Inter-Rater Agreement in Assessing Risk of Bias in Melanoma Prediction Studies Using the Prediction Model Risk of Bias Assessment Tool (PROBAST): Results from a Controlled Experiment on the Effect of Specific Rater Training.

Assessing the risk of bias (ROB) of studies is an important part of the conduct of systematic reviews and meta-analyses in clinical medicine. Among the many existing ROB tools, the Prediction Model Risk of Bias Assessment Tool (PROBAST) is a rather new instrument specifically designed to assess the ROB of prediction studies. In our study we analyzed the inter-rater reliability (IRR) of PROBAST and the effect of specialized training on the IRR. Six raters independently assessed the risk of bias (ROB) of all melanoma risk prediction studies published until 2021 (n = 42) using the PROBAST instrument. The raters evaluated the ROB of the first 20 studies without any guidance other than the published PROBAST literature. The remaining 22 studies were assessed after receiving customized training and guidance. Gwet's AC1 was used as the primary measure to quantify the pairwise and multi-rater IRR. Depending on the PROBAST domain, results before training showed a slight to moderate IRR (multi-rater AC1 ranging from 0.071 to 0.535). After training, the multi-rater AC1 ranged from 0.294 to 0.780 with a significant improvement for the overall ROB rating and two of the four domains. The largest net gain was achieved in the overall ROB rating (difference in multi-rater AC1: 0.405, 95%-CI 0.149-0.630). In conclusion, without targeted guidance, the IRR of PROBAST is low, questioning its use as an appropriate ROB instrument for prediction studies. Intensive training and guidance manuals with context-specific decision rules are needed to correctly apply and interpret the PROBAST instrument and to ensure consistency of ROB ratings.

Using the Prediction Model Risk of Bias Assessment Tool (PROBAST) to Evaluate Melanoma Prediction Studies.

Rising incidences of cutaneous melanoma have fueled the development of statistical models that predict individual melanoma risk. Our aim was to assess the validity of published prediction models for incident cutaneous melanoma using a standardized procedure based on PROBAST (Prediction model Risk Of Bias ASsessment Tool). We included studies that were identified by a recent systematic review and updated the literature search to ensure that our PROBAST rating included all relevant studies. Six reviewers assessed the risk of bias (ROB) for each study using the published "PROBAST Assessment Form" that consists of four domains and an overall ROB rating. We further examined a temporal effect regarding changes in overall and domain-specific ROB rating distributions. Altogether, 42 studies were assessed, of which the vast majority (n = 34; 81%) was rated as having high ROB. Only one study was judged as having low ROB. The main reasons for high ROB ratings were the use of hospital controls in case-control studies and the omission of any validation of prediction models. However, our temporal analysis results showed a significant reduction in the number of studies with high ROB for the domain "analysis". Nevertheless, the evidence base of high-quality studies that can be used to draw conclusions on the prediction of incident cutaneous melanoma is currently much weaker than the high number of studies on this topic would suggest.

Reporting Quality of Studies Developing and Validating Melanoma Prediction Models: An Assessment Based on the TRIPOD Statement.

Transparent and accurate reporting is essential to evaluate the validity and applicability of risk prediction models. Our aim was to evaluate the reporting quality of studies developing and validating risk prediction models for melanoma according to the TRIPOD (Transparent Reporting of a multivariate prediction model for Individual Prognosis Or Diagnosis) checklist. We included studies that were identified by a recent systematic review and updated the literature search to ensure that our TRIPOD rating included all relevant studies. Six reviewers assessed compliance with all 37 TRIPOD components for each study using the published "TRIPOD Adherence Assessment Form". We further examined a potential temporal effect of the reporting quality. Altogether 42 studies were assessed including 35 studies reporting the development of a prediction model and seven studies reporting both development and validation. The median adherence to TRIPOD was 57% (range 29% to 78%). Study components that were least likely to be fully reported were related to model specification, title and abstract. Although the reporting quality has slightly increased over the past 35 years, there is still much room for improvement. Adherence to reporting guidelines such as TRIPOD in the publication of study results must be adopted as a matter of course to achieve a sufficient level of reporting quality necessary to foster the use of the prediction models in applications.

Pilot Assessment of the Angiosome Concept by Intra-operative Fluorescence Angiography After Tibial Bypass Surgery.

