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Background: Despite the availability of individual-level data of infants accessing HIV DNA-PCR testing service, there has been little in-depth analysis of such data. Therefore, we describe trends in risk of HIV infection among Malawi's HIV-exposed infants (HEI) with DNA-PCR HIV test result from 2013 to 2020., Methods: This is an implementation study using routinely collected patient-level HIV DNA-PCR test result data extracted from the national Laboratory Management Information System database managed by the Department of HIV/AIDS between 1 January 2013 and 30 June 2020. We calculated frequencies, proportions and odds ratio (OR) with their associated 95% CI. We performed a random-effects logistic regression to determine the risk factors associated with HIV infection in infants, controlling for the spatial autocorrelation between districts and adjusting for other variables., Results: We evaluated 255 229 HEI across 750 facilities in 28 districts. The HIV DNA-PCR test was performed within 2 months in 57% of the children. The overall HIV prevalence among all tested HEI between 2013 and 2020 was 7.2% (95% CI 7.1% to 7.3%). We observed a decreasing trend in the proportion of HEI that tested HIV positive from 7.0% (95% CI 6.6% to 7.4%) in 2013 to 5.7% (95% CI 5.4% to 5.9%) in 2015 followed by an increase to 9.9% (95% CI 9.6% to 10.2%) in 2017 and thereafter a decreasing trend between 2017 (i.e. 9.72% (95%CI: 9.43-10.01)) and 2020 (i.e. 3.86% (95%CI: 3.34-4.37)). The HIV prevalence increased by age of the HEI. There was spatial heterogeneity of HIV prevalence between districts of Malawi. The prevalence of HIV was higher among the HEI from the Northern region of Malawi., Conclusion: The main findings of the study are that the DNA test is performed within 2 months only in 57% of the children, that the decreasing trend of HIV prevalence among HEI observed up to 2015 was followed by an increase up to 2017 and a decrease afterwards, and that the risk of HIV infection increased with age at HIV testing. We summarised spatial and temporal trends of risk of HIV infection among HEI in Malawi between 2013 and 2020. There is need to ensure that all the HEI are enrolled in HIV care by 8 weeks of age in order to further reduce the risk of HIV in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aimed to systematically review the methodological and reporting quality of clinical practice guidelines (CPGs) developed in China and published in medical journals between 2014 and 2018., Study Design and Setting: We conducted a comprehensive search in multiple databases: MEDLINE (via PubMed), Embase, CBM (China Biology Medicine), CNKI (China National Knowledge Infrastructure) and Wanfang Data. We included all clinical practice guidelines developed in China between 2014 and 2018. The AGREE II tool and the RIGHT checklist were used to appraise the methodological quality and reporting quality of the included guidelines, respectively., Results: We identified 17,188 records, and included finally 573 CPGs. Most (n=507, 88.5%) were published in Chinese, and 508 (88.7%) were about Western medicine. Only 62 (10.8%) of the guidelines used the GRADE approach. The mean overall score of methodological quality over all guidelines was 19.4%, and the mean scores for the AGREE II domains were 28.6% (Scope and purpose), 17.0% (Stakeholder involvement), 11.7% (Rigor of development), 32.2% (Clarity of presentation), 14.2% (Applicability) and 12.8% (Editorial independence). The mean overall score for reporting quality over all guidelines was 30.2%, with the following mean scores for each RIGHT domain: 55.6% (Basic information), 43.8% (Background), 14.5% (Evidence), 29.2% (Recommendations), 10.7% (Review and quality assurance), 12.6% (Funding and declaration of interest) and 8.4% (Other information). Subgroup analyses found that both the methodological and reporting quality were generally higher among CPGs that used evidence grading systems or reported receiving funding., Conclusion: Both the methodological quality and the reporting quality of CPGs developed in China have improved over time, but are still below the international average., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Despite its critical role in containing outbreaks, the efficacy of contact tracing, measured as the sensitivity of case detection, remains an elusive metric. We estimated the sensitivity of contact tracing by applying unilist capture-recapture methods on data from the 2018-2020 outbreak of Ebola virus disease in the Democratic Republic of the Congo. To compute sensitivity, we applied different distributional assumptions to the zero-truncated count data to estimate the number of unobserved case-patients with any contacts and infected contacts. Geometric distributions were the best-fitting models. Our results indicate that contact tracing efforts identified almost all (n = 792, 99%) of case-patients with any contacts but only half (n = 207, 48%) of case-patients with infected contacts, suggesting that contact tracing efforts performed well at identifying contacts during the listing stage but performed poorly during the contact follow-up stage. We discuss extensions to our work and potential applications for the ongoing coronavirus pandemic.

Rationale: Until 2020, extensively drug-resistant tuberculosis (XDR-TB) was defined as TB with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]), any fluoroquinolone (FQ), and any second-line injectable drug (SLID). In 2019, the World Health Organization issued new recommendations for treating patients with drug-resistant TB, substantially limiting the role of SLIDs in MDR-TB treatment and thus putting the definition of XDR-TB into question. Objectives: To propose an up-to-date definition for XDR-TB. Methods: We used a large data set to assess treatment outcomes for patients with MDR-TB exposed to any type of longer regimen. We included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results. We performed logistic regression to estimate the adjusted odds ratios (aORs) for an unfavorable treatment outcome (failure, relapse, death, loss to follow-up), and estimates were stratified by the resistance pattern (FQ and/or SLID) and group A drug use (moxifloxacin/levofloxacin, linezolid, and/or bedaquiline). Measurements and Main Results: We included 11,666 patients with MDR-TB; 4,653 (39.9%) had an unfavorable treatment outcome. Resistance to FQs increased the odds of an unfavorable treatment outcome (aOR, 1.91; 95% confidence interval [CI], 1.63-2.23). Administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQs and/or SLIDs. Among patients with XDR-TB, compared with persons receiving no group A drug, aORs for an unfavorable outcome were 0.37 (95% CI, 0.20-0.69) with linezolid only, 0.40 (95% CI, 0.21-0.77) with bedaquiline only, and 0.21 (95% CI, 0.12-0.38) with both. Conclusions: Our study supports a new definition of XDR-TB as MDR-TB and additional resistance to FQ plus bedaquiline and/or linezolid and helps assess the adequacy of this definition for surveillance and treatment choice.

Background: The cost and complexity of the polymerase chain reaction (PCR) test are barriers to diagnosis and treatment of hepatitis C virus (HCV) infection. We investigated the cost-effectiveness of testing strategies using antigen instead of PCR testing., Methods: We developed a mathematical model for HCV to estimate the number of diagnoses and cases of liver disease. We compared the following testing strategies: antibody test followed by PCR in case of positive antibody (baseline strategy); antibody test followed by HCV-antigen test (antibody-antigen); antigen test alone; PCR test alone. We conducted cost-effectiveness analyses considering either the costs of HCV testing of infected and uninfected individuals alone (A1), HCV testing and liver-related complications (A2), or all costs including HCV treatment (A3). The model was parameterized for the country of Georgia. We conducted several sensitivity analyses., Results: The baseline scenario could detect 89% of infected individuals. Antibody-antigen detected 86% and antigen alone 88% of infected individuals. PCR testing alone detected 91% of the infected individuals: the remaining 9% either died or spontaneously recovered before testing. In analysis A1, the baseline strategy was not essentially more expensive than antibody-antigen. In analysis A2, strategies using PCR became cheaper than antigen-based strategies. In analysis A3, antibody-antigen was again the cheapest strategy, followed by the baseline strategy, and PCR testing alone., Conclusions: Antigen testing, either following a positive antibody test or alone, performed almost as well as the current practice of HCV testing. The cost-effectiveness of these strategies depends on the inclusion of treatment costs., Competing Interests: The authors declare there are no competing interests. Sonjelle Shilton is employed by FIND, Geneva, Switzerland, Barbara Bertisch is employed by Checkin Helvetiaplatz and Maia Butsashvili is employed by Clinic Neolab., (©2021 Sadeghimehr et al.)

