Saniya Sabzwari

Updates: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline. Clinical question: What is the role of drugs in the treatment of patients with covid-19? Context: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics. What is new?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19. About this guideline: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact. Future recommendations: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.

CLINICAL QUESTION: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. RECOMMENDATION: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). HOW THIS GUIDELINE WAS CREATED: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. UNDERSTANDING THE NEW RECOMMENDATION: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. UPDATES: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. READERS NOTE: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.

BACKGROUND: The developing world has had limited quality research and in Pakistan, research is still in its infancy. We conducted a study to assess the proportion of junior faculty involved in research to highlight their attitude towards research, and identify the factors associated with their research involvement. METHODS: A cross-sectional study was conducted in four medical universities/teaching hospitals in Pakistan, representing private and public sectors. A pre-tested, self-administered questionnaire was used to collect information from 176 junior faculty members of studied universities/hospitals. Logistic regression analysis was used to identify factors related to attitudes and barriers in research among those currently involved in research with those who were not. RESULTS: Overall, 41.5% of study subjects were currently involved in research. A highly significant factor associated with current research involvement was research training during the post-graduate period (p < 0.001). Other factors associated with current involvement in research were male gender, working in the public sector and previous involvement in research. Overall, a large majority (85.2%) of doctors considered research helpful in their profession and had a positive attitude towards research; nevertheless this positive attitude was more frequently reported by doctors who were currently involved in research compared to those who were not (OR = 4.69; 95% CI = 1.54-14.26). Similarly, a large proportion (83.5%) of doctors considered research difficult to conduct; higher by doctors who were not presently involved in research (OR = 2.74; 95% CI = 1.20-6.22) CONCLUSION: Less than half of the study participants were currently involved in research. Research output may improve if identified barriers are rectified. Further studies are recommended in this area.

The elderly population in South Asia is growing. In Pakistan trained caregivers are scarce and culturally not acceptable. This study assessed the level of stress experienced by caregivers of the elderly and determined the association of care giving burden with different characteristics of the elderly. A cross-sectional, questionnaire based study was conducted using nonprobability purposive sampling. All consenting participants aged 60 years and above needing help with at least one activity of daily living or two instrumental activities of daily living were included. 350 participants were assessed for perceived care giver burden. Care providers were mostly female (68.9%). Half (50.3%) of the caregivers had a positive score on a perceived care burden scale. Financial impact had a strong correlation (0.79) with perceived caregiver burden. Higher dependency levels of a physical and cognitive nature posed greater burden on caregivers. Behavioural issues of the elderly such as verbal abuse and difficulty sleeping were predictors of a higher caregiver burden. Caregiver burden is a significant issue for those caring for elderly family members in Karachi, Pakistan.