Adverse perinatal outcomes associated with timing of initiation of antiretroviral therapy: Systematic review and meta-analysis.

BACKGROUND: The World Health Organization (WHO) recommends immediate initiation of lifelong antiretroviral therapy (ART) for all people living with HIV, including pregnant women. As a result, an increasing number of women living with HIV conceive while taking ART, the vast majority of whom reside in low- and middle-income countries (LMICs). We aimed to assess the association between timing of ART initiation and perinatal outcomes. METHODS: We conducted a systematic literature review by searching PubMed, CINAHL (EBSCOhost), Global Health (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials and four clinical trial databases (WHO International Clinical Trials Registry Platform, the Pan African Clinical Trials Registry, the ClinicalTrials.gov database, and the ISRCTN Registry) from 1 January 1980 to 28 April 2018. We identified studies reporting specific perinatal outcomes among pregnant women living with HIV according to timing of ART initiation and extracted data. Perinatal outcomes assessed were preterm birth (<37 weeks), very preterm birth (<32 weeks), low birthweight (<2500 g), very low birthweight (<1500 g), small for gestational age (<10th centile), very small for gestational age (<3rd centile) and neonatal death (<29 days). Random-effects meta-analyses examined perinatal outcomes associated with preconception and antenatal ART initiation as well as according to trimesters of antenatal initiation. We performed quality assessments and subgroup and sensitivity analyses, and assessed the effect of adjustment for confounders. This systematic review and meta-analyses is registered with PROSPERO, number CRD42021248987. RESULTS: Of 51 874 unique citations, 25 studies (eight prospective and 17 retrospective cohort studies) were eligible for analysis, including 40 920 women living with HIV. Preconception ART initiation was associated with a significantly increased risk of preterm birth (relative risk 1.16; 95% confidence interval [CI] 1.03-1.31) compared with antenatal ART initiation. Preconception ART initiation was not significantly associated with very preterm birth, low birthweight, very low birthweight, small for gestational age, very small for gestational age, or neonatal death. First trimester exposure (i.e. preconception or first trimester initiation) was not significantly associated with any increased risk of adverse perinatal outcomes. No significant association between timing of ART initiation and adverse perinatal outcomes was found in the studies of higher quality and those conducted in LMICs. CONCLUSION: Preconception ART initiation is associated with preterm birth but no other adverse perinatal outcomes. In LMICs, where most pregnant women living with HIV reside, the timing of ART initiation was not associated with any adverse perinatal outcomes.

Methodological conduct of prognostic prediction models developed using machine learning in oncology: a systematic review.

BACKGROUND: Describe and evaluate the methodological conduct of prognostic prediction models developed using machine learning methods in oncology. METHODS: We conducted a systematic review in MEDLINE and Embase between 01/01/2019 and 05/09/2019, for studies developing a prognostic prediction model using machine learning methods in oncology. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, Prediction model Risk Of Bias ASsessment Tool (PROBAST) and CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) to assess the methodological conduct of included publications. Results were summarised by modelling type: regression-, non-regression-based and ensemble machine learning models. RESULTS: Sixty-two publications met inclusion criteria developing 152 models across all publications. Forty-two models were regression-based, 71 were non-regression-based and 39 were ensemble models. A median of 647 individuals (IQR: 203 to 4059) and 195 events (IQR: 38 to 1269) were used for model development, and 553 individuals (IQR: 69 to 3069) and 50 events (IQR: 17.5 to 326.5) for model validation. A higher number of events per predictor was used for developing regression-based models (median: 8, IQR: 7.1 to 23.5), compared to alternative machine learning (median: 3.4, IQR: 1.1 to 19.1) and ensemble models (median: 1.7, IQR: 1.1 to 6). Sample size was rarely justified (n = 5/62; 8%). Some or all continuous predictors were categorised before modelling in 24 studies (39%). 46% (n = 24/62) of models reporting predictor selection before modelling used univariable analyses, and common method across all modelling types. Ten out of 24 models for time-to-event outcomes accounted for censoring (42%). A split sample approach was the most popular method for internal validation (n = 25/62, 40%). Calibration was reported in 11 studies. Less than half of models were reported or made available. CONCLUSIONS: The methodological conduct of machine learning based clinical prediction models is poor. Guidance is urgently needed, with increased awareness and education of minimum prediction modelling standards. Particular focus is needed on sample size estimation, development and validation analysis methods, and ensuring the model is available for independent validation, to improve quality of machine learning based clinical prediction models.

