Randomized clinical trials of machine learning interventions in health care: a systematic review

Importance: Despite the potential of machine learning to improve multiple aspects of patient care, barriers to clinical adoption remain. Randomized clinical trials (RCTs) are often a prerequisite to large-scale clinical adoption of an intervention, and important questions remain regarding how machine learning interventions are being incorporated into clinical trials in health care. Objective: To systematically examine the design, reporting standards, risk of bias, and inclusivity of RCTs for medical machine learning interventions. Evidence Review: In this systematic review, the Cochrane Library, Google Scholar, Ovid Embase, Ovid MEDLINE, PubMed, Scopus, and Web of Science Core Collection online databases were searched and citation chasing was done to find relevant articles published from the inception of each database to October 15, 2021. Search terms for machine learning, clinical decision-making, and RCTs were used. Exclusion criteria included implementation of a non-RCT design, absence of original data, and evaluation of nonclinical interventions. Data were extracted from published articles. Trial characteristics, including primary intervention, demographics, adherence to the CONSORT-AI reporting guideline, and Cochrane risk of bias were analyzed. Findings: Literature search yielded 19737 articles, of which 41 RCTs involved a median of 294 participants (range, 17-2488 participants). A total of 16 RCTS (39%) were published in 2021, 21 (51%) were conducted at single sites, and 15 (37%) involved endoscopy. No trials adhered to all CONSORT-AI standards. Common reasons for nonadherence were not assessing poor-quality or unavailable input data (38 trials [93%]), not analyzing performance errors (38 [93%]), and not including a statement regarding code or algorithm availability (37 [90%]). Overall risk of bias was high in 7 trials (17%). Of 11 trials (27%) that reported race and ethnicity data, the median proportion of participants from underrepresented minority groups was 21% (range, 0%-51%). Conclusions and Relevance: This systematic review found that despite the large number of medical machine learning-based algorithms in development, few RCTs for these technologies have been conducted. Among published RCTs, there was high variability in adherence to reporting standards and risk of bias and a lack of participants from underrepresented minority groups. These findings merit attention and should be considered in future RCT design and reporting.Published versionThis study was supported by grants K23-DK125718 (Dr Shung) and K08-DE030216 (Dr Kann) from the National Institutes of Health, grant T32GM007753 from the National Institute of General Medical Sciences (Ms Plana), and grant F30-CA260780 from the National Cancer Institute (Ms Plana)

Ovarian absence: a systematic literature review and case series report

Abstract Ovarian absence is an uncommon condition that most frequently presents unilaterally. Several etiologies for the condition have been proposed, including torsion, vascular accident, and embryological defect. A systematic review was conducted to describe the clinical presentation of ovarian absence, as well as its associations with other congenital anomalies, through a systematic search of Cochrane Library, ClinicalTrials.gov, Google Scholar, Ovid Embase, Ovid Medline, PubMed, Scopus, and Web of Science. Exclusion criteria included cases with suspicion for Differences of Sex Development, lack of surgically-confirmed ovarian absence, and karyotypes other than 46XX. Our search yielded 12,120 citations, of which 79 studies were included. 10 additional studies were found by citation chasing resulting in a total 113 cases including two unpublished cases presented in this review. Abdominal/pelvic pain (30%) and infertility/subfertility (19%) were the most frequent presentations. Ovarian abnormalities were not noted in 28% of cases with pre-operative ovarian imaging results. Approximately 17% of cases had concomitant uterine abnormalities, while 22% had renal abnormalities. Renal abnormalities were more likely in patients with uterine abnormalities (p < 0.005). Torsion or vascular etiology was the most frequently suspected etiology of ovarian absence (52%), followed by indeterminate (27%) and embryologic etiology (21%). Most cases of ovarian absence are likely attributable to torsion or vascular accidents, despite many references to the condition as “agenesis” in the literature. Imaging may fail to correctly diagnose ovarian absence, and diagnostic laparoscopy may be preferable in many cases as genitourinary anatomy and fertility considerations can be assessed during the procedure. Fertility is likely minimally or not affected in women with unilateral ovarian absence

Evaluation of daratumumab for the treatment of multiple myeloma in patients with high-risk cytogenetic factors: a systematic review and meta-analysis

