Urologists regularly develop clinical risk prediction models to support clinical decisions. In contrast to traditional performance measures, decision curve analysis (DCA) can assess the utility of ...models for decision making. DCA plots net benefit (NB) at a range of clinically reasonable risk thresholds.
To provide recommendations on interpreting and reporting DCA when evaluating prediction models.
We informally reviewed the urological literature to determine investigators’ understanding of DCA. To illustrate, we use data from 3616 patients to develop risk models for high-grade prostate cancer (n=313, 9%) to decide who should undergo a biopsy. The baseline model includes prostate-specific antigen and digital rectal examination; the extended model adds two predictors based on transrectal ultrasound (TRUS).
We explain risk thresholds, NB, default strategies (treat all, treat no one), and test tradeoff. To use DCA, first determine whether a model is superior to all other strategies across the range of reasonable risk thresholds. If so, that model appears to improve decisions irrespective of threshold. Second, consider if there are important extra costs to using the model. If so, obtain the test tradeoff to check whether the increase in NB versus the best other strategy is worth the additional cost. In our case study, addition of TRUS improved NB by 0.0114, equivalent to 1.1 more detected high-grade prostate cancers per 100 patients. Hence, adding TRUS would be worthwhile if we accept subjecting 88 patients to TRUS to find one additional high-grade prostate cancer or, alternatively, subjecting 10 patients to TRUS to avoid one unnecessary biopsy.
The proposed guidelines can help researchers understand DCA and improve application and reporting.
Decision curve analysis can identify risk models that can help us make better clinical decisions. We illustrate appropriate reporting and interpretation of decision curve analysis.
Decision curve analysis (DCA) is a method to evaluate whether risk prediction models can have utility for supporting treatment decisions. This guide for researchers explains what DCA is, how to interpret it, and how to report its results.
The objective of this study was to compare performance of logistic regression (LR) with machine learning (ML) for clinical prediction modeling in the literature.
We conducted a Medline literature ...search (1/2016 to 8/2017) and extracted comparisons between LR and ML models for binary outcomes.
We included 71 of 927 studies. The median sample size was 1,250 (range 72–3,994,872), with 19 predictors considered (range 5–563) and eight events per predictor (range 0.3–6,697). The most common ML methods were classification trees, random forests, artificial neural networks, and support vector machines. In 48 (68%) studies, we observed potential bias in the validation procedures. Sixty-four (90%) studies used the area under the receiver operating characteristic curve (AUC) to assess discrimination. Calibration was not addressed in 56 (79%) studies. We identified 282 comparisons between an LR and ML model (AUC range, 0.52–0.99). For 145 comparisons at low risk of bias, the difference in logit(AUC) between LR and ML was 0.00 (95% confidence interval, −0.18 to 0.18). For 137 comparisons at high risk of bias, logit(AUC) was 0.34 (0.20–0.47) higher for ML.
We found no evidence of superior performance of ML over LR. Improvements in methodology and reporting are needed for studies that compare modeling algorithms.
Non-typhoidal Salmonella (NTS) are a frequent cause of invasive infections in sub-Saharan Africa. They are frequently multidrug resistant (co-resistant to ampicillin, trimethoprim-sulfamethoxazole, ...and chloramphenicol), and resistance to third-generation cephalosporin and fluoroquinolone non-susceptibility have been reported. Third-generation cephalosporins and fluoroquinolones are often used to treat invasive NTS infections, but azithromycin might be an alternative. However, data on antibiotic treatment efficacy in invasive NTS infections are lacking. In this study, we aimed to assess the spatiotemporal distribution of antimicrobial resistance in invasive NTS infections in sub-Saharan Africa and to describe the available evidence and recommendations on antimicrobial treatment.
We conducted a systematic review of all available literature on antimicrobial resistance and treatment in invasive NTS infections. We performed a random effects meta-analysis to assess the temporal distribution of multidrug resistance, third-generation cephalosporin resistance, and fluoroquinolone non-susceptibility. We mapped these data to assess the spatial distribution. We provided a narrative synthesis of the available evidence and recommendations on antimicrobial treatment.
