two treatments for footrot changed following a review of the evidence (ii to obtain a consensus opinion following group discussions (iii to capture complementary qualitative data to place their beliefs within a broader clinical context. Grounded in a Bayesian statistical framework, probabilistic elicitation (roulette method was used to quantify the beliefs of eleven veterinary surgeons during two one-day workshops. There was considerable heterogeneity in veterinary surgeons' beliefs before they listened to a review of the evidence. After hearing the evidence, seven participants quantifiably changed their beliefs. In particular, two participants who initially believed that foot trimming with topical oxytetracycline was the better treatment, changed to entirely favour systemic and topical oxytetracycline instead. The results suggest that a substantial amount of the variation in beliefs related to differences in veterinary surgeons' knowledge of the evidence. Although considerable differences in opinion still remained after the evidence review, with several participants having non-overlapping 95% credible intervals, both groups did achieve a consensus opinion. Two key findings from the qualitative data were: (i veterinary surgeons believed that farmers are unlikely to actively seek advice on lameness, suggesting a proactive veterinary approach is required (ii more attention could be given to improving the way in which veterinary advice is delivered to farmers. In summary this study has: (i demonstrated a practical method for probabilistically quantifying how veterinary surgeons' beliefs change (ii revealed that the evidence that currently exists is capable of changing veterinary opinion (iii suggested that improved transfer of research
Higgins, Helen M; Green, Laura E; Green, Martin J; Kaler, Jasmeet
Footrot is a widespread, infectious cause of lameness in sheep, with major economic and welfare costs. The aims of this research were: (i) to quantify how veterinary surgeons' beliefs regarding the efficacy of two treatments for footrot changed following a review of the evidence (ii) to obtain a consensus opinion following group discussions (iii) to capture complementary qualitative data to place their beliefs within a broader clinical context. Grounded in a Bayesian statistical framework, probabilistic elicitation (roulette method) was used to quantify the beliefs of eleven veterinary surgeons during two one-day workshops. There was considerable heterogeneity in veterinary surgeons' beliefs before they listened to a review of the evidence. After hearing the evidence, seven participants quantifiably changed their beliefs. In particular, two participants who initially believed that foot trimming with topical oxytetracycline was the better treatment, changed to entirely favour systemic and topical oxytetracycline instead. The results suggest that a substantial amount of the variation in beliefs related to differences in veterinary surgeons' knowledge of the evidence. Although considerable differences in opinion still remained after the evidence review, with several participants having non-overlapping 95% credible intervals, both groups did achieve a consensus opinion. Two key findings from the qualitative data were: (i) veterinary surgeons believed that farmers are unlikely to actively seek advice on lameness, suggesting a proactive veterinary approach is required (ii) more attention could be given to improving the way in which veterinary advice is delivered to farmers. In summary this study has: (i) demonstrated a practical method for probabilistically quantifying how veterinary surgeons' beliefs change (ii) revealed that the evidence that currently exists is capable of changing veterinary opinion (iii) suggested that improved transfer of research knowledge into
Higgins, Helen M.; Green, Laura E.; Green, Martin J.; Kaler, Jasmeet
Footrot is a widespread, infectious cause of lameness in sheep, with major economic and welfare costs. The aims of this research were: (i) to quantify how veterinary surgeons’ beliefs regarding the efficacy of two treatments for footrot changed following a review of the evidence (ii) to obtain a consensus opinion following group discussions (iii) to capture complementary qualitative data to place their beliefs within a broader clinical context. Grounded in a Bayesian statistical framework, probabilistic elicitation (roulette method) was used to quantify the beliefs of eleven veterinary surgeons during two one-day workshops. There was considerable heterogeneity in veterinary surgeons’ beliefs before they listened to a review of the evidence. After hearing the evidence, seven participants quantifiably changed their beliefs. In particular, two participants who initially believed that foot trimming with topical oxytetracycline was the better treatment, changed to entirely favour systemic and topical oxytetracycline instead. The results suggest that a substantial amount of the variation in beliefs related to differences in veterinary surgeons’ knowledge of the evidence. Although considerable differences in opinion still remained after the evidence review, with several participants having non-overlapping 95% credible intervals, both groups did achieve a consensus opinion. Two key findings from the qualitative data were: (i) veterinary surgeons believed that farmers are unlikely to actively seek advice on lameness, suggesting a proactive veterinary approach is required (ii) more attention could be given to improving the way in which veterinary advice is delivered to farmers. In summary this study has: (i) demonstrated a practical method for probabilistically quantifying how veterinary surgeons’ beliefs change (ii) revealed that the evidence that currently exists is capable of changing veterinary opinion (iii) suggested that improved transfer of research knowledge
Kreeftmeijer-Vegter Annemarie R
Full Text Available Abstract Background Intravenous (IV artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe. Methods Hospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated. Results Of the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%. The mean time to 50% parasite clearance (PCT50, 90% and 99% were 4.4 hours (3.9 - 5.2, 14.8 hours (13.0 - 17.2, and 29.5 hours (25.9 - 34.4 respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain. Conclusions Data from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment. Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug.
Full Text Available This review has two components. The first is a selective, narrative background of some of the issues surrounding acute whiplash. The latter part is a more systematic review of the available evidence concerning the management of acute whiplash as it stood in March 2001.
Valmaggia, Lucia R; Latif, Leila; Kempton, Matthew J; Rus-Calafell, Maria
The aim of this paper is to provide a review of controlled studies of the use of Virtual Reality in psychological treatment (VRT). Medline, PsychInfo, Embase and Web of Science were searched. Only studies comparing immersive virtual reality to a control condition were included. The search resulted in 1180 articles published between 2012 and 2015, of these, 24 were controlled studies. The reviewed studies confirm the effectiveness of VRT compared to treatment as usual, and show similar effectiveness when VRT is compared to conventional treatments. Current developments and future research are discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Brand, P.L.; Baraldi, E.; Bisgaard, H.
causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast...... preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes Udgivelsesdato: 2008/10...
Han, Leona C.; Delpe, Sophia; Shah, Nilay D.; Ziegenfuss, Jeanette Y.; Tilburt, Jon C.; Karnes, R. Jeffrey; Nguyen, Paul L.; Gross, Cary P.; Yu, James B.; Trinh, Quoc-Dien; Sun, Maxine; Ranasinghe, Weranja K.B.; Kim, Simon P.
Purpose: To perform a national survey of radiation oncologists and urologists about the type of resources used and the level of evidence needed to change clinical practice in localized prostate cancer. Methods and Materials: From a random sample, 1422 physicians were mailed a survey assessing the types of information used and what level of evidence could alter their clinical practice in prostate cancer. Multivariable logistic regression models were used to identify differences in physician characteristics for each outcome. Results: Survey response rates were similar for radiation oncologists and urologists (44% vs 46%; P=.46). Specialty-specific journals represented the most commonly used resource for informing the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P<.001) but more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006). Both radiation oncologists and urologists most commonly reported large randomized, clinical trials as the level of evidence to change treatment recommendations for localized prostate cancer (85% vs 77%; P=.009). Conclusions: Both specialties rely on their own specialty-specific journals and view randomized, clinical trials as the level of evidence needed to change clinical practice. Our study provides a context on meaningful ways of disseminating evidence for localized prostate cancer
Bruno Bertolucci Ortiz
Full Text Available Objective: To investigate whether inpatients with disorganized schizophrenia are more resistant to treatment. Method: Eighty-five inpatients were assessed at admission and at discharge for schizophrenia subtype, symptom severity, and treatment resistance criteria. Results: Disorganized patients were significantly more treatment-resistant than paranoid patients (60%, p = 0.001, and presented worse scores on the Positive and Negative Syndrome Scale (PANSS, the Clinical Global Impression Scale (CGI-S, and the Global Assessment of Functioning Scale (GAF (p < 0.001. Although the difference was not significant, 80% of treatment-resistant patients with disorganized schizophrenia responded to clozapine. Conclusion: Patients with the disorganized subtype of schizophrenia should benefit from clozapine as a second-line agent.
Julia R G Raifman
Full Text Available BACKGROUND: Low rates of adherence to artemisinin-based combination therapy (ACT regimens increase the risk of treatment failure and may lead to drug resistance, threatening the sustainability of current anti-malarial efforts. We assessed the impact of text message reminders on adherence to ACT regimens. METHODS: Health workers at hospitals, clinics, pharmacies, and other stationary ACT distributors in Tamale, Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment. The messaging system automatically randomized self-enrolled individuals to the control group or the treatment group with equal probability; those in the treatment group were further randomly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals. The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation. We estimated the impact of the messages on treatment completion using logistic regression. RESULTS: 1140 individuals enrolled in both the study and the text reminder system. Among individuals in the control group, 61.5% took the full course of treatment. The simple text message reminders increased the odds of adherence (adjusted OR 1.45, 95% CI [1.03 to 2.04], p-value 0.028. Receiving an additional message did not result in a significant change in adherence (adjusted OR 0.77, 95% CI [0.50 to 1.20], p-value 0.252. CONCLUSION: The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment. Further research is needed to develop the most effective text message content and frequency. TRIAL REGISTRATION: ClinicalTrials.gov NCT01722734.
