Intracluster correlation coefficients in osteoarthritis cluster randomized trials: A systematic review.

OBJECTIVES: The design, analysis, and interpretation of cluster randomized clinical trials (RCTs) require accounting for potential correlation of observations on individuals within the same cluster. Reporting of observed intracluster correlation coefficients (ICCs) in cluster RCTs, as recommended by Consolidated Standards of Reporting Trials (CONSORT), facilitates sample size calculation of future cluster RCTs and understanding of the trial statistical power. Our objective was to summarize observed ICCs in osteoarthritis (OA) cluster RCTs. DESIGN: Systematic review of knee/hip OA cluster RCTs. We searched Cochrane Central Register of Controlled Trials for trials published from 2012, when CONSORT cluster RCTs extension was published, to September 2022. We calculated the proportion of cluster RCTs that reported observed ICCs. Of those that did, we extracted observed ICCs. PROSPERO: CRD42022365660. RESULTS: We screened 1121 references and included 20 cluster RCTs. Only 5 trials (25%) reported the observed ICC for at least one outcome variable. ICC values for pain outcomes were: 0, 0.01, 0.18; for physical function outcomes were: 0, 0.06, 0.13 (knee)/0.27 (hip); Western Ontario and McMaster Universities Arthritis Index (WOMAC) total: 0.02, 0.02; symptoms of anxiety/depression: 0.22; disability: 0; and global change: 0. One out of four (25%) trials reported an ICC that was larger than the ICC used for sample size calculation and thus was underpowered. CONCLUSIONS: Despite CONSORT statement recommendations for reporting cluster RCTs, few OA trials reported the observed ICC. Given the importance of the ICC to interpretation of trial results and future trial design, this reporting gap warrants attention.

Neuro-psychiatric manifestations in patients with systemic lupus erythematosus: A systematic review and results from the Swiss lupus cohort study.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with neuro-psychiatric (NP) manifestations. Frequency and patterns of neuro-psychiatric systemic lupus erythematosus (NPSLE) vary substantially between patients. We conducted a systematic review (SR) of the literature and examined prevalence and characteristics of NPSLE in the Swiss SLE cohort study (SSCS). METHODS: The SR search was performed between January 1999 and January 2020. We included prospective/cross-sectional studies focusing on NPSLE. We secured study characteristics, cohort compositions and frequencies of NP manifestations, assessed heterogeneity across reports and investigated sources of variation using meta-regression models. Regarding the SSCS, we reviewed all patients included and classified NP manifestations. RESULTS: The SR searches identified 530 studies. We included 22 studies in our meta-analysis, the mean frequency of NPSLE ranged from 10.6% to 96.4%. The frequency of NPSLE in the SSCS was 28.1%. Severe events including cerebrovascular insults, seizures and psychosis appeared in 7.1%, 5.3% and 6.5% respectively. There was a linear relationship between duration of SLE and cumulative incidence of NPSLE. CONCLUSIONS: The spectrum of NPSLE is very broad. The diagnostic work-up and rates of reported manifestations varied substantially across studies. We call for concerted efforts and consensus regarding definitions of NPSLE that will facilitate accurate diagnosis and attribution to SLE, particularly with a view to timely intervention and patient outcomes.

Outcomes and costs of Ranibizumab and Aflibercept treatment in a health-service research context.