Country Level Diversity of the HIV-1 Pandemic between 1990 and 2015.

The global diversity of HIV forms a major challenge to the development of an HIV vaccine, as well as diagnostic, drug resistance, and viral load assays, which are essential to reaching the UNAIDS 90:90:90 targets. We sought to determine country level HIV-1 diversity globally between 1990 and 2015. We assembled a global HIV-1 molecular epidemiology database through a systematic literature search and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from 1 January 1990 to 31 December 2015. We collected additional unpublished data through a global survey of experts. Prevalence studies with original HIV-1 subtyping data collected between 1990 and 2015 were included. This resulted in a database with 383,519 subtyped HIV-1 samples from 116 countries over four time periods (1990 to 1999, 2000 to 2004, 2005 to 2009, and 2010 to 2015). We analyzed country-specific numbers of distinct HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in each time period. We also analyzed country-specific proportions of infections due to HIV-1 recombinants, CRFs, and URFs and calculated the Shannon diversity index for each country. Finally, we analyzed global temporal trends in each of these measures of HIV-1 diversity. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries such as Chad, Democratic Republic of the Congo, Angola, and Republic of the Congo have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe (Spain and France) and North America (United States) (up to 39 distinct HIV-1 variants in Spain). The proportion of HIV-1 infections due to recombinants was highest in Southeast Asia (>95% of infections in Viet Nam, Cambodia, and Thailand), China, and West and Central Africa, mainly due to high proportions of CRF01_AE and CRF02_AG. Other CRFs played major roles (>75% of HIV-1 infections) in Estonia (CRF06_cpx), Iran (CRF35_AD), and Algeria (CRF06_cpx). The highest proportions of URFs (>30%) were found in Myanmar, Republic of the Congo, and Argentina. Global temporal analysis showed consistent increases over time in country level numbers of distinct HIV-1 variants and proportions of CRFs and URFs, leading to increases in country level HIV-1 diversity. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to prevention and treatment efforts. HIV-1 molecular epidemiological surveillance needs to be continued and improved.IMPORTANCE This is the first study to analyze global country level HIV-1 diversity from 1990 to 2015. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe and North America. The proportion of HIV-1 infections due to recombinants was highest in South-East Asia, China, and West and Central Africa. The highest proportions of URFs were found in Myanmar, Republic of the Congo, and Argentina. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to HIV vaccine development and diagnostic, drug resistance, and viral load assays.

PRISMA-S: an extension to the PRISMA statement for reporting literature searches in systematic reviews.

BACKGROUND: Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration. METHODS: The checklist was developed using a three-stage Delphi survey process, followed by a consensus conference and public review process. RESULTS: The final checklist includes sixteen reporting items, each of which is detailed with exemplar reporting and rationale. CONCLUSIONS: The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and, therefore, reproducible.

Risk Factors for Mobility Decline in Community-Dwelling Older Adults: A Systematic Literature Review.

Mobility is essential to maintaining independence for older adults. This systematic review aimed to summarize evidence about self-reported risk factors for self-reported mobility decline; and to provide an overview of published prognostic models for self-reported mobility decline among community-dwelling older adults. Databases were searched from inception to June 2, 2020. Studies were screened by two independent reviewers who extracted data and assessed study quality. Sixty-one studies (45,187 participants) were included, providing information on 107 risk factors. High-quality evidence and moderate/large effect sizes for the association with mobility decline were found for older age beyond 75 years, the presence of widespread pain, and mobility modifications. Moderate-high quality evidence and small effect sizes were found for a further 21 factors. Three model development studies demonstrated acceptable model performance, limited by high risk of bias. These findings should be considered in intervention development, and in developing a prediction instrument for practical application.

A systematic review exploring the evidence reported to underpin exercise dose in clinical trials of rheumatoid arthritis.

We aimed to evaluate the evidence reported to underpin exercise dose in randomised controlled trials (RCTs) using strengthening exercise in RA. We searched six different databases between 1 January 2000 and 3 April 2019. We included RCTs, where a main component of the intervention and/or control used strengthening exercise. Evidence sources cited to underpin dose were judged for their quality, consistency and applicability. Thirty-two RCTs were reviewed. Four (12.5%) piloted the intervention without using dose-escalation designs to determine optimal dose-response. Twenty (62.5%) reported no evidence underpinning dose. Where reported, quality, consistency and applicability of the underpinning evidence was a cause for methodological concern. The majority of RCTs did not report the evidence underpinning dose. When reported, the evidence was often not applicable to the clinical population. Frequently, the dose used differed to the dose reported/recommended by the underpinning evidence. Our findings illustrate exercise dose may not be optimised for use with clinical populations prior to evaluation by RCT.