Raifman, Julia R G; Lanthorn, Heather E; Rokicki, Slawa; Fink, Günther
Low rates of adherence to artemisinin-based combination therapy (ACT) regimens increase the risk of treatment failure and may lead to drug resistance, threatening the sustainability of current anti-malarial efforts. We assessed the impact of text message reminders on adherence to ACT regimens. Health workers at hospitals, clinics, pharmacies, and other stationary ACT distributors in Tamale, Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment. The messaging system automatically randomized self-enrolled individuals to the control group or the treatment group with equal probability; those in the treatment group were further randomly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals. The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation. We estimated the impact of the messages on treatment completion using logistic regression. 1140 individuals enrolled in both the study and the text reminder system. Among individuals in the control group, 61.5% took the full course of treatment. The simple text message reminders increased the odds of adherence (adjusted OR 1.45, 95% CI [1.03 to 2.04], p-value 0.028). Receiving an additional message did not result in a significant change in adherence (adjusted OR 0.77, 95% CI [0.50 to 1.20], p-value 0.252). The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment. Further research is needed to develop the most effective text message content and frequency. ClinicalTrials.gov NCT01722734.
Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophyla...
Mustian, Karen M.; Janelsins, Michelle; Peppone, Luke J.; Kamen, Charles
Up to 90% of cancer patients report symptoms of insomnia during and after treatment. Symptoms of insomnia include excessive daytime sleepiness, difficulty falling asleep, difficulty staying asleep, and waking up too early. Insomnia symptoms are among the most prevalent, distressing and persistent cancer- and cancer treatment-related toxicities reported by patients, and can be severe enough to increase cancer morbidity and mortality. Despite the ubiquity of insomnia symptoms, they are under-sc...
Allen, Karina L; O'Hara, Caitlin B; Bartholdy, Savani; Renwick, Beth; Keyes, Alexandra; Lose, Anna; Kenyon, Martha; DeJong, Hannah; Broadbent, Hannah; Loomes, Rachel; McClelland, Jessica; Serpell, Lucy; Richards, Lorna; Johnson-Sabine, Eric; Boughton, Nicky; Whitehead, Linette; Treasure, Janet; Wade, Tracey; Schmidt, Ulrike
Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882). © 2016 Wiley Periodicals, Inc.
Byun, Tara McAllister; Hitchcock, Elaine R.; Swartz, Michelle T.
Purpose To document the efficacy of ultrasound biofeedback treatment for misarticulation of the North American English rhotic in children. Because of limited progress in the first cohort, a series of two closely related studies was conducted in place of a single study. The studies differed primarily in the nature of tongue-shape targets (e.g., retroflex, bunched) cued during treatment. Method Eight participants received 8 weeks of individual ultrasound biofeedback treatment targeting rhotics. In Study 1, all 4 participants were cued to match a bunched tongue-shape target. In Study 2, participants received individualized cues aimed at eliciting the tongue shape most facilitative of perceptually correct rhotics. Results Participants in Study 1 showed only minimal treatment effects. In Study 2, all participants demonstrated improved production of rhotics in untreated words produced without biofeedback, with large to very large effect sizes. Conclusions The results of Study 2 indicate that with proper parameters of treatment, ultrasound biofeedback can be a highly effective intervention for children with persistent rhotic errors. In addition, qualitative comparison of Studies 1 and 2 suggests that treatment for the North American English rhotic should include opportunities to explore different tongue shapes, to find the most facilitative variant for each individual speaker. PMID:25088034
Sabine Nunes Boilesen
Full Text Available Abstract Objective: To study the evidence on the role of water and fluid intake in the prevention and treatment of functional intestinal constipation in children and adolescents. Source of data: A search was carried out in the Medline database (between 1966 and 2016 for all published articles containing the following words: constipation, water, and fluids, published in Portuguese, English, and Spanish. All original articles that assessed children and adolescents were selected by title and abstract. The references of these articles were also evaluated. Synthesis of data: A total of 1040 articles were retrieved. Of these, 24 were selected for reading. The study included 11 articles that assessed children and adolescents. The articles were divided into two categories, those that evaluated water and fluid intake as a risk factor for intestinal constipation and those that evaluated their role in the treatment of intestinal constipation. Five articles were included in the first category. The criteria for assessing fluid intake and bowel rhythm were different in each study. Three studies demonstrated an association between low fluid intake and intestinal constipation. Regarding treatment, five articles with heterogeneous methodologies were found. None of them clearly identified the favorable role of fluid intake in the treatment of intestinal constipation. Conclusion: There are few articles on the association between fluid intake and intestinal constipation. Epidemiological evidence indicates an association between lower fluid intake and intestinal constipation. Further clinical trials and epidemiological studies that consider the international recommendations for fluid intake by children and adolescents are required.
Fox, Susan H; Katzenschlager, Regina; Lim, Shen-Yang; Ravina, Bernard; Seppi, Klaus; Coelho, Miguel; Poewe, Werner; Rascol, Olivier; Goetz, Christopher G; Sampaio, Cristina
The objective was to update previous evidence-based medicine reviews of treatments for motor symptoms of Parkinson's disease published between 2002 and 2005. Level I (randomized, controlled trial) reports of pharmacological, surgical, and nonpharmacological interventions for the motor symptoms of Parkinson's disease between January 2004 (2001 for nonpharmacological) and December 2010 were reviewed. Criteria for inclusion, clinical indications, ranking, efficacy conclusions, safety, and implications for clinical practice followed the original program outline and adhered to evidence-based medicine methodology. Sixty-eight new studies qualified for review. Piribedil, pramipexole, pramipexole extended release, ropinirole, rotigotine, cabergoline, and pergolide were all efficacious as symptomatic monotherapy; ropinirole prolonged release was likely efficacious. All were efficacious as a symptomatic adjunct except pramipexole extended release, for which there is insufficient evidence. For prevention/delay of motor fluctuations, pramipexole and cabergoline were efficacious, and for prevention/delay of dyskinesia, pramipexole, ropinirole, ropinirole prolonged release, and cabergoline were all efficacious, whereas pergolide was likely efficacious. Duodenal infusion of levodopa was likely efficacious in the treatment of motor complications, but the practice implication is investigational. Entacapone was nonefficacious as a symptomatic adjunct to levodopa in nonfluctuating patients and nonefficacious in the prevention/delay of motor complications. Rasagiline conclusions were revised to efficacious as a symptomatic adjunct, and as treatment for motor fluctuations. Clozapine was efficacious in dyskinesia, but because of safety issues, the practice implication is possibly useful. Bilateral subthalamic nucleus deep brain stimulation, bilateral globus pallidus stimulation, and unilateral pallidotomy were updated to efficacious for motor complications. Physical therapy was revised
Barnett, Miya L; Lau, Anna S; Miranda, Jeanne
Mobilizing lay health workers (LHWs) to deliver evidence-based treatments (EBTs) is a workforce strategy to address mental health disparities in underserved communities. LHWs can be leveraged to support access to EBTs in a variety of ways, from conducting outreach for EBTs delivered by professional providers to serving as the primary treatment providers. This critical review provides an overview of how LHW-supported or -delivered EBTs have been leveraged in low-, middle-, and high-income countries (HICs). We propose a conceptual model for LHWs to address drivers of service disparities, which relate to the overall supply of the EBTs provided and the demand for these treatments. The review provides illustrative case examples that demonstrate how LHWs have been leveraged globally and domestically to increase access to mental health services. It also discusses challenges and recommendations regarding implementing LHW-supported or -delivered EBTs.
Wilt, Timothy J; MacDonald, Roderick; Brasure, Michelle; Olson, Carin M; Carlyle, Maureen; Fuchs, Erika; Khawaja, Imran S; Diem, Susan; Koffel, Erin; Ouellette, Jeannine; Butler, Mary; Kane, Robert L
Pharmacologic interventions are often prescribed for insomnia disorder. To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder. Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents. 35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents. Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence. Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to moderate-strength evidence). Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants, and for most pharmacologic interventions in older adults, was insufficient or low strength. Evidence was also insufficient to compare efficacy within or across pharmacotherapy classes or versus behavioral therapy. Harms evidence reported in trials was judged insufficient or low strength; observational studies suggested that use of hypnotics for insomnia was associated with increased risk for dementia, fractures, and major injury. The FDA documents reported that most pharmacotherapies had risks for cognitive and behavioral changes, including driving impairment, and other adverse effects, and they advised dose reduction in women and in older adults. Most trials were small and short term and enrolled individuals meeting stringent criteria. Minimum important differences in outcomes were often not established or reported. Data were scant for many treatments. Eszopiclone, zolpidem, and
Galun, Danijel; Basaric, Dragan; Zuvela, Marinko; Bulajic, Predrag; Bogdanovic, Aleksandar; Bidzic, Nemanja; Milicevic, Miroslav
Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome. PMID:26380652
Fitzsimmons, Suzanne; Schoenfelder, Deborah Perry
Depression is a problem that will continue to burden older adults and challenge health care providers. Failing to recognize and effectively treat depression in institutionalized older adults is sanctioning these members of society to live their final years in despair and emotional suffering. The wheelchair biking program described in this evidence-based practice guideline provides a refreshing, safe, innovative tool to address depression and improve quality of life in older adults.
