BACKGROUND: Growing political attention to antimicrobial resistance (AMR) offers a rare opportunity for achieving meaningful action. Many governments have developed national AMR action plans, but most have not yet implemented policy interventions to reduce antimicrobial overuse. A systematic evidenc...e map can support governments in making evidence-informed decisions about implementing programs to reduce AMR, by identifying, describing, and assessing the full range of evaluated government policy options to reduce antimicrobial use in humans.
METHODS AND FINDINGS: Seven databases were searched from inception to January 28, 2019, (MEDLINE, CINAHL, EMBASE, PAIS Index, Cochrane Central Register of Controlled Trials, Web of Science, and PubMed). We identified studies that (1) clearly described a government policy intervention aimed at reducing human antimicrobial use, and (2) applied a quantitative design to measure the impact. We found 69 unique evaluations of government policy interventions carried out across 4 of the 6 WHO regions. These evaluations included randomized controlled trials (n = 4), non-randomized controlled trials (n = 3), controlled before-and-after designs (n = 7), interrupted time series designs (n = 25), uncontrolled before-and-after designs (n = 18), descriptive designs (n = 10), and cohort designs (n = 2). From these we identified 17 unique policy options for governments to reduce the human use of antimicrobials. Many studies evaluated public awareness campaigns (n = 17) and antimicrobial guidelines (n = 13); however, others offered different policy options such as professional regulation, restricted reimbursement, pay for performance, and prescription requirements. Identifying these policies can inform the development of future policies and evaluations in different contexts and health systems. Limitations of our study include the possible omission of unpublished initiatives, and that policies not evaluated with respect to antimicrobial use have not been captured in this review.
CONCLUSIONS: To our knowledge this is the first study to provide policy makers with synthesized evidence on specific government policy interventions addressing AMR. In the future, governments should ensure that AMR policy interventions are evaluated using rigorous study designs and that study results are published.
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Human African trypanosomiasis (HAT), or sleeping sickness, is a painful and protracted disease transmitted through the bite of infected tsetse flies and it is found in rural parts of sub-Saharan Africa. Sleeping sickness has two clinical phases but this review focuses only on treatment of the second...-stage, which is characterized by neurological changes and almost invariably fatal without treatment. There are only a few drugs currently available for second-stage sleeping sickness, all with considerable adverse events and variable efficacy.
The review includes nine trials with 2577 participants. Each trial reported different comparisons of the drugs currently available to treat second stage HAT (melarsoprol, eflornithine, nifurtimox) so no meta-analysis was possible.
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Chromoblastomycosis (CMB) is a chronic fungal infection of the skin and the subcutaneous tissue caused by a transcutaneous traumatic inoculation of a specific group of dematiaceous fungi occurring mainly in tropical and subtropical zones worldwide. If not diagnosed at early stages, patients with CBM... require long term therapy with systemic antifungals, sometimes associated with physical methods. Unlike other neglected endemic mycoses, comparative clinical trials have not been performed for this disease. Nowadays, therapy is based on a few open trials and on expert opinion. Itraconazole either as monotherapy or associated with other drugs, or with physical methods, is widely used. Recently, photodynamic therapy has been successfully employed in combination with antifungals in patients presenting with CBM. In the present revision the most used therapeutic options against CBM are reviewed as well as the several factors that may have impact on the patient's outcome.
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In 2014, an estimated 40 million women of reproductive age were infected with Schistosoma haematobium, S. japonicum and/or S. mansoni. In both 2003 and 2006, the World Health Organization (WHO) recommended that all schistosome-infected pregnant and breastfeeding women be offered treatment, with praz...iquantel, either individually or during treatment campaigns. In 2006, WHO also stated the need for randomized controlled trials to assess the safety and efficacy of such treatment. Some countries have yet to follow the recommendation on treatment and many programme managers and pregnant women in other countries remain reluctant to follow the recommended approach.