Reporting guidelines for oncology research: helping to maximise the impact of your research.

Many reports of health research omit important information needed to assess their methodological robustness and clinical relevance. Without clear and complete reporting, it is not possible to identify flaws or biases, reproduce successful interventions, or use the findings in systematic reviews or meta-analyses. The EQUATOR Network (http://www.equator-network.org/) promotes responsible reporting and the use of reporting guidelines to improve the accuracy, completeness, and transparency of health research. EQUATOR supports researchers by providing online resources and training. EQUATOR Oncology, a project funded by Cancer Research UK, aims to support cancer researchers reporting their research through the provision of online resources. In this article, our objective is to highlight reporting issues related to oncology research publications and to introduce reporting guidelines that are designed to aid high-quality reporting. We describe generic reporting guidelines for the main study types, and explain how these guidelines should and should not be used. We also describe 37 oncology-specific reporting guidelines, covering different clinical areas (e.g., haematology or urology) and sections of the report (e.g., methods or study characteristics); most of these are little-used. We also provide some background information on EQUATOR Oncology, which focuses on addressing the reporting needs of the oncology research community.

The miRNA Mirage: How Close Are We to Finding a Non-Invasive Diagnostic Biomarker in Endometriosis? A Systematic Review.

BACKGROUND: Endometriosis is a common disorder of the reproductive age group, characterised by the presence of ectopic endometrial tissue. The disease not only causes enormous suffering to the affected women, but also brings a tremendous medical and economic burden to bear on society. There is a long lag phase between the onset and diagnosis of the disease, mainly due to its non-specific symptoms and the lack of a non-invasive test. Endometriosis can only be diagnosed invasively by laparoscopy. A specific, non-invasive test to diagnose endometriosis is an unmet clinical need. The recent discovery of microRNAs (miRNAs) as modulators of gene expression, and their stability and specificity, make them an attractive candidate biomarker. Various studies on miRNAs in endometriosis have identified their cardinal role in the pathogenesis of the disease, and have proposed them as potential biomarkers in endometriosis. Rationale/Objectives: The aims of this review were to study the role of circulatory miRNAs in endometriosis, and bring to light whether circulatory miRNAs could be potential non-invasive biomarkers to diagnose the disease. SEARCH METHODS: Three databases, PubMed, EMBASE, and BIOSIS were searched, using a combination of Mesh or Emtree headings and free-text terms, to identify literature relating to circulating miRNAs in endometriosis published from 1996 to 31 December 2017. Only peer-reviewed, full-text original research articles in English were included in the current review. The studies meeting the inclusion criteria were critically assessed and checked using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. The dysregulated miRNAs were assessed regarding the concordance between the various studies and their role in the disease. OUTCOMES: Nine studies were critically analysed, and 42 different miRNAs were found to be dysregulated in them, with only one common miRNA (miR-20a) differentially expressed in more than one study. miR-17-5p/20a, miR-200, miR-199a, miR-143, and miR-145 were explored for their pivotal role in the aetiopathogenesis of endometriosis. Wider implications: It is emerging that miRNAs play a central role in the pathogenesis of endometriosis and have the potential of being promising biomarkers. Circulating miRNAs as a non-invasive diagnostic tool may shorten the delay in the diagnosis of the disease, thus alleviating the suffering of women and reducing the burden on health care systems. However, despite numerous studies on circulating miRNAs in endometriosis, no single miRNA or any panel of them seems to meet the criteria of a diagnostic biomarker. The disagreement between the various studies upholds the demand of larger, well-controlled systematic validation studies with uniformity in the research approaches and involving diverse populations.

Perinatal outcomes associated with pre-exposure prophylaxis for HIV prevention during pregnancy: a systematic review and meta-analysis.