Since 2001, multidrug resistance was observed in 75% of NTS isolates from all sub-Saharan African regions (95% confidence interval, 70-80% and 65-84%). Third-generation cephalosporin resistance emerged in all sub-Saharan African regions and was present in 5% (95% confidence interval, 1-10%) after 2010. Fluoroquinolone non-susceptibility emerged in all sub-Saharan African regions but did not increase over time. Azithromycin resistance was reported in DR Congo. There were no reports on carbapenem resistance. We did not find high-quality evidence on the efficacy of antimicrobial treatment. There were no supranational guidelines. The "Access group" antibiotics ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol and "Watch group" antibiotics ceftriaxone, cefotaxime, and ciprofloxacin were recommended as the first-choice antibiotics in national guidelines or reviews. These also recommended (a switch to) oral fluoroquinolones or azithromycin.
In addition to the widespread multidrug resistance in invasive NTS infections in sub-Saharan Africa, resistance to third-generation cephalosporins and fluoroquinolone non-susceptibility was present in all regions. There was a lack of data on the efficacy of antimicrobial treatment in these infections, and supranational evidence-based guidelines were absent.
Early pregnancy loss (EPL) is a common event, with scope for long-term personal and societal impact. There are three decades worth of published evidence of profound psychological sequelae in a ...significant proportion of women. However, the wide variety of outcomes, screening instruments, assessment timings and geographical locations makes it challenging to form a coherent picture of the morbidity within the whole group and its subgroups.
This review aims to investigate three questions. (1) What is the evidence for depression, anxiety and post-traumatic stress disorder (PTSD) following a miscarriage or an ectopic pregnancy in women and/or their partners? (2) What is the intensity and duration of these conditions, and how do they compare to those without losses? (3) Which patients have been found to be at highest risk of psychopathology? Answers to these questions are salient not only in day-to-day clinical interactions with those experiencing EPL, whose psychological needs may not be prioritized, but should also form the basis for tailoring healthcare policy in terms of screening for and treating the associated psychological morbidity.
The following databases were searched, from the start of each database up to July 2017: MEDLINE (Ovid interface, 1948 onwards), Embase classic + Embase (Ovid interface, 1947 onwards), and PsychINFO (Ovid interface, 1806 onwards). Search strategies were developed using medical subject headings (MeSH). The concepts of psychological morbidity (anxiety, depression or PTSD) and pregnancy loss (miscarriage or ectopic pregnancy) were first expanded with the Boolean operator 'or', then linked together using 'and'. Included studies were of prospective cohort design, including women or men following EPL (with the majority to have experienced losses before 24 weeks gestation), and reporting standardized psychometric measures for anxiety, depression and post-traumatic stress disorder. The timing of follow-up had to be specified and standardized across participants. Manuscript quality and risk of bias was assessed using the Newcastle-Ottawa Scale.
We found evidence of significant depression and anxiety in the first month following EPL in women. Partners were also shown to display depression and anxiety, albeit to a generally lower level. There is also evidence of post-traumatic stress symptoms relating to the EPL in three studies.
In view of their high frequency, EPLs can significantly contribute to the overall burden of psychopathology within a population. Recognition of this impact is important, so that severely affected individuals may be screened and treated appropriately. Further research to establish risk factors to promptly identify and treat these patients, and to optimize their management, is crucial.
Some autoimmune diseases are associated with an increased risk of cardiovascular disease. We aimed to determine whether or not this is true, and to what extent, for a broad range of autoimmune ...conditions.
In this population-based study, we used linked primary and secondary care records from the Clinical Practice Research Datalink (CPRD), GOLD and Aurum datasets, to assemble a cohort of individuals across the UK who were newly diagnosed with any of 19 autoimmune diseases between Jan 1, 2000, and Dec 31, 2017, younger than 80 years at diagnosis, and free of cardiovascular diseases up to 12 months after diagnosis. We also assembled a matched cohort with up to five individuals matched on age, sex, socioeconomic status, region, and calendar year, who were free of autoimmune disease and free of cardiovascular diseases up to 12 months after study entry. Both cohorts were followed up until June 30, 2019. We investigated the incidence of 12 cardiovascular outcomes and used Cox proportional hazards models to examine differences in patients with and without autoimmune diseases.