Background Lung ultrasound (LUS) and computed tomography (CT) can both be used for diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19), but the agreement between LUS and CT is unknown. Purpose to compare the agreement of LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19. Materials and Methods We searched PubMed, Cochrane library, Embase, Chinese Biomedicine Literature, and WHO COVID-19 databases to identify studies that compared LUS with CT in the diagnosis of interstitial pneumonia caused by COVID-19. We calculated the pooled overall, positive and negative percent agreements, diagnostic odds ratio (DOR) and the area under the standard receiver operating curve (SROC) for LUS in the diagnosis of COVID-19 compared with CT. Results We identified 1896 records, of which nine studies involving 531 patients were finally included. The pooled overall, positive and negative percentage agreements of LUS for the diagnosis of interstitial pneumonia caused by COVID-19 compared with CT were 81% (95% confidence interval [CI] 43-99%), 96% (95% CI, 80-99%, I 2 = 92.15%) and 80% (95%CI, 60-92%, I 2 = 92.85%), respectively. DOR was 37.41 (95% CI, 9.43-148.49, I 2 = 63.9%), and the area under the SROC curve was 0.94 (95% CI, 0.92-0.96). The quality of evidence for both specificity and sensitivity was low because of heterogeneity and risk of bias. Conclusion The level of diagnostic agreement between LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19 is high. LUS can be therefore considered as an equally accurate alternative for CT in situations where molecular tests are not available.

Background: Hundreds of coronavirus disease 2019 (COVID-19) clinical practice guidelines (CPGs) and expert consensus statements have been developed and published since the outbreak of the epidemic. However, these CPGs are of widely variable quality. So, this review is aimed at systematically evaluating the methodological and reporting qualities of COVID-19 CPGs, exploring factors that may influence their quality, and analyzing the change of recommendations in CPGs with evidence published., Methods: We searched five electronic databases and five websites from 1 January to 31 December 2020 to retrieve all COVID-19 CPGs. The assessment of the methodological and reporting qualities of CPGs was performed using the AGREE II instrument and RIGHT checklist. Recommendations and evidence used to make recommendations in the CPGs regarding some treatments for COVID-19 (remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir) were also systematically assessed. And the statistical inference was performed to identify factors associated with the quality of CPGs., Results: We included a total of 92 COVID-19 CPGs developed by 19 countries. Overall, the RIGHT checklist reporting rate of COVID-19 CPGs was 33.0%, and the AGREE II domain score was 30.4%. The overall methodological and reporting qualities of COVID-19 CPGs gradually improved during the year 2020. Factors associated with high methodological and reporting qualities included the evidence-based development process, management of conflicts of interest, and use of established rating systems to assess the quality of evidence and strength of recommendations. The recommendations of only seven (7.6%) CPGs were informed by a systematic review of evidence, and these seven CPGs have relatively high methodological and reporting qualities, in which six of them fully meet the Institute of Medicine (IOM) criteria of guidelines. Besides, a rapid advice CPG developed by the World Health Organization (WHO) of the seven CPGs got the highest overall scores in methodological (72.8%) and reporting qualities (83.8%). Many CPGs covered the same clinical questions (it refers to the clinical questions on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir in COVID-19 patients) and were published by different countries or organizations. Although randomized controlled trials and systematic reviews on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir for patients with COVID-19 have been published, the recommendations on those treatments still varied greatly across COVID-19 CPGs published in different countries or regions, which may suggest that the CPGs do not make sufficient use of the latest evidence., Conclusions: Both the methodological and reporting qualities of COVID-19 CPGs increased over time, but there is still room for further improvement. The lack of effective use of available evidence and management of conflicts of interest were the main reasons for the low quality of the CPGs. The use of formal rating systems for the quality of evidence and strength of recommendations may help to improve the quality of CPGs in the context of the COVID-19 pandemic. During the pandemic, we suggest developing a living guideline of which recommendations are supported by a systematic review for it can facilitate the timely translation of the latest research findings to clinical practice. We also suggest that CPG developers should register the guidelines in a registration platform at the beginning for it can reduce duplication development of guidelines on the same clinical question, increase the transparency of the development process, and promote cooperation among guideline developers all over the world. Since the International Practice Guideline Registry Platform has been created, developers could register guidelines prospectively and internationally on this platform., Competing Interests: Yaolong Chen was one of the founders of the RIGHT checklist. Zijun Wang, Qi Zhou, Qianling Shi, Shuya Lu, Qinyuan Li, and Yaolong Chen participated in the development of “Rapid advice guidelines for management of children with COVID-19.” Xiaohui Wang, Siya Zhao, Jin Cao, and Yaolong Chen participated in the development of “Traditional Chinese Medicine Guidelines for coronavirus disease 2019 (COVID-19).” Yaolong Chen also participated in the development of “Recommendation of respiratory rehabilitation for PICS in critically ill patients with COVID⁃19” as a methodologist. But all authors declare that there are no conflicts of interest affecting the current work., (Copyright © 2021 Siya Zhao et al.)

Background: The aim of this review was to explore the quality assessment checklists development methods in previous researches using standardized patients (SPs), as well as to propose an evidence-based checklist development procedure for quality assessment of common conditions in primary health care (PHC) settings., Methods: We conducted a systematic review of studies that described checklist development method and extracted the methodology in terms of the developer, the basis and processes. Based on that, we formulated the development procedure according to the recommendations of the WHO Handbook for Guideline Development., Results: We identified a total of 13 articles, and proposed the following five key steps: (I) forming a multidisciplinary team; (II) selecting and evaluating relevant references; (III) extracting medical information and forming the basic items; (IV) clinical expert consensus on the items; and (V) pre-testing the item pool and determining final items., Discussion: SP has been proven to be an effective method to assess performance in practice. There are still some deficiencies in the developing of case-specific checklists using SPs. To ensure the validity and reliability of checklists, the development processes need to be more standardized and procedural.

Background: We aimed to estimate the disease burden of Tuberculosis (TB) and return on investment of TB care in selected high-burden countries of the Western Pacific Region (WPR) until 2030., Methods: We projected the TB epidemic in Viet Nam and Lao People's Democratic Republic (PDR) 2020-2030 using a mathematical model under various scenarios: counterfactual (no TB care); baseline (TB care continues at current levels); and 12 different diagnosis and treatment interventions. We retrieved previous modeling results for China and the Philippines. We pooled the new and existing information on incidence and deaths in the four countries, covering >80% of the TB burden in WPR. We estimated the return on investment of TB care and interventions in Viet Nam and Lao PDR using a Solow model., Findings: In the baseline scenario, TB incidence in the four countries decreased from 97•0/100,000/year (2019) to 90•1/100,000/year (2030), and TB deaths from 83,300/year (2019) to 71,100/year (2030). Active case finding (ACF) strategies (screening people not seeking care for respiratory symptoms) were the most effective single interventions. Return on investment (2020-2030) for TB care in Viet Nam and Lao PDR ranged US$4-US$49/dollar spent; additional interventions brought up to US$2•7/dollar spent., Interpretation: In the modeled countries, TB incidence will only modestly decrease without additional interventions. Interventions that include ACF can reduce TB burden but achieving the End TB incidence and mortality targets will be difficult without new transformational tools (e.g. vaccine, new diagnostic tools, shorter treatment). However, TB care, even at its current level, can bring a multiple-fold return on investment., Funding: World Health Organization Western Pacific Regional Office; Swiss National Science Foundation Grant 163878., Competing Interests: This study was funded by the World Health Organization Western Pacific Regional Office and the Swiss National Science Foundation (Grant 163878). We declare no competing interests. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the WHO., (© 2021 World Health Organization; licensee Elsevier.)