Background: The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and long-acting intramuscular injectable cabotegravir (CAB-LA) for HIV prevention in populations at substantial risk of HIV infection. Pregnancy is a period of elevated risk of maternal HIV infection and transmission to the infant. This systematic review and meta-analysis assessed the risk of adverse perinatal outcomes among HIV-negative pregnant women with exposure to any PrEP modality. Methods: We conducted a systematic review by searching Medline, EMBASE, CINAHL, Global Health, the Cochrane Library, WHO ICTR, ISRCTN, PACTR, and ClinicalTrials.gov for studies published between 1 January 2000 and 29 August 2023. We included studies reporting on the association of antenatal exposure to any PrEP modality with 13 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, spontaneous very PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA, miscarriage, stillbirth, or neonatal death (NND). Quality assessments of included studies were performed. Fixed-effect meta-analyses were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The protocol is registered with PROSPERO, CRD42022339825. Findings: Of 18,598 citations identified, 13 studies (eight randomised controlled trials (RCTs) and five cohort studies), assessing 8712 pregnant women in Africa, were included. Oral PrEP, compared to no PrEP, was not associated with PTB in meta-analyses of six RCTs (OR 0.73, 95% CI 0.43-1.26; I2 = 0.0%) or five unadjusted cohort studies (OR 0.84, 95% CI 0.69-1.03; I2 = 0.0%), but was associated with a reduced risk of PTB in three adjusted cohort studies (aOR 0.67; 95% CI 0.52-0.88, I2 = 0.0%). There was no association of oral PrEP with LBW, vLBW, SGA, or NND, compared to no PrEP. There was no association with PTB when oral TDF/emtricitabine (FTC) PrEP, oral TDF PrEP, and tenofovir vaginal gel were compared to each other. There was no association of the dapivirine vaginal ring with PTB or NND, compared to placebo or oral TDF/FTC PrEP. We found no data on CAB-LA. Interpretation: We found no evidence of adverse perinatal outcomes associated with PrEP exposure during pregnancy. Our findings support the WHO recommendation to provide oral PrEP to women of reproductive age and pregnant women. More data is needed to assess the safety of all PrEP modalities in pregnancy. Funding: None.

Prediction model protocols indicate better adherence to recommended guidelines for study conduct and reporting.

BACKGROUND AND OBJECTIVE: Protocols are invaluable documents for any research study, especially for prediction model studies. However, the mere existence of a protocol is insufficient if key details are omitted. We reviewed the reporting content and details of the proposed design and methods reported in published protocols for prediction model research. METHODS: We searched MEDLINE, Embase, and the Web of Science Core Collection for protocols for studies developing or validating a diagnostic or prognostic model using any modeling approach in any clinical area. We screened protocols published between Jan 1, 2022 and June 30, 2022. We used the abstract, introduction, methods, and discussion sections of The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement to inform data extraction. RESULTS: We identified 30 protocols, of which 28 were describing plans for model development and six for model validation. All protocols were open access, including a preprint. 15 protocols reported prospectively collecting data. 21 protocols planned to use clustered data, of which one-third planned methods to account for it. A planned sample size was reported for 93% development and 67% validation analyses. 16 protocols reported details of study registration, but all protocols reported a statement on ethics approval. Plans for data sharing were reported in 13 protocols. CONCLUSION: Protocols for prediction model studies are uncommon, and few are made publicly available. Those that are available were reasonably well-reported and often described their methods following current prediction model research recommendations, likely leading to better reporting and methods in the actual study.

Comparative risk of adverse perinatal outcomes associated with classes of antiretroviral therapy in pregnant women living with HIV: systematic review and meta-analysis.

