Background Oral nirmatrelvir/ritonavir (Paxlovid®) aims to avoid severe COVID‐19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. Due to its novelty, there are currently few published study results. It remains to be evaluated for which indications and patient populations the drug is suitable. Objectives To assess the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid®) plus standard of care compared to standard of care with or without placebo, or any other intervention for treating COVID‐19 and for preventing SARS‐CoV‐2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in‐between publication of review updates. Search methods We searched the Cochrane COVID‐19 Study Register, Scopus, and WHO COVID‐19 Global literature on coronavirus disease database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 11 July 2022. This is a LSR. We conduct monthly update searches that are being made publicly available on the open science framework (OSF) platform. Selection criteria Studies were eligible if they were randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus standard of care with standard of care with or without placebo, or any other intervention for treatment of people with confirmed COVID‐19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS‐CoV‐2 infection. We screened all studies for research integrity. Studies were ineligible if they had been retracted, or if they were not prospectively registered including appropriate ethics approval. Data collection and analysis We followed standard Cochrane methodology and used the Cochrane risk of bias 2 tool. We rated the certainty of evidence using the GRADE approach for the following outcomes: 1. to treat outpatients with mild COVID‐19; 2. to treat inpatients with moderate‐to‐severe COVID‐19: mortality, clinical worsening or improvement, quality of life, (serious) adverse events, and viral clearance; 3. to prevent SARS‐CoV‐2 infection in post‐exposure prophylaxis (PEP); and 4. pre‐exposure prophylaxis (PrEP) scenarios: SARS‐CoV‐2 infection, development of COVID‐19 symptoms, mortality, admission to hospital, quality of life, and (serious) adverse events. We explored inequity by subgroup analysis for elderly people, socially‐disadvantaged people with comorbidities, populations from LICs and LMICs, and people from different ethnic and racial backgrounds. Main results As of 11 July 2022, we included one RCT with 2246 participants in outpatient settings with mild symptomatic COVID‐19 comparing nirmatrelvir/ritonavir p...

BackgroundOral nirmatrelvir/ritonavir (Paxlovid®) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. Due to its novelty, there are currently few published study results. It remains to be evaluated for which indications and patient populations the drug is suitable. ObjectivesTo assess the e icacy and safety of nirmatrelvir/ritonavir (Paxlovid®) plus standard of care compared to standard of care with or without placebo, or any other intervention for treating COVID-19 and for preventing SARS-CoV-2 infection.To explore equity aspects in subgroup analyses.To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in-between publication of review updates. Search methodsWe searched the Cochrane COVID-19 Study Register, Scopus, and WHO COVID-19 Global literature on coronavirus disease database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 11 July 2022. This is a LSR. We conduct monthly update searches that are being made publicly available on the open science framework (OSF) platform. Selection criteriaStudies were eligible if they were randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus standard of care with standard of care with or without placebo, or any other intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection.Nirmatrelvir combined with ritonavir for preventing and treating COVID-19 (Review)

Background Mpox was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on 23 July 2022, following the identification of thousands of cases in several non‐endemic countries in previous months. There are currently no licenced therapeutics for treating mpox; however, some medications may be authorized for use in an outbreak. The efficacy and safety of possible therapeutic options has not been studied in humans with mpox. There is a need to investigate the evidence on safety and effectiveness of treatments for mpox in humans; should any therapeutic option be efficacious and safe, it may be approved for use around the world. Objectives There are two parts to this Cochrane Review: a review of evidence from randomized controlled trials (RCTs), and a narrative review of safety data from non‐randomized studies. Randomized controlled trials review To systematically review the existing evidence on the effectiveness of therapeutics for mpox infection in humans compared to: a) another different therapeutic for mpox, or b) placebo, or c) supportive care, defined as the treatment of physical and psychological symptoms arising from the disease. Non‐randomized studies review To assess the safety of therapeutics for mpox infection from non‐randomized studies (NRS). Search methods Randomized controlled trials review We searched the following databases up to 25 January 2023: MEDLINE (OVID), Embase (OVID), Biosis previews (Web of Science), CAB Abstracts (Web of science), and Cochrane CENTRAL (Issue 1 2023). We conducted a search of trial registries (Clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP)) on 25 January 2023. There were no date or language limits placed on the search. We undertook a call to experts in the field for relevant studies or ongoing trials to be considered for inclusion in the review. Non‐randomized studies review We searched the following databases on 22 September 2022: Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9 of 12, 2022), published in the Cochrane Library; MEDLINE (Ovid); Embase (Ovid); and Scopus (Elsevier). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress. Selection criteria For the RCT review and the narrative review, any therapeutic for the treatment of mpox in humans was eligible for inclusion, including tecovirimat, brincidofovir, cidofovir, NIOCH‐14, immunomodulators, and vaccine immune globulin. Randomized controlled trials review Studies were eligible for the main review if they were of randomized controlled design and investigated the effectiveness or safety of therapeutics in human mpox infection. Non‐randomized st...

Background Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low‐ and middle‐income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first‐line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug‐resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first‐line antimicrobials, such as chloramphenicol, has re‐appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. Objectives To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. Selection criteria We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. Data collection and analysis We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. Main results We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39...

Objectives: To assess the effectiveness of respiratory interventions and case isolation measures in reducing or preventing the transmission of mpox in humans and to inform future focused reviews on mpox transmission. Methods: The WHO Clinical Management and Infection Prevention and Control guideline 2022 development group developed three structured research questions concerning respiratory and isolation infection prevention control measures for mpox. We conducted a systematic review that included a broad search of five electronic databases. In a two-stage process, we initially sought only randomized controlled trials and observational comparative studies; when the search failed to yield eligible studies, the subsequent search included all study designs including clinical and environmental sampling studies. Results: To inform the questions the review team synthesized route of transmission data in mpox. There were 2420/3924 (61.7%) cases in which investigators identified transmission occurring through direct physical sexual contact. There proved to be no reported mpox cases in which investigators identified inhalation as a single route of transmission. There were 2/3924 (0.05%) cases in which investigators identified fomite as a single route of transmission. Clinical and environmental sampling studies generally failed to isolate mpox virus in saliva, oropharangeal swabs, mpox skin lesions, and hospital room air. Conclusions: Current findings provide compelling evidence that transmission of mpox occurs through direct physical contact. Because investigators have not reported any cases of transmission via inhalation alone the impact of respiratory infection prevention control measures in reducing transmission will be minimal. Avoiding physical contact with others, covering mpox lesions and wearing a medical mask is likely to reduce onward mpox transmission; there may be minimal reduction in transmission from additionally physically isolating patients.