BACKGROUND: To compare anti-VEGF treatments for macular disease in terms of costs and clinical outcomes. METHODS: We identified patients suffering from macular disease and treated either with aflibercept, ranibizumab or both at the largest public eye clinic in Switzerland between January 1st and December 31st 2016 who were insured in one of the two participating health insurance companies. Clinical data were extracted from the electronic health record system. The health insurers provided the health claim costs for the ophthalmologic care and the total health care costs of each patient in the observation period. Using multivariate regression models, we assessed the monthly ophthalmologic and the monthly total costs of patients with no history of switching (ranibizumab vs. aflibercept), patients with a history of switching from ranibizumab to aflibercept, patients switching during the observation period and a miscellaneous group. We examined baseline differences in age, proportion of males, visual acuity (letters), central retinal thickness (CRT) and treatment history before entering the study. We investigated treatment intensity and compared the changes in letters and CRT. RESULTS: The analysis involved 488 eyes (361 patients), 182 on ranibizumab treatment, and 63 on aflibercept treatment, 160 eyes with a history of switching from ranibizumab to aflibercept, and 45 switchers during follow-up and 38 eyes of the miscellaneous group. Compared to ranibizumab, monthly costs of ophthalmologic treatment were slightly higher for aflibercept treatment + 175.0 CHF (95%CI: 1.5 CHF to 348.3 CHF; p = 0.048) as were the total monthly costs + 581.0 CHF (95%CI: 159.5 CHF to 1002.4 CHF; p = 0.007). Compared to ranibizumab, the monthly treatment intensity with aflibercept was similar (+ 0.057 injections/month (95%CI -0.023 to 0.137; p = 0.162), corresponding to a projected annual number of 5.4 injections for ranibizumab vs. 6.1 injections for aflibercept. During follow-up, visus dropped by 0.7 letters with ranibizumab and increased by 0.6 letters with aflibercept (p = 0.243). CRT dropped by - 14.9 µm with ranibizumab and by - 19.5 µm with aflibercept (p = 0.708). The monthly costs of all other groups examined were higher. CONCLUSION: These real-life data show that aflibercept treatment is equally expensive, and clinical outcomes between the two drugs are similar.

Thromboelastometry and Thrombelastography Analysis under Normal Physiological Conditions - Systematic Review.

BACKGROUND: Studies investigating thromboelastometry or thrombelastography analyses in a physiological context are scattered and not easy to access. OBJECTIVE: To systematically retrieve and describe published reports studying healthy subjects and targeting at the correlation of ROTEM® and TEG® measurements with conventional parameters of hemostasis. METHODS: Systematic Review: Papers were searched in Medline, Scopus and the Science Citation Index database. Reference lists of included studies and of reviews were screened. To be included papers had to report ROTEM or TEG data on healthy subjects. Two reviewers screened papers for inclusion, read full texts of potentially relevant papers, and extracted data of included papers. RESULTS: Searches identified 1,721 records of which 1,713 were either excluded immediately or after reading the full text. The remaining 8 studies enrolled 632 subjects. The association of conventional parameters of hemostasis with ROTEM and with TEG was investigated in one and two studies, respectively. Overall correlation was limited and ranged from 0.0 to 0.40 (total thrombus generation vs. fibrinogen; clotting time INTEM vs. activated partial thromboplastin time). CONCLUSIONS: Studies assessing the relationship between thromboelastometry or thromboelastography analyses and conventional parameters of hemostasis in healthy subjects remains scarce, and correlations are limited. Further research is needed to understand the physiology of thromboelastometry and thromboelastography parameters.

Deep Learning Models Used in the Diagnostic Workup of Keratoconus: A Systematic Review and Exploratory Meta-Analysis.

PURPOSE: The prevalence of keratoconus in the general population is reported to be up to 1 of 84. Over the past 2 decades, diagnosis and management evolved rapidly, but keratoconus screening in clinical practice is still challenging and asks for improving the accuracy of keratoconus detection. Deep learning (DL) offers considerable promise for improving the accuracy and speed of medical imaging interpretation. We establish an inventory of studies conducted with DL algorithms that have attempted to diagnose keratoconus. METHODS: This systematic review was conducted according to the recommendations of the PRISMA statement. We searched (Pre-)MEDLINE, Embase, Science Citation Index, Conference Proceedings Citation Index, arXiv document server, and Google Scholar from inception to February 18, 2022. We included studies that evaluated the performance of DL algorithms in the diagnosis of keratoconus. The main outcome was diagnostic performance measured as sensitivity and specificity, and the methodological quality of the included studies was assessed using QUADAS-2. RESULTS: Searches retrieved 4100 nonduplicate records, and we included 19 studies in the qualitative synthesis and 10 studies in the exploratory meta-analysis. The overall study quality was limited because of poor reporting of patient selection and the use of inadequate reference standards. We found a pooled sensitivity of 97.5% (95% confidence interval, 93.6%-99.0%) and a pooled specificity of 97.2% (95% confidence interval, 85.7%-99.5%) for topography images as input. CONCLUSIONS: Our systematic review found that the overall diagnostic performance of DL models to detect keratoconus was good, but the methodological quality of included studies was modest.