Background: Integrase strand transfer inhibitor (INSTI) dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended by World Health Organisation as preferred first-line regimen in pregnant women living with human immunodeficiency virus (HIV) (WLHIV). Non-nucleoside reverse transfer inhibitor (NNRTI)-based ART and protease inhibitor (PI)-based ART are designated as alternative regimens. The impact of different ART regimens on perinatal outcomes is uncertain. We aimed to assess the comparative risk of adverse perinatal outcomes in WLHIV receiving different classes of ART. Materials and methods: A systematic literature review was conducted by searching PubMed, CINAHL, Global Health, and EMBASE for studies published between Jan 1, 1980, and July 14, 2023. We included studies reporting on the association of pregnant WLHIV receiving different classes of ART with 11 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Pairwise random-effects meta-analyses compared the risk of each adverse perinatal outcome among WLHIV receiving INSTI-ART, NNRTI-ART, PI-ART, and nucleoside reverse transfer inhibitor (NRTI)-based ART, and compared specific "third drugs" from different ART classes. Subgroup and sensitivity analyses were conducted based on country income status and study quality. Results: Thirty cohort studies published in 2006-2022, including 222,312 pregnant women, met the eligibility criteria. Random-effects meta-analyses found no evidence that INSTI-ART is associated with adverse perinatal outcomes compared to NNRTI-ART and PI-ART. We found that PI-ART is associated with a significantly increased risk of SGA (RR 1.28, 95% confidence interval (95% CI) [1.09, 1.51], p = 0.003) and VSGA (RR 1.41, 95% CI [1.08, 1.83], p = 0.011), compared to NNRTI-ART. Specifically, lopinavir/ritonavir (LPV/r) was associated with an increased risk of SGA (RR 1.40, 95% CI [1.18, 1.65], p = 0.003) and VSGA (RR 1.84, 95% CI [1.37, 2.45], p = 0.002), compared to efavirenz, but not compared to nevirapine. We found no evidence that any class of ART or specific "third drug" was associated with an increased risk of PTB. Conclusion: Our findings support the recommendation of INSTI-ART as first-line ART regimen for use in pregnant WLHIV. However, the increased risks of SGA and VGSA associated with PI-ART, compared to NNRTI-ART, may impact choice of second- and third-line ART regimens in pregnancy.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021248987.

Reporting completeness of nutrition and diet-related randomised controlled trials protocols.

BACKGROUND AND AIMS: There is a need to consolidate reporting guidance for nutrition randomised controlled trial (RCT) protocols. The reporting completeness in nutrition RCT protocols and study characteristics associated with adherence to SPIRIT and TIDieR reporting guidelines are unknown. We, therefore, assessed reporting completeness and its potential predictors in a random sample of published nutrition and diet-related RCT protocols. METHODS: We conducted a meta-research study of 200 nutrition and diet-related RCT protocols published in 2019 and 2021 (aiming to consider periods before and after the start of the COVID pandemic). Data extraction included bibliometric information, general study characteristics, compliance with 122 questions corresponding to items and subitems in the SPIRIT and TIDieR checklists combined, and mention to these reporting guidelines in the publications. We calculated the proportion of protocols reporting each item and the frequency of items reported for each protocol. We investigated associations between selected publication aspects and reporting completeness using linear regression analysis. RESULTS: The majority of protocols included adults and elderly as their study population (n = 73; 36.5%), supplementation as intervention (n = 96; 48.0%), placebo as comparator (n = 89; 44.5%), and evaluated clinical status as the outcome (n = 80; 40.0%). Most protocols described a parallel RCT (n = 188; 94.0%) with a superiority framework (n = 141; 70.5%). Overall reporting completeness was 52.0% (SD = 10.8%). Adherence to SPIRIT items ranged from 0% (n = 0) (data collection methods) to 98.5% (n = 197) (eligibility criteria). Adherence to TIDieR items ranged from 5.5% (n = 11) (materials used in the intervention) to 98.5% (n = 197) (description of the intervention). The multivariable regression analysis suggests that a higher number of authors [ß = 0.53 (95%CI: 0.28-0.78)], most recent published protocols [ß = 3.19 (95%CI: 0.24-6.14)], request of reporting guideline checklist during the submission process by the journal [ß = 6.50 (95%CI: 2.56-10.43)] and mention of SPIRIT by the authors [ß = 5.15 (95%CI: 2.44-7.86)] are related to higher reporting completeness scores. CONCLUSIONS: Reporting completeness in a random sample of 200 diet or nutrition-related RCT protocols was low. Number of authors, year of publication, self-reported adherence to SPIRIT, and journals' endorsement of reporting guidelines seem to be positively associated with reporting completeness in nutrition and diet-related RCT protocols.

Perinatal outcomes associated with combination antiretroviral therapy compared with monotherapy.