Quesada Mena, Luis Diego
Available literary evidence is reviewed on the current management of hypertrophic cardiomyopathy. The bibliographical search is carried out in physical and online texts, cardiology journals, databases (MEDLINE), original studies, reviews and metaanalysis. Literature in English and Spanish is included from the first descriptions of the disease in the fifties, until the date of the investigation. Clinical management of patients is compared and recommendations published by consensus groups of international associations [es
Ellis, Amy E; Simiola, Vanessa; Brown, Laura; Courtois, Christine; Cook, Joan M
The purpose of this paper was to systematically review and synthesize the empirical literature on the effects of evidence-based therapy relationship (EBR) variables in the psychological treatment for adults who experienced trauma-related distress. Studies were identified using comprehensive searches of PsycINFO, Medline, Published International Literature on Traumatic Stress, and Cumulative Index to Nursing and Allied Health Literature databases. Included in the review were articles published between 1980 and 2015, in English that reported on the impact of EBRs on treatment outcome in clinical samples of adult trauma survivors. Nineteen unique studies met inclusion criteria. The bulk of the studies were on therapeutic alliance and the vast majority found that alliance was predictive of or associated with a reduction in various symptomotology. Methodological concerns included the use of small sample sizes, little information on EBRs beyond alliance as well as variability in its measurement, and non-randomized assignment to treatment conditions or the lack of a comparison group. More research is needed on the roles of client feedback, managing countertransference, and other therapist characteristics on treatment outcome with trauma survivors. Understanding the role of EBRs in the treatment of trauma survivors may assist researchers, clinicians, and psychotherapy educators to improve therapist training as well as client engagement and retention in treatment.
Full Text Available Introduction: Effective first-line treatments for posttraumatic stress disorder (PTSD are well established, but their generalizability to child abuse (CA-related Complex PTSD is largely unknown. Method: A quantitative review of the literature was performed, identifying seven studies, with treatments specifically targeting CA-related PTSD or Complex PTSD, which were meta-analyzed, including variables such as effect size, drop-out, recovery, and improvement rates. Results: Only six studies with one or more cognitive behavior therapy (CBT treatment conditions and one with a present centered therapy condition could be meta-analyzed. Results indicate that CA-related PTSD patients profit with large effect sizes and modest recovery and improvement rates. Treatments which include exposure showed greater effect sizes especially in completers’ analyses, although no differential results were found in recovery and improvement rates. However, results in the subgroup of CA-related Complex PTSD studies were least favorable. Within the Complex PTSD subgroup, no superior effect size was found for exposure, and affect management resulted in more favorable recovery and improvement rates and less drop-out, as compared to exposure, especially in intention-to-treat analyses. Conclusion: Limited evidence suggests that predominantly CBT treatments are effective, but do not suffice to achieve satisfactory end states, especially in Complex PTSD populations. Moreover, we propose that future research should focus on direct comparisons between types of treatment for Complex PTSD patients, thereby increasing generalizability of results.
Carmichael, A R
There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia.
A. R. Carmichael
Full Text Available There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia.
Langer, David A; Jensen-Doss, Amanda
The shared decision-making (SDM) model is one in which providers and consumers of health care come together as collaborators in determining the course of care. The model is especially relevant to youth mental health care, when planning a treatment frequently entails coordinating both youth and parent perspectives, preferences, and goals. The present article first provides the historical context of the SDM model and the rationale for increasing our field's use of SDM when planning psychosocial treatments for youth and families. Having established the potential utility of SDM, the article then discusses how to apply the SDM model to treatment planning for youth psychotherapy, proposing a set of steps consistent with the model and considerations when conducting SDM with youth and families.
Fristad, Mary A.; MacPherson, Heather A.
Objective Pediatric bipolar spectrum disorders (BPSDs) are serious conditions associated with morbidity and mortality. Although most treatment research examined pharmacotherapy for pediatric BPSDs, growing literature suggests that psychosocial interventions are also important to: provide families with an understanding of symptoms, course, and treatment of BPSDs; teach youth and parents methods for coping with symptoms (e.g., problem-solving, communication, cognitive-behavioral skills); and prevent relapse. Method Thirteen psychosocial intervention trials for pediatric BPSDs were identified via a comprehensive literature search and evaluated according to the Task Force on the Promotion and Dissemination of Psychological Procedures guidelines. All interventions were examined adjunctive to pharmacotherapy and/or treatment as usual (TAU). Results No well-established or questionably efficacious treatments were identified. Family psychoeducation plus skill building was probably efficacious (i.e., Multi-Family Psychoeducational Psychotherapy, Family-Focused Treatment); cognitive-behavioral therapy (CBT) was possibly efficacious. Dialectical behavior therapy (DBT) and interpersonal and social rhythm therapy (IPSRT) were experimental. Limited research precluded subdivision of treatments by format and age. Only single- and multiple-family psychoeducation plus skill building and CBT were evaluated with children. Only single-family psychoeducation plus skill building and DBT, and individual (commonly with limited familial involvement) CBT and IPSRT were evaluated with adolescents. Conclusions Psychosocial interventions that involve families, psychoeducation, and skill building may offer added benefit to pharmacotherapy and/or other TAU. Limitations of current research include few outcome studies, small samples, and failure to use stringent control conditions or randomization. The review concludes with a discussion of mediators and moderators, recommendations for best practice
Ames, Philip; Galor, Anat
Dry eye has gained recognition as a public health problem given its high prevalence, morbidity and cost implications. Although dry eye is common and affects patients’ quality of life, only one medication, cyclosporine 0.05% emulsion, has been approved by the US FDA for its treatment. In this review, we summarize the basic science and clinical data regarding the use of cyclosporine in the treatment of dry eye. Randomized controlled trials showed that cyclosporine emulsion outperformed vehicles in the majority of trials, consistently decreasing corneal staining and increasing Schirmer scores. Symptom improvement was more variable, however, with ocular dryness shown to be the most consistently improved symptom over vehicle. PMID:25960865
Bhidayasiri, Roongroj; Sringean, Jirada; Thanawattano, Chusak
The manifestations of nocturnal movements in Parkinson's disease (PD) are protean, with major disabilities related to nocturnal hypokinesia. While it can be assessed by clinical interviews and screening instruments, these are often inaccurate and prone to recall bias. In light of advances in sensor technology, we explored the use of sensors in the study of nocturnal hypokinesia, by performing a systematic review of the professional literature on this topic. Evidence suggests that nocturnal hypokinesia exists even in patients in the early stages, and PD patients turned significantly less and with much slower speed and acceleration than controls, partly related to low nocturnal dopamine level. We conducted another systematic review to evaluate the evidence of the efficacy of dopaminergic agents in the treatment of nocturnal hypokinesia. Several lines of evidence support the use of long-acting drugs or by continuous administration of short-acting agents to control symptoms. Sensor parameters could be considered as one of the important objective outcomes in future clinical trials investigating potential drugs to treat nocturnal hypokinesia. Physicians should be aware of this technology as it can aid the clinical assessment of nocturnal hypokinesia and enhance the quality of patient care. In addition, the use of sensors currently is being considered for various aspects of research on early diagnosis, treatment, and rehabilitation of PD patients. Copyright © 2015 Elsevier Ltd. All rights reserved.
Gupta, Aditya K; Foley, Kelly A
Low-level laser therapy (LLLT) is currently in use to stimulate hair growth and is quickly gaining in popularity due to the ease of use and absence of side effects. In 2015 alone, the number of LLLT devices with the Food and Drug Administration clearance has doubled. To consolidate evidence and establish which data are still required for the widespread acceptance of LLLT for hair loss therapy. A thorough search of the PubMed database was conducted to obtain studies investigating LLLT for androgenetic alopecia in men and women. Nine trials were identified for comb and helmet/cap devices, five of which were randomized controlled trials. Data comparison across LLLT trials and with traditional hair loss therapy (minoxidil, finasteride) was not straight forward because there was a lack of visual evidence, sample sizes were low, and there were large variations in study duration and efficacy measurements. There are a number of unanswered questions about the optimum treatment regimen, including maintenance treatment and the long-term consequences of LLLT use. Moving forward, protocols should be standardized across trials. Moreover, it is recommended that future trials include visual evidence and trial duration be expanded to 12 months.
Marletta, Giuseppe; Canfora, Angela; Roscani, Francesco; Cernicchiaro, Lucia; Cutrera, Maria; Russo, Marianna; Artioli, Giovanna; Sarli, Leopoldo
Evidence-based medicine offers effective pathways of pharmacological treatment for chronic pain that may compromise the quality of life of patients; this is one of the main reasons why more and more people resort to traditional and complementary approaches, to try to maintain or regain their health. The effectiveness of the various forms of complementary treatments often cannot be proven objectively, which is why, given the need to find more concrete evidence of the effectiveness of complementary therapies with particular reference to the method of healing touch massage, a review of the literature was conducted in order to gather evidence of the efficacy of the specific method regarding pain and other health outcomes of patients with malignant disease to support a proposal for improvement, based on the practice of healing touch massage conducted by nurses. Systematic review. There are several examples (in some cases specifically regarding patients with tumors) of the positive effects of healing touch massage on pain, anxiety and fatigue, and also on biochemical parameters. The way to full recognition by both the institutional and the scientific community seems to promise fairly well, although it should be noted that the achievement of this goal will require further research avoiding the limitations of previous studies.
Carlos Noronha Neto
. Currently, the best treatment for forms of pre-eclampsia is being discussed at different times in pregnancy and puerperium, with the objective to reduce the high rates of maternal and fetal morbidity and mortality. Considering the pathophysiology of the event, anticipation of delivery is the best treatment for pre-eclampsia. The use of magnesium sulfate is recommended in all cases of severe pre-eclampsia and eclampsia for prevention and treatment of seizures. Likewise, treatment of hypertensive crises is recommended. Hydralazine, nifedipine and labetalol have been the most commonly used drugs for this purpose, but their use depends on the familiarity of the treating physician. Antenatal corticoid therapy is indicated whenever there is an imminent risk of preterm delivery between 24 and 34 weeks. In contrast, there is insufficient evidence to recommend bed rest and routine plasma volume expansion, and there is an urgent need for randomized clinical trials to determine whether maintenance antihypertensive treatment in pregnant women has benefits or risks for mothers and fetuses in all clinical forms of disease, particularly in cases of pure pre-eclampsia.