Background: In December 2019, a pneumonia caused by SARS-CoV-2 emerged in Wuhan, China and has rapidly spread around the world since then. This study is to explore the patient characteristics and transmission chains of COVID-19 in the population of Gansu province, and support decision-making., Methods: We collected data from Gansu Province National Health Information Platform. A cross-sectional study was conducted, including patients with COVID-19 confirmed between January 23 and February 6, 2020, and analyzed the gender and age of the patients. We also described the incubation period, consultation time and sources of infection in the cases, and calculated the secondary cases that occurred within Gansu for each imported case., Results: We found thirty-six (53.7%) of the patients were women and thirty-one (46.3%) men, and the median ages were 40 (IQR 31-53) years. Twenty-eight (41.8%) of the 67 cases had a history of direct exposure in Wuhan. Twenty-five (52.2%) cases came from ten families, and we found no clear reports of modes of transmission other than family clusters. The largest number of secondary cases linked to a single source was nine., Conclusion: More women than men were diagnosed with COVID-19 in Gansu Province. Although the age range of confirmed cases of COVID-19 in Gansu Province covered almost all age groups, most patients with confirmed COVID-19 tend to be middle aged persons. The most common suspected mode of transmission was through family cluster. Gansu and other settings worldwide should continue to strengthen the utilization of big data in epidemic control.

Introduction: HIV incidence varies widely between sub-Saharan African (SSA) countries. This variation coincides with a substantial sociobehavioural heterogeneity, which complicates the design of effective interventions. In this study, we investigated how sociobehavioural heterogeneity in sub-Saharan Africa could account for the variance of HIV incidence between countries., Methods: We analysed aggregated data, at the national-level, from the most recent Demographic and Health Surveys of 29 SSA countries (2010-2017), which included 594,644 persons (183,310 men and 411,334 women). We preselected 48 demographic, socio-economic, behavioural and HIV-related attributes to describe each country. We used Principal Component Analysis to visualize sociobehavioural similarity between countries, and to identify the variables that accounted for most sociobehavioural variance in SSA. We used hierarchical clustering to identify groups of countries with similar sociobehavioural profiles, and we compared the distribution of HIV incidence (estimates from UNAIDS) and sociobehavioural variables within each cluster., Results: The most important characteristics, which explained 69% of sociobehavioural variance across SSA among the variables we assessed were: religion; male circumcision; number of sexual partners; literacy; uptake of HIV testing; women's empowerment; accepting attitude toward people living with HIV/AIDS; rurality; ART coverage; and, knowledge about AIDS. Our model revealed three groups of countries, each with characteristic sociobehavioural profiles. HIV incidence was mostly similar within each cluster and different between clusters (median (IQR); 0.5/1000 (0.6/1000), 1.8/1000 (1.3/1000) and 5.0/1000 (4.2/1000))., Conclusions: Our findings suggest that the combination of sociobehavioural factors play a key role in determining the course of the HIV epidemic, and that similar techniques can help to predict the effects of behavioural change on the HIV epidemic and to design targeted interventions to impede HIV transmission in SSA., Competing Interests: The authors declare there are no competing interests., (©2021 Merzouki et al.)

Background: Public or patient versions of guidelines (PVGs) are derivative documents that "translate" recommendations and their rationale from clinical guidelines for health professionals into a more easily understandable and usable format for patients and the public. PVGs from different groups and organizations vary considerably in terms of quality of their reporting. In order to address this issue, we aimed to develop a reporting checklist for developers of PVGs and other potential users., Methods: First, we collected a list of potential items through reviewing a sample of PVGs, existing guidance for developing and reporting PVGs or other similar evidence-based patient tools, as well as qualitative studies on original studies of patients' needs about the content and/or reporting of information in PVGs or similar evidence-based patient tools. Second, we conducted a two-round Delphi consultation to determine the level of consensus on the items to be included in the final reporting checklist. Third, we invited two external reviewers to provide comments on the checklist., Results: We generated the initial list of 45 reporting items based on a review of a sample of 30 PVGs, four PVG guidance documents, and 46 relevant studies. After the two-round Delphi consultation, we formed a checklist of 17 items grouped under 12 topics for reporting PVGs., Conclusion: The RIGHT-PVG reporting checklist provides an international consensus on the important criteria for reporting PVGs.

