Flexible Parametric Survival Analysis Research Articles

Association of lifetime lactation and characteristics of menopause: a longitudinal cohort study.

Lactation has many established benefits for women's long-term health; however, its influence on menopause is less clear. This study investigated the association between lifetime duration of lactation and the timing and type of menopause in midlife women. We analyzed survey data on 19,783 parous women aged 40 to 65 years at enrollment in the Alberta's Tomorrow Project (2000-2022), a prospective community-based cohort study in Alberta, Canada. Duration of lifetime lactation across all births was categorized as: <1 month (reference group; 19.8% of women), 1-3 months (12.1%), 4-6 months (11.7%), 7-12 months (18.8%), and ≥ 13 months (37.7%). Women were classified as premenopause, natural menopause (age at 1 year after the final menstrual period), surgical menopause (age at bilateral oophorectomy), or indeterminate menopause (age at premenopausal hysterectomy with ovarian preservation). Flexible parametric survival analysis and multinomial logistic regression were used to analyze menopause timing and type, respectively, according to lactation status and controlling for birth year, education, parity, hormonal contraceptive use, and smoking. In a dose-response manner, longer lactation was associated with reduced risk of natural menopause before age 50 (for ≥ 13 months of lactation, adjusted hazard ratio at age 45: 0.68, 95% CI 0.59-0.78), surgical menopause before age 55 (age 45: 0.56, 0.50-0.63), and indeterminate menopause before age 50 (age 45: 0.75, 0.69-0.82). Longer lactation was associated with lower odds of surgical (adjusted odds ratio 0.54, 95% CI 0.45-0.66) and indeterminate menopause (0.63, 0.55-0.73), compared to natural menopause. Optimizing the timing of natural menopause and reducing risks of early surgical and indeterminate menopause may be novel maternal benefits of breastfeeding.

An analysis of the virtual cardio-oncology research initiative (VICORI) resource: bleeding risk among cancer patients beyond 1-year post-myocardial infarction

Abstract Introduction Cardiovascular disease (CVD) and cancer are common causes of morbidity and mortality. Advancements in treatment strategies for both diseases have resulted in a growing population who live with both conditions. Myocardial infarction (MI) represents approximately 20% of all CVD admissions in cancer patients and 10% of patients who present with an acute MI have cancer. Managing MI patients with cancer require careful balancing of their ischaemic and bleeding risks. While dual antiplatelet therapy (DAPT) increases a patient’s bleeding risk, cancer patients are at further increased risk due to a range of direct and indirect cancer effects. While our recent studies demonstrated an increased bleeding risk in cancer patients in the 1st year after MI (the period of intensive APT), it is currently not known if this risk is sustained beyond this period. VICORI is the world’s first whole-country cardio-oncology research platform, linking data from the National Cancer Registration and Analysis Service, National Institute for Cardiovascular Outcomes Research and Hospital Episode Statistics [1]. We investigated the risk of bleeding among MI patients in the 2nd year post-MI, where a large majority of patients would have completed a course of DAPT, stratified by the presence or absence of cancer. Methods In this retrospective observational study, we investigated the risk of bleeding following an MI between 2006-2019, in patients with and without cancer. Cancer was defined as a diagnosis of cancer in the 1-year preceding MI. Patients who lived past the 1st year after MI were followed-up from 12 to 24 months after their MI. We used inverse probability weighting based on propensity scores to produce a balanced cohort of patients with and without cancer. Cox proportional hazard and flexible parametric modelling were used to investigate cancer as a predictor of bleeding. Subgroup analyses were performed on stent status, MI and cancer type. Results Of 506280 patients presenting with MI, 5666 (1.1%) had cancer while 500614 (98.9%) did not. Prostate (n=1377), colorectal (n=1024), lung (n=490), breast (n=448) and bladder (n=334) cancers were among the most common types of cancers. The rate (hazard) of bleeding in MI was higher in patients with cancer in the 2nd year post-MI (HR:1.42, 95%CI 1.29-1.56) compared to those without. From the flexible parametric survival analysis, the risk of bleeding in cancer patients in the 2nd year post-MI was lower compared to the 1st year but remained statistically significant compared to non-cancer patients. Conclusion In this large real-world study, cancer patients have a persistent, increased bleeding risk beyond the 1-year post-MI period, compared to those without cancer, and this risk differed by type of cancer. Further work is needed to identify specific patient characteristics in each patient sub-group which alters one’s ischaemic or bleeding risk so they can be balanced favourably with personalised strategies.

Unilateral Oophorectomy and Age at Natural Menopause: ALongitudinal Community-Based Cohort Study.

To determine the association between unilateral oophorectomy (UO) and age at natural menopause. Secondary analysis of survey data from Alberta's Tomorrow Project (2000-2022). Prospective cohort study in Alberta, Canada. 23 630 women; 548 experienced UO and 23 082 did not experience UO. Flexible parametric survival analysis was used to analyse age at natural menopause, and logistic regression was used to analyse early menopause and premature ovarian insufficiency by UO status, controlling for birth year, parity, age at menarche, past infertility, hormonal contraceptive use and smoking. Age at natural menopause occurred by a final menstrual period without medical cause and sub-classified as early menopause (< 45 years) and premature ovarian insufficiency (< 40 years). Compared to no UO, any UO was associated with elevated risk of earlier age at natural menopause, which was strongest in early midlife (adjusted HR at age 40 1.71, 95% CI 1.31-2.19) and diminished over time. Compared to age 55 years at UO, risks of earlier age at natural menopause were largest and uniform in magnitude when UO occurred between approximately ages 20-40 years (adjusted HR for UO at age 30 2.32, 1.46-3.54) and then diminished as age at UO approached the average age at natural menopause. Any UO was associated with higher odds of early menopause (adjusted OR 1.90, 1.30-2.79) and premature ovarian insufficiency (adjusted OR 3.75, 1.72-8.16). Unilateral oophorectomy is associated with earlier age at natural menopause, particularly when performed before 40 years of age.

Association of parity with the timing and type of menopause: A longitudinal cohort study.

We investigated the time-varying association between parity and timing of natural menopause, surgical menopause, and premenopausal hysterectomy among 23,728 women aged 40-65 years at enrollment in the Alberta's Tomorrow Project cohort study (2000-2022), using flexible parametric survival analysis. Overall, natural menopause was most common by study end (57.2%), followed by premenopausal hysterectomy (11.4%) and surgical menopause (5.3%). Risks of natural menopause before age 50 years were elevated for 0 births (adjusted hazard ratio at age 45: 1.33, 95% CI 1.18-1.49) and 1 birth (age 45: 1.21, 1.07-1.38), but similar for ≥3 births (age 45: 0.95, 0.85-1.06), compared to 2 births (reference). Elevated risks of surgical menopause before age 45 years for 0 births (age 40: 1.37, 1.09-1.69) and 1 birth (age 40: 1.11, 0.85-1.45) attenuated when excluding women with past infertility or recurrent pregnancy loss, and reduced risks were observed over time for ≥3 births (age 50: 0.84, 0.75-0.94). Risks of premenopausal hysterectomy were lower before age 50 years for 0 births (age 45: 0.82, 0.76-0.88) but elevated after age 40 years for ≥3 births (age 50: 1.25, 1.08-1.45). These complex associations necessitate additional research on the sociobiological impacts of childbearing on gynecologic health.

Development and validation of a practical score to predict 3-year distant metastatic free survival in nasopharyngeal carcinoma incorporating the number of lymph node regions.