Mauch, V.; Bonsu, F.; Gyapong, M.; Awini, E.; Suarez, P.; Marcelino, B.; Melgen, R. E.; Lönnroth, K.; Nhung, N. V.; Hoa, N. B.; Klinkenberg, E.
The National Tuberculosis Programs of Ghana, Viet Nam and the Dominican Republic. To assess the direct and indirect costs of tuberculosis (TB) diagnosis and treatment for patients and households. Each country translated and adapted a structured questionnaire, the Tool to Estimate Patients' Costs. A
Conclusions: Haemolysis is commonly associated with the class of artemisinin drugs when used for the treatment of severe malaria. Potential causes of this safety issue are discussed. Although no deaths attributed to haemolysis have been reported so far, this safety issue may lead to life-threatening anaemia and is particularly worrying for regions where safe blood products are not readily available.
van den Brink, Wim
This review summarizes our current knowledge of the pharmacological treatment of substance use disorders and pathological gambling using data mainly from randomized controlled trials and meta-analyses regarding these randomized controlled trials. The review is restricted to the selection of first
Laur, Celia V; McNicholl, Tara; Valaitis, Renata; Keller, Heather H
There is increasing awareness of the detrimental health impact of frailty on older adults and of the high prevalence of malnutrition in this segment of the population. Experts in these 2 arenas need to be cognizant of the overlap in constructs, diagnosis, and treatment of frailty and malnutrition. There is a lack of consensus regarding the definition of malnutrition and how it should be assessed. While there is consensus on the definition of frailty, there is no agreement on how it should be measured. Separate assessment tools exist for both malnutrition and frailty; however, there is intersection between concepts and measures. This narrative review highlights some of the intersections within these screening/assessment tools, including weight loss/decreased body mass, functional capacity, and weakness (handgrip strength). The potential for identification of a minimal set of objective measures to identify, or at least consider risk for both conditions, is proposed. Frailty and malnutrition have also been shown to result in similar negative health outcomes and consequently common treatment strategies have been studied, including oral nutritional supplements. While many of the outcomes of treatment relate to both concepts of frailty and malnutrition, research questions are typically focused on the frailty concept, leading to possible gaps or missed opportunities in understanding the effect of complementary interventions on malnutrition. A better understanding of how these conditions overlap may improve treatment strategies for frail, malnourished, older adults.
Annis, Helen M.; Chan, David
Interaction of offender type by treatment program was examined for 100 adult offenders with alcohol and drug problems assigned to a group therapy program and 50 to routine care. Offenders who were classified high in self-image showed greater improvement in the group therapy program. (Author/HLM)
May, Anna C.; Rudy, Brittany M.; Davis, Thompson E., III; Matson, Johnny L.
Specific phobias are among the most common anxiety disorders, especially in children. Unfortunately, a paucity of literature exists regarding the treatment of specific phobia in young children, despite the knowledge that traditional techniques (i.e., cognitive-behavioral therapy [CBT]) may not be practical. Therefore, the purpose of this article…
Moore, R Andrew; Derry, Sheena; Wiffen, Philip J
The International Headache Society (IHS) provides guidance on the conduct of trials for acute treatment of episodic tension-type headache (TTH), a common disorder with considerable disability. Electronic and other searches identified randomised, double-blind trials of oral drugs treating episodic...
Norum, Jan; Nieder, Carsten
Prostate cancer (PC) is the most common cancer in Western countries. More than one third of PC patients develop metastatic disease, and the 5-year expected survival in distant disease is about 35%. During the last few years, new treatments have been launched for metastatic castrate-resistant prostate cancer (mCRPC). We aimed to review the current literature on health economic analysis on the treatment of metastatic prostate cancer (mPC), compare the studies, summarize the findings and make the results available to administrators and decision makers. A systematic literature search was done for economic evaluations (cost-minimization, cost-effectiveness, cost-utility, cost-of-illness, cost-of-drug, and cost-benefit analyses). We employed the PubMed ® search engine and searched for publications published between 2012 and 2016. The terms used were "prostate cancer", "metastatic" and "cost". An initial screening of all headlines was performed, selected abstracts were analysed, and finally the full papers investigated. Study characteristics, treatment and comparator, country, type of evaluation, perspective, year of value, time horizon, efficacy data, discount rate, total costs and sensitivity analysis were analysed. The quality was assessed using the Quality of Health Economic Studies (QHES) instrument. A total of 227 publications were detected and screened, 58 selected for full-text assessment and 31 included in the final analyses. Despite the significant international literature on the treatment of mCRPC, there were only 15 studies focusing on cost-effectiveness analysis (CEA). Medical treatment constituted two thirds of the selected studies. Significant costs in the treatment of mCRPC were disclosed. In the pre-docetaxel setting, both abiraterone acetate (AA) and enzalutamide were concluded beyond accepted cost/quality-adjusted life year limits. In the docetaxel refractory setting, most studies concluded that enzalutamide was cost-effective and superior to AA. In
Eisenberg, Daniel; Downs, Marilyn F; Golberstein, Ezra
Mental illness stigma refers to negative stereotypes and prejudices about people with mental illness, and is a widespread phenomenon with damaging social, psychological, and economic consequences. Despite considerable policy attention, mental illness stigma does not appear to have declined significantly in recent years. Interpersonal contact with persons with mental illness has been identified as a promising approach to reducing mental illness stigma. This study investigates the effect of contact with mental health treatment users on stigma using an observational research design that is free of self-selection bias. The research design is based on the quasi-experiment in which university students are assigned to live together as roommates. Survey data were collected from first-year undergraduates at two large universities in the United States (N = 1605). Multivariable regressions were used to estimate the effect of assignment to a roommate with a history of mental health treatment on a brief measure of stigmatizing attitudes. Contact with a treatment user caused a modest increase in stigma (standardized effect size = 0.15, p = 0.03). This effect was present among students without a prior treatment history of their own, but not among those with a prior history. The findings indicate that naturalistic contact alone does not necessarily yield a reduction in mental illness stigma. This may help explain why stigma has not declined in societies such as the United States even as treatment use has risen substantially. The findings also highlight the importance of isolating the specific components, beyond contact per se, that are necessary to reduce stigma in contact-based interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.
Goodwin, Guy M; Holmes, Emily A; Andersson, Erik; Browning, Michael; Jones, Andrew; Lass-Hennemann, Johanna; Månsson, Kristoffer Nt; Moessnang, Carolin; Salemink, Elske; Sanchez, Alvaro; van Zutphen, Linda; Visser, Renée M
This ECNP meeting was designed to build bridges between different constituencies of mental illness treatment researchers from a range of backgrounds with a specific focus on enhancing the development of novel, evidence based, psychological treatments. In particular we wished to explore the potential for basic neuroscience to support the development of more effective psychological treatments, just as this approach is starting to illuminate the actions of drugs. To fulfil this aim, a selection of clinical psychologists, psychiatrists and neuroscientists were invited to sit at the same table. The starting point of the meeting was the proposition that we know certain psychological treatments work, but we have only an approximate understanding of why they work. The first task in developing a coherent mental health science would therefore be to uncover the mechanisms (at all levels of analysis) of effective psychological treatments. Delineating these mechanisms, a task that will require input from both the clinic and the laboratory, will provide a key foundation for the rational optimisation of psychological treatments. As reviewed in this paper, the speakers at the meeting reviewed recent advances in the understanding of clinical and cognitive psychology, neuroscience, experimental psychopathology, and treatment delivery technology focussed primarily on anxiety disorders and depression. We started by asking three rhetorical questions: What has psychology done for treatment? What has technology done for psychology? What has neuroscience done for psychology? We then addressed how research in five broad research areas could inform the future development of better treatments: Attention, Conditioning, Compulsions and addiction, Emotional Memory, and Reward and emotional bias. Research in all these areas (and more) can be harnessed to neuroscience since psychological therapies are a learning process with a biological basis in the brain. Because current treatment approaches
Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: "non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver". Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.
Gabriela Lacet Silva Ferreira
Full Text Available In view of the limitations of antifungal agents used in the treatment of oral candidiasis and the wide variety of natural products that have been studied as treatment of this disease, this systematic literature review proposed to evaluate whether scientific evidence attesting to the efficacy of natural products in the treatment of this disease exists. A systematic search in PubMed, MEDLINE, SciELO, Lilacs, and Cochrane Library databases was accomplished using the associations among the keywords Candida albicans, phytotherapy, biological products, denture stomatitis, and oral candidiasis in both English and Portuguese. Four independent observers evaluated the methodological quality of the resulting articles. Three studies were included for detailed analysis and evaluated according to the analysis protocol based on the CONSORT (Consolidated Standards of Reporting Trials 2010 statement. The tested products were different in all studies. Two studies mentioned random samples, but no study described the sample allocation. No study mentioned sample calculations, a prior pilot study, or examiner calibration, and only one trial reported sample losses. Differences between the tested products and the methodological designs among these studies did not allow the existence of scientific evidence related to the effectiveness of these products for the proposed subjects to be confirmed.
DeWilde, Kaitlin E.; Levitch, Cara F.; Murrough, James W.; Mathew, Sanjay J.; Iosifescu, Dan V.
Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is a significant public health threat. Current treatments for MDD primarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant in MDD. We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with the NIMH Research Domain Criteria (RDoC) initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of other glutamatergic agents other than ketamine currently being tested as novel antidepressants. PMID:25649308
Keshen, Aaron; Helson, Thomas
Psychostimulants have been assessed in bulimia nervosa patients with comorbid attention deficit/hyperactivity disorder (ADHD), but few studies have examined the impact of psychostimulants on bulimia nervosa patients without comorbid ADHD. The aim of this study was to examine psychostimulants as a potential treatment for bulimia nervosa and to assess the concern of weight loss, given the medication's appetite-suppressing effects. This retrospective study describes 6 case reports of outpatients who were prescribed a psychostimulant specifically for their bulimia nervosa. The number of binge/purge days per months and body mass index were assessed. All patients demonstrated reductions in the number of binge/purge days per month, and 1 patient experienced total remission of bulimic symptoms. Minor fluctuations in weight were observed, but no clinically significant reductions in weight were noted. These findings support the need for clinical trials to examine the efficacy and safety of this potential treatment. © 2017, The American College of Clinical Pharmacology.
Full Text Available Thymoquinone (TQ, the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of TQ as observed in various in vitro and in vivo animal models and discussed the pharmacological properties of TQ to rationalize its supplementary role in potentiating the efficacy of standard therapeutic modalities namely surgery, radiotherapy, chemotherapy, and immunotherapy. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical levels to delineate its implied utility as a novel complementary adjuvant therapy for cancer treatment.
Lang, Russell; Mahoney, Richard; El Zein, Farah; Delaune, Elizabeth; Amidon, Megan
What treatment improves social interactions and reduces reports of anxiety symptoms in individuals with autism spectrum disorders (ASD) and a co-occurring anxiety disorder? Systematic reviews and randomized clinical trials suggest that cognitive behavior therapy in tandem with direct instruction of social skills using applied behavior analysis intervention components may be effective for treating anxiety in individuals with high functioning ASD. For individuals with ASD, an anxiety disorder, and an intellectual disability, systematic desensitization may be effective. Intervention should emphasize teaching social skills. Reinforcers (ie, rewards based upon the client's interests) should be used to encourage participation in therapy. Treatment should incorporate visual aides and family involvement. Intervention components involving abstract concepts, visualization, and discussions of emotions are less useful given difficulties in abstract reasoning and communication inherent to ASD.
Tappeiner, Christoph; Mesquida, Marina; Adán, Alfredo; Anton, Jordi; Ramanan, Athimalaipet V; Carreno, Ester; Mackensen, Friederike; Kotaniemi, Kaisu; de Boer, Joke H; Bou, Rosa; de Vicuña, Carmen García; Heiligenhaus, Arnd
To report on experience using the anti-interleukin 6 receptor antibody tocilizumab (TCZ) to treat severe and therapy-refractory uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective data were gathered from patients with JIA receiving TCZ treatment for uveitis. JIA and related uveitis data (disease onset, activity, structural complications, and topical and systemic antiinflammatory treatment) were evaluated at the start of TCZ (baseline) and every 3 months during TCZ therapy. A total of 17 patients (14 women) with active uveitis were included (mean age 15.3 ± 6.9 yrs, mean followup time 8.5 mos). In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, methotrexate (MTX), and other synthetic and biological disease-modifying antirheumatic drugs, including ≥ 1 tumor necrosis factor-α (TNF-α) inhibitor. Uveitis inactivity was achieved in 10 patients after a mean of 5.7 months of TCZ treatment (in 3 of them, it recurred during followup) and persisted in the remaining 7 patients. By using TCZ, systemic corticosteroids or immunosuppressives could be spared in 7 patients. Macular edema was present in 5 patients at baseline and improved in all of them under TCZ treatment. Arthritis was active in 11 patients at the initial and in 6 at the final followup visit. TCZ appears to represent a therapeutic option for severe JIA-associated uveitis that has been refractory to MTX and TNF-α inhibitors in selected patients. The present data indicate that inflammatory macular edema responds well to TCZ in patients with JIA-associated uveitis.
Sundar, Shyam; Olliaro, Piero L
Visceral leishmaniasis (VL) is a life-threatening disease. Traditional treatment with pentavalent antimony injections has become ineffective in the area with the world?s highest prevalence of disease (North Bihar, India) and is becoming less effective elsewhere as well. A replacement is needed, best if it can be given to more patients outside the hospital. Miltefosine is the first oral drug registered for VL. Given daily under medical supervision for 4 weeks, it cures 94% of patients (both ch...
Russell Lang; Richard Mahoney; Farah El Zein; et al
Russell Lang, Richard Mahoney, Farah El Zein, Elizabeth Delaune, Megan AmidonTexas State University-San Marcos, TX, USADate of preparation: 23rd December 2010 Conflict of interest: None declaredClinical question: What treatment improves social interactions and reduces reports of anxiety symptoms in individuals with autism spectrum disorders (ASD) and a co-occurring anxiety disorder? Results: Systematic reviews and randomized clinical trials suggest that cognitive behavior therapy in tandem wi...
Full Text Available To review the potential role of stem cells in treating degenerative disc disease of the intervertebral disc (IVD. A review was performed of articles from the Medline database concerning stem cells and degenerative disc disease (DDD. To discuss the data, the papers were classified as: review, in vitro, experimental, and clinical. The currently available treatments were basically for symptom reduction, not to revert the IVD degenerative process. The use of mesenchymal stem cells (MSC is being proposed as an option of treatment for DDD. In vitro studies have shown that the MSC are able to differentiate into NP cells and that the MSC also reduce the inflammatory levels of the degenerated IVD. Besides, experimental studies demonstrated that the MSC remained viable when injected into the IVD, and that they were able to regenerate partially from the degenerated IVD and its structure. The few clinical studies found in the literature presented diverging results. The use of MSC is being widely studied and shows promising results for the treatment of DDD. Although many advances are being achieved in studies in vitro and experimental, there is a lack of clinical studies to prove the role of MSC in DDD management.
Lehners, Nicola; Hayden, Patrick J; Goldschmidt, Hartmut; Raab, Marc-Steffen
Despite the progress made in the treatment of patients with multiple myeloma over recent decades, a significant cohort with high-risk disease as defined by specific clinical and genetic criteria continue to respond poorly to standard treatment. These patients represent a particular challenge to the treating physician and require early identification as well as personalized treatment strategies. In this review, we discuss the prognostic impact of adverse clinical, radiological and genetic factors, evaluate available scoring systems and highlight key aspects of the therapeutic management of high-risk myeloma. MEDLINE and recent scientific meetings' databases were searched for the keywords 'high-risk' and 'multiple myeloma' and relevant studies relating to both diagnostic and therapeutic approaches were identified. Expert commentary: A case is made for intensive induction using combinations of novel agents, early high-dose therapy supported by autologous stem cell transplantation and the widespread use of maintenance therapies. Novel therapeutic options, especially in the field of immunotherapy, are currently explored in clinical trials and have the potential to further improve outcomes for patients with high-risk multiple myeloma.
Patti, Marco G
Gastroesophageal reflux disease (GERD) is prevalent worldwide, particularly in developed countries. It is estimated that the prevalence of GERD in the United States is approximately 20% and that it is increasing because of the epidemic of obesity. To review the pathophysiology, clinical presentation, diagnostic evaluation, and treatment of GERD. A search of PubMed was conducted for the years spanning 1985 to 2015 and included the following terms: heartburn, regurgitation, dysphagia, gastroesophageal reflux disease, cough, aspiration, laryngitis, GERD, GORD, endoscopy, manometry, pH monitoring, proton pump inhibitors, open fundoplication, and laparoscopic fundoplication. Only articles in English were included. Lifestyle modifications, proton pump inhibitors, and laparoscopic fundoplication are proven treatment modalities for GERD. Endoscopic procedures have not been proven as effective. A Roux-en-Y gastric bypass is the procedure of choice when GERD and morbid obesity coexist. Gastroesophageal reflux disease is a highly prevalent disease. Once the diagnosis has been established, the best results are obtained by a multidisciplinary team with the goal of individualizing treatment for patients.
Nalliah, Chrishan J; Sanders, Prashanthan; Kalman, Jonathan M
Prevalence rates of atrial fibrillation (AF) and obstructive sleep apnea (OSA) are rising on a global scale. Epidemiological data have consistently demonstrated an independent association between the 2 conditions. Investigators pose that pathophysiologic features of OSA enable progression of the AF substrate; these features include abnormalities of gas exchange, autonomic remodeling, atrial stretch, and inflammation. Furthermore, many of the mechanistic perturbations that impact the AF substrate in OSA can be substantially attenuated by effective treatment with continuous positive airway pressure (CPAP). Clear associations of OSA treatment and improved AF control have been observed across multiple clinical contexts. However, the precision and generalizability of these findings are unclear in view of the data's observational nature. Although risk factor management has emerged as a critical component of AF treatment, effective control of many AF risk factors can be challenging in the longer term. In view of the efficacy and sustainability of CPAP therapy, OSA raises its profile as a prime candidate for intervention. However, translation of this strategy to the broader framework for AF management requires robust data from randomized controlled trials. © 2016 Wiley Periodicals, Inc.