OBJECTIVES: The "angiosome" concept as a model for decision making in revascularisation of patients with critical limb ischaemia (CLI) has been subject to lively discussion in recent years. The aim of this prospective pilot study was to use intra-operative fluorescence angiography to provide further data on the angiosome concept on the level of microcirculation after tibial bypass surgery. DESIGN, MATERIALS, AND METHODS: This was a prospective analysis of 40 patients presenting with CLI Rutherford stage IV to VI before and after tibial bypass surgery. The macrocirculation was measured by the ankle brachial index. Skin microcirculation was assessed by intra-operative fluorescence angiography. The alteration of microcirculation was compared in direct and indirect revascularised angiosomes. Clinical follow-up investigations were performed and the wound healing rate was compared between the different revascularisation methods. RESULTS: Cumulated microcirculation parameters showed a significant improvement after surgery (ingress, ingress rate p<.001). Likewise, general microcirculatory improvement was observed in each foot angiosome after revascularisation, regardless of the tibial artery revascularised. Furthermore, a comparison of the direct (DR) and the indirect revascularised (IR) angiosomes did not show a significant difference concerning the improvement of microcirculation (difference DR-IR, ingress: 1.69, 95% CI 71.73-75.11; ingress rate: 0.08, 95% CI -12.91 to 13.07). The wound healing rate was similar in both groups, although the time to wound healing was faster by on average 2.5 months in the DR group (p=.083). CONCLUSION: Microcirculatory improvement was seen over the whole foot after tibial bypass. Therefore, fluorescence angiography is a promising tool to evaluate the angiosome concept in future larger studies. Clinicaltrials.gov: NCT03012750.

Malnutrition According to Mini Nutritional Assessment Is Associated With Severe Functional Impairment in Geriatric Patients Before and up to 6 Months After Hip Fracture.

OBJECTIVES: Hip fractures (HFs) in old age frequently cause severe functional impairment and deteriorating autonomy in everyday life. Many older patients with HFs are malnourished or at risk of malnutrition. In this study, we examined the relationship between nutritional status of geriatric patients before HF and their functional and clinical course up to 6 months after hospital discharge. DESIGN: Observational study with follow-up after 6 months. SETTING: Four wards of the department of trauma and orthopedic surgery of a large urban maximum care hospital (Klinikum Nürnberg, Nuremberg, Germany). PARTICIPANTS: Geriatric patients aged ≥75 years with surgically repaired proximal femoral fracture. MEASUREMENTS: Prefracture nutritional status was determined by Mini Nutritional Assessment (MNA). Comorbidities and complications during hospital stay were obtained from medical documentation. Functional status before HF, postoperatively, at hospital discharge, and 6 months later was assessed by Barthel Index for activities of daily living (ADL) and patients' mobility level and related to MNA categories. Associations were evaluated using χ(2), Fisher exact, Kruskal-Wallis, Mann-Whitney-U, Jonckheere-Terpstra, and Cochrane-Armitage tests as appropriate, as well as analysis of covariance with repeated measures. RESULTS: Of 97 included patients, 17% were malnourished and 38% at risk of malnutrition before HF. Participants with (risk of) malnutrition were equally mobile but more dependent in ADL prior to HF than well-nourished patients (P < .001). Independent of nutritional status, after 6 months 68% of participants had not regained their prefracture level of independence in ADL. According to analysis of covariance, the ADL development over time until follow-up 6 months after hospital discharge did not depend on nutritional status. However, at follow-up malnourished patients more often suffered from remaining losses in ADL ≥25% of initial Barthel Index points (P = .033) and less often had regained their prefracture mobility level (P = .020) than well-nourished patients. Clinical course did not differ significantly between the groups with different nutritional status. CONCLUSIONS: In this study with geriatric HF patients from all functional and cognitive levels, worse prefracture nutritional status was associated with worse functional status and more frequent remaining functional loss, whereas the trajectory of ADL recovery and clinical course did not differ significantly. Further studies with sufficient statistical power are needed to substantiate these inconclusive results. In order to clarify the association of nutritional status with functional and clinical course in geriatric patients after HF, they should preferably focus on the role of nutritional management during the hospital stay.

INTERBED: internet-based guided self-help for overweight and obese patients with full or subsyndromal binge eating disorder. A multicenter randomized controlled trial.

