The method, entitled “elicit-provide-elicit”, is a patient centred method which is adaptable to a range of clinical situations. Recent clinical trials show that the introduction of advanced communication skills based on this method in general practice allows primary care physicians to prescribe... significantly less antibiotics while maintaining a high degree of patient satisfac-tion, without impacting patient recovery time and consultation times.
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This document is part three in a series of explainers on vaccine development and distribution. Part one focused on how vaccines work to protect our bodies from disease-carrying germs. Part two focused on the ingredients in a vaccine and the three clinical trial phases.
This document outlines the... next part of the vaccine journey: the steps from completing the clinical trial phases through to distribution.
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COVAXINTM, India's indigenous COVID-19 vaccine by Bharat Biotech is developed in collaboration with the Indian Council of Medical Research (ICMR) - National Institute of Virology (NIV). The indigenous, inactivated vaccine is developed and manufactured in Bharat Biotech's BSL-3 (Bio-Safety Level 3) h...igh containment facility.
The vaccine received DCGI approval for Phase I & II Human Clinical Trials and the trials commenced across India from July, 2020.
After successful completion of the interim analysis from the Phase 1 & 2 clinical trials of COVAXINTM, Bharat Biotech received DCGI approval for Phase 3 clinical trials in 26,000 participants in over 25 centres across India.
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The COVID-19 vaccine tracker and landscape compiles detailed information of each COVID-19 vaccine candidate in development by closely monitoring their progress through the pipeline.
The COVID-19 vaccine tracker:
Provides summary tables of COVID-19 vaccine candidates in both clinical and pre-...clinical development;
Provides analysis and visualization for several COVID-19 vaccine candidate categories;
Tracks the progress of each vaccine from pre-clinical, Phase 1, Phase 2 through to Phase 3 efficacy studies and including Phase 4 registered as interventional studies;
Provides links to published reports on safety, immunogenicity and efficacy data of the vaccine candidates;
Includes information on key attributes of each vaccine candidate and
Allows users to search for COVID-19 vaccines through various criteria such as vaccine platform, schedule of vaccination, route of administration, developer, trial phase and clinical endpoints.
The database is updated regularly - twice a week (Tuesday and Friday, 17:00 CET).
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Exciting news this week with @Pfizer reporting their mRNA vaccine is 90% effective, based on their Phase III clinical trial data. Dr. Tom looks inside the virus to break down how mRNA vaccines work, and whether news this promising means we can finally relax.
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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DOI: 10.5772/intechopen.102891Little progress has been made since the 1960s and 19. 70s to widen the therapeutic arsenal against Trypanosoma cruzi, the causative pathogen of Chagas disease, which remains a frustrating and perplexing infectious disease. This chapter focuses on the strategic and opera...tional challenges in the clinical drug development of a novel antitrypanosomal agent for Chagas disease. The various elements that contribute to a robust assessment of treatment effect including dose selection, choice of patient population, trial methodology, endpoint measures, and regulatory perspectives are discussed. The learnings herein should serve as resource to help researchers and other stakeholders optimize their clinical development plans and speed delivery of new medicines to patients with Chagas disease.
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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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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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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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Medicines and Allied Substances [No. 3 of 2013 47 | An Act to continue the existence of the Pharmaceutical Regulatory Authority and re-name it as the Zambia Medicines Regulatory Authority; provide for the functions and powers of the Authority; provide for the registration and regulation of pharmacie...s, health shops and agro-veterinary shops; provide for the registration and regulation of medicines and allied substances; provide for the regulation of the manufacture, importation, exportation, possession, storage, distribution, supply, promotion, advertising, sale and use of medicines and allied substances; provide for the regulation and control of clinical trials; repeal and replace the Pharmaceutical Act, 2004; and provide for matters connected with, or incidental to, the foregoing.
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The Lancet Volume 390, Issue 10110p2397-2409November 25, 2017.
Human African trypanosomiasis (HAT), also called sleeping sickness, is a parasitic infection that almost invariably progresses to death, unless treatment is provided. HAT caused devastating epidemics during the 20th century. Thanks to ...sustained and coordinated efforts during the past 15 years the number of reported cases has fallen to a historic low. Fewer than 3,000 cases were reported in 2015, and the disease is targeted for elimination by the World Health Organization. Despite recent success, HAT still poses a heavy burden on the rural communities where this highly focal disease occurs, most notably in Central Africa. Since patients are also reported from non-endemic countries outside Africa, HAT should be considered in differential diagnosis for all travellers, tourists, migrants and expatriates who have visited or lived in endemic areas. In the absence of a vaccine, disease control relies on case detection and treatment, and vector control. Available drugs are sub-optimal, but ongoing clinical trials give hope for safer and simpler treatments.