Of 22 009 375 individuals identified from the CPRD databases, we identified 446 449 eligible individuals with autoimmune diseases and 2 102 830 matched controls. In the autoimmune cohort, mean age at diagnosis was 46·2 years (SD 19·8), and 271 410 (60·8%) were women and 175 039 (39·2%) were men. 68 413 (15·3%) people with and 231 410 (11·0%) without autoimmune diseases developed incident cardiovascular disease during a median of 6·2 years (IQR 2·7–10·8) of follow-up. The incidence rate of cardiovascular disease was 23·3 events per 1000 patient-years among patients with autoimmune disease and 15·0 events per 1000 patient-years among those without an autoimmune disease (hazard ratio HR 1·56 95% CI 1·52–1·59). An increased risk of cardiovascular disease with autoimmune disease was seen for every individual cardiovascular disease and increased progressively with the number of autoimmune diseases present (one disease: HR 1·41 95% CI 1·37–1·45; two diseases: 2·63 2·49–2·78); three or more diseases: 3·79 3·36–4·27), and in younger age groups (age <45 years: 2·33 2·16–2·51; 55–64 years: 1·76 1·67–1·85; ≥75 years: 1·30 1·24–1·36). Among autoimmune diseases, systemic sclerosis (3·59 2·81–4·59), Addison's disease (2·83 1·96–4·09), systemic lupus erythematosus (2·82 2·38–3·33), and type 1 diabetes (2·36 2·21–2·52) had the highest overall cardiovascular risk.
These findings warrant targeted cardiovascular prevention measures, in particular in younger patients with autoimmune diseases, and further research into pathophysiological mechanisms underlying these complications.
Horizon 2020 Marie Skłodowska-Curie Actions and European Society of Cardiology.
Accurate rapid diagnostic tests for SARS-CoV-2 infection would be a useful tool to help manage the COVID-19 pandemic. Testing strategies that use rapid antigen tests to detect current infection have ...the potential to increase access to testing, speed detection of infection, and inform clinical and public health management decisions to reduce transmission. This is the second update of this review, which was first published in 2020.
To assess the diagnostic accuracy of rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Sources of heterogeneity investigated included setting and indication for testing, assay format, sample site, viral load, age, timing of test, and study design.
We searched the COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) on 08 March 2021. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions.
We included studies of people with either suspected SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen tests. We included evaluations of single applications of a test (one test result reported per person) and evaluations of serial testing (repeated antigen testing over time). Reference standards for presence or absence of infection were any laboratory-based molecular test (primarily reverse transcription polymerase chain reaction (RT-PCR)) or pre-pandemic respiratory sample.
We used standard screening procedures with three people. Two people independently carried out quality assessment (using the QUADAS-2 tool) and extracted study results. Other study characteristics were extracted by one review author and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test, and pooled data using the bivariate model. We investigated heterogeneity by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status.