Background: Coronavirus disease 2019 (COVID-19) has become a constant threat to people's lives, bringing huge challenges to the global public health and medical service system. In order to ensure the timeliness and reliability of the recommendations in guidelines, the working group of the Rapid Advice Guidelines for Management of Children with COVID-19 decided to update the guideline to incorporate the latest evidence to guide the management of COVID-19 in children and adolescent., Methods: We will update the guidelines, originally developed as a rapid advice guideline, into a standard guideline. We will follow the clinical practice guideline (CPG) update manuals of the National Institute for Health and Clinical Excellence (NICE) and the Spanish National Health System (SNHS). The updated guidelines will also follow the RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist and Checklist for the Reporting of Updated Guidelines (CheckUp)., Discussion: Through systematic search, evaluation and grading of the best available relevant clinical evidence, combined with the experience of frontline clinical experts in the fight against the epidemic and the wishes of patients and their caretakers, we will update our previous rapid advice guidelines into a high-quality, implementable standard guidelines for the management of COVID-19 in children and adolescent., Trial Registration: The standard guideline update has been registered at the International Practice Guidelines Registry Platform (http://guidelines-registry.cn/?lang=en, registration No. IPGRP-2020CN101)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-290). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Background: In response to the ongoing epidemic of coronavirus disease 2019 (COVID-19), China has carried out restrictive disease containment measures across the country., Methods: In this cross-sectional study, we collected demographic and epidemiological data of 376 laboratory-confirmed cases of COVID-19 among children younger than 18 years of age. Using descriptive statistics and odds ratios, we described the odds of exposure outside the family after the implementation of control measures compared to before., Results: Children diagnosed on or after February 4, 2020, had a lower odds of exposure to COVID-19 outside of the family compared to those diagnosed before February 3, 2020 (OR =0.594, 95% CI: 0.391 to 0.904). In the stratified analysis, children aged 0 to 5 years had the lowest odds of exposure outside of the family (OR =0.420, 95% CI: 0.196 to 0.904) compared to the other age groups assessed., Conclusions: Our study on the children infected with COVID-19 as well as their exposure within family provided evidence that the implementation of containment measures was effective in reducing the odds of exposure outside of the family, especially for preschool children. Continuation of these efforts, coupled with tailored prevention and health education messaging for younger aged children, may help to reduce the transmission of COVID-19 among children until other therapeutic interventions or vaccines are available., Competing Interests: Conflicts of Interests: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-214).The authors have no conflict of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Background: Several systematic reviews and meta-analyses have assessed the association between egg consumption and human health, but the evidence is often conflicting., Methods: We conducted a systematic literature search to find all systematic reviews and meta-analyses that assess the association between egg consumption and any type of health outcome. We used AMSTAR to evaluate the methodological quality of the reviews, and GRADE to determine the quality of evidence. We visualized the results using a human anatomy diagram and evidence mapping., Results: Our search revealed 29 systematic reviews and meta-analyses. Eight studies were of high methodological quality, 16 studies of medium quality, and five studies of low quality. We identified 34 primary outcomes from the included 29 reviews, which were combined into a total of 22 different health outcomes. Two of the primary outcomes were based on high-quality evidence, 18 on moderate-quality evidence, and 14 on low-quality evidence. Egg consumption was associated with an increased risk of two diseases and decreased risk of six outcomes. For ten outcomes, no significant association was found, and for four outcomes, different reviews came to conflicting conclusions., Conclusions: The association between egg consumption and the risk of cancer, diabetes, cardiovascular diseases and other related diseases has been studied in several meta-analyses. The evidence from different studies on the same topic was often conflicting, which can complicate the making of dietary recommendations., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4243). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Introduction: Within many sub-Saharan African countries including Malawi, HIV prevalence varies widely between regions. This variability may be related to the distribution of population groups with specific sociobehavioural characteristics that influence the transmission of HIV and the uptake of prevention. In this study, we intended to identify groups of people in Malawi with similar risk profiles., Methods: We used data from the Demographic and Health Survey in Malawi (2015 to 2016), and stratified the analysis by sex. We considered demographic, socio-behavioural and HIV-related variables. Using Latent Class Analysis (LCA), we identified groups of people sharing common sociobehavioural characteristics. The optimal number of classes (groups) was selected based on the Bayesian information criterion. We compared the proportions of individuals belonging to the different groups across the three regions and 28 districts of Malawi., Results: We found nine groups of women and six groups of men. Most women in the groups with highest risk of being HIV positive were living in female-headed households and were formerly married or in a union. Among men, older men had the highest risk of being HIV positive, followed by young (20 to 25) single men. Generally, low HIV testing uptake correlated with lower risk of having HIV. However, rural adolescent girls had a low probability of being tested (48.7%) despite a relatively high HIV prevalence. Urban districts and the Southern region had a higher percentage of high-prevalence and less tested groups of individuals than other areas., Conclusions: LCA is an efficient method to find groups of people sharing common HIV risk profiles, identify particularly vulnerable sub-populations, and plan targeted interventions focusing on these groups. Tailored support, prevention and HIV testing programmes should focus particularly on female household heads, adolescent girls living in rural areas, older married men and young men who have never been married., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objectives: To compare and analyse the recommendations from clinical practice guidelines (CPGs) on gout worldwide, examine the consistency across CPGs, and provide suggestions to develop and update gout guidelines., Methods: We conducted systematic searches in MEDLINE, CBM, GIN, NICE, NGC, WHO, SIGN, DynaMed, UpToDate, and Best Practice databases, from their inception to August 2019 to identify and select CPGs related to gout. We used the search terms "gout", "hyperuricaemia" and "guideline". After two rounds of screening, we included the eligible CPGs of gout according to the pre-defined inclusion and exclusion criteria. Methodological quality of included guidelines was assessed with the AGREE-II instrument. The general characteristics of included guidelines and the recommendations were extracted, and the consistency of recommendations across guidelines was compared and analysed., Results: A total of 15 gout guidelines including 359 recommendations were retrieved. The main topics covered by the recommendations were diagnosis, pharmacologic treatment of gout flares, pharmacologic urate-lowering therapy (ULT) of chronic gouty arthritis, lifestyle interventions, prophylaxis, and management of asymptomatic hyperuricaemia. The results of AGREE-II appraisal showed that only two guidelines achieved high scores (≥50%) in all six domains. There was substantial discrepancy between the guidelines in recommendations covering the value of computed tomography (CT) and x-rays for diagnosis, the use of corticosteroids as a first-line treatment for flare, the use of colchicine, indications for ULT, the use of febuxostat as first-line ULT, the administration of allopurinol, and the timing of ULT initiation., Conlusions: A number of countries are devoting themselves to the development of gout guidelines, but the process of updating guidelines is slower than that suggested by the WHO. Methodological quality is not satisfactory in most guidelines, and recommendations between guidelines are not consistent.

The recent lifting of COVID-19 related restrictions in Switzerland causes uncertainty about the future of the epidemic. We developed a compartmental model for SARS-CoV-2 transmission in Switzerland and projected the course of the epidemic until the end of year 2020 under various scenarios. The model was age-structured with three categories: children (0-17), adults (18-64) and seniors (65- years). Lifting all restrictions according to the plans disclosed by the Swiss federal authorities by mid-May resulted in a rapid rebound in the epidemic, with the peak expected in July. Measures equivalent to at least 90% reduction in all contacts were able to eradicate the epidemic; a 56% reduction in contacts could keep the intensive care unit occupancy under the critical level and delay the next wave until October. In scenarios where strong contact reductions were only applied in selected age groups, the epidemic could not be suppressed, resulting in an increased risk of a rebound in July, and another stronger wave in September. Future interventions need to cover all age groups to keep the SARS-CoV-2 epidemic under control., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Estill J et al.)

[This corrects the article DOI: 10.21037/atm-20-3754.]., (2020 Annals of Translational Medicine. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3754). WMW reports that he is currently working for WHO and the position is responsible officer for pediatric care guidelines. The other authors have no conflicts of interest to declare.

Background: To clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children., Methods: A total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in western China were enrolled in this study and followed up until discharge and quarantine 14 days later., Results: Eleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD =7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test., Conclusions: Children with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3192). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

This project aims to evaluate the methods and reporting quality of practice guidelines of five different viruses that have caused Public Health Emergencies of International Concern (PHEIC) over 20 past years: the severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Zika virus and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We systematically searched databases, guideline websites and government health agency websites from their inception to February 02, 2020 to extract practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus, SARS-CoV-2 and the diseases they caused. The literature was screened independently by four researchers. Then, fifteen researchers evaluated the quality of included guidelines using the AGREE-II (Appraisal of Guidelines for Research and Evaluation II, for methodological quality) instrument and RIGHT (Reporting Items for practice Guidelines in Healthcare, for reporting quality) statement. Finally, a total of 81 guidelines were included, including 21 SARS-CoV guidelines, 11 Ebola virus (EBOV) guidelines, 9 MERS-CoV guidelines, 10 Zika Virus guidelines and 30 SARS-CoV-2 guidelines. The evaluation of the methodological quality indicated that the mean scores of each domain for guidelines of each virus were all below 60%, the scores for guidelines in the domains of "clarity of presentation" being the highest and in the "editorial independence" lowest. The mean reporting rate of each domain for guidelines of each virus was also less than 60%: the reporting rates for the domain "background" were highest, and for the domain "funding and interests" lowest. The methodological and reporting quality of the practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus and SARS-CoV-2 guidelines tend to be low. We recommend to follow evidence-based methodology and the RIGHT statement on reporting when developing guidelines., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.03.130). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

BackgroundIn December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then.AimThis study aims to understand the research gaps related to COVID-19 and propose recommendations for future research.MethodsWe undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies.ResultsWe included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R 0 ). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January.ConclusionThe number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.