Park, Alayna L; Tsai, Katherine H; Guan, Karen; Chorpita, Bruce F
This study examined patterns of evidence-based treatment (EBT) delivery following a county-wide EBT reform initiative. Data were gathered from 60 youth and their 21 providers, who were instructed to deliver therapy as they normally would under the EBT initiative. Results showed limited applicability of county-supported EBTs to this service sample, and that most youth did not receive traditional delivery of EBTs. Findings suggest that it may be unrealistic to expect providers to deliver EBTs with fidelity with all clients, and that EBT implementation may be best thought of as a strategy for improving mental health services rather than a goal.
Schlottmann, Francisco; Patti, Marco G
Esophageal achalasia is a rare disorder characterized by a failure of the lower esophageal sphincter to relax during swallowing, combined with aperistalsis of the esophageal body. Treatment is not curative, but aims to eliminate the outflow resistance caused by the nonrelaxing lower esophageal sphincter. Current evidence suggests that both laparoscopic Heller myotomy and per oral endoscopic myotomy (POEM) are very effective in the relief of symptoms in patients with achalasia. Specifically, for type III achalasia, POEM may achieve higher success rates. However, POEM is associated to a very high incidence of pathologic reflux, with the risk of exchanging one disease-achalasia-with another-gastroesophageal reflux.
Mishkind, Matthew C; Norr, Aaron M; Katz, Andrea C; Reger, Greg M
This review provides an overview of the current evidence base for and clinical applications of the use of virtual reality (VR) in psychiatric practice, in context of recent technological developments. The use of VR in psychiatric practice shows promise with much of the research demonstrating clinical effectiveness for conditions including post-traumatic stress disorder, anxiety and phobias, chronic pain, rehabilitation, and addictions. However, more research is needed before the use of VR is considered a clinical standard of practice in some areas. The recent release of first generation consumer VR products signals a change in the viability of further developing VR systems and applications. As applications increase so will the need for good quality research to best understand what makes VR effective, and when VR is not appropriate for clinical services. As the field progresses, it is hopeful that the flexibility afforded by this technology will yield superior outcomes and a better understanding of the underlying mechanisms impacting those outcomes.
Amaladoss, Alfred; Roberts, Nasreen; Amaladoss, Franklin
Mood stabilizers and anticonvulsants have been frequently used to control behaviors in children and adolescent with nonaffective disorders. The purpose of this study was to review the literature to evaluate the evidence of these agents as treatment options in this subset of patients. We reviewed all the literature between 1949 and 2009 on the use of anticonvulsants and mood stabilizers in controlling severe behavior dysregulation and aggression in child and adolescent who do not meet the criteria for any mood disorder. The review revealed a total of 19 studies. Of the different mood stabilizers/anticonvulsants, both lithium and divalproex showed some promise in treating children and adolescents with nonmood disorders. Larger studies are nevertheless needed to support the ongoing use of these current anticonvulsants and mood stabilizers in children and adolescents with nonmood disorders. Also, further investigation to the potential use in the long term would need to be established, bearing in mind the balance of side effects and treatment benefit.
Full Text Available Jay H Shubrook,1 Babak Baradar Bokaie,2 Sarah E Adkins31Primary Care Department, Clinical Research and Diabetes Services, Touro University College of Osteopathic Medicine, Vallejo, CA, USA; 2The Diabetes Institute at Ohio University, Ohio University, Athens, OH, USA; 3Pharmacy Practice and Administration, College of Pharmacy, Ohio State University, Athens, OH, USA Abstract: In the last decade, researchers have gained a greater understanding of the pathophysiologic mechanisms of type 2 diabetes as a chronic and progressive disease. One of the more recent treatment targets is the kidney. The kidneys become maladaptive in diabetes by increasing the reabsorption of glucose above the normal physiologic renal threshold. This discovery has led to the development of the sodium/glucose cotransporter 2 inhibitors (SGLT2. These agents readjust the renal threshold for glucose reabsorption to a lower level and decrease glucose reabsorption, while increasing urinary glucose when the glucose is above the renal threshold and subsequently lowering plasma glucose. The mechanism of action of the SGLT2 inhibitors is insulin independent, which makes them a novel treatment of diabetes. At the time of preparation of this manuscript, there were three SGLT2 inhibitors available in the US. This manuscript focuses on empagliflozin, the newest SGLT2 inhibitor, the trials in its development, and the clinical data available to date. Further, the authors propose future applications of empagliflozin, including in the treatment of type 1 diabetes, and its potential role in renoprotection. Keywords: SGLT-2 inhibitors, empagliflozin, type 2 diabetes, kidneys, type 1 diabetes, glucosuria
Miller, Rhondene M; Kaiser, Ronald S
The complicated nature of chronic pain involves an interplay between psychological and physical factors, often resulting in increased emotional distress and reduced quality of life. This review is designed to help the medical practitioner who is working with chronic pain patients to be aware of psychological assessment techniques that can add to comprehensive patient understanding and more effectively guide treatment. Enhanced ability to assess and understand the emotional life of the chronic pain patient provides a basis for intervening and treating more successfully. There are a broad range of assessment techniques, some of which require a background in psychology and some that do not, that can identify psychological differences in chronic pain patients and serve to guide intervention strategies. Chronic pain is often comorbid with depression, anxiety, catastrophizing, and various ineffective coping strategies. Some patients, however, have demonstrated more adaptive and effective strategies for cognitively and behaviorally coping with pain and normalizing their lives. Proper assessment enables the individualization of treatment to overcome and/or build upon each patient's psychological frame of mind to maximize the potential for effective functioning. The use of standardized and documented psychological assessment techniques can lead to a better understanding of chronic pain patients and contribute in ways that can enhance response to medical treatment and improve quality of life. It is recommended that certain psychological tools be included to supplement the medical assessment of patients who have chronic pain. A basic assessment can include a short psychological-based clinical interview along with brief measures of depression, anxiety, and coping strategies. It is also recommended that the pain physician have access to professional psychological practitioners as a resource for more complicated assessments and psychological intervention services.
Gentile, Christopher L.; Nivala, Angela M.; Gonzales, Jon C.; Pfaffenbach, Kyle T.; Wang, Dong; Wei, Yuren; Jiang, Hua; Orlicky, David J.; Petersen, Dennis R.; Maclean, Kenneth N.
The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD. PMID:21957160
Johri, A M; Heyland, D K; Hétu, M-F; Crawford, B; Spence, J D
As the incidence of metabolic syndrome increases, there is also a growing interest in finding safe and inexpensive treatments to help lower associated risk factors. L-carntine, a natural dietary supplement with the potential to ameliorate atherosclerosis, has been the subject of recent investigation and controversy. A majority of studies have shown benefit of L-C supplementation in the metabolic syndrome or cardiovascular risk factors. However, recent work has suggested that dietary L-C may accelerate atherosclerosis via gut microbiota metabolites, complicating the role of L-C supplementation in health. Copyright © 2014 Elsevier B.V. All rights reserved.
Olga Borisovna Yershova
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.
Smith, Gigi; Wagner, Janelle L; Edwards, Jonathan C
As new research has increased our understanding of epilepsy and the challenges patients with epilepsy face, the role of the nurse as an educator and advocate has grown. This article, the second in a two-part series, addresses the most important aspects of assessing and caring for patients with epilepsy-highlighting the seizure first-aid instructions that all family members of a patient with epilepsy should have; the teaching points to share with parents of young children with epilepsy; and online epilepsy resources for patients, family members, and health care professionals. The authors also discuss current medical, surgical, neurostimulatory, and dietary approaches to epilepsy treatment.