OBJECTIVES: Increasing numbers of women living with HIV (WLHIV) worldwide receive combination antiretroviral therapy (cART) during pregnancy. We aimed to assess the risk of adverse perinatal outcomes in pregnant WLHIV receiving cART compared with pregnant WLHIV receiving zidovudine monotherapy. DESIGN: Systematic review and meta-analysis. METHODS: We searched four electronic literature databases (PubMed, CINAHL, Global Health, EMBASE) for studies published between 1 January 1980 and 20 April 2020 using a comprehensive search strategy. Studies reporting data on WLHIV receiving cART compared with WLHIV receiving monotherapy for 11 adverse perinatal outcomes were sought: preterm birth (PTB), very PTB, spontaneous PTB, low birthweight (LBW), very LBW, preterm and term LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Random-effects meta-analyses were conducted to calculate relative risk (RR) and 95% confidence intervals (95% CI). RESULTS: We included 30 studies reporting on 317 101 pregnant women in 27 countries. WLHIV receiving cART were at increased risk of PTB (RR 1.32, 95% CI 1.18-1.46), LBW (1.35, 1.19-1.53), SGA (1.32, 1.13-1.53), VSGA (1.64, 1.34-2.02), and stillbirth (2.41, 1.83-3.17) compared to WLHIV receiving monotherapy. The significance of these results was maintained in subgroup analyses for studies conducted in low and middle-income countries and average quality studies. Additionally, WLHIV receiving nonnucleoside reverse transcriptase inhibitor-based cART were associated with increased risk of PTB, LBW, and stillbirth, while WLHIV receiving protease inhibitor-based cART were associated with increased risk of PTB, compared with WLHIV receiving monotherapy. CONCLUSION: Pregnant WLHIV receiving cART are associated with increased risk of adverse perinatal outcomes, compared with WLHIV receiving monotherapy.

Adverse perinatal outcomes attributable to HIV in sub-Saharan Africa from 1990 to 2020: Systematic review and meta-analyses.

BACKGROUND: Maternal HIV infection and antiretroviral drugs (ARVs) are associated with increased risks of adverse perinatal outcomes. The vast majority of pregnant women living with HIV (WLHIV) reside in sub-Saharan Africa. We aimed to determine the burden of adverse perinatal outcomes attributable to HIV and ARVs in sub-Saharan Africa between 1990 and 2020. METHODS: We conduct a systematic review of studies on the association of pregnant WLHIV with adverse perinatal outcomes in sub-Saharan Africa. We perform random-effects meta-analyses to determine the risk difference (attributable risk, AR) of perinatal outcomes among WLHIV receiving no ARVs, monotherapy, or combination antiretroviral therapy (cART) initiated antenatally or preconception, compared to HIV-negative women. We estimate numbers of perinatal outcomes attributable to HIV and ARVs by combining the AR values with numbers of WLHIV receiving different ARV regimens in each country in sub-Saharan Africa annually between 1990 and 2020. RESULTS: We find that WLHIV receiving no ARVs or cART initiated antenatally or preconception, but not monotherapy, have an increased risk of preterm birth (PTB), low birthweight (LBW) and small for gestational age (SGA), compared to HIV-negative women. Between 1990 and 2020, 1,921,563 PTBs, 2,119,320 LBWs, and 2,049,434 SGAs are estimated to be attributable to HIV and ARVs in sub-Saharan Africa, mainly among WLHIV receiving no ARVs, while monotherapy and preconception and antenatal cART averted many adverse outcomes. In 2020, 64,585 PTBs, 58,608 LBWs, and 61,112 SGAs were estimated to be attributable to HIV and ARVs, the majority among WLHIV receiving preconception cART. CONCLUSIONS: As the proportion of WLHIV receiving preconception cART increases, the burden of adverse perinatal outcomes among WLHIV in sub-Saharan Africa is likely to remain high. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42021248987.

Pregnant women living with HIV (WLHIV) are at higher risk of adverse birth outcomes, such as babies born too soon (premature birth), babies born too small (low birthweight) or small-for-gestational-age (smaller than expected based on the weeks of pregnancy). It is unknown how many cases of these outcomes are attributable to HIV in sub-Saharan Africa, where most pregnant WLHIV reside. We conduct a search for published studies to determine the risk of adverse birth outcomes among WLHIV. We find that around 2 million premature births, low birthweight babies, and small-for-gestational-age babies are attributable to HIV in sub-Saharan Africa between 1990 and 2020. We conclude that adverse birth outcomes among WLHIV in sub-Saharan Africa are likely to remain high for the foreseeable future. Our findings could guide strategies to improve the health of WLHIV and their children in this region.

Artificial intelligence in lung cancer diagnostic imaging: a review of the reporting and conduct of research published 2018-2019.