Randomised Controlled Trials Assessing the Clinical Value of Urodynamic Studies: A Systematic Review and Meta-analysis.

Context: The role of urodynamic studies (UDSs) in the diagnosis of lower urinary tract symptoms (LUTS) is crucial. Although expert statements and guidelines underline their value for clinical decision-making in various clinical settings, the academic debate as to their impact on patient outcomes continues. Objective: To summarise the evidence from all randomised controlled trials assessing the clinical usefulness of UDS in the management of LUTS. Evidence acquisition: For this systematic review, searches were performed without language restrictions in three electronic databases until November 18, 2020. The inclusion criteria were randomised controlled study design and allocation to receive UDS or not prior to any clinical management. Quality assessment was performed by two reviewers independently, using the Cochrane Collaboration's tool for assessing the risk of bias. A random-effect meta-analysis was performed on the uniformly reported outcome parameters. Evidence synthesis: Eight trials were included, and all but two focused on women with pure or predominant stress urinary incontinence (SUI). A meta-analysis of six studies including 942 female patients was possible for treatment success, as defined by the authors (relative risk 1.00, 95% confidence interval: 0.93-1.07), indicating no difference in efficacy when managing women with UDS. Conclusions: Although UDSs are not replaceable in diagnostics, since there is no other equivalent method to find out exactly what the lower urinary tract problem is, there are little data supporting its impact on outcomes. Randomised controlled trials have focussed on a small group of women with uncomplicated SUI and showed no added value, but these findings cannot be extrapolated to the overall patient population with LUTS, warranting further well-designed trials. Patient summary: Despite urodynamics being the gold standard to assess lower urinary tract symptoms (LUTS), as it is the only method that can specify lower urinary tract dysfunction, more studies assessing the clinical usefulness of urodynamic studies (UDSs) in the management of LUTS are needed. UDS investigation is not increasing the probability of success in the treatment of stress urinary incontinence.

Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. DESIGN: Systematic review and network meta-analysis of randomised trials. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656.

Keratoconus Characteristics Used in Randomized Trials of Surgical Interventions-A Systematic Review.

PURPOSE: To investigate descriptions and inclusion criteria of keratoconus used in randomized trials assessing the efficacy of surgical and nonsurgical interventions. METHODS: Systematic review: we searched (Pre-)Medline and the Cochrane Library from inception until December 2018 and checked the reference lists of included articles and reviews. We included randomized trials assessing the efficacy of any kind of keratoconus treatment. No language restrictions were imposed. We assessed articles against the inclusion criteria, extracted relevant data including any kind of keratoconus description, and examined the methodological quality. RESULTS: Searches retrieved 459 nonduplicate records, and we included 57 randomized controlled trials investigating 9 different surgical interventions with the most used primary outcome measure being maximum keratometry. Only 15 (26.3%) described eligibility parameters regarding keratoconus staging/classification, of which 12 studies used the Amsler-Krumeich classification. Eleven studies were published before 1997 (before publication of the Consolidated Standards of Reporting Trials statement), and none of these described the use of a classification. From 1997 onward, 15 of 46 studies (32.6%) described the incorporation of a classification system (P = 0.051). The average methodological quality of included trails was modest. CONCLUSIONS: The evidence from randomized trials, even after introduction of the Consolidated Standards of Reporting Trials statement, remains ill-formed regarding a careful definition of keratoconus. This is unfortunate because imprecisions regarding the specification of included patients preclude clinicians to assess applicability, that is, the extent to which they can use inferences drawn from study participants regarding efficacy and adverse events in the care of individual patients.

Metaepidemiological Inventory of Diagnostic Studies on Urodynamics.