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Diabetes mellitus (DM) is a global epidemic with significant morbidity. Diabetic
retinopathy (DR) is the specific microvascular complication of DM and affects 1 in 3 persons with DM. DR remains a leading cause of vision loss in working adult populations. Patients with severe levels of DR are report...ed to have poorer quality of life and reduced levels of physical, emotional, and social well-being, and they utilize more health care resources.
Epidemiological studies and clinical trials have shown that optimal control of blood glucose, blood pressure, and blood lipids can reduce the risk of developing retinopathy and slow its progression. Timely treatment with laser photocoagulation, and increasingly, the appropriate use of intraocular administration of vascular endothelial growth factor (VEGF) inhibitors can prevent visual loss in vision- threatening retinopathy, particularly diabetic macular edema (DME). Since visual loss may not be present in the earlier stages of retinopathy, regular screening of persons with diabetes is essential to enable early intervention.
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In 2014, the World Heart Federation (WHF) launched
an initiative to develop a series of Roadmaps [1e6]. Their
aim is to identify potential roadblocks on the pathway to
effective prevention, detection, and management of cardiovascular disease (CVD), along with evidence-based
solutions to overcome... them. The resulting documents
provide a framework to translate strategic intent into action
on integrating epidemiology, population, and cardiovascular outcome trial data into national plans for optimal
CVD management.
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The cardiovascular disease continuum begins with risk factors such as diabetes mellitus (DM), progresses to vasculopathy and myocardial dysfunction, and finally ends with cardiovascular death. Diabetes is associated with a 2- to 4-fold increased risk for heart failure (HF). Moreover, HF patients wit...h DM have a worse prognosis than those without DM. Diabetes can cause myocardial ischemia via micro- and macrovasculopathy and can directly exert deleterious effects on the myocardium. Hyperglycemia, hyperinsulinemia, and insulin resistance can cause alterations in vascular homeostasis. Then, reduced nitric oxide and increased reactive oxygen species levels favor inflammation leading to atherothrombotic progression and myocardial dysfunction. The classification, diagnosis, and treatment of HF for a patient with and without DM remain the same. Until now, drugs targeting neurohumoral and metabolic pathways improved mortality and morbidity in HF with reduced ejection fraction (HFrEF). Therefore, all HFrEF patients should receive guideline-directed medical therapy. By contrast, drugs modulating neurohumoral activity did not improve survival in HF with preserved ejection fraction (HFpEF) patients. Trials investigating whether sodium-glucose cotransporter-2 inhibitors are effective in HFpEF are on-going. This review will summarize the epidemiology, pathophysiology, and treatment of HF in diabetes.
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Background
Low- and middle-income countries now experience the highest prevalence and mortality rates of cardiovascular disease.
Main text
While improving the availability and delivery of proven, effective therapies will no doubt mitigate this burden, we posit that studies evaluating cardiovasc...ular disease risk factors, management strategies and service delivery, in diverse settings and diverse populations, are equally critical to improving outcomes in low- and middle-income countries. Focusing on examples drawn from four cardiovascular diseases — coronary artery disease, stroke, diabetes and kidney disease — we argue that ethnicity, culture and context matter in determining the risk factors for disease as well as the comparative effectiveness of medications and other interventions, particularly diet and lifestyle interventions.
Conclusion
We believe that a host of cohort studies and randomized control trials currently being conducted or planned in low- and middle-income countries, focusing on previously understudied race/ethnic groups, have the potential to increase knowledge about the cause(s) and management of cardiovascular diseases across the world.
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The evolving epidemic of type 2 diabetes mellitus has challenged health-care professionals. It stands among the leading causes of mortality in the present world. It warrants new and versatile approaches to improve mortality and the associated huge quality-adjusted life years lost to it once diagnose...d. A possible venue to lower the incidence is to assess the safety and efficacy of various diabetes prevention strategies. Diet and exercise have a well-developed role in the prevention of weight gain and, ultimately, diabetes mellitus type II in high-risk individuals. However, high-risk individuals can also benefit from adjunct pharmacotherapy. In light of this information, we decided to conduct a systematic review of randomized controlled trials. This article summarizes the evidence in the literature on the pharmacological prevention of diabetes in high-risk individuals.
