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.

Optimising plasma clozapine levels to improve treatment response: an individual patient data meta-analysis and receiver operating characteristic curve analysis.

BACKGROUND: Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response. AIMS: Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice. METHOD: We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response. RESULTS: We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223-558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine. CONCLUSIONS: Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.

Nail changes due to chemotherapy: a prospective observational study of 129 patients.

BACKGROUND: Nail changes due to systemic drugs are common, especially with anticancer treatments due to involvement of nail plate, nail bed and periungual area. OBJECTIVE: To study the pattern of nail changes occurring due to chemotherapy in patients suffering from various malignancies. MATERIALS AND METHODS: A prospective, observational study was conducted at various health care centres, Nashik, India, for 15 months. The timing of administration of chemotherapy and onset of nail changes were recorded and evaluated by a dermatologist at regular interval. RESULTS: A total of 129 diagnosed cases of various malignancies who received chemotherapy were included. The most common malignancy noted was breast cancer, that is n = 42 (32.5%) followed by oral cancer, that is n = 24 (18.6%). Chemotherapy agents included taxanes (n = 54), cyclophosphamide (n = 42) and prednisolone (n = 28). Nail changes were noted in 92 patients (71.3%). The most common nail changes observed were chromonychia (n = 70, 54.26%), followed by nail dystrophy (n = 38, 29.45%). CONCLUSION: Nail toxicity is quite common side effect of anticancer agents. Nail changes due to chemotherapy depend on the nail structure involved and the severity of insult. Awareness among dermatologists and oncologists of these nail changes and their culprit agent can promote early diagnosis and may avoid inadvertent measures.

Evaluation of Emblica officinalis fruit powder as a growth promoter in commercial broiler chickens.

AIM: The present study was conducted to evaluate the dietary addition of Emblica officinalis (Amla) fruit powder as a growth promoter in commercial broiler chickens. MATERIALS AND METHODS: An experiment was conducted on 135 commercial broiler chicks (Ven-Cobb 400 strain) divided into three groups with three replicates of 15 chicks each. Three treatment groups were as follows - T1: Basal diet as per BIS standards; T2: Basal diet supplemented with 0.4% of E. officinalis fruit powder; and T3: Basal diet supplemented with 0.8% of E. officinalis fruit powder. RESULTS: The average body weights at the end of the 6(th) week were significantly higher (p<0.05) in groups T2 and T3 compared to group T1. Feed intake, feed conversion ratio and feed cost per kg live weight production were similar among the treatment groups. The net profit per bird was the highest in group T2 (Rs. 19.22/bird) followed by group T3 (Rs. 17.86/bird) and the lowest in group T1 (Rs. 14.61/bird). CONCLUSION: Based on the results of the present study, it was concluded that dietary addition of E. officinalis (Amla) fruit powder had a positive effect on growth performance and net profit per bird in commercial broiler chickens.

Push-out bond strength of root fillings made with C-Point and BC sealer versus gutta-percha and AH Plus after the instrumentation of oval canals with the Self-Adjusting File versus WaveOne.

AIM: To compare the push-out bond strength exhibited by root fillings performed with either C-Point and Endosequence® BC sealer™ (BC Sealer) or gutta-percha and AH Plus® after the instrumentation of oval canals with either the Self-Adjusting File (SAF) System or WaveOne (WO) reciprocating file. METHODOLOGY: Eighty extracted premolars were selected and divided randomly into the following four groups (n = 20): group 1, SAF instrumentation and filling using gutta-percha and AH Plus sealer; group 2, SAF instrumentation and C-Point and BC sealer filling; group 3, WO instrumentation and filling using gutta-percha and AH Plus sealer; and group 4, WO instrumentation and filling with C-Point and BC sealer. Sodium hypochlorite (5.25%) and EDTA (17%) were used as irrigants for all groups. After the sealer was set completely, the teeth were prepared for micro push-out assessment using 1.0-mm-thick root slices. Loading was performed with a universal testing machine at a speed of 0.5 mm min(-1) . Two-way anova and Student's t-test for pairwise comparisons were used to compare groups. RESULTS: All specimens filled with C-Point and BC sealer were associated with significantly higher push-out bond strength compared with gutta-percha and AH Plus sealer (P < 0.001). The bond strength was higher for the coronal and apical samples of the C-Point/BC sealer/SAF group (6.6 ± 0.3 and 3.2 ± 0.3 MPa) versus those of the gutta-percha/AH Plus/WO group (4.8 ± 0.3 and 1.8 ± 0.3 MPa), by 38% and by 80% in the coronal and apical parts, respectively (P < 0.001, P < 0.0001). Adhesive bond failure was more common in the WaveOne-instrumented group in general and in the buccal and lingual recesses in this group in particular. CONCLUSIONS: In oval canals, the instrument used and the root filling material significantly affected the push-out values of root fillings. The highest value was recorded in oval root canals instrumented with the SAF System and filled with C-Point and BC sealer, whereas the lowest strength was noted in oval canals instrumented with WaveOne and filled with gutta-percha and AH Plus sealer.

Clinico-biochemical and therapeutic studies on notoedric mange in pet rabbits.

Two male and two female pet rabbits of about 1 year of age, naturally infested with Notoedres cuniculi were studied in the present investigation. Clinical examination revealed presence of crustaceous lesions on the head, ear pinnae, both the limbs and external genitalia. Microscopic examination of skin scrapings confirmed presence of Notoedres mange infestation. Biochemical parameters revealed altered values of total serum protein, albumin, globulin, and activities of aspartate amino transferase, alanine amino transferase and alkaline phosphatase respectively. The affected rabbits were treated with two injections of Ivermectin (400 µg/kg, subcutaneously, at interval of 15 days) along with supportive therapy. This treatment showed appreciable improvement in clinical signs and restoration in biochemical parameters.