We included 155 study cohorts (described in 166 study reports, with 24 as preprints). The main results relate to 152 evaluations of single test applications including 100,462 unique samples (16,822 with confirmed SARS-CoV-2). Studies were mainly conducted in Europe (101/152, 66%), and evaluated 49 different commercial antigen assays. Only 23 studies compared two or more brands of test. Risk of bias was high because of participant selection (40, 26%); interpretation of the index test (6, 4%); weaknesses in the reference standard for absence of infection (119, 78%); and participant flow and timing 41 (27%). Characteristics of participants (45, 30%) and index test delivery (47, 31%) differed from the way in which and in whom the test was intended to be used. Nearly all studies (91%) used a single RT-PCR result to define presence or absence of infection. The 152 studies of single test applications reported 228 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies, with consistently high specificities. Average sensitivity was higher in symptomatic (73.0%, 95% CI 69.3% to 76.4%; 109 evaluations; 50,574 samples, 11,662 cases) compared to asymptomatic participants (54.7%, 95% CI 47.7% to 61.6%; 50 evaluations; 40,956 samples, 2641 cases). Average sensitivity was higher in the first week after symptom onset (80.9%, 95% CI 76.9% to 84.4%; 30 evaluations, 2408 cases) than in the second week of symptoms (53.8%, 95% CI 48.0% to 59.6%; 40 evaluations, 1119 cases). For those who were asymptomatic at the time of testing, sensitivity was higher when an epidemiological exposure to SARS-CoV-2 was suspected (64.3%, 95% CI 54.6% to 73.0%; 16 evaluations; 7677 samples, 703 cases) compared to where COVID-19 testing was reported to be widely available to anyone on presentation for testing (49.6%, 95% CI 42.1% to 57.1%; 26 evaluations; 31,904 samples, 1758 cases). Average specificity was similarly high for symptomatic (99.1%) or asymptomatic (99.7%) participants. We observed a steady decline in summary sensitivities as measures of sample viral load decreased. Sensitivity varied between brands. When tests were used according to manufacturer instructions, average sensitivities by brand ranged from 34.3% to 91.3% in symptomatic participants (20 assays with eligible data) and from 28.6% to 77.8% for asymptomatic participants (12 assays). For symptomatic participants, summary sensitivities for seven assays were 80% or more (meeting acceptable criteria set by the World Health Organization (WHO)). The WHO acceptable performance criterion of 97% specificity was met by 17 of 20 assays when tests were used according to manufacturer instructions, 12 of which demonstrated specificities above 99%. For asymptomatic participants the sensitivities of only two assays approached but did not meet WHO acceptable performance standards in one study each; specificities for asymptomatic participants were in a similar range to those observed for symptomatic people. At 5% prevalence using summary data in symptomatic people during the first week after symptom onset, the positive predictive value (PPV) of 89% means that 1 in 10 positive results will be a false positive, and around 1 in 5 cases will be missed. At 0.5% prevalence using summary data for asymptomatic people, where testing was widely available and where epidemiological exposure to COVID-19 was suspected, resulting PPVs would be 38% to 52%, meaning that between 2 in 5 and 1 in 2 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed.
Antigen tests vary in sensitivity. In people with signs and symptoms of COVID-19, sensitivities are highest in the first week of illness when viral loads are higher. Assays that meet appropriate performance standards, such as those set by WHO, could replace laboratory-based RT-PCR when immediate decisions about patient care must be made, or where RT-PCR cannot be delivered in a timely manner. However, they are more suitable for use as triage to RT-PCR testing. The variable sensitivity of antigen tests means that people who test negative may still be infected. Many commercially available rapid antigen tests have not been evaluated in independent validation studies. Evidence for testing in asymptomatic cohorts has increased, however sensitivity is lower and there is a paucity of evidence for testing in different settings. Questions remain about the use of antigen test-based repeat testing strategies. Further research is needed to evaluate the effectiveness of screening programmes at reducing transmission of infection, whether mass screening or targeted approaches including schools, healthcare setting and traveller screening.
COVID-19 also affects pregnant and breastfeeding women. Hence, clinicians and policymakers require reliable evidence on COVID-19 epidemiology and consequences in this population. We aimed to assess ...the susceptibility of pregnant women to SARS-CoV-2 and women's perceived impact of the pandemic on their breastfeeding practices, medical counseling and social support. We performed a cross-sectional study using an online survey in primary care in Belgium. Pregnant and breastfeeding women and women who breastfed in the preceding four weeks were eligible to participate. The survey was distributed through social media in April 2020. In total, 6470 women participated (i.e., 2647 pregnant and 3823 breastfeeding women). Overall, 0.3% of all respondents reported to have tested positive for SARS-CoV-2, not indicating a higher susceptibility of pregnant women to contracting COVID-19. More than 90% refuted that the pandemic affected their breastfeeding practices, nor indicated that the coronavirus was responsible for breastfeeding cessation. Half of the women even considered giving longer breastmilk because of the coronavirus. In contrast, women's medical counseling and social support were negatively affected by the lockdown. Women without previous breastfeeding experience and in the early postpartum period experienced a higher burden in terms of reduced medical counseling and support. In the future, more consideration and alternative supportive measures such as tele-visits by midwives or perinatal organizations are required for these women.