BACKGROUND: Binge eating disorder (BED) is a prevalent clinical eating disorder associated with increased psychopathology, psychiatric comorbidity, overweight and obesity, and increased health care costs. Since its inclusion in the DSM-IV, a few randomized controlled trials (RCTs) have suggested efficacy of book-based self-help interventions in the treatment of this disorder. However, evidence from larger RCTs is needed. Delivery of self-help through new technologies such as the internet should be investigated in particular, as these approaches have the potential to be more interactive and thus more attractive to patients than book-based approaches. This study will evaluate the efficacy of an internet-based guided self-help program (GSH-I) and cognitive-behavioral therapy (CBT), which has been proven in several studies to be the gold standard treatment for BED, in a prospective multicenter randomized trial. METHODS: The study assumes the noninferiority of GSH-I compared to CBT. Both treatments lasted 4 months, and maintenance of outcome will be assessed 6 and 18 months after the end of treatment. A total of 175 patients with BED and a body mass index between 27 and 40 kg/m2 were randomized at 7 centers in Germany and Switzerland. A 20% attrition rate was assumed. As in most BED treatment trials, the difference in the number of binge eating days over the past 28 days is the primary outcome variable. Secondary outcome measures include the specific eating disorder psychopathology, general psychopathology, body weight, quality of life, and self-esteem. Predictors and moderators of treatment outcome will be determined, and the cost-effectiveness of both treatment conditions will be evaluated. RESULTS: The methodology for the INTERBED study has been detailed. CONCLUSIONS: Although there is evidence that CBT is the first-line treatment for BED, it is not widely available. As BED is still a recent diagnostic category, many cases likely remain undiagnosed, and a large number of patients either receive delayed treatment or never get adequate treatment. A multicenter efficacy trial will give insight into the efficacy of a new internet-based guided self-help program and will allow a direct comparison to the evidence-based gold standard treatment of CBT in Germany. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40484777. German Clinical Trial Register DRKS00000409.

Estimated prevalence of compulsive buying in Germany and its association with sociodemographic characteristics and depressive symptoms.

The aim of this study was to estimate the prevalence of compulsive buying and its association with sociodemographic characteristics and depressive symptoms in a nationally representative sample of the German population using the validated German version of the Compulsive Buying Scale (CBS; Faber and O'Guinn, 1992) in order to have a direct comparison with U.S. findings. The point prevalence of compulsive buying in the weighted representative sample (N=2,350) was estimated to be 6.9%. This was somewhat higher than the percentage in the American sample assessed in 2004 (5.8%). No significant difference was found between women and men (6.9% and 6.8%, respectively). Age was inversely related to the prevalence of compulsive buying. Individuals with compulsive buying reported more depressive symptoms assessed via the German version of the Brief Patient Health Questionnaire Mood Scale (PHQ-9). Further research on this topic is needed to establish a clearer delineation of when excessive buying is clinically significant and should be treated and how it could be prevented.

Assessment of multiple ordinal endpoints.

Ranking multivariate ordinal data and applying a non-parametric test is an analytical approach commonly employed to compare treatments. We study three types of ranking and demonstrate how to combine them. The ranking methods rest upon partial orders of the multidimensional measurements or upon the sum of ranks. Since their usage is simple as regards statistical assumptions and technical realization, they are also adapted for health professionals without deep statistical knowledge. Our goal is discussing differences between the approaches and disclosing possible statistical consequences of their usage.

Comparison of confidence intervals for adjusted attributable risk estimates under multinomial sampling.

The epidemiologic concept of the adjusted attributable risk is a useful approach to quantitatively describe the importance of risk factors on the population level. It measures the proportional reduction in disease probability when a risk factor is eliminated from the population, accounting for effects of confounding and effect-modification by nuisance variables. The computation of asymptotic variance estimates for estimates of the adjusted attributable risk is often done by applying the delta method. Investigations on the delta method have shown, however, that the delta method generally tends to underestimate the standard error, leading to biased confidence intervals. We compare confidence intervals for the adjusted attributable risk derived by applying computer intensive methods like the bootstrap or jackknife to confidence intervals based on asymptotic variance estimates using an extensive Monte Carlo simulation and within a real data example from a cohort study in cardiovascular disease epidemiology. Our results show that confidence intervals based on bootstrap and jackknife methods outperform intervals based on asymptotic theory. Best variants of computer intensive confidence intervals are indicated for different situations.