Thomas, M; Jordan, M; Hamborg-Petersen, E
Ankle sprains are the most relevant injuries of the lower extremities and can lead to damage to ligaments and osteochondral lesions. Up to 50 % of patients with a sprained ankle later develop a lesion of the cartilage in the ankle joint or an osteochondral lesion of the talus. This can lead to osteoarthritis of the injured ankle joint. Spontaneous healing is possible in all age groups in cases of a bone bruise in the subchondral bone but in isolated chondral injuries is only useful in pediatric patients. In many cases chondral and osteochondral injuries lead to increasing demarcation of the affected area and can result in progressive degeneration of the joint if not recognized in time. There also exist a certain number of osteochondral changes of the articular surface of the talus without any history of relevant trauma, which are collectively grouped under the term osteochondrosis dissecans. Perfusion disorders are discussed as one of many possible causes of these alterations. Nowadays, chondral and osteochondral defects can be treated earlier due to detection using very sensitive magnetic resonance imaging (MRI) and computed tomography (CT) techniques. The use of conservative treatment only has a chance of healing in pediatric patients. Conservative measures for adults should only be considered as adjuvant treatment to surgery.Based on a comprehensive analysis of the current literature, this article gives an overview and critical analysis of the current concepts for treatment of chondral and osteochondral injuries and lesions of the talus. With arthroscopic therapy curettage and microfracture of talar lesions are the predominant approaches or retrograde drilling of the defect is another option when the chondral coating is retained. Implantation of autologous chondral cells or homologous juvenile cartilage tissue is also possible with arthroscopic techniques. Osteochondral fractures (flake fracture) are usually performed as a mini-open procedure supported by
Syed Sulaiman Syed Azhar
Full Text Available Abstract Background There is substantial evidence to support the association between tuberculosis (TB and tobacco smoking and that the smoking-related immunological abnormalities in TB are reversible within six weeks of cessation. Therefore, connecting TB and tobacco cessation interventions may produce significant benefits and positively impact TB treatment outcomes. However, no study has extensively documented the evidence of benefits of such integration. SCIDOTS Project is a study from the context of a developing nation aimed to determine this. Methods An integrated TB-tobacco intervention was provided by trained TB directly observed therapy short-course (DOTS providers at five chest clinics in Malaysia. The study was a prospective non-randomized controlled intervention using quasi-experimental design. Using Transtheoretical Model approach, 120 eligible participants who were current smokers at the time of TB diagnosis were assigned to either of two treatment groups: conventional TB DOTS plus smoking cessation intervention (integrated intervention or SCIDOTS group or conventional TB DOTS alone (comparison or DOTS group. At baseline, newly diagnosed TB patients considering quitting smoking within the next 30 days were placed in the integrated intervention group, while those who were contemplating quitting were assigned to the comparison group. Eleven sessions of individualized cognitive behavioral therapy with or without nicotine replacement therapy were provided to each participant in the integrated intervention group. The impacts of the novel approach on biochemically validated smoking cessation and TB treatment outcomes were measured periodically as appropriate. Results A linear effect on both 7-day point prevalence abstinence and continuous abstinence was observed over time in the intervention group. At the end of 6 months, patients who received the integrated intervention had significantly higher rate of success in quitting smoking when
van den Bekerom, Michel P J; Struijs, Peter A A; Blankevoort, Leendert; Welling, Lieke; van Dijk, C Niek; Kerkhoffs, Gino M M J
Ankle sprains are common problems in acute medical care. The variation in treatment observed for the acutely injured lateral ankle ligament complex in the first week after the injury suggests a lack of evidence-based management strategies for this problem. To analyze the effectiveness of applying rest, ice, compression, and elevation (RICE) therapy begun within 72 hours after trauma for patients in the initial period after ankle sprain. Eligible studies were published original randomized or quasi-randomized controlled trials concerning at least 1 of the 4 subtreatments of RICE therapy in the treatment of acute ankle sprains in adults. MEDLINE, Cochrane Clinical Trial Register, CINAHL, and EMBASE. The lists of references of retrieved publications also were checked manually. We extracted relevant data on treatment outcome (pain, swelling, ankle mobility or range of motion, return to sports, return to work, complications, and patient satisfaction) and assessed the quality of included studies. If feasible, the results of comparable studies were pooled using fixed- or random-effects models. After deduction of the overlaps among the different databases, evaluation of the abstracts, and contact with some authors, 24 potentially eligible trials remained. The full texts of these articles were retrieved and thoroughly assessed as described. This resulted in the inclusion of 11 trials involving 868 patients. The main reason for exclusion was that the authors did not describe a well-defined control group without the intervention of interest. Insufficient evidence is available from randomized controlled trials to determine the relative effectiveness of RICE therapy for acute ankle sprains in adults. Treatment decisions must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines.
Full Text Available Russell Lang, Richard Mahoney, Farah El Zein, Elizabeth Delaune, Megan AmidonTexas State University-San Marcos, TX, USADate of preparation: 23rd December 2010 Conflict of interest: None declaredClinical question: What treatment improves social interactions and reduces reports of anxiety symptoms in individuals with autism spectrum disorders (ASD and a co-occurring anxiety disorder? Results: Systematic reviews and randomized clinical trials suggest that cognitive behavior therapy in tandem with direct instruction of social skills using applied behavior analysis intervention components may be effective for treating anxiety in individuals with high functioning ASD. For individuals with ASD, an anxiety disorder, and an intellectual disability, systematic desensitization may be effective.Implementation: Intervention should emphasize teaching social skills. Reinforcers (ie, rewards based upon the client's interests should be used to encourage participation in therapy. Treatment should incorporate visual aides and family involvement. Intervention components involving abstract concepts, visualization, and discussions of emotions are less useful given difficulties in abstract reasoning and communication inherent to ASD.Keywords: autism, ASD, Asperger's, anxiety, cognitive behavior therapy, applied behavior analysis
Full Text Available Rujuta Saksena, Serena T WongThe Cancer Institute of New Jersey, New Brunswick, NJ, USAAbstract: The PI3K/Akt/mTOR (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway regulates several key cellular functions and its dysregulation creates an environment that promotes tumorigenesis as well as resistance to therapy. The mTOR inhibitor everolimus has emerged as a promising agent in the treatment of breast cancer and was recently approved in combination with exemestane for advanced hormone receptor–positive disease after progression on a nonsteroidal aromatase inhibitor. Everolimus may also be effective in combination with cytotoxic and human epidermal growth factor receptor-2-directed therapies for the treatment of other subtypes of breast cancer. This paper highlights preclinical and clinical data that have emerged on the role of mTOR inhibition in breast cancer. Although generally well tolerated, everolimus carries a unique side effect profile of which both patients and providers should be made aware. Recommendations related to the administration of everolimus in the clinical setting are also discussed.Keywords: everolimus, breast cancer, mTOR inhibition
Shlofmitz, Evan; Martinsen, Brad J; Lee, Michael; Rao, Sunil V; Généreux, Philippe; Higgins, Joe; Chambers, Jeffrey W; Kirtane, Ajay J; Brilakis, Emmanouil S; Kandzari, David E; Sharma, Samin K; Shlofmitz, Richard
The presence of severe coronary artery calcification is associated with higher rates of angiographic complications during percutaneous coronary intervention (PCI), as well as higher major adverse cardiac events compared with non-calcified lesions. Incorporating orbital atherectomy (OAS) for effective preparation of severely calcified lesions can help maximize the benefits of PCI by attaining maximal luminal gain (or stent expansion) and improve long-term outcomes (by reducing need for revascularization). Areas covered: In this manuscript, the prevalence, risk factors, and impact of coronary artery calcification on PCI are reviewed. Based on current data and experience, the authors review orbital atherectomy technique and best practices to optimize lesion preparation. Expert Commentary: The coronary OAS is the only device approved for use in the U.S. as a treatment for de novo, severely calcified coronary lesions to facilitate stent delivery. Advantages of the device include its ease of use and a mechanism of action that treats bi-directionally, allowing for continuous blood flow during treatment, minimizing heat damage, slow flow, and subsequent need for revascularization. The OAS technique tips reviewed in this article will help inform interventional cardiologists treating patients with severely calcified lesions.
Full Text Available Motor vehicle accident (MVA victims may suffer both acute and post-traumatic stress disorders (PTSD. With PTSD affecting social, interpersonal and occupational functioning, clinicians as well as the National Institute of Health are very interested in identifying the most effective psychological treatment to reduce PTSD. From research findings, eye movement desensitization and reprocessing (EMDR therapy is considered as one of the effective treatment of PTSD. In this paper, we present the results of a meta-analysis of fMRI studies on PTSD after MVA through activation likelihood estimation. We found that PTSD following MVA is characterized by neural modifications in the anterior cingulate cortex (ACC, a cerebral structure involved in fear-conditioning mechanisms. Basing on previous findings in both humans and animals, which demonstrate that desensitization techniques and extinction protocols act on the limbic system, the effectiveness of EMDR and of cognitive behavioral therapies (CBT may be related to the fact that during these therapies the ACC is stimulated by desensitization.
Boccia, Maddalena; Piccardi, Laura; Cordellieri, Pierluigi; Guariglia, Cecilia; Giannini, Anna Maria
Motor vehicle accident (MVA) victims may suffer both acute and post-traumatic stress disorders (PTSD). With PTSD affecting social, interpersonal and occupational functioning, clinicians as well as the National Institute of Health are very interested in identifying the most effective psychological treatment to reduce PTSD. From research findings, eye movement desensitization and reprocessing (EMDR) therapy is considered as one of the effective treatment of PTSD. In this paper, we present the results of a meta-analysis of fMRI studies on PTSD after MVA through activation likelihood estimation. We found that PTSD following MVA is characterized by neural modifications in the anterior cingulate cortex (ACC), a cerebral structure involved in fear-conditioning mechanisms. Basing on previous findings in both humans and animals, which demonstrate that desensitization techniques and extinction protocols act on the limbic system, the effectiveness of EMDR and of cognitive behavioral therapies (CBT) may be related to the fact that during these therapies the ACC is stimulated by desensitization. PMID:25954183
Jesus, Cátia; Jesus, Inês; Agius, Mark
Psychiatric patients requiring therapy with antipsychotics have a greater incidence of becoming overweight or obese compared with the general population. Many of these patients are often treated with second-generation (atypical) antipsychotics (SGAs), which are associated with weight gain, dyslipidaemia, and other metabolic derangements. The most important and first line of treatment for the metabolic syndrome is lifestyle changes including diet and exercise. However, other approaches like the use of medication (e.g. Metformin) have been also used, mainly when the lifestyle changes are difficult to achieve. Therefore, the treatment of antipsychotic-induced weight gain with metformin may be an option after the lifestyle and dietary changes fail. The use of metformin is still experimental and off license regarding the treatment of metabolic syndrome in Psychiatric patients, however we wished to assess the evidence for its use. Our study is a literature based research. For our research we reviewed 12 Pubmed published articles from 2006 to 2013. Metformin have been reported to counteract effectively antipsychotic-induced body weight gain and has been demonstrated to improve glycaemic control and promote a moderate weight loss in both diabetic and non-diabetic subjects. Metformin use appears to be a benefit when started early in the course of treatment and mostly in young adults newly exposed to antipsychotic drugs.