Objective: The aim of this study was to assess the quality of global clinical practice guidelines (CPGs) on gout., Methods: We systematically searched MEDLINE, CBM (Chinese Biomedical Literature database), GIN (Guidelines International Network), NICE (National Institute for Health and Clinical Excellence), NGC (National Guideline Clearinghouse), WHO (World Health Organization), SIGN (Scottish Intercollegiate Guidelines Network), DynaMed, UpToDate, and Best Practice databases from their inception until January 2017 to identify and select CPGs related to gout. Two reviewers independently assessed the eligible gout CPGs using the AGREE II instrument., Results: We evaluated 15 CPGs published between 2007 and 2017, produced by 13 different developers. Quality of evidence and strength of recommendations were presented in 14 (93%) and 13 (87%) CPGs, respectively. The mean scores (±SD) for each AGREE II domain were as follows: (i) scope and purpose: 75% (±17%), (ii) stakeholder involvement: 39% (±19%), (iii) rigor of development: 43% (±17%), (iv) clarity and presentation: 82% (±14%), (v) applicability: 31% (±12%), and (vi) editorial independence: 23% (±29%)., Conclusions: The quality of gout CPGs was suboptimal, and various incompatible grading systems of quality of evidence and strength of recommendations were used. The use of a standardized international grading system is essential to ensure high methodological quality of gout CPGs. Tools such as AGREE II could substantially improve the development and update of future gout CPGs.

Introduction: Socio-behavioural factors may contribute to the wide variance in HIV prevalence between and within sub-Saharan African (SSA) countries. We studied the associations between socio-behavioural variables potentially related to the risk of acquiring HIV., Methods: We used Bayesian network models to study associations between socio-behavioural variables that may be related to HIV. A Bayesian network consists of nodes representing variables, and edges representing the conditional dependencies between variables. We analysed data from Demographic and Health Surveys conducted in 29 SSA countries between 2010 and 2016. We predefined and dichotomized 12 variables, including factors related to age, literacy, HIV knowledge, HIV testing, domestic violence, sexual activity and women's empowerment. We analysed data on men and women for each country separately and then summarized the results across the countries. We conducted a second analysis including also the individual HIV status in a subset of 23 countries where this information was available. We presented summary graphs showing associations that were present in at least six countries (five in the analysis with HIV status)., Results: We analysed data from 190,273 men (range across countries 2295 to 17,359) and 420,198 women (6621 to 38,948). The two variables with the highest total number of edges in the summary graphs were literacy and rural/urban location. Literacy was negatively associated with false beliefs about AIDS and, for women, early sexual initiation, in most countries. Literacy was also positively associated with ever being tested for HIV and the belief that women have the right to ask their husband to use condoms if he has a sexually transmitted infection. Rural location was positively associated with false beliefs about HIV and the belief that beating one's wife is justified, and negatively associated with having been tested for HIV. In the analysis including HIV status, being HIV positive was associated with female-headed household, older age and rural location among women, and with no variables among men., Conclusions: Literacy and urbanity were strongly associated with several factors that are important for HIV acquisition. Since literacy is one of the few variables that can be improved by interventions, this makes it a promising intervention target., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objectives: We examine long-term retention of adults, adolescents and children on antiretroviral therapy under different HIV treatment guidelines in Malawi., Design: Prospective cohort study., Setting and Participants: Adults and children starting ART between 2005 and 2015 in 21 health facilities in southern Malawi., Methods: We used survival analysis to assess retention at clinic level, Cox regression to examine risk factors for loss to follow up, and competing risk analysis to assess long-term outcomes of people on antiretroviral therapy (ART)., Results: We included 132,274 individuals in our analysis, totalling 270,256 person years of follow up (PYFU; median per patient 1.3, interquartile range (IQR) 0.26-3.1), 62% were female and the median age was 32 years. Retention on ART was lower in the first year on ART compared to subsequent years for all guideline periods and age groups. Infants (0-3 years), adolescents and young adults (15-24 years) were at highest risk of LTFU. Comparing the different calendar periods of ART initiation we found that retention improved initially, but remained stable thereafter., Conclusion: Even though the number of patients and the burden on health care system increased substantially during the study period of rapid ART expansion, retention on ART improved in the early years of ART provision, but gains in retention were not maintained over 5 years on ART. Reducing high attrition in the first year of ART should remain a priority for ART programs, and so should addressing poor retention among adolescents, young adults and men., Competing Interests: The authors have declared that no competing interests exist.

Objective: To analyse the epidemiological trends of tuberculosis in the Siberian and Far Eastern federal districts, the areas with the highest disease burden in the Russian Federation., Methods: We applied principal coordinate analysis to study a total of 68 relevant variables on tuberculosis epidemiology, prevention and control. Data on these variables were collected over 2003-2016 in all 21 regions of the Siberian federal district and Far Eastern federal district (total population: 25.5 million) through the federal and departmental reporting system. We identified the regions with a favourable or unfavourable tuberculosis epidemiological profile and ranked them as low or high priority for specific interventions., Findings: The median number of tuberculosis notifications in the regions was 123.3 per 100 000 population (range: 54.5-265.7) in 2003, decreasing to 82.3 per 100 000 (range: 52.9-178.3) in 2016. We found large variations in the tuberculosis epidemiological profile across different regions. The principal coordinate analysis revealed that three aggregated indicators accounted for 55% of the variation. The first coordinate corresponded to tuberculosis prevalence and case notifications in the regions; the second to the severity of the disease among patients; and the third to the percentage of multidrug-resistant tuberculosis among tuberculosis patients. The regions where intervention was most urgently needed were Chukotka Autonomous Okrug, Jewish Autonomous Oblast and Tyva Republic., Conclusion: The variability in tuberculosis epidemiology across regions was likely due to differences in the quality of antituberculosis services. Precision in defining necessary interventions, as determined through the principal coordinate analysis approach, can guide focused tuberculosis control efforts., ((c) 2019 The authors; licensee World Health Organization.)

Introduction: In recent years, assisted reproductive technology (ART) has developed rapidly, leading to an increasing number of clinical practice guidelines in this field. However, the reporting quality of current clinical practice guidelines in ART is still unknown. Objective To evaluate the reporting quality of clinical practice guidelines in the field of ART using the RIGHT checklist., Method: Relevant guidelines were identified by electronic search of PubMed, Chinese Biomedical Literature Database (CBM), Wan Fang Database and Chinese National Knowledge Infrastructure (CNKI) from the beginning of the database to October, 2017. We also searched the websites of the guideline development organizations, including Guidelines International Network (GIN), National Guideline Clearinghouse (NGC) and the National Institute for Health and Care Excellence (NICE), as well as from two medical associations, including the European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM). We used Google Scholar to find additional clinical practice guidelines (CPGs) as well. Two investigators searched the database, selected guidelines independently based on the inclusion criteria, and extracted the relevant information., Result: Fifteen guidelines (i.e. six developed by individual institutions and 9 by associations) were included. On average, 12.7 out of 35 items in the RIGHT standard (36.3%) were reported in each guideline. Five items were not reported by any of these guidelines. The reporting proportion of the seven domains (i.e. Basic information; Background; Evidence; Recommendations; Review and quality assurance; Funding and declaration and management of interests; Other information) were 46.7%, 40.8%, 45.3%, 29.5%, 53.3%, 10.0%, 26.7%, respectively., Conclusion: At present, the reporting quality of guidelines for ART is poor, especially regarding the funding. In the future guideline development, more consideration should be given to reporting, dissemination and implementation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Acupuncture is widely used worldwide, and systematic reviews on acupuncture are increasingly being published. Although acupuncture systematic reviews share several essential elements with other systematic reviews, some essential information for the application of acupuncture is not covered by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Considering this, we aimed to develop an extension of the PRISMA statement for acupuncture systematic reviews., Methods: We used the PRISMA statement as a starting point, and conducted this study referring to the development strategy recommended by the EQUATOR network. The initial items were collected through a wide survey among evidence users and a review of relevant studies. We conducted a three-round Delphi survey and one-day face-to-face meeting to select items and formulate the checklist. After the consensus meeting, we drafted the manuscript (including the checklist) and sent it to our advisory experts for comments, following which the checklist was refined and circulated to a group of acupuncture systematic review authors for pilot test. We also selected a sample of acupuncture systematic reviews published in 2017 to test the checklist., Results: A checklist of five new sub-items (including sub items) and six modified items was formulated, involving content related to title, rationale, eligibility criteria, literature search, data extraction, and study characteristics. We clarified the rationales of the items and provided examples for each item for additional guidance., Conclusion: The PRISMA for Acupuncture checklist is developed for improving the reporting of systematic reviews of acupuncture interventions., Trial Registration: We have registered the study on the EQUATOR network ( http://www.equator-network.org/library/reporting-guidelines-under-development/#91 ).