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Patients with diabetes are at increased risk of developing cardiovascular disease (CVD) with its manifestations of coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), and stroke, as well as aortic and peripheral artery diseases. In addition, diabetes is a major risk factor f...or developing chronic kidney disease (CKD), which in itself is associated with developing CVD. The combination of diabetes with these cardio-renal comorbidities enhances the risk not only for cardiovascular (CV) events but also for CV and all-cause mortality. The current European Society of Cardiology (ESC) Guidelines on the management of cardiovascular disease in patients with diabetes are designed to guide prevention and management of the manifestations of CVD in patients with diabetes based on data published until end of January 2023. Over the last decade, the results of various large cardiovascular outcome trials (CVOTs) in patients with diabetes at high CV risk with novel glucose- lowering agents, such as sodium–glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), but also novel non-steroidal mineralocorticoid receptor antagonists (MRAs), such as finerenone have substantially expanded available therapeutic op-
tions, leading to numerous evidence-based recommendations for the management of this patient population.
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Background
Asthma education, a key component of long-term asthma management, is challenging in resource-limited settings with shortages of clinical staff. Task-shifting educational roles to lay (non-clinical) staff is a potential solution. We conducted a randomised controlled trial of an enhanced a...sthma care intervention for children in Malawi, which included reallocation of asthma education tasks to lay-educators. In this qualitative sub-study, we explored the experiences of asthmatic children, their families and lay-educators, to assess the acceptability, facilitators and barriers, and perceived value of the task-shifting asthma education intervention.
Methods
We conducted six focus group discussions, including 15 children and 28 carers, and individual interviews with four lay-educators and a senior nurse. Translated transcripts were coded independently by three researchers and key themes identified.
Results
Prior to the intervention, participants reported challenges in asthma care including the busy and sometimes hostile clinical environment, lack of access to information and the erratic supply of medication. The education sessions were well received: participants reported greater understanding of asthma and their treatment and confidence to manage symptoms. The lay-educators appreciated pre-intervention training, written guidelines, and access to clinical support. Low education levels among carers presented challenges, requiring an open, non-critical and individualised approach.
Discussion
Asthma education can be successfully delivered by lay-educators with adequate training, supervision and support, with benefits to the patients, their families and the community. Wider implementation could help address human resource shortages and support progress towards Universal Health Coverage.
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The Asthma Control Questionnaire (ACQ)1 was developed and validated to measure the primary clinical goal of asthma management as identified by international guidelines. They indicate that to achieve good control, treatment should minimise day and night time symptoms, activity limitation, airway narr...owing and rescue bronchodilator use and thus reduce the risk of life-threatening exacerbations and long-term morbidity. The importance of including all aspects of control in the assessment of individual patients was emphasised by a recent factor analysis which showed that clinical asthma is composed of distinct components which are not closely correlated with each other.6 However, in some studies it may not be possible to collect airway calibre or short-acting β2-agonists data. Previous analysis of non-clinical trial data suggested that when ACQ scores are analysed as group data, the heterogeneity of the way in which individual patients present with inadequate control is lost in the estimation of the mean and the need to measure each individual component of asthma control may become unnecessary. In this analysis, ACQ data from a clinical trial was used to evaluate the measurement properties (reliability, responsiveness, validity and interpretability), of three shortened versions of the ACQ. In addition, we have examined whether the precision and accuracy of estimating the effect of the intervention on asthma control was maintained when the two questions concerning airway calibre and short-acting β2-agonists use were omitted from the trial analysis.