Impact of a multidimensional infection control strategy on catheter-associated urinary tract infection rates in the adult intensive care units of 15 developing countries: findings of the International Nosocomial Infection Control Consortium (INICC).

PURPOSE: We aimed to evaluate the impact of a multidimensional infection control strategy for the reduction of the incidence of catheter-associated urinary tract infection (CAUTI) in patients hospitalized in adult intensive care units (AICUs) of hospitals which are members of the International Nosocomial Infection Control Consortium (INICC), from 40 cities of 15 developing countries: Argentina, Brazil, China, Colombia, Costa Rica, Cuba, India, Lebanon, Macedonia, Mexico, Morocco, Panama, Peru, Philippines, and Turkey. METHODS: We conducted a prospective before-after surveillance study of CAUTI rates on 56,429 patients hospitalized in 57 AICUs, during 360,667 bed-days. The study was divided into the baseline period (Phase 1) and the intervention period (Phase 2). In Phase 1, active surveillance was performed. In Phase 2, we implemented a multidimensional infection control approach that included: (1) a bundle of preventive measures, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback of CAUTI rates, and (6) feedback of performance. The rates of CAUTI obtained in Phase 1 were compared with the rates obtained in Phase 2, after interventions were implemented. RESULTS: We recorded 253,122 urinary catheter (UC)-days: 30,390 in Phase 1 and 222,732 in Phase 2. In Phase 1, before the intervention, the CAUTI rate was 7.86 per 1,000 UC-days, and in Phase 2, after intervention, the rate of CAUTI decreased to 4.95 per 1,000 UC-days [relative risk (RR) 0.63 (95% confidence interval [CI] 0.55-0.72)], showing a 37% rate reduction. CONCLUSIONS: Our study showed that the implementation of a multidimensional infection control strategy is associated with a significant reduction in the CAUTI rate in AICUs from developing countries.

Impact of a multidimensional infection control strategy on central line-associated bloodstream infection rates in pediatric intensive care units of five developing countries: findings of the International Nosocomial Infection Control Consortium (INICC).

PURPOSE: To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control strategy including a practice bundle to reduce the rates of central line-associated bloodstream infection (CLAB) in patients hospitalized in pediatric intensive care units (PICUs) of hospitals, which are members of the INICC, from nine cities of five developing countries: Colombia, India, Mexico, Philippines, and Turkey. METHODS: CLAB rates were determined by means of a prospective surveillance study conducted on 1,986 patients hospitalized in nine PICUs, over a period of 12,774 bed-days. The study was divided into two phases. During Phase 1 (baseline period), active surveillance was performed without the implementation of the multi-faceted approach. CLAB rates obtained in Phase 1 were compared with CLAB rates obtained in Phase 2 (intervention period), after implementation of the INICC multidimensional infection control program. RESULTS: During Phase 1, 1,029 central line (CL) days were recorded, and during Phase 2, after implementing the CL care bundle and interventions, we recorded 3,861 CL days. The CLAB rate was 10.7 per 1,000 CL days in Phase 1, and in Phase 2, the CLAB rate decreased to 5.2 per 1,000 CL days (relative risk [RR] 0.48, 95% confidence interval [CI] 0.29-0.94, P = 0.02), showing a reduction of 52% in the CLAB rate. CONCLUSIONS: This study shows that the implementation of a multidimensional infection control strategy was associated with a significant reduction in the CLAB rates in the PICUs of developing countries.

Socioeconomic impact on device-associated infections in limited-resource neonatal intensive care units: findings of the INICC.

PURPOSE: To evaluate the impact of country socioeconomic status and hospital type on device-associated healthcare-associated infections (DA-HAIs) in neonatal intensive care units (NICUs). METHODS: Data were collected on DA-HAIs from September 2003 to February 2010 on 13,251 patients in 30 NICUs in 15 countries. DA-HAIs were defined using criteria formulated by the Centers for Disease Control and Prevention. Country socioeconomic status was defined using World Bank criteria. RESULTS: Central-line-associated bloodstream infection (CLA-BSI) rates in NICU patients were significantly lower in private than academic hospitals (10.8 vs. 14.3 CLA-BSI per 1,000 catheter-days; p < 0.03), but not different in public and academic hospitals (14.6 vs. 14.3 CLA-BSI per 1,000 catheter-days; p = 0.86). NICU patient CLA-BSI rates were significantly higher in low-income countries than in lower-middle-income countries or upper-middle-income countries [37.0 vs. 11.9 (p < 0.02) vs. 17.6 (p < 0.05) CLA-BSIs per 1,000 catheter-days, respectively]. Ventilator-associated-pneumonia (VAP) rates in NICU patients were significantly higher in academic hospitals than in private or public hospitals [13.2 vs. 2.4 (p < 0.001) vs. 4.9 (p < 0.001) VAPs per 1,000 ventilator days, respectively]. Lower-middle-income countries had significantly higher VAP rates than low-income countries (11.8 vs. 3.8 per 1,000 ventilator-days; p < 0.001), but VAP rates were not different in low-income countries and upper-middle-income countries (3.8 vs. 6.7 per 1,000 ventilator-days; p = 0.57). When examined by hospital type, overall crude mortality for NICU patients without DA-HAIs was significantly higher in academic and public hospitals than in private hospitals (5.8 vs. 12.5%; p < 0.001). In contrast, NICU patient mortality among those with DA-HAIs was not different regardless of hospital type or country socioeconomic level. CONCLUSIONS: Hospital type and country socioeconomic level influence DA-HAI rates and overall mortality in developing countries.