Introduction: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost-effective. To guide their HIV testing programmes, countries require appropriate metrics that can be measured. The cost-per-diagnosis is potentially a useful metric., Methods: We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of "core" testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core-testing as above plus additional testing beyond this ("additional-testing"), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosis and the incremental cost-effectiveness ratio (ICER) of the additional-testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars)., Results: There was a strong graded relationship between the cost-per-diagnosis and the ICER. Overall, the ICER was below $500 per-DALY-averted (the cost-effectiveness threshold used in primary analysis) so long as the cost-per-diagnosis was below $315. This threshold cost-per-diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional-testing did not appear cost-effective even at a cost-per-diagnosis of below $50, while restricting to men additional-testing was cost-effective up to a cost-per-diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost-effective fell to $256 when the cost-effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum., Conclusions: For testing programmes in low-income settings in southern African there is an extremely strong relationship between the cost-per-diagnosis and the cost-per-DALY averted, indicating that the cost-per-diagnosis can be used to monitor the cost-effectiveness of testing programmes., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objective: To assess the association between timing of maternal combination ART (cART) initiation and stillbirth among HIV-infected pregnant women in Malawi's Option B+ programme., Methods: Cohort study of HIV-infected pregnant women delivering singleton live or stillborn babies at ≥28 weeks of gestation using routine data from maternity registers between 1 January 2012 and 30 June 2015. We defined stillbirth as death of a foetus at ≥28 weeks of gestation. We report proportions of stillbirth according to timing of maternal cART initiation (before pregnancy, 1st or 2nd trimester, or 3rd trimester or labour). We used logistic regression, with robust standard errors to account for clustering of women within health facilities, to investigate the association between timing of cART initiation and stillbirth., Results: Of 10 558 mother-infant pairs abstracted from registers, 8380 (79.4%) met inclusion criteria. The overall rate of stillbirth was 25 per 1000 deliveries (95% confidence interval 22-29). We found no significant association between timing of maternal cART initiation and stillbirth. In multivariable models, older maternal age, male sex of the infant, breech vaginal delivery, delivery at < 34 weeks of gestation and experience of any maternal obstetric complication were associated with higher odds of stillbirth. Deliveries managed by a mission hospital or health centre were associated with lower odds of stillbirth., Conclusion: Pregnant women's exposure to cART, regardless of time of its initiation, was not associated with increased odds of stillbirth., (© 2019 John Wiley & Sons Ltd.)

Objectives: We systematically analysed recommendations from gout guidelines as an example, to provide a basis for developing a reporting standard of recommendations in clinical practice guidelines (CPGs)., Design: Systematic review without meta-analysis., Methods: We systematically searched MEDLINE and all relevant guideline websites (National Institute for Health and Care Excellence, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, WHO, Guidelines International Network, DynaMed, UpTodate, Best Practice) from their inception to January 2017 to identify and select gout CPGs. We used search terms such as 'gout', 'hyperuricemia' and 'guideline'. We included the eligible CPGs of gout according to the predefined inclusion and exclusion criteria after screening titles, abstracts and full texts. The characteristics of recommendations reported in the included guidelines were extracted and analysed., Results: A total of 15 gout guidelines with a range of 5-80 recommendations were retrieved. Several indicators were used in the gout guidelines to facilitate identification of recommendations, including grouping all recommendations in a summary section, formatting recommendations in a particular or special way, using locating words for recommendations and indicating the strength of recommendation and quality of evidence. We found some components commonly used in the recommendations. The wording of recommendations varied across guidelines. Recommendations were detailed and explained in the section of rationale and explanation of recommendations. In some guidelines, recommendations were accompanied with other material to assist their reporting., Conclusions: Variability and inconsistency were found on the reporting and presentation of recommendations in gout guidelines. Several points for reporting recommendation can be summarised. First, we suggested summarising and highlighting the core recommendations in a guideline. Second, guideline developers should try to structure and write recommendations reasonably. Third, it was necessary to detail and explain the recommendations and their rationale. Finally, describing and providing other potential useful contents was also a helpful way for clear reporting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The 90-90-90 target states that by 2020, 90% of people living with HIV should be diagnosed, 90% of those diagnosed treated, and 90% of those treated virally suppressed. We assessed the actions needed in each country of sub-Saharan Africa to achieve the 90-90-90 target., Methods: We developed a mathematical model to assess the number of patients needing to start antiretroviral therapy (ART) between 2017 and 2020 to achieve 81% coverage by 2020 in each country, and the proportion of treated patients who are virally suppressed in four scenarios, combining two scenarios of retention (current-level or perfect), and routine viral load monitoring (current or universal coverage). We performed two separate simulations, one using observed failure rates from cohort studies, and one with considerably lower failure rates to set a theoretical lower limit., Results: Our model projected that 2.9 million people started ART in 2017 in sub-Saharan Africa. If, depending on scenario, at least 2.2-2.7 million patients continue to start ART annually, 81% ART coverage will be reached in 2020 in sub-Saharan Africa on average. In 37% of the countries, a multiple-fold increase in annual number of patients starting ART is needed. Virological suppression >90% in 2020 could be reached only in the best-case scenario assuming low probability of treatment failure, elimination of treatment interruptions, and universal routine viral load monitoring., Conclusion: The 90-90-90 target is realistic in sub-Saharan Africa on average, but not necessarily in all individual countries. Each country should identify and focus on the specific gaps needing attention., (© 2018 John Wiley & Sons Ltd.)

Objective: To compare birth weight and weight gain in HIV-exposed, uninfected (HEU) infants up to 24 months old, who enrolled in the Malawian national HIV care clinic (HCC) programme either before or after Option B+ (OB+) was implemented., Design, Setting and Participants: HIV-exposed infants enrol in the HCC programme as soon as possible after birth and are followed up to at least 24 months old. This analysis includes HEU infants with recorded birth weight, date of birth, gender and at least one follow-up weight measurement from 21 health facilities in central and southern Malawi (January 2010-December 2014). Weight-for-age z scores (WAZ) were derived and compared by birth period using linear regression at birth and mixed effects models for postnatal weight gain up to 24 months old., Results: Of 6845 HEU infants included in this study, 88.5% were born after OB+. The proportion of infants exposed in utero to combination antiretroviral therapy (ART) significantly increased after OB+ was implemented, and infants were exposed to ART for a longer time. There was no significant difference in WAZ at birth (P = 0.654) among HEU infants by birth period, but postnatal weight gain was faster among HEU infants born in the Option B+ period than infants born pre-Option B+., Conclusion: Birth weight was not affected by longer exposure to ART during pregnancy after OB+ was introduced, when weight gain in HEU infants was faster, possibly because their mothers were in better health.