Introduction and hypothesis
Pregnancy and childbirth are considered risk factors for pelvic floor dysfunction, including anorectal dysfunction. We aimed to assess the effect of obstetric events on ...anal incontinence and constipation after delivery.
Methods
We systematically reviewed the literature by searching MEDLINE, Embase and CENTRAL. We included studies in women after childbirth examining the association between obstetric events and anorectal dysfunction assessed through validated questionnaires. We selected eligible studies and clustered the data according to the type of dysfunction, obstetric event and interval from delivery. We assessed risk of bias using the Newcastle Ottawa Scale and we performed a random-effects meta-analysis and reported the results as odds ratios (ORs) with their 95% confidence intervals. Heterogeneity across studies was assessed using I
2
statistics.
Results
Anal sphincter injury (OR: 2.44 1.92–3.09) and operative delivery were risk factors for anal incontinence (forceps—OR :1.35 1.12–1.63; vacuum—OR: 1.17 1.04–1.31). Spontaneous vaginal delivery increased the risk of anal incontinence compared with caesarean section (OR: 1.27 1.07–1.50). Maternal obesity (OR:1.48 1.28–1.72) and advanced maternal age (OR: 1.56 1.30–1.88) were risk factors for anal incontinence. The evidence on incontinence is of low certainty owing to the observational nature of the studies. No evidence was retrieved regarding constipation after delivery because of a lack of standardised validated assessment tools.
Conclusions
Besides anal sphincter injury, forceps delivery, maternal obesity and advanced age were associated with higher odds of anal incontinence, whereas caesarean section is protective. We could not identify obstetric risk factors for postpartum constipation, as few prospective studies addressed this question and none used a standardised validated questionnaire.
Rapid diagnosis or exclusion of SARS-CoV-2 infection is essential for correct medical management decisions regarding COVID-19. High-throughput laboratory-based reverse transcriptase (RT)-PCR testing ...is accurate with longer turnaround times, while rapid antigen tests show moderate sensitivity. In search of a fast and reliable COVID-19 test, we aimed to validate the rapid miDiagnostics COVID-19 PCR test. We recruited symptomatic and asymptomatic participants in a mobile COVID-19 test center in Belgium. We collected three nasopharyngeal samples from each participant. The index sample was tested on the miDiagnostics COVID-19 PCR reader, the reference sample was tested on the reference TaqPath COVID-19 PCR test in the Belgian Reference Center for Respiratory Pathogens of University Hospitals Leuven, and a third sample was collected for discordance testing with the PerkinElmer SARS-CoV-2 PCR kit. A total of 770 participants yielded 763 sets of included nasopharyngeal samples. Overall positive percent agreement and negative percent agreement of the miDiagnostics COVID-19 PCR test were 95.5% (92.6% to 97.4%) and 94.9% (92.3 to 96.8%), rising to 98.6% (96.5% to 99.6%) and 96.5% (92.6% to 98.7%) in symptomatic patients. Discordance testing reclassified 15 of 21 false-positive cases as true positive. A retest of the miDiagnostics PCR test was performed in 61 tests (7.4%) due to a technical error. The miDiagnostics COVID-19 PCR test showed excellent clinical accuracy. The fast and reliable results allow for rapid correct diagnosis and tailored medical management decisions regarding COVID-19.
A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and ...inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases.
In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex.
Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years SD 21·4). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017–19 vs 2000–02 1·04 95% CI 1·00–1·09). The largest increases were seen in coeliac disease (2·19 2·05–2·35), Sjogren's syndrome (2·09 1·84–2·37), and Graves' disease (2·07 1·92–2·22); pernicious anaemia (0·79 0·72–0·86) and Hashimoto's thyroiditis (0·81 0·75–0·86) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 13·1% women and 668 264 7·4% men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 1·64–1·81), rheumatoid arthritis (1·52 1·45–1·59), Graves' disease (1·36 1·30–1·43), and systemic lupus erythematosus (1·35 1·25–1·46). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 95% CI 17·3–40·7), coeliac disease (28·4 25·2–32·0), and thyroid disease (Hashimoto's thyroiditis 13·3 11·8–14·9 and Graves' disease 6·7 5·1–8·5), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases.
Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases.
Research Foundation Flanders.
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