BACKGROUND: Urodynamic investigations have a pivotal role in the diagnosis of lower urinary tract symptoms. Despite expert statements and guidelines supporting their usefulness for clinical decision making in various clinical domains, the academic debate remains controversial. OBJECTIVE: To provide a metaepidemiological inventory of studies assessing the diagnostic properties of urodynamic investigations. DESIGN, SETTING, AND PARTICIPANTS: Systematic searches without language restrictions were performed in (Pre-)Medline, EMBASE, and the Cochrane Library from inception until August 31, 2018. Checking of reference lists of included studies and reviews complemented searches. Records were compiled and screened for possible inclusion by reading title and abstracts by two teams of two research fellows. Inclusion criteria were as follows: prospective data collection and urodynamic investigations performed either as a diagnostic test or using a therapy monitoring instrument. No a priori selection on clinical domain was done. Double reading was performed on records marked "included." Extraction into a developed and piloted matrix was performed in duplicate and checked by a third research fellow. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Of each included article, study specifics, objective, study design, type of data collection, clinical domain, type and description of test used, and type of outcome were extracted and attributed to a framework. RESULTS AND LIMITATIONS: Electronic searches retrieved 20 841 records. After screening, 299 abstracts were considered relevant. The main reasons for exclusion were as follows: animal studies, no primary data, editorial/opinion based on published data or reviews, primary objective of the study being not the assessment of urodynamic investigations, and post hoc (opportunistic) correlation studies. CONCLUSIONS: To our knowledge, this is the first comprehensive collection of studies assessing the clinical usefulness of urodynamic investigations. The collection is the starting point for a series of systematic reviews assessing the diagnostic properties of urodynamic investigations. PATIENT SUMMARY: The usefulness of urodynamic investigations for clinical decision making is under debate. We established an inventory of diagnostic studies on urodynamics to assess the value of urodynamics in various clinical applications.

Expert consensus on relevant risk predictors for the occurrence of osteoporotic fractures in specific clinical subgroups - Delphi survey.

BACKGROUND: There is an ongoing discussion about incorporating additional risk factors to established WHO fracture risk assessment tool (FRAX) to improve the prediction accuracy in clinical subgroups. We aimed to reach an expert consensus on possible additional predictive parameters for specific clinical subgroups. METHODS: Two-round modified Delphi survey: We generated a shortlist of experts from the authors' lists of the pertinent literature and complemented the list with experts known to the authors. Participants were asked to name possible relevant risk factors besides the FRAX-parameters for the occurrence of osteoporotic fractures. Experts specified these possible predictors for specific subgroups of patients. In the second round the expert panel was asked to weight each parameter of every subgroup assigning a number between one (not important) to ten (very important). We defined the threshold for an expert consensus if the interquartile range (IQR) of a predictor was ≤2. The cut-off value of the median attributed weights for a relevant predictor was set at ≥7. RESULTS: Eleven experts of seven countries completed both rounds of the Delphi. The participants agreed on nine additional parameters for seven categories. For the category "secondary osteoporosis", "older adults" and "nursing home patients", there was a consensus that history of previous falls was relevant, while for men and postmenopausal women, there was a consensus that the spine fracture status was important. For the group "primary and secondary osteoporosis" the experts agreed on the parameters "high risk of falls", "lumbar spine bone mineral density (BMD)" and "sarcopenia". CONCLUSION: This Delphi survey reached a consensus on various parameters that could be used to refine the currently existing FRAX for specific clinical situations or patient groups. The results may be useful for studies aiming at improving the predictive properties of instruments for fracture prediction.

Test performance of optical coherence tomography angiography in detecting retinal diseases: a systematic review and meta-analysis.