Objectives: We aimed to examine the declaration of interests (DOIs), management of conflict of interest (COI), and the funders for World Health Organization (WHO) guidelines., Study Design and Setting: We examined all Guidelines Review Committee (GRC)-approved WHO guidelines published in English from January 2007 (inception of the GRC) to November 2016. We obtained a list of all such guidelines from the GRC Secretariat. Characteristics of guidelines including funders and individual contributors' DOI were independently extracted by two researchers. Binary logistic regression was used to assess the association between declarations and the number of organizations involved in development., Results: A total of 176 guidelines fulfilled inclusion criteria, encompassing 14 clinical or public health fields. Funders were reported in 128 (73%) of the guidelines: the most common were governments. DOI for external contributors were reported in 157 (89%) of the guidelines: 75 (48%) indicated no contributors with COI, 57 (36%) reported contributors with COI, and 25 (16%) reported collecting DOI but not whether COI existed. Financial COI were reported more frequently than nonfinancial COI. Of 57 guidelines that reported COI, 45 (79%) indicated how the COI were managed., Conclusion: The majority of WHO guidelines reported their funding sources and the DOI and COI of external contributors in their guideline documents. However, there is a need for improvement, in particular for reporting of funders and their role, declaration processes, and management of COI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Antiretroviral therapy (ART) reduces HIV transmission, but treated patients may again become infectious. We used a mathematical model to determine whether ART as prevention is more effective if viral load (VL) is routinely monitored and patients lost to follow-up (LTFU) traced., Methods: We simulated ART cohorts to parameterize a deterministic transmission model calibrated to Malawi. We investigated the following strategies for improving treatment and retention: monitoring VL every 12 or 24 months, tracing patients LTFU, or a generic strategy leading to uninterrupted treatment. We tested 3 scenarios, where ART scale-up continues at current (Universal ART), reduced (Failed scale-up), or accelerated speed (Test&Treat)., Results: In the Universal ART scenario, between 2017 and 2020 (2050), monitoring VL every 24 months prevented 0.5% (0.9%), monitoring every 12 months prevented 0.8% (1.4%), tracing prevented 0.3% (0.5%), and uninterrupted treatment prevented 5.5% (9.9%) of HIV infections. Failed scale-up resulted in 25% more infections than the Universal ART scenarios, whereas Test&Treat resulted in 7%-8% less., Conclusions: Test&Treat reduces transmission of HIV, despite individual cases of treatment failure and ART interruption. Whereas viral load monitoring and tracing have only a minor impact on transmission, interventions that aim to minimize treatment interruptions can further increase the preventive effect of ART.

Background: Caesarean section (CS) is not recommended for PMTCT in Malawi HIV Guidelines, contrary to most high-income countries where CS is indicated if viral suppression is sub-optimal pre-delivery. We describe patterns of CS in HIV-infected and uninfected women in Malawi and explored if insight into the use of Elective CS (ECS) for PMTCT could be obtained., Methods: We used routinely collected data from individual medical records from 17 large health facilities in the central and southern regions of Malawi, from January 2010 to December 2013. We included data from maternity registers from all HIV-positive women, and randomly selected around every fourth woman with negative or unknown HIV status. We used multivariable logistic regressions and cluster-based robust standard errors to examine independent associations of patient- and facility characteristics with CS and ECS., Results: We included 62,033 women in the analysis. The weighted percentage of women who had a spontaneous vaginal delivery was 80.0% (CI 95% 79.5-80.4%); 2.4% (95% CI 2.3-2.6%) had a vacuum extraction; 2.3% (95% CI 2.2-2.5%) had a vaginal breech delivery; 14.0% (95% CI 13.6-14.4%) had a CS while for 1.3% (95% CI 1.2-1.4%) the mode of delivery was not recorded. Prevalence of CS without recorded medical or obstetric indication (ECS) was 5.1%, (n = 3152). Presence of maternal and infant complications and older age were independently associated with CS delivery. HIV-positive women were less likely to have ECS than HIV negative women (aOR 0.65; 95%-CI 0.57-0.74). Among HIV-positive women, those on antiretrovirals (ARV's) for ≥4 weeks prior to delivery were less likely to have ECS than HIV-positive women who had not received ARVs during pregnancy (aOR 0.81; 95% CI 0.68-0.96)., Conclusions: The pattern of CS's in Malawi is largely determined by maternal and infant complications. Positive HIV status was negatively associated with CS delivery, possibly because health care workers were concerned about the risk of occupational HIV transmission and the known increased risk of post-operative complications. Our results leave open the possibility that CS is practiced to prevent MTCT given that ECS was more common among women at high risk of MTCT due to no or short exposure to ARV's.

Background: To move towards ending AIDS by 2030, HIV resources should be allocated cost-effectively. We used the Optima HIV model to estimate how global HIV resources could be retargeted for greatest epidemiological effect and how many additional new infections could be averted by 2030., Methods: We collated standard data used in country modelling exercises (including demographic, epidemiological, behavioural, programmatic, and expenditure data) from Jan 1, 2000, to Dec 31, 2015 for 44 countries, capturing 80% of people living with HIV worldwide. These data were used to parameterise separate subnational and national models within the Optima HIV framework. To estimate optimal resource allocation at subnational, national, regional, and global levels, we used an adaptive stochastic descent optimisation algorithm in combination with the epidemic models and cost functions for each programme in each country. Optimal allocation analyses were done with international HIV funds remaining the same to each country and by redistributing these funds between countries., Findings: Without additional funding, if countries were to optimally allocate their HIV resources from 2016 to 2030, we estimate that an additional 7·4 million (uncertainty range 3·9 million-14·0 million) new infections could be averted, representing a 26% (uncertainty range 13-50%) incidence reduction. Redistribution of international funds between countries could avert a further 1·9 million infections, which represents a 33% (uncertainty range 20-58%) incidence reduction overall. To reduce HIV incidence by 90% relative to 2010, we estimate that more than a three-fold increase of current annual funds will be necessary until 2030. The most common priorities for optimal resource reallocation are to scale up treatment and prevention programmes targeting key populations at greatest risk in each setting. Prioritisation of other HIV programmes depends on the epidemiology and cost-effectiveness of service delivery in each setting as well as resource availability., Interpretation: Further reductions in global HIV incidence are possible through improved targeting of international and national HIV resources., Funding: World Bank and Australian NHMRC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: With limited funds available, meeting global health targets requires countries to both mobilize and prioritize their health spending. Within this context, countries have recognized the importance of allocating funds for HIV as efficiently as possible to maximize impact. Over the past six years, the governments of 23 countries in Africa, Asia, Eastern Europe and Latin America have used the Optima HIV tool to estimate the optimal allocation of HIV resources., Methods: Each study commenced with a request by the national government for technical assistance in conducting an HIV allocative efficiency study using Optima HIV. Each study team validated the required data, calibrated the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost functions for interventions, and used the model to calculate the optimal allocation of available funds to best address national strategic plan targets. From a review and analysis of these 23 country studies, we extract common themes around the optimal allocation of HIV funding in different epidemiological contexts., Results and Discussion: The optimal distribution of HIV resources depends on the amount of funding available and the characteristics of each country's epidemic, response and targets. Universally, the modelling results indicated that scaling up treatment coverage is an efficient use of resources. There is scope for efficiency gains by targeting the HIV response towards the populations and geographical regions where HIV incidence is highest. Across a range of countries, the model results indicate that a more efficient allocation of HIV resources could reduce cumulative new HIV infections by an average of 18% over the years to 2020 and 25% over the years to 2030, along with an approximately 25% reduction in deaths for both timelines. However, in most countries this would still not be sufficient to meet the targets of the national strategic plan, with modelling results indicating that budget increases of up to 185% would be required., Conclusions: Greater epidemiological impact would be possible through better targeting of existing resources, but additional resources would still be required to meet targets. Allocative efficiency models have proven valuable in improving the HIV planning and budgeting process., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Objectives: To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe., Methods: Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program. Risk factors for major PI resistance were assessed by logistic regression. Third-line treatment was provided as Darunavir/r, Raltegravir, or Dolutegravir and Zidovudine, Abacavir Lamivudine, or Tenofovir., Results: Genotypes were performed on 86 patients who had good adherence to treatment. The median duration of first- and second-line ART was 3.8 years (interquartile range [IQR], 2.3-5.1) and 2.6 years (IQR, 1.6-4.9), respectively. The median HIV viral load and CD4 cell count were 65 210 copies/mL (IQR, 8728-208 920 copies/mL) and 201 cells/mm 3 (IQR, 49-333 cells/mm 3 ). Major PI resistance-associated mutations (RAMs) were demonstrated in 44 (51%) non-nucleoside reverse transcriptase inhibitor RAMs in 72 patients (83%) and nucleoside reverse transcriptase inhibitors RAMs in 62 patients (72%). PI resistance was associated with age >24 years ( P = .003) and CD4 cell count <200 cells/mm 3 ( P = .007). In multivariable analysis, only age >24 years was significantly associated (adjusted odds ratio, 4.75; 95% confidence interval, 1.69-13.38; P = .003) with major PI mutations. Third-line DRV/r- and InSTI-based therapy achieved virologic suppression in 29/36 patients (81%) after 6 months., Conclusions: The prevelance of PI mutations was high. Adolescents and young adults had a lower risk of acquiring major PI resistance mutations, possibly due to poor adherence to ART. Third-line treatment with a regimen of Darunavir/r, Raltegravir/Dolutegravir, and optimized nucleoside reverse transcriptase inhibitors was effective.

Background: Prioritizing investments across health interventions is complicated by the nonlinear relationship between intervention coverage and epidemiological outcomes. It can be difficult for countries to know which interventions to prioritize for greatest epidemiological impact, particularly when budgets are uncertain., Methods: We examined four case studies of HIV epidemics in diverse settings, each with different characteristics. These case studies were based on public data available for Belarus, Peru, Togo, and Myanmar. The Optima HIV model and software package was used to estimate the optimal distribution of resources across interventions associated with a range of budget envelopes. We constructed "investment staircases", a useful tool for understanding investment priorities. These were used to estimate the best attainable cost-effectiveness of the response at each investment level., Findings: We find that when budgets are very limited, the optimal HIV response consists of a smaller number of 'core' interventions. As budgets increase, those core interventions should first be scaled up, and then new interventions introduced. We estimate that the cost-effectiveness of HIV programming decreases as investment levels increase, but that the overall cost-effectiveness remains below GDP per capita., Significance: It is important for HIV programming to respond effectively to the overall level of funding availability. The analytic tools presented here can help to guide program planners understand the most cost-effective HIV responses and plan for an uncertain future.

Background: The incidence of anal cancer is high in HIV-positive MSM. We modeled the impact of screening strategies and combination antiretroviral therapy (cART) coverage on anal cancer incidence in Switzerland., Methods: Individual-based, dynamic simulation model parameterized with Swiss HIV Cohort Study and literature data. We assumed all men to be human papillomavirus infected. CD4 cell count trajectories were the main predictors of anal cancer. From 2016 we modeled cART coverage either as below 100% (corresponding to 2010-2015) or as 100%, and the following four screening strategies: no screening, yearly anal cytology (Papanicolaou smears), yearly anoscopy and targeted anoscopy 5 years after CD4 count dropped below 200 cells/μl., Results: Median nadir CD4 cell count of 6411 MSM increased from 229 cells/μl during 1980-1989 to 394 cells/μl during 2010-2015; cART coverage increased from 0 to 83.4%. Modeled anal cancer incidence peaked at 81.7/100 000 in 2009, plateaued 2010-2015 and will decrease to 58.7 by 2030 with stable cART coverage, and to 52.0 with 100% cART coverage. With yearly cytology, incidence declined to 38.2/100 000 by 2030, with yearly anoscopy to 32.8 and with CD4 cell count guided anoscopy to 51.3. The numbers needed to screen over 15 years to prevent one anal cancer case were 384 for yearly cytology, 313 for yearly anoscopy and 242 for CD4 cell count-dependent screening., Conclusion: Yearly screening of HIV-positive MSM may reduce anal cancer incidence substantially, with a number needed to screen that is comparable with other screening interventions to prevent cancer.

Background: Adherence to antiretroviral therapy (ART) is crucial to preventing mother-to-child transmission of human immunodeficiency virus (HIV) and ensuring the long-term effectiveness of ART, yet data are sparse from African routine care programs on maternal adherence to triple ART., Methods: We analyzed data from women who started ART at 13 large health facilities in Malawi between September 2011 and October 2013. We defined adherence as the percentage of days "covered" by pharmacy claims. Adherence of ≥90% was deemed adequate. We calculated inverse probability of censoring weights to adjust adherence estimates for informative censoring. We used descriptive statistics, survival analysis, and pooled logistic regression to compare adherence between pregnant and breastfeeding women eligible for ART under Option B+, and nonpregnant and nonbreastfeeding women who started ART with low CD4 cell counts or World Health Organization clinical stage 3/4 disease., Results: Adherence was adequate for 73% of the women during pregnancy, for 66% in the first 3 months post partum, and for about 75% during months 4-21 post partum. About 70% of women who started ART during pregnancy and breastfeeding adhered adequately during the first 2 years of ART, but only about 30% of them had maintained adequate adherence at every visit. Risk factors for inadequate adherence included starting ART with an Option B+ indication, at a younger age, or at a district hospital or health center., Conclusions: One-third of women retained in the Option B+ program adhered inadequately during pregnancy and breastfeeding, especially soon after delivery. Effective interventions to improve adherence among women in this program should be implemented., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background & Aims: Hepatitis C (HCV) is a leading cause of morbidity and mortality in people who live with HIV. In many countries, access to direct acting antiviral agents to treat HCV is restricted to individuals with advanced liver disease (METAVIR stage F3 or F4). Our goal was to estimate the long term impact of deferring HCV treatment for men who have sex with men (MSM) who are coinfected with HIV and often have multiple risk factors for liver disease progression., Methods: We developed an individual-based model of liver disease progression in HIV/HCV coinfected MSM. We estimated liver-related morbidity and mortality as well as the median time spent with replicating HCV infection when individuals were treated in liver fibrosis stages F0, F1, F2, F3 or F4 on the METAVIR scale., Results: The percentage of individuals who died of liver-related complications was 2% if treatment was initiated in F0 or F1. It increased to 3% if treatment was deferred until F2, 7% if it was deferred until F3 and 22% if deferred until F4. The median time individuals spent with replicating HCV increased from 5years if treatment was initiated in F2 to almost 15years if it was deferred until F4., Conclusions: Deferring HCV therapy until advanced liver fibrosis is established could increase liver-related morbidity and mortality in HIV/HCV coinfected individuals, and substantially prolong the time individuals spend with a replicating HCV infection., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)