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The report provides a brief introduction to patents and licences and their effect on the market for antiretroviral (ARV) medicines. It gives an overview of the patent landscape with respect to a select number of ARV medicines in developing countries as of April 2014. The focus is primarily on those ...ARVs that are recommended by the World Health Organization (WHO) as well as new ARVs that have either recently obtained regulatory approval or are in phase III clinical trials.
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The protozoan parasite Trypanosoma cruzi causes Chagas disease, an important public health problem throughout Latin America. Current therapeutic options are characterised by limited efficacy, long treatment regimens and frequent toxic side-effects. Advances in this area have been compromised by gaps... in our knowledge of disease pathogenesis, parasite biology and drug activity. Nevertheless, several factors have come together to create a more optimistic scenario. Drug-based research has become more systematic, with increased collaborations between the academic and commercial sectors, often within the framework of not-for-profit consortia. High-throughput screening of compound libraries is being widely applied, and new technical advances are helping to streamline the drug development pipeline. In addition, drug repurposing and optimisation of current treatment regimens, informed by laboratory research, are providing a basis for new clinical trials. Here, we will provide an overview of the current status of Chagas disease drug development, highlight those areas where progress can be expected, and describe how fundamental research is helping to underpin the process.
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After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenge...s of the clinical trials of fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules. In cell culture, fexinidazole has an IC50 of around 1 µM against Trypanosoma brucei and is more than 100-fold less toxic to mammalian cells. In the mouse model, fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT). This greatly facilitates the diagnosis and treatment algorithm for gHAT, increasing the attainable coverage and paving the way towards the envisaged goal of zero transmission by 2030.
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Each year, ≈795 000 individuals in the United States experience a stroke, of which 87% (690 000) are ischemic and 185 000 are recurrent.1 Approximately 240 000 individuals experience a transient ischemic attack (TIA) each year.2 The risk of recurrent stroke or TIA is high but can be mitiga...ted with appropriate secondary stroke prevention. In fact, cohort studies have shown a reduction in recurrent stroke and TIA rates in recent years as secondary stroke prevention strategies have improved.3,4 A meta-analysis of randomized controlled trials (RCTs) of secondary stroke prevention therapies published from 1960 to 2009 showed a reduction in annual stroke recurrence from 8.7% in the 1960s to 5.0% in the 2000s, with the reduction driven largely by improved blood pressure (BP) control and use of antiplatelet therapy.5 The changes may have been influenced by changes in diagnostic criteria and differing sensitivities of diagnostic tests over the years.
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Background
Noncommunicable diseases are major contributors to morbidity and mortality worldwide. Modifying the risk factors for these conditions, such as physical inactivity, is thus essential. Addressing the context or circumstances in which physical activity occurs may promote physical activity a...t a population level. We assessed the effects of infrastructure, policy or regulatory interventions for increasing physical activity.
Methods
We searched PubMed, Embase and clinicaltrials.gov to identify randomised controlled trials (RCTs), controlled before-after (CBAs) studies, and interrupted time series (ITS) studies assessing population-level infrastructure or policy and regulatory interventions to increase physical activity. We were interested in the effects of these interventions on physical activity, body weight and related measures, blood pressure, and CVD and type 2 diabetes morbidity and mortality, and on other secondary outcomes. Screening and data extraction was done in duplicate, with risk of bias was using an adapted Cochrane risk of bias tool. Due to high levels of heterogeneity, we synthesised the evidence based on effect direction.
Results
We included 33 studies, mostly conducted in high-income countries. Of these, 13 assessed infrastructure changes to green or other spaces to promote physical activity and 18 infrastructure changes to promote active transport. The effects of identified interventions on physical activity, body weight and blood pressure varied across studies (very low certainty evidence); thus, we remain very uncertain about the effects of these interventions. Two studies assessed the effects of policy and regulatory interventions; one provided free access to physical activity facilities and showed that it may have beneficial effects on physical activity (low certainty evidence). The other provided free bus travel for youth, with intervention effects varying across studies (very low certainty evidence).