Objective: This study aimed to describe the methodologies used to develop and evaluate models that use artificial intelligence (AI) to analyse lung images in order to detect, segment (outline borders of), or classify pulmonary nodules as benign or malignant. Methods: In October 2019, we systematically searched the literature for original studies published between 2018 and 2019 that described prediction models using AI to evaluate human pulmonary nodules on diagnostic chest images. Two evaluators independently extracted information from studies, such as study aims, sample size, AI type, patient characteristics, and performance. We summarised data descriptively. Results: The review included 153 studies: 136 (89%) development-only studies, 12 (8%) development and validation, and 5 (3%) validation-only. CT scans were the most common type of image type used (83%), often acquired from public databases (58%). Eight studies (5%) compared model outputs with biopsy results. 41 studies (26.8%) reported patient characteristics. The models were based on different units of analysis, such as patients, images, nodules, or image slices or patches. Conclusion: The methods used to develop and evaluate prediction models using AI to detect, segment, or classify pulmonary nodules in medical imaging vary, are poorly reported, and therefore difficult to evaluate. Transparent and complete reporting of methods, results and code would fill the gaps in information we observed in the study publications. Advances in knowledge: We reviewed the methodology of AI models detecting nodules on lung images and found that the models were poorly reported and had no description of patient characteristics, with just a few comparing models' outputs with biopsies results. When lung biopsy is not available, lung-RADS could help standardise the comparisons between the human radiologist and the machine. The field of radiology should not give up principles from the diagnostic accuracy studies, such as the choice for the correct ground truth, just because AI is used. Clear and complete reporting of the reference standard used would help radiologists trust in the performance that AI models claim to have. This review presents clear recommendations about the essential methodological aspects of diagnostic models that should be incorporated in studies using AI to help detect or segmentate lung nodules. The manuscript also reinforces the need for more complete and transparent reporting, which can be helped using the recommended reporting guidelines.

Global associations of key populations with HIV-1 recombinants: a systematic review, global survey, and individual participant data meta-analysis.

Introduction: Global HIV infections due to HIV-1 recombinants are increasing and impede prevention and treatment efforts. Key populations suffer most new HIV infections, but their role in the spread of HIV-1 recombinants is unknown. We conducted a global analysis of the associations between key populations and HIV-1 recombinants. Methods: We searched PubMed, EMBASE, CINAHL, and Global Health for HIV-1 subtyping studies published from 1/1/1990 to 31/12/2015. Unpublished data was collected through a global survey. We included studies with HIV-1 subtyping data of key populations collected during 1990-2015. Key populations assessed were heterosexual people (HET), men who have sex with men (MSM), people who inject drugs (PWID), vertical transmissions (VERT), commercial sex workers (CSW), and transfusion-associated infections (BLOOD). Logistic regression was used to determine associations of key populations with HIV-1 recombinants. Subgroup analyses were performed for circulating recombinant forms (CRFs), unique recombinant forms (URFs), regions, and time periods. Results: Eight hundred and eighty five datasets including 77,284 participants from 83 countries were included. Globally, PWID were associated with the greatest odds of recombinants and CRFs (OR 2.6 [95% CI 2.46-2.74] and 2.99 [2.83-3.16]), compared to HET. CSW were associated with increased odds of recombinants and URFs (1.59 [1.44-1.75] and 3.61 [3.15-4.13]). VERT and BLOOD were associated with decreased odds of recombinants (0.58 [0.54-0.63] and 0.43 [0.33-0.56]). MSM were associated with increased odds of recombinants in 2010-2015 (1.43 [1.35-1.51]). Subgroup analyses supported our main findings. Discussion: As PWID, CSW, and MSM are associated with HIV-1 recombinants, increased preventative measures and HIV-1 molecular surveillance are crucial within these key populations. Systematic review registration: PROSPERO [CRD42017067164].

Developing evidence-based patient-focused learning materials to support health behaviour change for people living with psoriatic arthritis.