OBJECTIVE: To investigate the diagnostic accuracy of optical coherence tomography angiography (OCTA) in detecting vascular characteristics of chorio-retinal disease. METHODS: Evidence acquisition: We searched Web of Science, Scopus, and Medline by the citation of references and complemented these electronic searches by checking the list of references of included and review articles. Screening, selection, assessment, and extraction was performed in parallel by two authors. RESULTS: Evidence synthesis: Systematic review and exploratory meta-analysis. The ten studies that contributed to the meta-analysis enrolled 440 eyes and allowed constructing ten two-by-two tables. The tables reported on detection of choroidal neovascularization (CNV) in eyes suffering from either age-related macular degeneration (4), central serous chorioretinopathy (2), myopia (2), foveomacular vitelliform dystrophy (1), or a mixed cohort suffering from multiple retinal diseases (1). Of the ten studies, six used a cohort and four a case-control design. We found a pooled sensitivity of 0.90 (95% confidence intervals (CIs): 0.82-0.95) and a pooled specificity of 0.97 (95% CI: 0.89-0.99). Corresponding positive and negative likelihood ratios were 32.3 (95% CI: 7.4-141.6) and 0.10 (95% CI: 0.06-0.20), respectively. No pooling was possible for retinal vascular parameters of diabetic retinopathy, polypoidal choroidal vasculopathy, or detection of CNV activity. CONCLUSIONS: The results of highly biased and heterogeneous studies assessing the diagnostic performance of OCTA highlight the need for further analyses of methodologically sound and sufficiently sized clinical evaluations.

Expert Consensus on Predictive Parameters for the Occurrence of a Fall and a Contralateral Hip Fracture 1 and 3 Years After Hip Fracture: A Delphi Survey.

BACKGROUND: Early identification of people at risk for a contralateral hip fracture would be desirable to favorably influence patients' prognosis. A recent systematic review failed to depict stringent patterns of risk parameters to be used for decision-making in clinical practice. OBJECTIVE: To perform a consensus study using the Delphi method to reach an expert consensus on predictive parameters for the occurrence of a fall and a contralateral hip fracture 1 and 3 years after hip fracture. METHODS: A list of potential members of the expert panel was identified based on the authors' list of a recently conducted systematic review. Participating experts were asked to name parameters determining the probability for a fall and a contralateral hip fracture 1 and 3 years after an occurred hip fracture, separately. Additionally, we asked how those stated parameters should be measured. All mentioned parameters were compiled and sent back to the experts asking them to weight each single parameter by assigning a number between 1 (not important) and 10 (very important). The survey was conducted online using the REDCap software package. We defined expert agreement if the interquartile range of attributed weights for a parameter was ≤2. A relevant parameter had at least a median weight of 8. RESULTS: Twelve experts from 7 countries completed the survey. Presence of fall history and mental and general health status were considered relevant irrespective of the outcome. For falling within 1 and 3 years, the number of medications and residential status were considered relevant, while for fractures within 1 and 3 years, osteoporosis management was considered important. CONCLUSION: Using the insights gained in this consensus study, empiric studies need to be set up assessing the prognostic value of the selected parameters.

Evidence assessing the diagnostic performance of medical smartphone apps: a systematic review and exploratory meta-analysis.

OBJECTIVE: The number of mobile applications addressing health topics is increasing. Whether these apps underwent scientific evaluation is unclear. We comprehensively assessed papers investigating the diagnostic value of available diagnostic health applications using inbuilt smartphone sensors. METHODS: Systematic Review-MEDLINE, Scopus, Web of Science inclusive Medical Informatics and Business Source Premier (by citation of reference) were searched from inception until 15 December 2016. Checking of reference lists of review articles and of included articles complemented electronic searches. We included all studies investigating a health application that used inbuilt sensors of a smartphone for diagnosis of disease. The methodological quality of 11 studies used in an exploratory meta-analysis was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool and the reporting quality with the 'STAndards for the Reporting of Diagnostic accuracy studies' (STARD) statement. Sensitivity and specificity of studies reporting two-by-two tables were calculated and summarised. RESULTS: We screened 3296 references for eligibility. Eleven studies, most of them assessing melanoma screening apps, reported 17 two-by-two tables. Quality assessment revealed high risk of bias in all studies. Included papers studied 1048 subjects (758 with the target conditions and 290 healthy volunteers). Overall, the summary estimate for sensitivity was 0.82 (95 % CI 0.56 to 0.94) and 0.89 (95 %CI 0.70 to 0.97) for specificity. CONCLUSIONS: The diagnostic evidence of available health apps on Apple's and Google's app stores is scarce. Consumers and healthcare professionals should be aware of this when using or recommending them. PROSPERO REGISTRATION NUMBER: 42016033049.