Conclusions
Evidence from 33 studies assessing infrastructure, policy and regulatory interventions for increasing physical activity showed varying results. The certainty of the evidence was mostly very low, due to study designs included and inconsistent findings between studies. Despite this drawback, the evidence indicates that providing access to physical activity facilities may be beneficial; however this finding is based on only one study. Implementation of these interventions requires full consideration of contextual factors, especially in low resource settings.
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Background
The core clinical symptoms of addiction include an enhanced incentive for drug taking (craving), impaired self-control (impulsivity and compulsivity), emotional dysregulation (negative mood) and increased stress reactivity. Symptoms related to impaired self-control involve reduced activi...ty in anterior cingulate cortex (ACC), adjacent prefrontal cortex (mPFC) and other brain areas. Behavioral training such as mindfulness meditation can increase the function of control networks including those leading to improved emotion regulation and thus may be a promising approach for the treatment of addiction.
Methods
In a series of randomized controlled trials (RCTs), we tested whether increased ACC/mPFC activity is related to better self-control abilities in executive functions, emotion regulation and stress response in healthy and addicted populations. After a brief mindfulness training (Integrative Body-Mind Training, IBMT), we used the Positive and Negative Affect Schedule (PANAS) and Profile of Mood States (POMS) to measure emotion regulation, salivary cortisol for the stress response and fMRI for brain functional and DTI structural changes. Relaxation training was used to serve as an active control.
Results
In both smokers and nonsmokers, improved self-control abilities in emotion regulation and stress reduction were found after training and these changes were related to increased ACC/mPFC activity following training. Compared with nonsmokers, smokers showed reduced ACC/mPFC activity in the self-control network before training, and these deficits were ameliorated after training.
Conclusions
These results indicate that promoting emotion regulation and improving ACC/mPFC brain activity can help for addiction prevention and treatment.
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One in three people globally suffers from at least one form of malnutrition, leading to poor health outcomes and low productivity in the workplace. The workplace offers an important, relatively unexploited opportunity to address malnutrition in all its forms. This narrative literature review aims to... understand the impact of workforce nutrition programmes on nutrition, health, and business outcomes, based on high-strength-of-evidence studies. We used PubMed as our primary research database, complemented by Google Scholar, to identify systematic reviews, meta-analyses, and randomised controlled trials published between January 2010 and October 2021. In total, 26 records were included. We found that comprehensive workforce nutrition programmes, including a variety of intervention areas, and/or programmes targeting high-risk categories of workers (overweight/obese or (pre-)diabetic) were more likely to be effective on nutrition, health, and business outcomes. Within comprehensive and targeted programmes, individualised counselling and worksite environmental modifications were often mentioned as the most effective components. However, a high degree of heterogeneity in outcome measures and programme designs made it difficult to draw strong conclusions on the impact of workforce nutrition interventions. Limited evidence was found on business outcomes, longer-term effects of interventions, and programme implementation in LMICs. Therefore, further research is needed to address these evidence gaps.
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The article from the African Journal of Thoracic and Critical Care Medicine provides updated guidelines on endoscopic lung volume reduction (ELVR) for treating advanced emphysema, a severe form of chronic obstructive pulmonary disease (COPD), which is prevalent in South Africa and other low- and mid...dle-income countries. The guidelines focus on identifying suitable patients based on specific criteria, such as age, lung function, and the presence of hyperinflation, while ruling out contraindications like pulmonary hypertension and recent smoking.
ELVR aims to reduce lung volume in the most damaged areas, improving breathing mechanics and quality of life. Various devices, including endobronchial valves, intrabronchial valves, and coils, are reviewed with evidence from clinical trials supporting their use. The guidelines emphasize careful patient selection and recommend only performing ELVR in specialized centers due to its high cost and risk of complications, such as pneumothorax.
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