Use of ROC curve analysis for prediction gives fallacious results: Use predictivity-based indices.

ABSTRACT: The area under the ROC curve is frequently used for assessing the predictive efficacy of a model, and the Youden index is commonly used to provide the optimal cut-off. Both are misleading tools for predictions. A ROC curve is drawn for the sensitivity of a quantitative test against its (1 - specificity) at different values of the test. Both sensitivity and specificity are retrospective in nature as these are indicators of correct classification of already known conditions. They are not indicators of future events and are not valid for predictions. Predictivity intimately depends on the prevalence which may be ignored by sensitivity and specificity. We explain this fallacy in detail and illustrate with several examples that the actual predictivity could differ greatly from the ROC curve-based predictivity reported by many authors. The predictive efficacy of a test or a model is best assessed by the percentage correctly predicted in a prospective framework. We propose predictivity-based ROC curves as tools for providing predictivities at varying prevalence in different populations. For optimal cut-off for prediction, in place of the Youden index, we propose a P-index where the sum of positive and negative predictivities is maximum after subtracting 1. To conclude, for correctly assessing adequacy of a prediction models, predictivity-based ROC curves should be used instead of the usual sensitivity-specificity-based ROC curves and the P-index should replace the Youden index.

Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme.

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.

The minimum effective dose (ED90) of prophylactic oxytocin infusion during cesarean delivery in patients with and without obesity: an up-down sequential allocation dose-response study.

BACKGROUND: Obesity is associated with greater oxytocin requirement during labor induction or augmentation. There are scant data exploring the intra-operative requirement during cesarean delivery in patients with obesity, and none comparing it with those without obesity. We evaluated the minimum effective dose (ED90) of an oxytocin infusion to achieve adequate uterine tone during cesarean delivery in patients with and without obesity. METHODS: Patients (body mass index ≥30 kg/m2 represented patients with obesity) undergoing cesarean delivery using subarachnoid block were included. This prospective dual-arm dose-finding study used a 9:1 biased sequential allocation design. Oxytocin infusion was initiated at 13 IU/h at cord clamping in the first patient of each group. Uterine tone was graded as satisfactory or unsatisfactory by the obstetrician four minutes after initiation of the infusion. The dose of oxytocin infusion for subsequent patients was determined according to the response of the previous patient in the group. Oxytocin-associated side effects were evaluated. Dose-response data for the groups was evaluated using log-logistic function and ED90 estimates derived from fitted equations using the delta method. RESULTS: The ED90 of oxytocin was significantly higher for patients with obesity (n = 40) compared with those without obesity (n = 40) [25.7 IU/h, 95% CI 18.6 to 32.9) vs. 16.6 IU/h, 95% CI 14.9 to 18.3)]; relative ratio 1.55 [95% CI 1.09 to 2.01] (P = 0.019). CONCLUSIONS: Patients with obesity require a higher intra-operative oxytocin infusion dose rate to achieve a satisfactorily contracted uterus after fetal delivery when compared with patients without obesity.

Is Follow-up Co-Morbidity Assessment via Laboratory Investigations in Older High Energy Trauma Patients Justified? - A Prospective-Retrospective Study

@#Introduction: The objective of the current study was to test our hypothesis that older patients sustaining high energy trauma need to be evaluated for their comorbidities similar to geriatric patients sustaining low energy trauma. Materials and methods: This study was a retrospectiveprospective analysis of 173 patients of more than 50 years of age enrolled between November 2017 and December 2018. Herewith, we have compared retrospectively collected laboratory investigations of 124 fragility fracture patients with prospectively collected laboratory investigations of 49 patients with high energy trauma. The laboratory investigations, including the liver function tests, renal function tests, indices of calcium metabolism, serum electrolytes, complete blood counts, and bone mineral density (BMD) scores. Results: Both groups were similar to each other as far as baseline demographic characteristics were concerned. The proportion of female patients and patients with nonosteoporotic range BMD (T-score >-2.5) was significantly higher in the high-energy fracture group (P value <0.05). Hypoalbuminemia (<3.4gm/dl) 17.3%, abnormalities sodium (<135mmol/L or >148mmol/L) 23.2%, Anaemia (<10g/dl) 12.7%, Hypercalcemia (>10.4mg/dl) 16.3%, Vitamin D deficiency (<20ng/ml) 17.3% are the common laboratory abnormality found in study population. No statistically significant difference was found among the two groups in terms of laboratory investigation abnormalities. Conclusion: The laboratory investigation abnormality in an older patient with a clinical fracture is independent of the mechanism of injury. The results of the current study emphasise the need for a comprehensive laboratory workup in older patients with either high- energy fractures or fragility fractures.

Outcomes in Nonagenarians with Hip Fractures Treated Conservatively and Surgically

@#Introduction: We aimed to assess the clinical outcomes in nonagenarians following a hip fracture. We also further investigated the factors that influence these outcomes, such as method of treatment (operative versus conservative), comorbidities, and pre-morbid function. Materials and methods: We studied 65 nonagenarians that were identifiable from our hospital hip fracture database. We reviewed various parameters of these patients admitted after sustaining a hip fracture (neck of femur or intertrochanteric) and investigated how these parameters affected patient outcomes. The main outcomes studied were: inpatient morbidity, and mortality at one year. Results: Inpatient morbidity was more likely in patients with an ASA grade of 3 to 5. Urinary tract infection was the most common medical complication. The 1-year mortality was 15.4% and was significantly influenced by advancing age. Surgically managed patients had a 1-year mortality rate (14.3%) slightly less than non-operative patients (17.4%). Post injury mobility was significantly better in those who received operative treatment with 63% of surgical cases regaining ambulatory status versus 7% of conservatively managed patients. Conclusions: We presented the outcomes of hip fractures in an extreme age group in the population. In nonagenarians with hip fractures surgery was associated with a 1-year mortality rate of 14.3% which is comparable to the general hip fracture population and less than the mortality rate of conservatively managed patients (17.4%). The primary advantage of surgery would be that two-thirds of patients return to ambulatory status. This information is useful to counsel patients and their families especially since the elderly are often more fearful of surgical intervention.