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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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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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This document updates the earlier version published in April 2020. In recent weeks, information on the potential use of chloroquine or hydroxychloroquine for the treatment of people with COVID-19 has been disseminated in academic journals and public media. Although there are now ongoing clinical tri...als testing the efficacy and safety of several medicines for COVID-19, as of the date of this document, there is a lack of quality evidence to demonstrate chloroquine and/or hydroxychloroquine are effective in the treatment of COVID-19. Evidence is recently emerging via small studies with sub-optimal methodologies that are conflicting.
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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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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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The technical note from the Global Task Force on Cholera Control (GTFCC) examines the risks and benefits of vaccinating pregnant women with WHO-prequalified oral cholera vaccines (OCVs) during mass vaccination campaigns. It highlights that three WHO-approved vaccines (Dukoral®, Shanchol™, and Euv...ichol®) offer sustained protection and a strong safety profile.
While these vaccines are not explicitly contraindicated for pregnant women, there is limited clinical data on their use during pregnancy. However, studies indicate that pregnant women with cholera face higher risks of fetal loss, stillbirth, and complications, especially if they experience severe dehydration. Some evidence suggests that vaccination can reduce cholera incidence in pregnant women and indirectly protect infants.
Although no controlled trials have focused on pregnant women, retrospective studies in Guinea and Zanzibar showed no significant increase in adverse pregnancy outcomes after OCV administration. The GTFCC concludes that the benefits of vaccination outweigh the risks, particularly in high-risk areas, and recommends including pregnant women in cholera vaccination campaigns while continuing to monitor safety data.
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Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to ...prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians.
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WHO has updated its guidelines for COVID-19 therapeutics, with revised recommendations for patients with non-severe COVID-19. This is the 13th update to these guidelines.
Updated risk rates for hospital admission in patients with non-severe COVID-19
The guidance includes updated risk rates for... hospital admission in patients with non-severe COVID-19.
The current COVID-19 virus variants tend to cause less severe disease while immunity levels are higher due to vaccination, leading to lower risks of severe illness and death for most patients.
This update includes new baseline risk estimates for hospital admission in patients with non-severe COVID-19. The new ‘moderate risk’ category now includes people previously considered to be high risk including older people and/or those with chronic conditions, disabilities, and comorbidities of chronic disease. The updated risk estimates will assist healthcare professionals to identify individuals at high, moderate or low risk of hospital admission, and to tailor treatment according to WHO guidelines:
**High: **People who are immunosuppressed remain at higher risk if they contract COVID-19, with an estimated hospitalization rate of 6%.
**Moderate: **People over 65 years old, those with conditions like obesity, diabetes and/or chronic conditions including chronic obstructive pulmonary disease, kidney or liver disease, cancer, people with disabilities and those with comorbidities of chronic disease are at moderate risk, with an estimated hospitalization rate of 3%.
Low: Those who are not in the high or moderate risk categories are at low risk of hospitalization (0.5%). Most people are low risk.
Review of COVID-19 treatments for people with non-severe COVID-19
WHO continues to strongly recommend nirmatrelvir-ritonavir (also known by its brand name ‘Paxlovid’) for people at high-risk and moderate risk of hospitalization. The recommendations state that nirmatrelvir-ritonavir is considered the best choice for most eligible patients, given its therapeutic benefits, ease of administration and fewer concerns about potential harms. Nirmatrelvir-ritonavir was first recommended by WHO in April 2022.
If nirmatrelvir-ritonavir is not available to patients at high-risk of hospitalization, WHO suggests the use of molnupiravir or remdesivir instead.
WHO suggests against the use of molnupiravir and remdesivir for patients at moderate risk, judging the potential harms to outweigh the limited benefits in patients at moderate risk of hospital admission.
For people at low risk of hospitalization, WHO does not recommend any antiviral therapy. Symptoms like fever and pain can continue to be managed with analgesics like paracetamol.
WHO also recommends against use of a new antiviral (VV116) for patients, except in clinical trials.
The update also includes a strong recommendation against the use of ivermectin for patients with non-severe COVID-19. WHO continues to advise that in patients with severe or critical COVID-19, ivermectin should only be used in clinical trials.
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