The improvement in diagnosis and treatment for nasopharyngeal carcinoma (NPC) has shifted the pattern of failure toward distant metastasis. This study aimed to develop a simplified prognostic scoring model to predict distant metastatic free survival (DMFS) for NPC patients. Patients with non-metastatic NPC were identified from a retrospective cohort diagnosed between 2010 and 2018. Flexible parametric survival analysis was used to identify potential predictors for DMFS and establish a scoring model. The prognostic accuracy between the 8th AJCC system and the scoring model was compared using Harrell's C-index. Of the total 393 patients, the median follow-up time was 85 months. The 3-year DMFS rate was 83.3%. Gender, T-stage, pre-EBV (cut-off 2300 copies/ml), and the number of metastatic lymph node regions were identified as independent risk factors for distant metastasis and were included in the final scoring model. Our established model achieved a high C-index in predicting DMFS (0.79) and was well-calibrated. The score divided patients into two categories: low-risk (score 0-4) and high-risk (score 5-7), corresponding with the predicted 3-year DMFS of 96% and 64.5%, respectively. A feasible and applicative prognostic score was established and validated to discriminate NPC patients into low- and high-risk groups.

Associations Between Self-Rated Health and Mortality in the Norwegian Women and Cancer (NOWAC) Study.

We investigated the association between self-rated health (SRH) and cancer incidence and SRH and all-cause mortality among Norwegian women. We used data from 110,104 women in the Norwegian Women and Cancer (NOWAC) cohort aged 41-70 years at baseline. We used flexible parametric survival analysis with restricted cubic splines to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SRH and mortality in the entire cohort. We employed the same method in a multistate design to assess associations between baseline SRH and 1) cancer incidence, and 2) all-cause mortality in subgroups of women who did and did not receive a cancer diagnosis during follow-up. With very good SRH as reference category for all associations and median age at end of follow-up, lower SRH was associated with increased mortality (HRgood SRH 1.19, 95% CI 1.12-1.26) and HRpoor SRH 1.81, 95% CI 1.66-1.97). Lower SRH at baseline was associated with cancer incidence (HRgood SRH 1.14, 95% CI 1.08-1.20 and HRpoor SRH 1.44, 95% CI: 1.32-1.58). Poor baseline SRH was associated with increased mortality for women who received a cancer diagnosis (HRpoor SRH 1.20, 95% CI 1.04-1.39), and SRH showed a strong association with increased mortality for women who stayed cancer free (HRgood SRH 1.59, 95% CI 1.44-1.77 and HRpoor SRH 3.34, 95% CI 2.91-3.84). Lower SRH at baseline predicted increased cancer risk and all-cause mortality in middle-aged to older women. Poor SRH at baseline predicted all-cause mortality in women who later received a cancer diagnosis. Both good and poor SRH at baseline predicted all-cause mortality in women who stayed cancer-free, and the association was stronger for these women compared to both the entire cohort and to women who were subsequently diagnosed with cancer.

Mortality Rates and a Clinical Predictive Model for the Elderly on Maintenance Hemodialysis: A Large Observational Cohort Study of 17,354 Asian Patients

Introduction: Mortality following hemodialysis initiation may influence the decision to initiate hemodialysis in elderly patients. Our objective is to demonstrate mortality following hemodialysis initiation in elderly patients (≥70 years) and to derive a prediction risk score based on clinical and laboratory indicators to determine risk of all-cause mortality in patients aged ≥80 years. Methods: We identified elderly patients (≥70 years) who initiated maintenance hemodialysis between January 2005 and December 2016 using data from the Thai Renal Replacement Therapy (TRT) registry. The mortality rate was determined based on age categories. A predictive risk score for all-cause mortality was created for 4,451 patients aged ≥80 years by using demographics, laboratory values, and interview-based parameters. Using a flexible parametric survival analysis, we predicted mortality 3 months, 6 months, 1 year, 5 years, and 10 years after hemodialysis initiation. Results: 17,354 patients (≥70 years) were included, mean age 76.9 ± 5.1 years, 46.5% male, and 6,309 (36.4%) died. Patients aged <80 years had a median survival time of 110.6 months. A 9-point risk score was developed to predict mortality in patients aged ≥80 years: age >85 years, male, body mass index <18.5 kg/m², hemoglobin <10.0 g/dL, albumin <3.5 g/dL, substantial assistance required in daily living (1 point each), and Karnofsky Performance Status (KPS) score <50 (3 points). C-statistic of 0.797 indicated high model discrimination. Internal validation demonstrated good agreement between observed and anticipated mortalities. Conclusions: Hemodialysis is appropriate for patients aged 70–80 years. A risk score for mortality in patients aged ≥80 years has been developed. The score is based on seven readily obtainable and evaluable clinical characteristics.