OBJECTIVES: In psoriatic arthritis (PsA), self-management is important for patient function and quality of life. Behaviour change can be difficult, patients could benefit from high-quality support to initiate change. Our aim was to codesign the project as theory-informed, evidence-based, patient-focused, materials supporting healthy lifestyle changes for patients diagnosed with PsA. METHODS: Development of the materials was overseen by a steering group of patients with PsA, psychologists, rheumatologists, a design team and researchers. First, a literature review was performed to establish the evidence base for behaviours and potential interventions in PsA, including diet, weight, alcohol, smoking, exercise, anxiety, depression and stress. An initial roundtable of patients with PsA prioritised areas and content ideas. Draft materials including a website and downloadable materials were produced. A second roundtable of patients with PsA collected feedback on the draft content and design. A third roundtable was held with patients with PsA and a fourth with clinicians to refine the materials and ensuring that they were evidence based, accessible, interesting, and helpful to initiate and maintain change. A final evaluation survey was performed to review the draft website before launching the final materials. RESULTS: 15 candidate topics were prioritised. A website and set of postcards summarising the topics were developed by the design team and refined following feedback from the roundtable groups. CONCLUSION: This project created patient-focused resources to support behaviour change. It addresses common concerns of patients with PsA about how they may optimise their health by providing practical and brief interventions to challenge and support them to make changes.

Overinterpretation of findings in machine learning prediction model studies in oncology: a systematic review.

OBJECTIVES: In biomedical research, spin is the overinterpretation of findings, and it is a growing concern. To date, the presence of spin has not been evaluated in prognostic model research in oncology, including studies developing and validating models for individualized risk prediction. STUDY DESIGN AND SETTING: We conducted a systematic review, searching MEDLINE and EMBASE for oncology-related studies that developed and validated a prognostic model using machine learning published between 1st January, 2019, and 5th September, 2019. We used existing spin frameworks and described areas of highly suggestive spin practices. RESULTS: We included 62 publications (including 152 developed models; 37 validated models). Reporting was inconsistent between methods and the results in 27% of studies due to additional analysis and selective reporting. Thirty-two studies (out of 36 applicable studies) reported comparisons between developed models in their discussion and predominantly used discrimination measures to support their claims (78%). Thirty-five studies (56%) used an overly strong or leading word in their title, abstract, results, discussion, or conclusion. CONCLUSION: The potential for spin needs to be considered when reading, interpreting, and using studies that developed and validated prognostic models in oncology. Researchers should carefully report their prognostic model research using words that reflect their actual results and strength of evidence.

Reporting guidelines used varying methodology to develop recommendations.

BACKGROUND AND OBJECTIVES: We investigated the developing methods of reporting guidelines in the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network's database. METHODS: In October 2018, we screened all records and excluded those not describing reporting guidelines from further investigation. Twelve researchers performed duplicate data extraction on bibliometrics, scope, development methods, presentation, and dissemination of all publications. Descriptive statistics were used to summarize the findings. RESULTS: Of the 405 screened records, 262 described a reporting guidelines development. The number of reporting guidelines increased over the past 3 decades, from 5 in the 1990s and 63 in the 2000s to 157 in the 2010s. Development groups included 2-151 people. Literature appraisal was performed during the development of 56% of the reporting guidelines; 33% used surveys to gather external opinion on items to report; and 42% piloted or sought external feedback on their recommendations. Examples of good reporting for all reporting items were presented in 30% of the reporting guidelines. Eighteen percent of the reviewed publications included some level of spin. CONCLUSION: Reporting guidelines have been developed with varying methodology. Reporting guideline developers should use existing guidance and take an evidence-based approach, rather than base their recommendations on expert opinion of limited groups of individuals.

Systematic review highlights high risk of bias of clinical prediction models for blood transfusion in patients undergoing elective surgery.

BACKGROUND: Blood transfusion can be a lifesaving intervention after perioperative blood loss. Many prediction models have been developed to identify patients most likely to require blood transfusion during elective surgery, but it is unclear whether any are suitable for clinical practice. STUDY DESIGN AND SETTING: We conducted a systematic review, searching MEDLINE, Embase, PubMed, The Cochrane Library, Transfusion Evidence Library, Scopus, and Web of Science databases for studies reporting the development or validation of a blood transfusion prediction model in elective surgery patients between January 1, 2000 and June 30, 2021. We extracted study characteristics, discrimination performance (c-statistics) of final models, and data, which we used to perform risk of bias assessment using the Prediction model risk of bias assessment tool (PROBAST). RESULTS: We reviewed 66 studies (72 developed and 48 externally validated models). Pooled c-statistics of externally validated models ranged from 0.67 to 0.78. Most developed and validated models were at high risk of bias due to handling of predictors, validation methods, and too small sample sizes. CONCLUSION: Most blood transfusion prediction models are at high risk of bias and suffer from poor reporting and methodological quality, which must be addressed before they can be safely used in clinical practice.