Importance: The addition of daratumumab to backbone multiple myeloma (MM) regimens is associated with improved response rates and progression-free survival (PFS). Whether improved outcomes are also associated with this regimen among patients with cytogenetically defined high-risk MM (HRMM) remains unclear. Objective: To measure PFS associated with adding daratumumab to backbone MM regimens among patients with HRMM. Data Sources: For this systematic review and meta-analysis, MEDLINE, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, clinical trials registries, and meeting libraries were searched from inception to January 2, 2020, using terms reflecting multiple myeloma and daratumumab. Study Selection: Included studies were phase 3 randomized clinical trials that compared backbone MM regimens with the same regimen plus daratumumab in newly diagnosed or relapsed or refractory MM, such that the only difference between the intervention and control groups was use of daratumumab and reported outcomes by cytogenetic risk. High-risk MM was defined as the presence of t(4;14), t(14;16), or del(17p). Data Extraction and Synthesis: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 investigators independently extracted study data, with disagreements resolved by a third investigator. Quality was assessed by the Cochrane risk-of-bias method. Main Outcomes and Measures: Data on effectiveness were extracted using hazard ratios (HRs) for PFS. Relative log-HRs were pooled using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran Q and the I2statistic. Results: Of 5194 studies screened, 6 phase 3 trials were eligible, including 3 trials for newly diagnosed MM (2528 patients; 358 with HRMM) and 3 trials for relapsed or refractory MM (1533 patients; 222 with HRMM). Among patients with newly diagnosed HRMM, the addition of daratumumab to backbone regimens was associated with improved PFS (pooled HR, 0.67; 95% CI, 0.47-0.95; P =.02), with little evidence of heterogeneity (Cochran Q, P =.77; I2= 0%). Similar results were seen among patients with relapsed or refractory HRMM (pooled HR, 0.45; 95% CI, 0.30-0.67; P &amp;lt;.001), again with little evidence of heterogeneity (Cochran Q, P =.63; I2= 0%). Conclusions and Relevance: This study suggests that incorporating daratumumab to backbone regimens may be associated with improved PFS among patients with newly diagnosed HRMM or relapsed or refractory HRMM.. © 2020 American Medical Association. All rights reserved

The global prevalence of human fascioliasis: a systematic review and meta-analysis

Background: Fascioliasis is a parasitic zoonosis that can infect humans and be a source of significant morbidity. The World Health Organization lists human fascioliasis as a neglected tropical disease, but the worldwide prevalence of fascioliasis data is unknown. Objective: We aimed to estimate the global prevalence of human fascioliasis. Data sources and methods: We performed a systematic review and prevalence meta-analysis. We used the following inclusion criteria: articles published in the English, Portuguese, or Spanish languages from December 1985 to October 2022 and studies assessing the prevalence of Fasciola in the general population with an appropriate diagnostic methodology, including longitudinal studies, prospective and retrospective cohorts, case series, and randomized clinical trials (RCTs). We excluded animal studies. Two reviewers independently reviewed the selected studies for methodological quality, performing critical standard measures from JBI SUMARI. A random-effects model was conducted of the summary extracted data on the prevalence proportions. We reported the estimates according to the GATHER statement. Results: In all, 5617 studies were screened for eligibility. Fifty-five studies from 15 countries were selected, including 154,697 patients and 3987 cases. The meta-analysis revealed a pooled prevalence of 4.5% [95% confidence interval (CI): 3.1–6.1; I 2  = 99.4%; T 2  = 0.07]. The prevalence in South America, Africa, and Asia was 9.0%, 4.8%, and 2.0%, respectively. The highest prevalence was found in Bolivia (21%), Peru (11%), and Egypt (6%). Subgroup analysis showed higher prevalence estimates in children, in studies from South America, and when Fas2-enzyme-linked immunosorbent assay (ELISA) was used as a diagnostic method. A larger study sample size ( p  = 0.027) and an increase in female percentage ( p  = 0.043) correlated with a decrease in prevalence. Multiple meta-regression showed a higher prevalence for hyperendemic than hypoendemic ( p  = 0.002) or mesoendemic ( p  = 0.013) regions. Conclusion: The estimated prevalence and projected disease burden of human fascioliasis are high. Study findings support that fascioliasis continues to be a globally neglected tropical disease. Strengthening epidemiological surveillance and implementing measures to control and treat fascioliasis is imperative in the most affected areas

SARS-CoV-2 Infection and COVID-19 Outcomes in Rheumatic Diseases: A Systematic Literature Review and Meta-Analysis

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients. METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle-Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel-Haenszel formula with random effects models. RESULTS: Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta-analyses, we identified an increased prevalence of SARS-CoV-2 infection in patients with an RMD (RR 1.53 [95% CI 1.16-2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08-2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID-19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD. CONCLUSION: Patients with RMDs have higher rates of SARS-CoV-2 infection and an increased mortality rate

Evolutionary constraint and innovation across hundreds of placental mammals

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes

Evolutionary constraint and innovation across hundreds of placental mammals.

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth\u27s vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes