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This study aimed to pinpoint independent predictors influencing overall survival (OS) and cancer-specific survival (CSS) in elderly patients with small cell lung cancer (SCLC) brain metastasis (BM), and to create and validate nomograms for OS and CSS prediction. Data from elderly SCLC BM patients were extracted out of the Surveillance, Epidemiology, and End Results database, including 1200 patients identified from 2010 and 2015 who were randomly allocated into a training set and an internal validation set at a proportion of 7:3, and 666 patients diagnosed between 2018 and 2020 as a temporal external validation set. Independent predictors for OS and CSS were determined through univariate Cox analysis, least absolute shrinkage and selection operator analysis, and multivariate Cox analysis sequentially. Nomograms for OS and CSS were constructed, and validated by the internal and temporal external validation sets. Age, N stage, chemotherapy, and liver metastasis were determined as independent predictors of OS and CSS, while radiotherapy and surgery were not. Nomograms were constructed based on these independent predictors. The results of the receiver operator characteristic curves, the areas under the curve and calibration curve demonstrated that the nomograms exhibited commendable discriminative ability and calibration. Moreover, decision curve analysis, net reclassification improvement, and integrated discrimination improvement also suggested that the nomograms possessed superior clinical usefulness and predictive capability relative to the TNM system. Prognostic nomograms for elderly patients with SCLC BM have been developed, demonstrating good performance in terms of accuracy, reliability, and practicality. [ABSTRACT FROM AUTHOR]

Hip fractures are a significant cause of mortality among older adults. However, predictive markers for an unfavorable prognosis are still lacking. Serum calcium is an essential element in several biochemical reactions in the body. This study investigated the role of the preoperative serum calcium level as a prognostic parameter for postoperative mortality in older adult patients with hip fractures. We conducted a prospective cohort study at the trauma center in our hospital, from January 1, 2015, to September 30, 2019. A total of 2333 older patients with hip fractures were recruited. This prospective cohort study was conducted in accordance with the criteria of STROCSS. Older adult patients with hip fractures were screened between January 2015 and September 2019 at the trauma center of our hospital. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between preoperative serum calcium level and all-cause mortality. All analyses were performed using EmpowerStats and the R software. A total of 2333 older adult patients with hip fractures were included in the study. The mean follow-up was 37.5 months. Overall, 770 patients (33%) died of all causes. The preoperative serum calcium concentrations were 2.18 ± 0.13 mmol/L. Linear multivariate Cox regression models showed that preoperative serum calcium levels were associated with mortality [hazard ratio (HR) 0.37, 95% CI 0.21-0.67; P =.0009] after adjusting for confounders. However, the linear association was unstable, and nonlinearity was identified. A preoperative serum calcium level of 2.3 mmol/L was an inflection point for prediction. When the preoperative serum calcium concentration was below 2.3 mmol/L, serum calcium concentration increased by 1 mmol/L, and mortality risk decreased by 77% (HR 0.23, 95% CI 0.13-0.43, P <.0001). In contrast, when the preoperative serum calcium concentration was more significant than 2.3 mmol/L, the mortality risk increased with serum calcium concentration (HR 6.27, 95% CI 1.65-23.74, P =.0069). The preoperative serum calcium level is nonlinearly associated with mortality in older adults with hip fractures, with a U-shaped association, and could be used as a potential predictor of prognosis. [ABSTRACT FROM AUTHOR]

Prior studies have shown an association between malnutrition and mortality. However, it is uncertain whether malnutrition assessed with the Mini Nutritional Assessment (MNA) instrument is suitable for providing long-term prognostic information regarding older adults admitted to hospital. The aim of the present study was to examine if MNA-assessed malnutrition was associated with long-term mortality in older adults admitted to hospital and for how long the association persisted. 1768 older adults (≥65 years old) admitted to a Swedish hospital were assessed with the 18-item MNA during 2008–2009 and followed-up after 10 years. All-cause mortality (ACM) was analyzed separately for the five follow-up periods 0 to ≤2 years, >2 to ≤4 years, >4 to ≤6 years, >6 to ≤8 years, and >8 to ≤10 years using Cox regression models adjusted for important demographic, nutritional, and clinical confounders. The participants were on average 78.1 years old at baseline, with 56.0% being females. At 10 years follow-up, 174 (94.1%) malnourished patients, 757 (75.9%) patients at risk of malnutrition, and 297 (50.7%) well-nourished patients had died. For all follow-up periods, malnourished patients and patients at risk of malnutrition had significantly higher risks of early death in the adjusted regression analyses when compared with well-nourished patients (all P < 0.05), with the highest risk observed for malnourished patients. For patients still alive at 8 years, the risk of death during the following two years was 2.7 times higher for patients being malnourished at baseline (P = 0.013) and 1.9 times higher for patients being at risk of malnutrition at baseline (P = 0.001), compared with patients being well-nourished at baseline. MNA-assessed malnutrition is an important independent predictor of long-term mortality in older adults admitted to hospital and the association is consistent over 10 years of follow-up. In clinical practice, MNA may provide long-term prognostic information to rule out those at low risk of mortality and therefore in less need of further assessment and intervention, such that the resources can focus on those in actual need of nutritional support. [ABSTRACT FROM AUTHOR]

• Previous Puumala virus infection is associated with lymphoid malignancy development. • The risk increases during the first 5 years after Puumala virus infection. • Puumala virus infection associates especially with mature B cell neoplasms. The Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal syndrome. Studies showing an increased risk of lymphoid malignancies after hantavirus infection, together with the observation that PUUV infects B cells, motivated us to study the risk of lymphoid malignancies after PUUV infection. We linked data from the Finnish Cancer Registry and National Infectious Diseases Register for 2009-2019. We used a time-dependent Cox regression model to evaluate the hazard of the lymphoid malignancies grouped according to the HAEMACARE classification. We identified 68 cases of lymphoid malignancies after PUUV infection among 16,075 PUUV-infected individuals during 61,114,826 person-years of observation. A total of 10 cases occurred within 3-<12 months and 38 within 1-<5 years after PUUV infection, and the risk of lymphoid malignancies increased with hazard ratios (HRs) of 2.0 (95% confidence interval [CI], 1.1-3.7) and 1.6 (95% CI, 1.2-2.3), respectively. The group of mature B cell neoplasms showed an increased risk 3-<12 months and 1-<5 years after PUUV infection, HR 2.2 (95% CI, 1.2-4.3) and HR 1.8 (95% CI, 1.3-2.5), respectively. PUUV infection is associated with lymphoid malignancies in the Finnish population, supporting the earlier studies. Further research is required to understand the pathophysiological mechanisms behind this association. [ABSTRACT FROM AUTHOR]

Background: Advanced paternal age has been reported to be associated with a variety of short-term outcomes in offspring, but long-term effects are rarely examined. The present study evaluated the impact of advanced paternal age on offspring's longevity.Methods: We studied the effect of paternal reproductive age on the lifespan of male offspring using a Chinese genealogy data set that spans 226 years of the Qing Dynasty (1683-1909). Multivariable-adjusted Cox regression analyses of 1274 men with survival data were used to calculate hazard ratios (HRs) of advanced parental age at reproduction. We also evaluated whether the lifespan of brothers differed when they were born to the same parents at different ages.Results: In models adjusted for maternal age, advanced paternal age was negatively associated with the lifespan of male offspring. Individuals born to fathers aged >40 years had a 32 % higher HR of a lifespan shorter than those born to fathers aged 25-29 years (adjusted HR 1.320, 95 % CI: 1.066-1.634). The adjusted HR for offspring born to fathers aged 35-39 years was 1.232 (95 % CI: 1.013-1.500). Older brothers born to fathers aged 20-34 years had a significantly lower risk of a reduced lifespan compared with their younger brothers with fathers aged ≥35 years at reproduction (P < 0.01).Conclusion: Advanced paternal age at reproduction is a negative factor for male offspring's life expectancy. With the sustained increase in paternal age over the past generation, further investigation is warranted into the impact on birth outcomes and public health. [ABSTRACT FROM AUTHOR]

Background: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not.Objective: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions.Methods: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold.Results: Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death.Limitations: Multicenter, retrospective study.Conclusion: Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) patients are prone to fall and fall-related injuries (FI). Vascular disease is common in PD and is positively associated with falls in elderly. We aimed to evaluate the association of vascular disease with FI risk in PD. A nationwide cohort study of patients with primary PD diagnosis in Sweden was performed using Swedish national registers. Patients with and without vascular disease were followed from PD diagnosis until subsequent FI or 2013-12-31. The association of vascular disease with FI risk was estimated as hazard ratio (HR) and 95 % confidence interval (CI) by Cox regression using attained age as underlying timescale. We identified 2734 and 6979 incident FI from 8025 PD patients with and 20,543 without vascular disease, respectively. Overall, vascular disease associated positively with subsequent FI, which was mainly driven by the significant risk elevation within the first 6 months following vascular disease (HR < 0.5year [95 % CI] for PD diagnosed ≤75 years is 1.61 [1.39–1.87] and for PD diagnosed >75 years is 1.48 [1.32–1.65]). Thereafter, the association attenuated to null before it rebounded five years after exposure in PD diagnosed ≤75 years (HR > 5year = 1.26, 95 % CI: 1.10–1.45); whereas for PD diagnosed >75 years, it dropped remarkably and remained non-significant 6 months after exposure. When vascular disease was restricted to stroke, we saw a similar temporal pattern except that the short-term HRs among younger patients were stronger, lasted longer, and declined continuously without rebound. Fall prevention is crucial to PD patients immediately after a vascular event. • Vascular disease associated with short-term risk of fall-related injury (FI) in PD. • Vascular disease-associated long-term FI risk depended on age at PD diagnosis. • Stroke, particularly, associated with a stronger and longer-lasting FI risk in PD. [ABSTRACT FROM AUTHOR]

• Multicentric cohort of n = 605 patients treated with definitive chemoradiotherapy for anal cancer. • Overall, T-category, N-category, age and KPS were associated with worse DFS. • In early stage disease, T-category, HIV status, age, performance status and elevated platelets were associated with worse DFS. Prognosis after chemoradiotherapy (CRT) for anal squamous cell carcinoma (ASCC) shows marked differences among patients according to TNM subgroups, however individualized risk assessment tools to better stratify patients for treatment (de-) escalation or intensified follow-up are lacking in ASCC. Patients' data from eight sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG), comprising a total of 605 patients with ASCC, treated with standard definitive CRT with 5-FU/Mitomycin C or Capecitabine/Mitomycin C between 2004–2018, were used to evaluate prognostic factors based on Cox regression models for disease-free survival (DFS). Evaluated variables included age, gender, Karnofsky performance score (KPS), HIV-status, T-category, lymph node status and laboratory parameters. Multivariate cox models were separately constructed for the whole cohort and the subset of patients with early-stage (cT1-2 N0M0) tumors. After a median follow-up of 46 months, 3-year DFS for patients with early-stage ASCC was 84.9%, and 67.1% for patients with locally-advanced disease (HR 2.4, p < 0.001). T-category (HR vs. T1: T2 2.02; T3 2.11; T4 3.03), N-category (HR versus N0: 1.8 for N1-3), age (HR 1.02 per year), and KPS (HR 0.8 per step) were significant predictors for DFS in multivariate analysis in the entire cohort. The model performed with a C-index of 0.68. In cT1-2N0 patients, T-category (HR 2.14), HIV status (HR 2.57), age (1.026 per year), KPS (HR 0.7 per step) and elevated platelets (HR 1.3 per 100/nl) were associated with worse DFS (C-index of 0.7). Classical clinicopathologic parameters like T-category, N-category, age and KPS remain to be significant prognostic factors for DFS in patients treated with contemporary CRT for ASCC. HIV and platelets were significantly associated with worse DFS in patients with early stage ASCC. [ABSTRACT FROM AUTHOR]

• Survival analysis, is one of the most developed fields of statistics in the last decades of the last century. • Failure prevention methods are necessary and should be adopted for industrial equipment to function well in. • The 75% probability of survival of solid bulk cargo is equivalent to an operational availability time of 444 h. • There is a significant difference between the survival curves of the covariates of shift, types of minerals, number of wagons and tons moved. • The results indicate a significant reduction in the probability of survival of equipment during operation time. In complex industrial systems, the deterioration of equipment and production of defective products are important points that increase the costs inherent to the production function. In this context, the purpose of this article is to estimate the survival of a group of pieces of industrial port equipment known as solid bulk conveyors, thus contributing to decision-making in the maintenance process. To achieve this goal, the Kaplan-Meier method was used to estimate the probability of global survival, and the survival curves were compared using the Log-rank test. To this end, the effect of each covariate on the survival time of the conveyors was analyzed using the Cox regression model, for which an analysis of residuals and influential observations was conducted. The 75% probability of survival of solid bulk cargo is equivalent to an operational availability time of 444 h. It was found that, of the 95 conveyors that were evaluated, 38 (40%) failed and 57 (60%) were censored by the end of the study. The results indicate a significant reduction in the probability of survival of equipment during operation time, as well as a significant difference between the survival curves of the covariates of shift, types of minerals, the number of wagons and tons moved, indicating that these are important predictors in the Cox regression model. [ABSTRACT FROM AUTHOR]

Background: Human milk oligosaccharides (HMOs) are unconjugated glycans associated with infant health and development.Objectives: To investigate the associations between HMO concentrations at 1 month and infant development throughout the first year of life.Methods: A prospective cohort of Brazilian women between 18-40 years of age and their infants was studied from baseline (between 28-35 gestational weeks) and followed at 1 (n = 73), 6 (n = 51), and 12 months (n = 45). A total of 19 HMOs were quantified by HPLC with fluorescence detection. Infant development was evaluated by the Brazilian Ages and Stages Questionnaire. A directed acyclic graph was used to define the minimally sufficient adjustment (gestational age at birth, gestational weight gain, prepregnancy BMI, maternal age, parity, and the mode of breastfeeding at 1 month). Cox regression models with HRs and Benjamini-Hochberg multiple corrections were performed to estimate associations of HMOs with the cumulative risk of inadequate development for 5 developmental domains or for ≥2 developmental domains in all women and in the subset of secretor women (defined as the presence or near absence of 2'-fucosyllactose and lacto-N-fucopentaose I).Results: The multivariate models with multiple corrections revealed an inverse association between lacto-N-tetrose (LNT) and the risk of inadequate development for personal-social skills (0.06; 95% CI: 0.01-0.76) and for ≥2 developmental domains (0.06; 95% CI: 0.01-0.59). The secretor mothers analysis also showed inverse associations with slightly different results for personal-social skills (0.09; 95% CI: 0.02-0.84) and ≥2 developmental domains (0.05; 95% CI: 0.01-0.70).Conclusions: Higher concentrations of LNT HMOs in Brazilian women are associated with their infants being less likely to be at risk of inadequate development for personal-social skills or for ≥2 developmental domains during the first year of life. [ABSTRACT FROM AUTHOR]

Background: Internal fixation is currently considered the gold standard in treatment for femoral neck fractures in adults. However, osteonecrosis of the femoral head (ONFH) after internal fixation would occur in quite proportion of patients with femoral neck fracture, even in Garden I femoral neck fracture. The purpose of this study was to determine the association between the blood biomarkers (serum albumin, pre-albumin, total protein and total lymphocyte count) and ONFH following internal fixation of Garden I femoral neck fracture in adults.Method: This is a single center cohort study, in which each patient who sustained a Garden I femoral neck fracture had been treated with internal fixation, and had adequate preoperative blood examinations. The serum albumin was categorized as ≥ 40g/L or < 40g/L. The pre-albumin was categorized as ≥ 22mg/dL or < 22mg/dL. The total protein was categorized as ≥ 65g/L or < 65 g/L. The total lymphocyte count was categorized as ≥1.1× 109 /L or <1.1×109 /L. Multivariate cox proportional hazards analysis was used to assess the association between blood markers and the osteonecrosis of femoral head during the 2-years follow-up period controlling the confounders.Result: A total of 10 cases of ONFH were identified. Multivariate Cox regression analysis revealed that low total lymphocyte count and hypertension state were significant independent risk factors for ONFH after internal fixation for Garden I femoral head fractures.Conclusion: Blood biomarkers were potential predictors for ONFH after internal fixation Garden I femoral neck fractures. We suggest that routine laboratory tests might can be used to assist surgeons to identify patients at great risk of ONFH. [ABSTRACT FROM AUTHOR]

By understanding prognostic biomarkers, we gain insights into disease biology and may improve design, conduct, and data analysis of clinical trials and real-world data. In this context, we used the Flatiron Health Electronic Health Record-derived deidentified database that provides treatment outcome and biomarker data from >280 oncology centers in the USA, organized into 17 cohorts defined by cancer type. In 122 694 patients, we analyzed demographic, clinical, routine hematology, and blood chemistry parameters within a Cox proportional hazard framework to derive a multivariable prognostic risk model for overall survival (OS), the 'Real wOrld PROgnostic score (ROPRO)'. We validated ROPRO in two independent phase I and III clinical studies. A total of 27 variables contributed independently and homogeneously across cancer indications to OS. In the largest cohort (advanced non-small-cell lung cancer), for example, patients with elevated ROPRO scores (upper 10%) had a 7.91-fold (95% confidence interval 7.45–8.39) increased death hazard compared with patients with low scores (lower 10%). Median survival was 23.9 months (23.3–24.5) in the lowest ROPRO quartile Q1, 14.8 months (14.4–15.2) in Q2, 9.4 months (9.1–9.7) in Q3, and 4.7 months (4.6–4.8) in Q4. The ROPRO model performance indicators [C-index = 0.747 (standard error 0.001), 3-month area under the curve (AUC) = 0.822 (0.819–0.825)] strongly outperformed those of the Royal Marsden Hospital Score [C-index = 0.54 (standard error 0.0005), 3-month AUC = 0.579 (0.577–0.581)]. We confirmed the high prognostic relevance of ROPRO in clinical Phase 1 and III trials. The ROPRO provides improved prognostic power for OS. In oncology clinical development, it has great potential for applications in patient stratification, patient enrichment strategies, data interpretation, and early decision-making in clinical studies. • Clinical routine variables can be combined into a high-quality prognostic score [Real wOrld PROgnostic score (ROPRO)] for overall survival. • ROPRO can be used for patient matching and baseline risk adjustment in clinical studies. • ROPRO can support patient enrichment in early clinical trials. [ABSTRACT FROM AUTHOR]

Previous studies report higher hospitalization rates in for-profit compared with nonprofit long-term care facilities (LTCFs), but have not included staffing data, a major potential confounder. Our objective was to examine the effect of ownership on hospital admission rates, after adjusting for facility staffing levels and other facility and resident characteristics, in a large Canadian province (British Columbia). Retrospective cohort study. Our cohort included individuals resident in a publicly funded LTCF in British Columbia at any time between April 1, 2012 and March 31, 2016. Health administrative data were extracted from multiple databases, including continuing care, hospital discharge, and Minimum Data Set (MDS 2.0) assessment records. Cox extended hazards regression was used to estimate hospitalization risk associated with facility- and resident-level factors. The cohort included 49,799 residents in 304 LTCF facilities (116 publicly owned and operated, 99 for-profit, and 89 nonprofit) over the study period. Hospitalization risk was higher for residents in for-profit (adjusted hazard ratio [adjHR] 1.34; 95% confidence interval [CI] 1.29–1.38) and nonprofit (adjHR 1.37; 95% CI 1.32–1.41) facilities compared with publicly owned and operated facilities, after adjustment for staffing, facility size, urban location, resident demographics, and case mix. Within subtypes, risk was highest in single-site facilities: for-profit (adjHR 1.42; 95% CI 1.36–1.48) and nonprofit (adjHR 1.38, 95% CI 1.33–1.44). This is the first Canadian study using linked health data from hospital discharge records, MDS 2.0, facility staffing, and ownership records to examine the adjusted effect of facility ownership characteristics on hospital use of LTCF residents. We found significantly lower adjHRs for hospital admission in publicly owned facilities compared with both for-profit and nonprofit facilities. Our finding that publicly owned facilities have lower hospital admission rates compared with for-profit and nonprofit facilities can help inform decision-makers faced with the challenge of optimizing care models in both nursing homes and hospitals as they build capacity to care for aging populations. [ABSTRACT FROM AUTHOR]

Aim Research regarding the effect of antipsychotic medications on the risk of upper respiratory infection (URI) progression to pneumonia in patients with schizophrenia is rare. This study investigated the effect of antipsychotic use on the risk of URI progression to pneumonia in patients with schizophrenia.Methods: This cohort study used the Taiwan's Nationwide Psychiatric Inpatient Medical Claims Database. From January 1, 1996 to December 31, 2012, 22,771 patients with schizophrenia were diagnosed as having the first URI episode after their first psychiatric admission and 135 of them developed pneumonia within 30 days. The duration and dosage of antipsychotics were assessed before and after URI. Cox regression with time-dependent model was used to assess the risk of antipsychotic use on the progression of URI to pneumonia.Results: Among first- and second-generation antipsychotics, clozapine was the only medication associated with an increased risk of developing pneumonia before URI (adjusted hazard ratio [aHR] = 2.05, P = .024). Clozapine was also the only drug significantly associated with an increased risk after URI (aHR = 1.92, P = .027). Regarding medication use after URI, the dosage of clozapine was significantly associated with an increased risk based on Cox regression with a time-dependent model (aHR = 1.95, P = .003).Conclusions: The use of clozapine was associated with URI progression to pneumonia in patients with schizophrenia. The dosage of clozapine used in the post-URI period was also associated with an increased risk. Clinicians should consider lowering clozapine dosage in patients with URI to prevent them developing pneumonia. [ABSTRACT FROM AUTHOR]

Background: Little is known of how frailty, a dynamic measure of physiological age, progresses relative to age or disability status. Operative treatment of adult spinal deformity (ASD) may play a role in frailty remediation and maintenance.Purpose: Compare frailty status, severe frailty development, and factors influencing severe frailty development among ASD patients undergoing operative or nonoperative treatment.Design: Retrospective review with maximum follow-up of 3 years.Setting: Prospective, multicenter, ASD database.Participants: Patients were consecutively enrolled from 13 participating centers.Inclusion Criteria: ≥18 years undergoing either operative or nonoperative treatment for ASD, exclusion criteria: spinal deformity of neuromuscular etiology, presence of active infection, or malignancy. The mean age of the participants analyzed were 54.9 for the operative cohort and 55.0 for the nonoperative cohort.Outcomes Measures: Frailty status, severe frailty development, and factors influencing severe frailty development.Methods: ASD patients (coronal scoliosis ≥20°, sagittal vertical axis (SVA) ≥5 cm, Pelvic Tilt (PT) ≥25°, or thoracic kyphosis ≥60°) >18 y/o, with Base Line (BL) frailty scores were included. Frailty was scored from 0 to 1 (not frail: <0.3, frail 0.3-0.5, severe frailty >0.5) through the use of ASD-frailty index (FI) which has been validated using the International Spine Study Group (ISSG) ASD database, European Spine Study Group ASD database, and the Scoli-RISK-1 Patient Database. The ISSG is funded through research grants from DePuy Synthes and individual donations and supported the current work. Operative (Op) and Nonoperative (Non-Op) patients were propensity matched. T-tests compared frailty among treatment groups and BL, 1, 2, and ≥3 years. An actuarial Kaplan-Meier survivorship analysis with log-rank (Mantel-Cox) test, adjusting for patients lost to follow-up, determined probability of severe frailty development. Multivariate Cox Regressions gauged the effect of sagittal malalignment, patient and surgical details on severe frailty development.Results: The analysis includes 472 patients (236 Op, 236 Non-Op) selected by propensity score matching from a cohort of 1,172. Demographics and comorbidities were similar between groups (p>.05). Op exhibited decreased frailty at all follow-up intervals compared with BL (BL: 0.22 vs Y1: 0.18; Y2: 0.16; Y3: 0.15, all p<.001). Non-Op displayed similar frailty from BL to 2Y follow up, and increased frailty at 3Y follow up (0.23 vs 0.25, p=.014). Compared with Non-Op, Op had lower frailty at 1Y (0.18 vs 0.24), 2Y (0.16 vs 0.23), and 3Y (0.15 vs 0.25; all p<.001). Cumulative probability of maintaining nonsevere frailty was (Op: 97.7%, Non-Op: 94.5%) at 1Y, (Op: 95.1%, Non-Op: 90.4%) at 2Y, and (Op: 95.1%, Non-Op: 89.1%) at ≥3Y, (p=.018). Among all patients, baseline depression (hazard ratio: 2.688[1.172-6.167], p=.020), Numeric Rating Scale (NRS) back pain scores (HR: 1.247[1.012-1.537], p=.039), and nonoperative treatment (HR: 2.785[1.167-6.659], p=.021) predicted severe frailty development with having a HR>1.0 and p value<.05. Among operative patients, 6-week postoperative residual SVA malalignment (SRS-Schwab SVA+modifier) (HR: 15.034[1.922-116.940], p=.010) predicted severe frailty development indicated by having a HR>1.0 and p value <.05.Conclusions: Non-Op patients were more likely to develop severe frailty, and at a quicker rate. Baseline depression, increased NRS back pain scores, nonoperative treatment, and postoperative sagittal malalignment at 6-week follow-up significantly predicted severe frailty development. Operative intervention and postoperative sagittal balance appear to play significant roles in frailty remediation and maintenance in ASD patients. Frailty is one factor, in a multifactorial conservation, that may be considered when determining operative or nonoperative values for ASD patients. Operating before the onset of severe frailty, may result in a lower complication risk and better long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

The predictive ability of the separate items of the full Mini Nutritional Assessment (MNA-F) instrument in relation to all-cause mortality (ACM) in older adults is unclear. The present study aimed to examine the magnitudes of the independent associations between separate MNA-F items and ACM among people aged ≥65 years old admitted to hospital. A secondary aim was to construct a trimmed MNA instrument (MNA-T) consisting of MNA-F items that contributed independently to predicting ACM, and compare its predictive ability with that of MNA-F and MNA short forms (MNA-SF). This prospective cohort study included 1768 individuals aged ≥65 years old admitted to a Swedish hospital who answered MNA-F in 2008. They were followed-up for ACM after two years using national registers. Associations with ACM were calculated using Cox regression analysis. Predictive abilities for ACM were calculated using an R2-type measure. After a mean follow-up time of 1.7 years (3006 person-years), 455 (25.7%) participants had died. In adjusted analyses, nine MNA-F items contributed independently to predicting ACM (P < 0.20) and were included in MNA-T. Five items (food intake, independent living, > 3 prescription drugs, fluid intake, self-assessed health status) had significant contributions (P < 0.05). MNA-T had a better predictive ability for ACM than MNA-F and MNA-SF. MNA-F could possibly benefit from excluding less important and more time-consuming items when used for predicting the ultimate consequence of malnutrition, an early death. MNA-T should be a more reliable instrument to use for this purpose. [ABSTRACT FROM AUTHOR]

Objectives: To describe the mortality patterns, comorbidities, and attendance at accident and emergency departments among children with Down syndrome in Hong Kong.Study Design: This is a population-based, retrospective cohort study of live births of children with Down syndrome delivered between 1995 and 2014, as identified from territory-wide hospitalization data in Hong Kong. The Kaplan-Meier product limit method was adopted to estimate the survival probabilities of children with Down syndrome by selected demographic and clinical characteristics. Cox regression analyses were conducted to examine associations of comorbidities and accident and emergency department accident and emergency departments attendances with mortality patterns.Results: There were 1010 live births of children with Down syndrome in Hong Kong within the study period and the average rate of live births with Down syndrome was 8.0 per 10 000 live births (95% CI, 6.8-9.30). The rate of live births with Down syndrome over the past 2 decades decreased from 11.8 per 10 000 live births in 1995 to 3.4 per 10 000 in 2014. Eighty-three patients with Down syndrome died during this period. The overall 6-month and 1- and 5-year survival probabilities were 95.8%, 94.4%, and 92.6%, respectively. There was a significant decrease in mortality rates over the study period, particularly among those born between 2000-2004 and 2005-2009 compared with those born between 1995 and 1999 (P < .05). Patients with Down syndrome without congenital cardiovascular anomalies and without low birth weight had lower mortality rates than those with these diagnoses.Conclusions: Over the past 2 decades, the early life mortality of children with Down syndrome in Hong Kong has improved significantly along with a reduction in Down syndrome live births. [ABSTRACT FROM AUTHOR]

The basic epidemiology of institutionalisation (the need for long-term care in an institution) in parkinsonism is unclear. We aimed to identify the incidence of, and risk factors for, institutionalisation in Parkinson's disease (PD) and atypical parkinsonism (AP). We analysed data from a prospective population-based incidence cohort of parkinsonism in North-East Scotland (the PINE study). 556 newly-diagnosed participants (PD, N = 200; AP, N = 98; controls, N = 258), recruited between 2002 and 2009, were prospectively followed life-long with data collection on place of residence. We determined the incidence and baseline predictors of institutionalisation using Cox regression. The median follow-up time was 9.3, 4.4, and 10.8 years in PD, AP, and controls respectively. 70 (35 %) PD, 53 (54 %) AP, and 43 (16 %) controls became institutionalised. The incidence rates of institutionalisation in PD, AP, and controls were 5.1, 20.8, and 1.8 per 100 person-years respectively. The median time to institutionalisation was 11.8 years in PD and 3.5 years in AP. Multivariable Cox regression showed that AP (HR versus PD = 3.05 [95 % CI 1.90,4.91]), increasing age (HR for 10-year increase = 1.82 [95 % CI 1.40,2.36]), poorer cognition (HR for MMSE<24 versus MMSE>27 = 2.62 [95 % CI 1.45, 4.73]), more-severe parkinsonian impairment (UPDRS part 3) (HR for 10-point increase = 1.25 [95 % CI 1.05, 1.48]) were independently associated with higher hazards of institutionalisation. Sex, co-morbidity, smoking history, and living alone were not associated with institutionalisation. Institutionalisation is much more frequent in parkinsonism, particularly in AP, than in controls. AP, older age, severe parkinsonian impairment, and poorer cognition were independent baseline predictors of institutionalisation. • This is one of the first studies to describe institutionalisation in a population-based incidence cohort of parkinsonism. • Institutionalisation is much more frequent in parkinsonism, particularly in atypical parkinsonism, than in controls. • Atypical parkinsonism, older age, higher UPDRS, and lower MMSE at baseline independently predicted institutionalisation. [ABSTRACT FROM AUTHOR]

Cow routines and behavioral responses are altered substantially following the installation of robot milking. The present study was designed to analyze the effect that switching from milking parlor to automatic milking system (AMS) had on the culling rate (due to various causes) of dairy cattle. For this purpose, culling records and causes for culling were tracked in 23 dairy farms in the Galicia region (NW Spain). The animals in these farms were monitored for 5 years. For the present study, that length of time was divided into three different stages, as follows: 2 years before switching from a milking parlor to AMS (stage 1), the 1st year following the implementation of AMS (stage 2) and the 2nd and 3rd years succeeding the implementation of AMS (stage 3). Cox models for survival analysis were used to estimate the time to culling due to different reasons during stage 1 in relation to stages 2 and 3. The data indicated that the risk of loss due to death or emergency slaughter decreased significantly following the installation of AMS. In contrast, the risk of culling due to low production, udder problems, infertility or lameness increased significantly. Low-production cows (such as cows in advanced lactation due to infertility) or sick cows (such as mastitic or lame cows) allegedly have a noticeable effect both on the performance and the amortization of the cost of AMS, which in turn would lead to a higher probability of elimination than in conventional systems. [ABSTRACT FROM AUTHOR]

Highlights • Cox regression was used to assess transitional statuses. • Survival curves showed variable ranges to limit transitional statuses. • Pair-up operation of system components gave the highest COP. • The COP rose by 2.72% by limiting undesirable statuses. Abstract The coefficient of performance (COP) of chiller systems drops when their operating statuses change frequently and deviate from the conventional pair-up operation of chillers, pumps and cooling towers. This paper analyses the chance of having transitional and unconventional operating statuses when the operating variables vary. 12,541 sets of operating conditions were collected from a chiller system at 15 min intervals over 8 months. 1901 sets of transitional statuses and 1565 sets of unconventional statuses were identified. Cox regression models were developed to analyze the impacts of ambient variables, flow- and temperature-related operating variables on transitional statuses. The temperatures of water entering and leaving the condensers were significant variables influencing the chance of switching on/off an extra cooling tower. Survival curves suggested the throttling range of significant variables to identify the chance of transitional statuses causing a COP fluctuation. Minimizing unnecessary transitional and unconventional statuses increased the average system COP by 2.72%. [ABSTRACT FROM AUTHOR]

Abstract Clinical trials and retrospective studies in the field of radiation oncology often consider time-to-event data as their primary endpoint. Such studies are susceptible to competing risks, i.e. competing events may preclude the occurrence of the event of interest or modify the chance that the primary endpoint occurs. Competing risks are frequently neglected and the event of interest is analysed with standard statistical methods. Here, we would like to create awareness of the problem and demonstrate different methods for survival data analysis in the presence of competing risks. [ABSTRACT FROM AUTHOR]

Highlights • Feature selection algorithms using multiple tests. • Screening for high-dimensional features or gene expressions. • A cross-validation algorithm to measure predictive capability of selected features. • Computation of the false discovery rate. • Multigene predictors for survival (e.g., the compound covariate predictor). • Survival data on lung cancer patients made available. • Copula-based methods for survival data with dependent censoring. Abstract Background and objective Univariate feature selection is one of the simplest and most commonly used techniques to develop a multigene predictor for survival. Presently, there is no software tailored to perform univariate feature selection and predictor construction. Methods We develop the compound.Cox R package that implements univariate significance tests (via the Wald tests or score tests) for feature selection. We provide a cross-validation algorithm to measure predictive capability of selected genes and a permutation algorithm to assess the false discovery rate. We also provide three algorithms for constructing a multigene predictor (compound covariate, compound shrinkage, and copula-based methods), which are tailored to the subset of genes obtained from univariate feature selection. We demonstrate our package using survival data on the lung cancer patients. We examine the predictive capability of the developed algorithms by the lung cancer data and simulated data. Results The developed R package, compound.Cox , is available on the CRAN repository. The statistical tools in compound.Cox allow researchers to determine an optimal significance level of the tests, thus providing researchers an optimal subset of genes for prediction. The package also allows researchers to compute the false discovery rate and various prediction algorithms. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Abstract The TMPRSS2-ERG gene fusion were frequently found in prostate cancer, and thought to play some fundamental mechanisms for the development of prostate cancer. However, until now, the clinical and prognostic significance of TMPRSS2-ERG gene fusion was not fully understood. In this study, based on the 281 prostate cancers that constructed from a historical watchful waiting cohort, the statistically significant associations between TMPRSS2-ERG gene fusion and clinicopathologic characteristics were identified. In addition, the Elastic Net algorithm was used to predict the patients with TMPRSS2-ERG fusion status, and good predictive results were obtained, indicating that this algorithm was suitable to this prediction problem. The differential gene network was constructed from the network, and the KEGG enrichment analysis demonstrated that the module genes were significantly enriched in several important pathways. Highlights • The clinicopathologic differences between ERG positive and ERG negative patients were analyzed. • The Elastic Net was used to predict the TMPRSS2-ERG fusion status. • A network was constructed from the differential genes between two tumor groups. [ABSTRACT FROM AUTHOR]

• Infusion of Bonsmara into Afrikaner immediately increased length of life. • Effects of infusion of Bonsmara into Afrikaner dissipated as backcrossing progressed. • Alternative strategies may be needed to increase length of life. The Afrikaner breed of cattle is indigenous to South Africa and due their hardiness has been used in forming several new composite breeds. In the 1980′s, Afrikaner breeders became concerned about a perceived loss in fertility and the lack of attention to performance traits. The "infusion project" was developed to target shortcomings of the Afrikaner breed with the introgression of Bonsmara alleles into Afrikaner cattle. However, documented evidence of resulting changes in the fitness of Afrikaner cattle is scant. A survival analysis of the infusion project's impact on longevity has been completed with the Cox model. The first backcross generation (BC1) and the initial Afrikaner-Bonsmara cross generation (F1) had the lower risk ratios at 0.815 and 0.837, respectively, when compared to the purebred Afrikaner indicating their greater longevity. The second (BC2) backcross generation did not differ in longevity relative to the purebreds (P ≥ 0.05). The infusion of Bonsmara impacted longevity in the short-term, possibly due to increased retained heterosis or the breed substitution effect. However, the effect on longevity diminished as the generations of backcrossing to Afrikaner progressed. [ABSTRACT FROM AUTHOR]

To estimate the hazard of incident idiopathic intracranial hypertension, a potentially blinding condition, among women using levonorgestrel intrauterine devices (LNG-IUD) compared to copper IUD, as conflicting associations have been reported. This retrospective, longitudinal cohort study identified women ages 18–45 years in a large care network (January 1, 2001, to December 31, 2015) using LNG-IUD, subcutaneous etonogestrel implant, copper IUD, tubal device/surgery, or hysterectomy. Incident idiopathic intracranial hypertension was defined as the first diagnosis code for after 1 year without any codes and following brain imaging or lumbar puncture. Kaplan-Meier analysis estimated time-dependent probabilities of idiopathic intracranial hypertension at 1 and 5 years after incident contraception use, stratified by type. Cox regression estimated the hazard of idiopathic intracranial hypertension associated with LNG-IUD use compared to copper IUD (primary comparison) after adjusting for sociodemographics and factors associated with idiopathic intracranial hypertension (e.g., obesity) or contraception selection. A sensitivity analysis with propensity score-adjusted models was performed. Of 268,280 women, 78,175 (29%) used LNG-IUD, 8715 (3%) etonogestrel implant, 20,275 (8%) copper IUD, 108,216 (40%) hysterectomy, 52,899 (20%) tubal device/surgery, and 208 (0.08%) developed idiopathic intracranial hypertension over a mean follow-up of 2.4 ± 2.4 years. Also, 1-/5-year Kaplan-Meier idiopathic intracranial hypertension probabilities were 0.0004/0.0021 for LNG-IUD and 0.0005/0.0006 for copper IUD users. LNG-IUD use did not show significantly different hazard of idiopathic intracranial hypertension compared to copper IUD (adjusted hazard ratio 1.84 [95% CI 0.88, 3.85]). Sensitivity analyses were similar. We did not observe a significantly increased hazard of idiopathic intracranial hypertension among women using LNG-IUD compared to copper IUDs. The lack of an association between LNG-IUD use and idiopathic intracranial hypertension in this large observational study provides reassurance to women considering initiation or continued use of this highly effective contraceptive method. [ABSTRACT FROM AUTHOR]

Background: Death by suicide is a preventable public health concern worldwide. The aim of this study is to investigate the probability of suicide death using baseline characteristics and simple medical facility visit history data using Cox regression, support vector machines (SVMs), and deep neural networks (DNNs).Method: This study included 819,951 subjects in the National Health Insurance Service (NHIS)-Cohort Sample Database from 2004 to 2013. The dataset was divided randomly into two independent training and validation groups. To improve the performance of predicting suicide death, we applied SVM and DNN to the same training set as the Cox regression model.Results: Among the study population, 2546 people died by intentional self-harm during the follow-up time. Sex, age, type of insurance, household income, disability, and medical records of eight ICD-10 codes (including mental and behavioural disorders) were selected by a Cox regression model with backward stepwise elimination. The area of under the curve (AUC) of Cox regression (0.688), SVM (0.687), and DNN (0.683) were approximately the same. The group with top .5% of predicted probability had hazard ratio of 26.21 compared to that with the lowest 10% of predicted probability.Limitations: This study is limited by the lack of information on suicidal ideation and attempts, other potential covariates such as information of medication and subcategory ICD-10 codes. Moreover, predictors from the prior 12-24 months of the date of death could be expected to show better performances than predictors from up to 10 years ago.Conclusions: We suggest a 10-year probability prediction model for suicide death using general characteristics and simple insurance data, which are annually conducted by the Korean government. Suicide death prevention might be enhanced by our prediction model. [ABSTRACT FROM AUTHOR]

Investigating clustering of floods has important social, economic and ecological implications. This study examines the clustering of Australian floods at different temporal scales and its possible physical mechanisms. Flood series with different severities are obtained by peaks-over-threshold (POT) sampling in four flood thresholds. At intra-annual scale, Cox regression and monthly frequency methods are used to examine whether and when the flood clustering exists, respectively. At inter-annual scale, dispersion indices with four-time variation windows are applied to investigate the inter-annual flood clustering and its variation. Furthermore, the Kernel occurrence rate estimate and bootstrap resampling methods are used to identify flood-rich/flood-poor periods. Finally, seasonal variation of horizontal wind at 850 hPa and vertical wind velocity at 500 hPa are used to investigate the possible mechanisms causing the temporal flood clustering. Our results show that: (1) flood occurrences exhibit clustering at intra-annual scale, which are regulated by climate indices representing the impacts of the Pacific and Indian Oceans; (2) the flood-rich months occur from January to March over northern Australia, and from July to September over southwestern and southeastern Australia; (3) stronger inter-annual clustering takes place across southern Australia than northern Australia; and (4) Australian floods are characterised by regional flood-rich and flood-poor periods, with 1987–1992 identified as the flood-rich period across southern Australia, but the flood-poor period across northern Australia, and 2001–2006 being the flood-poor period across most regions of Australia. The intra-annual and inter-annual clustering and temporal variation of flood occurrences are in accordance with the variation of atmospheric circulation. These results provide relevant information for flood management under the influence of climate variability, and, therefore, are helpful for developing flood hazard mitigation schemes. [ABSTRACT FROM AUTHOR]

Background: We investigated the association between social determinants and a broad selection of drug-related deaths in a general population.Methods: We conducted a follow-up of an 11% random sample of working-age Finnish residents for 1996-2007 linked with an oversampling of deaths and population registration data on social characteristics. We defined total drug-related deaths as those from psychoactive substance use disorders and drug-induced poisonings (drug-induced deaths) as well as drug-related accidents, homicides, illnesses, and suicides.Results: The number of drug-related deaths was three times that of drug-induced deaths. We found the highest hazard ratios (HRs) for total drug-related mortality for long-term unemployment (4.9; 95% confidence interval [CI], 4.3-5.6), short-term unemployment (3.9; 95% CI, 3.5-4.4), and retirement (5.8; 95% CI, 5.1-6.8). The HRs were highest for mortality related to psychoactive substance use disorders and lowest for mortality related to drug-related suicides. The differences were large for both sexes.Conclusions: Drug-related mortality was associated with social disadvantage; however, the strength of the association varied by drug-related cause of death. Primary and secondary prevention of drug use should particularly target disadvantaged groups. [ABSTRACT FROM AUTHOR]

Introduction The volume-outcome relationships in failed root canal treatments (RCTs) are rarely studied. Thus, we aimed to examine the association of failed RCTs with dentist and institutional volumes. Methods Ambulatory dental claims (2005–2010) of 1 million beneficiaries randomly selected from the National Health Insurance Research Database of Taiwan were used. This study is a population-based cohort study using a marginal Cox proportional hazards regression model in which the outcome variables cluster around individual patients. A total of 458,557 teeth that received first-ever RCT from 2005 to 2010 and were followed up until the end of 2010 were identified as the tooth cohort. These teeth were aggregated to 244,368 patients, 10,901 dentists, and 7122 institutions for analysis. Results Dentists in the second, third, and highest quartiles all showed a significantly lower hazard ratio of failed RCTs than those with the lowest case volume, and their adjusted hazard ratios (aHRs) were 0.93, 0.92, and 0.90, respectively. Medical institutions in the second, third, and highest quartiles also showed a significantly lower hazard ratio of failed RCTs than those with the lowest case volume, and their aHRs were 0.93, 0.89, and 0.81, respectively. Teeth with a history of periodontitis also exhibited a significantly higher aHR of failure events. The use of rubber dams significantly reduced the rates of failed RCTs. Conclusions Dentists and institutions with high care volumes tended to show good RCT outcomes. Such an effect was prominent and robust among dental institutions. [ABSTRACT FROM AUTHOR]

The focus of this study is on the properties of consecutive intervals consisting of pairs of clear periods (the Sun is shining) and dark periods (the Sun is obscured by clouds). Namely, the distribution of the duration length of clear and dark periods is studied and illustrated with results obtained for the climatic regime of Timisoara (Romania, Eastern Europe). Usual simple moment-based characteristics such as means and variances cannot be unambiguously estimated due to censoring. Seasonal changes in the length distributions have been studied through the (nonparametric) Kaplan-Meier estimates. Both dark and clear duration distributions are different among months. The correlation between clear and dark periods within one dark-clear pair is of substantial interest. Therefore, a rigorous approach based on Spearman's rank correlation coefficient is used instead. The dependence of duration distribution upon covariates is studied using the Cox regression model, which fits the hazard ratio incurred by a unit change in the explanatory variables. It is shown that increasing the extraterrestrial irradiance on horizontal surface and the clearness index during dark/clear periods increases significantly the dark/clear period end risk. The Cox regression model enables more complicated analyses, such as the non-additive effects (i.e. interactions) of several covariates. The clearness index of a dark period (CID) has a much stronger effect than the extraterrestrial irradiance on horizontal surface of a dark period (EID) and the CID-EID interaction is still significant after the interactions when the months are included. [ABSTRACT FROM AUTHOR]

Background Evidence for the relationship between exposure to ambient air pollution and the mortality of tuberculosis (TB) patients is limited. Methods We analyzed the association between long-term exposure to particulate matter < 2.5 μm in diameter (PM 2.5 ) and cause-specific mortality in a Chinese TB patients cohort from 2003 to 2013. Data from the Global Burden of Disease 2013 estimate were used to assess yearly average concentrations of PM 2.5 and ozone at the household addresses of participants. Cox regression was used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cause-specific mortality, controlling for demographic and other TB-related factors. Results There were 4444 eligible subjects, including 891 deaths, over a median follow-up of 2464 days. Per an interquartile range increase (2.06 μg/m 3 ), multivariable analysis indicated that exposure to PM 2.5 was significantly associated with overall mortality (aHR = 1.30, 95% CI: 1.19, 1.42), mortality from TB (aHR = 1.46, 95% CI: 1.15, 1.85), respiratory cancers (aHR = 1.72, 95% CI: 1.36, 2.19), other respiratory diseases (aHR = 1.19, 95% CI: 1.02, 1.38), and other cancers (aHR = 1.76, 95% CI: 1.33, 2.32). Conclusions Long-term exposure to PM 2.5 increases the risk of death from TB and other diseases among TB patients. It suggests that the control of ambient air pollution may help decreasing the mortality caused by TB. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, with a 5-y survival rate of ∼65%. Therefore, the identification of modifiable health factors to improve CRC survival is crucial.Objective: We investigated the association of 4 prediagnostic a priori diet quality indexes with CRC-specific and all-cause mortality in the Multiethnic Cohort (MEC).Methods: The MEC included >215,000 African-American, Native Hawaiian, Japanese-American, Latino, and white adults living in Hawaii and California who completed a validated quantitative food-frequency questionnaire in 1993-1996. CRC cases and deaths were identified through linkages to cancer registries and to state and national vital registries. Sex-specific HRs and 95% CIs were estimated for the Healthy Eating Index (HEI) 2010, the Alternative HEI (AHEI) 2010, the alternate Mediterranean Diet (aMED) score, and the Dietary Approaches to Stop Hypertension (DASH) index with CRC-specific and overall mortality as the primary outcomes. Ethnicity-specific analyses were the secondary outcomes.Results: Among 4204 MEC participants diagnosed with invasive CRC through 2010, 1976 all-cause and 1095 CRC-specific deaths were identified. A higher aMED score was associated with lower CRC-specific mortality in women [HR continuous pattern score divided by its respective SD (HR1SD): 0.86; 95% CI: 0.77, 0.96] but not in men (HR1SD: 1.01; 95% CI: 0.92, 1.11). A higher aMED score was also associated with lower all-cause mortality in women (HR1SD: 0.88; 95% CI: 0.81, 0.96) but not in men (HR1SD: 1.00; 95% CI: 0.93, 1.07). The HEI-2010, AHEI-2010, and DASH index were not significantly associated with CRC-specific or with all-cause mortality. The inverse relation for the aMED score was limited to African Americans and to colon (compared with rectal) cancer.Conclusions: The aMED score was related to lower mortality only in African-American women (1 of 5 ethnic groups studied). The results should be interpreted with caution due to the small numbers of cases within ethnic groups and the issue of multiple testing. [ABSTRACT FROM AUTHOR]

The effect of red and processed meats on cancer survival is unclear. We sought to examine the role of total and processed red meat consumption on all-cause mortality among patients with cancers of the upper aerodigestive tract (UADT) and lung, in order to test our hypothesis that red or processed meat was associated with overall mortality in these patients. Using data from a population-based case-control study conducted in Los Angeles County, we conducted a case-only analysis to examine the association of red or processed meat consumption on mortality after 12 years of follow-up, using a diet history questionnaire. Cox regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. Of 601 UADT cancer cases and 611 lung cancer cases, there were 248 and 406 deaths, respectively, yielding crude mortality rates of 0.07 and 0.12 deaths per year. Comparing the highest with lowest quartile of red meat consumption, the adjusted HR was 1.64 (95% CI, 1.04-2.57) among UADT cancer cases; for red or processed meat, the adjusted HR was 1.76 (95% CI, 1.10-2.82). A dose-response trend was observed. A weaker association was observed with red meat consumption and overall mortality among lung cancer cases. In conclusion, this case-only analysis demonstrated that increased consumption of red or processed meats was associated with mortality among UADT cancer cases and WAS weakly associated with mortality among lung cancer cases. [ABSTRACT FROM AUTHOR]

We explored the association between baseline gut microbiota (16S rRNA biomarker sequencing of stool samples) in 17 relapsing-remitting pediatric MS cases and risk of relapse over a mean 19.8 months follow-up. From the Kaplan-Meier curve, 25% relapsed within an estimated 166 days from baseline. A shorter time to relapse was associated with Fusobacteria depletion (p = 0.001 log-rank test), expansion of the Firmicutes (p = 0.003), and presence of the Archaea Euryarchaeota (p = 0.037). After covariate adjustments for age and immunomodulatory drug exposure, only absence (vs. presence) of Fusobacteria was associated with relapse risk (hazard ratio = 3.2 (95% CI: 1.2–9.0), p = 0.024). Further investigation is warranted. Findings could offer new targets to alter the MS disease course. [ABSTRACT FROM AUTHOR]

Background: Higher consumption of some polyphenols has been associated with a reduced risk of diabetes. However, no studies have evaluated the relation between all polyphenol subclasses and the incidence of diabetes.Objective: We aimed to prospectively examine the associations between the intake of total polyphenols and different groups of polyphenols (flavonoids, phenolic acids, stilbenes, lignans, and others) on the risk of incident diabetes in the PREDIMED (Prevención con Dieta Mediterránea) trial.Methods: This was an observational cohort analysis of the nondiabetic participants in the PREDIMED trial. This study was a multicenter, controlled, randomized, parallel-group feeding trial to assess the effects of either a Mediterranean diet that was supplemented with extra-virgin olive oil or nuts or advice to adhere to a low-fat control diet on cardiovascular outcomes in elderly men and women at high cardiovascular disease risk. From the 7447 randomly assigned participants, 3430 were selected because they were free of diabetes at baseline and filled out the food-frequency questionnaires (FFQs). Polyphenol intake was calculated by matching food consumption data from repeated FFQs with the Phenol-Explorer database on the polyphenol content of each reported food. HRs and 95% CIs for diabetes according to tertiles of polyphenol intake were estimated with the use of time-dependent Cox proportional hazards models.Results: Over a mean of 5.51 y of follow-up (18,900 person-years), there were 314 new cases of diabetes. After multivariable adjustment, we observed a 28% reduction in new-onset diabetes in the highest compared with the lowest tertile of total polyphenol intake (HR: 0.72; 95% CI: 0.52, 0.99; P-trend = 0.05). The intake of subclasses of polyphenols also was inversely associated with diabetes risk, including for total flavonoids (HR: 0.67; 95% CI: 0.48, 0.93; P-trend = 0.02), stilbenes (HR: 0.57; 95% CI: 0.38, 0.84; P-trend = 0.003), dihydroflavonols (HR: 0.59; 95% CI: 0.40, 0.88; P-trend = 0.003), and flavanones (HR: 0.69; 95% CI: 0.49, 0.97; P-trend = 0.03).Conclusions: A high intake of total polyphenols, total flavonoids (specifically flavanones and dihydroflavonols), and stilbenes is associated with a reduced risk of diabetes in elderly persons at high risk of cardiovascular disease. This trial was registered at http://www.controlled-trials.com as ISRCTN35739639. [ABSTRACT FROM AUTHOR]

Objective: understanding the labour characteristics of women attempting vaginal birth after caesarean (VBAC) may suggest how to improve intrapartum management and may enhance success rates. Promoting VBAC is a relevant factor in decreasing overall caesarean section (c-section) rates. However, the labour processes of women attempting VBAC are not well investigated. The aim of this paper is to compare multiparae planning a first VBAC (pVBAC) with primiparae and with multiparae planning a second vaginal birth, all starting to give birth vaginally, with regard to (a) perinatal characteristics, (b) the timing of intrapartal spontaneous rupture of membranes (SROM) and of interventions, and (c) labour duration, with respect to the first and second stages. Setting: cohort study of women planning vaginal birth in 47 obstetric units in Lower Saxony, Germany. Participants: 1897 primiparae, 211 multiparae with one previous c-section and 1149 multiparae with one previous vaginal birth. Measurements: secondary analysis of data from an existing cohort study. Kaplan-Meier estimates, log rank test, Wilcoxon test and shared frailty Cox regression models including time-varying covariates were used to compare the timing of interventions and labour duration between the subsamples. Analyses were done with the statistics programme Stata 13. Findings: perinatal and labour characteristics of multiparae with pVBAC mainly resembled those of primiparae and differed from those of multiparae planning a second vaginal birth. However, compared to primiparae, multiparae with pVBAC received oxytocin less often (48.82 versus 56.95%, p=0.024) and gave birth vaginally significantly less often (69.19 versus 83.40%, p < 0.001). The timing of intrapartal SROM (2.67 versus 3.42 hours, p = 0.112) and of interventions (amniotomy: 5.50 versus 5.83 hours, p = 0.198; oxytocin: 5.75 versus 6.00 hours, p=0.596; epidural: 4.00 versus 4.67 hours, p=0.416; opioids: 3.83 versus 3.78, p=0.851) was similar to that in primiparae although timings of all interventions but not of SROM differed significantly from that in multiparae with second vaginal birth (SROM: 2.67 versus 2.67 hours, p=0.481; amniotomy: 5.50 versus 3.93 hours, p< 0.001; oxytocin: 5.75 versus 4.25 hours, p< 0.001; epidural: 4.00 versus 3.50 hours, p = 0.009; 3.83 versus. 2.75 hours, p=0.026). Overall and first-stage labour duration were comparable to primiparae (overall labour duration: 8.83 versus 8.57 hours, HR=0.998, 95% CI=0.830-1.201, p=0.987; first stage: 7.42 versus 7.00 hours, HR=0.916, 95% CI=0.774-1.083, p = 0.303) but significantly longer than in other multiparae (overall labour duration: 8.83 versus 4.63 hours, HR=0.319, 95% CI=0.265-0.385, p< 0.001; first stage: 7.42 versus 4.25 hours, HR=0.402, 95% CI=0.339-0.478, p< 0.001). However, the second stage of labour was significantly shorter in multiparae with pVBAC than in primiparae (0.55 versus 0.77 hours, HR = 1.341, 95% CI = 1.049 -1.714, p=0.019), but longer than in multiparae with second vaginal birth (0.55 versus 0.22 hours, HR=0.334, 95% CI=0.262-0.426, p< 0.001). Key conclusion: labour patterns of multiparous women planning a VBAC differ from those of primiparae and other multiparous women. Multiparae with pVBAC should be considered as a distinct group of parturients. Implication for practice: expectations regarding labour progression for multiparae with first pVBAC should be similar to those for primiparae. However, the chance that the second stage of labour might be shorter than in primiparae is relevant and motivating information for pregnant women with a previous c-section in deciding the planned mode of birth. [ABSTRACT FROM AUTHOR]

Heat-related disorders, decreases in productivity and security risks are common phenomena when people live in extremely hot environments. To a certain extent, humans can adapt to extremely hot environments, but few studies have examined the causes of and factors influencing the aforementioned phenomena, especially in hot environments. In this paper, a climate chamber was built to simulate an extremely hot environment. Sixteen healthy male university students were asked to simulate manual labour by running. The physiological indexes (rectal temperature, heart rate and sweat production) were measured. The effects of human heat acclimatization in extremely hot environments were determined via paired sample t -tests. The time required to acclimate to the heat (in days) was determined based on the standard of thermal adaptation improvement. A Cox regression method was adopted to quantify the development of heat acclimatization and to rank the effects of several variables on heat acclimatization to determine the relationship between thermal parameters and heat acclimatization. The effects of heat acclimatization are significant, and heat acclimatization training can improve the adaptability of humans to extremely hot environments. The Cox regression method can be used to analyse heat acclimatization effectively. Both the dry bulb temperature and the relative humidity significantly affect heat acclimatization, with the effect of the former being more significant. [ABSTRACT FROM AUTHOR]

Context Continued exposure to compensation systems has been reported as deleterious to the health of participants. Understanding the associations with time to claim closure could allow for targeted interventions aimed at minimising the time participants are exposed to the compensation system. Study objective To identify the associations of extended time receiving compensation benefits with the aim of developing a prognostic model that predicts time to claim closure. Study design Prospective cohort study in people with whiplash associated disorder. Outcome measures Time to claim closure, in a privately underwritten fault based third party traffic crash insurance scheme in New South Wales, Australia. Method Cox proportional hazard regression modelling. Results Of the 246 participants, 25% remained in the compensation system longer than 24 months with 15% remaining longer than three years. Higher initial disability (Functional Rating Index ≥ 25 at baseline) (HRR: 95% CI, 1.916: 1.324–2.774, p < 0.001); and lower initial mental health as measured by SF-36 Mental Component Score (HRR: 95% CI, 0.973: 0.960–0.987, p < 0.001) were significantly and independently associated with an increased time-to-claim closure. Shorter time to claim closure was associated with having no legal involvement (HRR: 95% CI, 1.911: 1.169–3.123, p = 0.009); and, not having a prior claim for compensation (HRR: 95% CI, 1.523: 1.062–2.198, p = 0.022). Conclusions Health and insurance related factors are independently associated with time to claim closure. Both factors need to be considered by insurers in their assessment of complexity of claims. Interventions aimed at minimising the impact of these factors could reduce claimants’ exposure to the compensation system. In turn insurers can potentially reduce claims duration and cost, while improving the health outcomes of claimants. [ABSTRACT FROM AUTHOR]

Objectives: The neutrophil-to-lymphocyte ratio is gaining popularity as a low-cost biomarker of inflammation and outcome prediction. Intracerebral hemorrhage has high mortality and disability, which strongly influences societal development. This study aimed to research whether the neutrophil-to-lymphocyte ratio can predict hospital mortality in patients with severe intracerebral hemorrhage.Materials and Methods: It was a retrospective analysis of prospectively collected data. The survival analysis and proportional hazards models analyzed clinical data from the Medical Information Mart for Intensive Care III database of patients with intracerebral hemorrhage.Results: The records of 1,000 patients were included in our study. Two hundred forty-seven individuals died in the hospital, while 753 survived to discharge. According to data analysis, the neutrophil-to-lymphocyte ratio of the death group (11.21±7.81) significantly exceeded the survival group (7.94±6.04). The univariate Cox regression revealed that the neutrophil-to-lymphocyte ratio is a potential predictor of in-hospital mortality (HR:1.044; 95% CI:1.029-1.059; p <0.001). Furthermore, the proportional hazards model demonstrated that the risk of in-hospital death increased 2.34-fold for each increase in neutrophil-to-lymphocyte ratio when other factors were held constant. Following the ROC analysis, the Kaplan-Meier based on the proportional hazards model showed that patients with a neutrophil-to-lymphocyte ratio >7.68 on the first day of hospitalization had a higher risk of death.Conclusions: In patients with severe intracerebral hemorrhage, the neutrophil-to-lymphocyte ratio is a potential predictor of in-hospital mortality. [ABSTRACT FROM AUTHOR]

This study examines the risk factors of re-entry for 1,750 child protection cases in Singapore using a cumulative ecological–transactional risk model. Using administrative data, the present study found that the overall percentage of Child Protection Service (CPS) re-entry in Singapore is 10.5% based on 1,750 cases, with a range from 3.9% (within 1 year) to 16.5% (within 8 years after case closure). One quarter of the re-entry cases were observed to occur within 9 months from case closure. Seventeen risk factors, as identified from the extant literature, were tested for their utility to predict CPS re-entry in this study using a series of Cox regression analyses. A final list of seven risk factors (i.e., children's age at entry, case type, case closure result, duration of case, household income, family size, and mother's employment status) was used to create a cumulative risk score. The results supported the cumulative risk model in that higher risk score is related to higher risk of CPS re-entry. Understanding the prevalence of CPS re-entry and the risk factors associated with re-entry is the key to informing practice and policy in a culturally relevant way. The results from this study could then be used to facilitate critical case management decisions in order to enhance positive outcomes of families and children in Singapore's care system. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this work was to compare productive and reproductive performance between pure Holstein (H) and Swedish Red & White×Holstein crossbred (SRB/H) in first lactation dairy cows from the central region of Argentina. This study included 450 lactations from a commercial dairy of central-southern Argentina. The differences in mean daily milk yield, days to first breeding (DFB) and number of services per pregnancy (NS/P) between genotypes were evaluated. A Cox proportional hazard regression model was fitted to evaluate the breed effects on days open (DO) and adjusting by calving season and calving year. Days open were estimated trough survival curves for H breed and SRB/H crossbred using Kaplan–Meier method. Finally, average lactation curves were modeled for each genotype using a non-linear mixed model. Daily milk yield was not significantly different between genotypes. However, the cumulative 305-d yield and peak milk yield for pure H was higher than for SRB/H. Days to first breeding was lower for SRB/H than pure H. The NS/P was higher for pure H than for SRB/H. Regarding DO, SRB/H breed had 1.00–1.71 higher likelihood to become pregnant than pure H. Days open of 50% of pure H was 30 d higher than for SRB/H. The results showed that SRB/H crossbred were superior to pure H in terms of reproductive performance but inferior in terms of productive performance. Further studies may help to determine if the economics of dairying justifies the use of crossbreeding as a herd fertility enhancing tool. [Copyright &y& Elsevier]

Abstract: Introduction: This paper describes methamphetamine (MA) use patterns, specifically the duration of continuing abstinence (“time to relapse”) for periods averaging 5 years post-discharge from treatment for MA use, and the relationship with selected user and treatment characteristics. Methods: A sample of 350 treatment admissions from a large county substance use disorder (SUD) treatment system was randomly selected (within gender, race/ethnicity, treatment modality strata). Retrospective self-report data are from natural history interviews (NHI) conducted approximately 3 years after treatment and a follow-up of 2–3 years later. Relapse is defined as any use of MA with time as the number of months of continuous MA abstinence after treatment discharge until relapse. This outcome was constructed from a monthly MA use timeline using NHI data. A Cox model was used to examine time to relapse and predictors. Results: Sixty-one percent of the sample relapsed to MA use within 1 year after treatment discharge and 14% during years 2–5. Significant protective factors predicting longer time to relapse included having experienced serious MA-related psychiatric/behavioral problems (hazard ratio [HR]=0.75, p =0.027), longer duration of the index treatment episode (HR=0.93, p =0.001), and participating in self-help or other treatment during the post-treatment abstinence period (HR=0.29, p <0.001); risk factors for shorter time to relapse included having a parent with alcohol and/or drug use problems (HR=1.35, p =0.020) and involvement in MA sales (HR=1.48, p =0.002). Conclusions: Results contribute a long-term perspective on patterns of MA use following treatment and support a need for early post-treatment and long-term continuing care and relapse-prevention services. [Copyright &y& Elsevier]

Summary: Objectives: The time to positivity (TTP), measured as the time span between the start of incubation and the alert signal from the blood culture device, has been described as useful tool of prognosis in patients suffering from blood stream infection with Staphylococcus aureus, Escherichia coli and Klebsiella pneumonia. The present study investigates the relationship between TTP and in-hospital mortality in patients with monomicrobial Pseudomonas aeruginosa blood stream infection (PA-BSI). Methods: From 2006 until 2012 a retrospective cohort study was undertaken in 3 hospitals in the region surrounding Tübingen, Germany. Seventy-four patients with monomicrobial PA-BSI were studied. TTP and clinical parameters were determined and analyzed by receiver operating characteristic (ROC) analysis and Cox regression. Results: The in-hospital mortality of our clinical cohort was 33.78%. In multivariate Cox regression, a TTP ≤ 18 h proved to be independently associated with mortality (HR 3.83, P = 0.012) along with SAPS II score (HR 1.04, P = 0.006), cardiac disease (HR 0.33, P = 0.008) and appropriate definitive antimicrobial treatment (HR 0.21, P = 0.013). Conclusions: TTP is an easy-to-measure laboratory tool for prognosis in patients with monomicrobial PA-BSI, providing useful information in addition to clinical parameters. [Copyright &y& Elsevier]

Objective: childbearing women and their midwives differ in their diagnoses of the onset of labour. The symptoms women use to describe the onset of labour are associated with the process of labour. Perinatal factors and women's attitudes may be associated with the administration of epidural analgesia. Our study aimed to assess the correlation between women's perception of the onset of labour and the frequency and timing of epidural analgesia during labour. Design: prospective cohort study. Setting: 41 maternity units in Lower Saxony, Germany. Participants: 549 nulliparae (as defined in the "Methods" section) and 490 multiparae giving birth between April and October 2005. Women were included after 34 completed weeks of gestation with a singleton in vertex presentation and planned vaginal birth. Measurements: the association between women's symptoms at the onset of labour and the administration of epidural analgesia - frequency, timing in relation to onset of labour and cervical dilatation - was assessed. The analysis was performed by Kaplan-Meiers estimation, logistic regression and Cox regression. Findings: a total of 174 nulliparae and 49 multiparae received epidural analgesia during labour. Nulliparae received it at a median time of 5.47 hrs (range: 0.25-51.17 hrs) after onset of labour, at a median cervical dilatation of 3.3 cm (range: 1.0-10.0 cm). In multiparae, epidural analgesia was applied at a median time of 3.79 hrs (range: 0.42-28.55 hrs) after onset of labour; the median cervical dilatation was 3.0 cm (range: 1.0-8.0 cm). Women who were admitted with advanced cervical dilatation received epidural analgesia less often. Women who defined their onset of labour earlier than it was diagnosed by their midwives received epidural analgesia earlier. Gastrointestinal symptoms and irregular pain at the onset of labour were associated with later administration of epidural analgesia. Induction of labour was associated with a reduced interval from the onset of labour to epidural analgesia. Key conclusions: women's self-diagnosis of the onset of labour and their perception of their labour duration when meeting their midwives has some impact on their admission to the labour ward and the timing of epidural analgesia. Implications for practice: consideration of women's own perceptions and expectations regarding the onset and process of labour is necessary for individual care during labour. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Survival analysis is increasingly being used in perinatal epidemiology to assess time-varying risk factors for various pregnancy outcomes. Here we show how quantitative correction for exposure misclassification can be applied to a Cox regression model with a time-varying dichotomous exposure. Methods: We evaluated influenza vaccination during pregnancy in relation to preterm birth among 2267 non-malformed infants whose mothers were interviewed as part of the Slone Birth Defects Study during 2006 through 2011. The hazard of preterm birth was modeled using a time-varying exposure Cox regression model with gestational age as the time-scale. The effect of exposure misclassification was then modeled using a probabilistic bias analysis that incorporated vaccination date assignment. The parameters for the bias analysis were derived from both internal and external validation data. Results: Correction for misclassification of prenatal influenza vaccination resulted in an adjusted hazard ratio (AHR) slightly higher and less precise than the conventional analysis: Bias-corrected AHR 1.04 (95% simulation interval, 0.70–1.52); conventional AHR, 1.00 (95% confidence interval, 0.71–1.41). Conclusions: Probabilistic bias analysis allows epidemiologists to assess quantitatively the possible confounder-adjusted effect of misclassification of a time-varying exposure, in contrast with a speculative approach to understanding information bias. [Copyright &y& Elsevier]

Abstract: Background: Associations between type 2 diabetic patients and a higher risk of developing cancer have been reported worldwide. Recently, a protective effect of metformin has been described. Aim: To examine in the Belgian primary care population the relation between presence of type 2 diabetes with and without metformin treatment and the occurrence of malignancies. Design of study: Retrospective cohort study, based on the Intego database, an ongoing Belgian general practice-based morbidity registry, covering 90 general practitioners and including about 1.5 million patient-years between 1994 and 2008. Method: Cox proportional hazard analysis comparing emergence of malignancy in patients with and without type 2 diabetes, and among patients with diabetes comparing emergence of malignancy in those treated with various antidiabetic drugs. Results: Malignancies occurred more in type 2 diabetic patients compared to non-diabetic controls (HR=1.84; 95% CI=1.51–2.24), adjusted for age, gender and weight. Treatment with both metformin and ‘other’ antidiabetic agents was related to decreased cancer risk (HR=0.24 and 0.22) compared to diet only in men but not in women. Conclusion: In this Belgian primary care setting, diabetic patients have higher cancer prevalences than non-diabetic patients. Moreover, in diabetic men, not only metformin but also other antidiabetic agents were associated with lower cancer risks. [Copyright &y& Elsevier]

Objective: To examine the incidence rate of breast cancer in a cohort of women undergoing treatment for infertility, comparing the rate in women who had in vitro fertilization (IVF) with those who did not. Design: Population-based cohort study using linked hospital and registry data. Setting: Hospital. Patient(s): All women aged 20–44 years seeking hospital investigation and treatment for infertility in Western Australia during the period 1983–2002 (n = 21,025). Intervention(s): None. Main Outcome Measure(s): Hazard ratios (HRs) for breast cancer. Result(s): There was no overall increase in the rate of breast cancer in women who had IVF (HR 1.10, 95% confidence interval [CI] 0.88–1.36), but there was an increased rate in women who commenced IVF at a young age. Women who commenced hospital infertility treatment at 24 years and required IVF had an unadjusted HR of breast cancer of 1.59 (95% CI 1.05–2.42) compared with women of the same age who had infertility treatment but no IVF. When adjusted for late age at first delivery, which is associated with an increased rate of breast cancer, and delivery of twins and higher-order multiples, which is associated with a decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI 1.01–2.40). Hazard ratios were not elevated in women who commenced treatment at age 40 and required IVF (adjusted HR 0.87, 95% CI 0.62–1.22). Conclusion(s): Commencing IVF treatment at a young age is associated with an increased rate of breast cancer. [ABSTRACT FROM AUTHOR]