Fox, Nigel A
Searches were made using the Cochrane Central Register of Controlled Trials, Medline, Embase, Latin American and Caribbean Health Sciences Literature, Bibliografia Brasileira de Odontologia and SciELO (the Scientific Electronic Library Online). Studies chosen were randomised controlled trials (RCT) or quasi-RCT comparing all types of oral and functional orthopaedic appliances with placebo or no treatment, in children of 15 years old or younger. Data were independently extracted by two review authors. Authors were contacted for additional information. Risk ratios with 95% confidence intervals were calculated for all important dichotomous outcomes. A total of 384 trials were identified, of which only one, reporting results from a total of 23 patients, was suitable for inclusion in the review. Data provided in the published report did not answer all the questions from this review, but did answer some: the results presented favour treatment. At present there is not sufficient evidence to state that oral appliances or functional orthopaedic appliances are effective in the treatment of obstructive sleep apnoea (OSA) syndrome in children. Oral appliances or functional orthopaedic appliances may be helpful in the treatment of children with craniofacial anomalies which are risk factors for apnoea.
Full Text Available Head and neck squamous cell carcinoma (HNSCC accounts for a large oncologic burden in the developing countries. In patients with locally advanced head and neck cancer multimodality treatment is warranted. Radiation therapy with concurrent chemotherapy has long been considered the standard for patients with disease involving the oropharynx, larynx and hypopharynx. However, addition of chemotherapy to radiotherapy increases treatment related toxicity by many folds and compliance rates decrease. In this context a systemic therapy, which when used concurrent with radiation with favorable toxicity profile is of great importance for improving disease control in locally advanced HNSCC. Anti-epithelial growth factor receptor targeted therapy emerged as a potential treatment option. In recent years many trials were conducted to find the optimum treatment option with the combination of these targeted agents. The initial trials showed excellent results with minimal morbidity and led to great enthusiasm across the globe to incorporate these regimens as a standard of care. However, subsequently many trials failed to maintain such results and now there is little agreement to the initial results achieved with these drugs. Based on the current evidence we cannot recommend the replacement of cisplatin with targeted therapy in concurrent setting. It may be considered in patients with altered renal parameters, hypersensitivity or intolerance to cisplatin. The addition of targeted therapy in addition to chemotherapy in the concurrent setting can’t also be recommended as the benefit is doubtful and is associated with a significant increase in toxicity.
V. V. Malinovskaya
Full Text Available The paper presents a comparative analysis of the results of clinical laboratory trials carried out on the basis of 10 different medical and preventive treatment facilities drawing on the principles and methodology of evidence-based medicine, which confirmed the certainty of clinical effectiveness of Viferon® medications in the treatment of acute respiratory viral infections (ARVI and influenza in adults. The algorithm included an assessment of antiviral, immunomodulatory, anti-inflammatory, anti-oxidant actions of the medication under the conditions of concurrent, unmasked, randomized, placebo-controlled, clinical immunological studies and a retrospective analysis in keeping with the “Guidelines for Good Clinical Practice”. Thereby, it was shown that the use of Viferon® medications (suppositories, gel in the treatment of adults with influenza and ARVI, whether with viral or viral-bacterial etiology, contributes to a statistically significant reduction in duration of principal clinical symptoms and the disease as a whole, as well as a decrease of immune and interferon system imbalance and a faster elimination of viral antigens. On the basis of the proven antiviral therapeutic effectiveness and immunomodulatory action, safety and high tolerability, easy-to-administer form in the outpatient settings, Viferon® has been recommended as a disease-modifying agent in the treatment of influenza and ARVI in adults.
Full Text Available The terms ‘mucositis’ and ‘stomatitis’ are often used interchangeably. Mucositis, however, pertains to pharyngeal-esophago-gastrointestinal inflammation that manifests as red, burn-like sores or ulcerations throughout the mouth. Stomatitis is an inflammation of the oral tissues proper, which can present with or without sores, and is made worse by poor dental hygiene. Mucositis is observed in a variety of immunosuppressed patients, but is most often consequential to cancer therapy. It appears as early as the third day of intervention, and is usually established by Day 7 of treatment. Mucositis increases mortality and morbidity and contributes to rising health care costs. The precise immune components involved in the etiology of mucositis are unclear, but evidence-based research (EBR data has shown that applications of granulocyte–macrophage-colony stimulating factor prevent the onset or the exacerbation of oropharyngeal mucositis. The molecular implications of this observation are discussed from the perspective of future developments of complementary and alternative treatments for this condition. It must be emphasized that this article is meant to be neither a review on mucositis and the various treatments for it, nor a discussion paper on its underlying molecular immunology. It is a statement of the implications of EBR for CAM-based interventions for mucositis. It explores and discusses the specific domain of molecular immunology in the context of mucositis and its direct implications for EBR research in CAM-based treatments for mucositis.
Full Text Available Alberto Gajofatto Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy Abstract: Siponimod (BAF312 is a synthetic molecule belonging to the sphingosine-1-phosphate (S1P modulator family, which has putative neuroprotective properties and well-characterized immunomodulating effects mediated by sequestration of B and T cells in secondary lymphoid organs. Compared to fingolimod (ie, precursor of the S1P modulators commercially available for the treatment of relapsing–remitting [RR] multiple sclerosis [MS], siponimod exhibits selective affinity for types 1 and 5 S1P receptor, leading to a lower risk of adverse events that are mainly induced by S1P3 receptor activation, such as bradycardia and vasoconstriction. In addition, S1P1 and S1P5 receptors are expressed by neurons and glia and could mediate a possible neuroprotective effect of the drug. A Phase II clinical trial of siponimod for RR MS showed a significant effect of the active drug compared to placebo on reducing gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI after 3 months of treatment. In a recently completed Phase III trial, treatment with siponimod was associated with a significant reduction in disability progression in secondary progressive (SP MS patients compared to placebo. In this article, current evidence supporting siponimod efficacy for SP MS is reviewed. Keywords: multiple sclerosis, siponimod, progression, disability, treatment
Dorsey, Shannon; Pullmann, Michael D; Berliner, Lucy; Koschmann, Elizabeth; McKay, Mary; Deblinger, Esther
The goal of this study was to examine the impact of supplementing Trauma-focused Cognitive Behavioral Therapy (TF-CBT; Cohen et al., 2006) with evidence-based engagement strategies on foster parent and foster youth engagement in treatment, given challenges engaging foster parents in treatment. A randomized controlled trial of TF-CBT standard delivery compared to TF-CBT plus evidence-based engagement strategies was conducted with 47 children and adolescents in foster care and one of their foster parents. Attendance, engagement, and clinical outcomes were assessed 1 month into treatment, end of treatment, and 3 months post-treatment. Youth and foster parents who received TF-CBT plus evidence-based engagement strategies were more likely to be retained in treatment through four sessions and were less likely to drop out of treatment prematurely. The engagement strategies did not appear to have an effect on the number of canceled or no-show sessions or on treatment satisfaction. Clinical outcomes did not differ by study condition, but exploratory analyses suggest that youth had significant improvements with treatment. Strategies that specifically target engagement may hold promise for increasing access to evidence-based treatments and for increasing likelihood of treatment completion. Copyright © 2014 Elsevier Ltd. All rights reserved.
Smyth, Bobby P; Lyons, Suzi; Cullen, Walter
New psychoactive substances (NPS) have hedonic effects that may lead to dependence. Headshops selling NPS increased in number in Ireland from late 2009. Legislation was enacted in May and August of 2010 that caused their closure. It is unknown whether such events impact the rate of NPS use disorders. We conducted a population-based study using the Irish national database of episodes of addiction treatment between 2009 and 2012. We examined trends in the rate of NPS-related treatment episodes among young adults. Joinpoint trend analysis software was used to identify significant changes in trend. Of the 31 284 episodes of addiction treatment commenced by adults aged 18 to 34 years, 756 (2.4%) were NPS related. In 2012, the 12-month moving average rate had fallen 48% from its peak in 2010, from 9.0/100 000 to 4.7/100 000. Joinpoint analysis indicated that the rate of NPS related episodes increased by 218% (95% confidence interval 86 to 445, P = 0.001) every 4 months until the first third of 2010. From that point, the rate declined by 9.8% (95% confidence interval -14.1 to -5.4, P = 0.001) per 4-month period. There was no significant trend change in the rate of non-NPS related treatment episodes. Over the 2 years after the enactment of prohibition-styled legislation targeting NPS and headshops, the rate of NPS related addiction treatment episodes among young adults declined progressively and substantially. We found no coinciding trend change in the rate of episodes linked to other drug groups. [Smyth BP, Lyons S, Cullen W. Decline in new psychoactive substance use disorders following legislation targeting headshops: Evidence fromnational addiction treatment data. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.
The Medline, Cochrane CENTRAL, Biomed Central, Database of Open Access Journals (DOAJ), OpenJ-Gate, Bibliografia Brasileira de Odontologia (BBO), LILACS, IndMed, Sabinet, Scielo, Scirus (Medicine), OpenSIGLE and Google Scholar databases were searched. Hand searching was performed for journals not indexed in the databases. References of included trials were checked. Prospective clinical trials with test and control groups with a follow up of at least one year were included. Data abstraction was conducted independently and clinical and methodologically homogeneous data were pooled using a fixed-effects model. Eighteen trials were included. From these 32 individual dichotomous datasets were extracted and analysed. The majority of the results show no differences between both types of intervention. A high risk of selection-, performance-, detection- and attrition bias was identified. Existing research gaps are mainly due to lack of trials and small sample size. The current evidence indicates that the failure rate of high-viscosity GIC/ART restorations is not higher than, but similar to that of conventional amalgam fillings after periods longer than one year. These results are in line with the conclusions drawn during the original systematic review. There is a high risk that these results are affected by bias, and thus confirmation by further trials with suitably high numbers of participants is needed.