Disparities in alcohol- and substance-related hospitalizations and deaths across sexual orientations in Canada: a longitudinal study

ObjectivesWe aim to quantify disparities in substance-related acute events (i.e. hospitalizations and deaths for substances, including alcohol, cannabis, opioids, narcotics, and/or illicit drugs) across sexual orientations based on health administrative data. Study designThis was a longitudinal analysis from six waves of the Canadian Community Health Survey (2009–2014) linked to hospitalization/mortality data in Ontario, Canada. MethodsThe study sample consisted of survey respondents aged ≥15 (weighted n = 15,406,000) who provided a valid response to the question about sexual orientation. The primary outcome was substance-related acute events, including hospitalizations and deaths due to alcohol, cannabis, opioids, narcotics, and/or illicit drugs. Disparities in substance-related acute events across sexual orientation and gender were examined using flexible parametric survival analysis. ResultsBisexual women had hazard ratios of 2.46 (95% confidence interval: 1.46–4.15) for any substance-related acute event and 2.67 (95% confidence interval: 1.42–5.00) for non-alcohol substance acute events compared to heterosexual women. Lesbian women did not exhibit significant differences in acute event risk compared to heterosexual women. Gay and bisexual men demonstrated elevated but not statistically significant risks compared to heterosexual men. ConclusionsBisexual women face higher risks of substance-related acute events, potentially due to self-medication of unique stressors brought on by discrimination and isolation. Enhanced education and training for healthcare professionals are essential to increase awareness and sensitivity toward the heightened substance use risk among lesbian, gay, and bisexual individuals. Targeted interventions aimed at reducing substance use problems among bisexual individuals warrant increased funding and research.

Factors affecting the first 24-hour mortality of patients receiving emergency medical service (EMS) in a sub-urban area: a retrospective cohort study

Background: Saraburi province in central Thailand connects the capital to the north and northeast. A hospital-based model drives the Emergency Medical Service (EMS) system in Saraburi’s vicinity. We studied factors related to death within 24 hours of EMS patients. Methods: Patients who received EMS from the high-level operation team of Saraburi Hospital from 1 May 2017 - 7 July 2019 were enrolled in the study. Various factors that may affect death within 24 hours were collected. Data were analyzed by flexible parametric survival analysis using an exploratory model. Result: Out of 2,321 patients, 118 died within 24 hours. The factors associated with a statistically significant increase in the hazard ratio of death within 24 hours were male sex (aHR, 1.69; 95% CI, 1.05-2.71; p = 0.031), time from symptom onset to calling for medical assistance within two hours (aHR, 3.04; 95% CI, 1.12-8.24; p = 0.029), diastolic blood pressure &lt; 60 mmHg (aHR, 3.21; 95% CI, 1.01-10.21; p = 0.049), pulse &lt; 50 or ≥120 beats/min (aHR, 2.17; 95% CI, 1.00-4.71; p = 0.050), Glasgow Coma Scale ≤ 8 (aHR, 16.16; 95% CI, 6.68-39.11; p &lt; 0.001), transport time &gt;15 min (aHR, 2.02; 95% CI, 1.01-4.03; p = 0.046) and present prehospital life-saving intervention (aHR, 3.52; 95% CI, 1.30-9.51, p = 0.013). Factors associated with a statistically significant decrease in this ratio were the distance from the scene to the hospital &gt;10 km (aHR, 0.35; 95% CI, 0.18-0.71; p = 0.004), and the synchronized operation with the Basic Life Support (BLS) team (aHR, 0.40; 95%CI, 0.20-0.81; p=0.010). Conclusions: The study emphasizes the importance of early intervention, synchronized operations, and access to appropriate levels of care in improving patient outcomes and reducing mortality in patients receiving EMS. Further prospective studies are required to confirm these results.

Association of infertility with type and timing of menopause: a prospective cohort study.

What is the association between past infertility and the type and timing of menopause in midlife women? Women with a history of infertility were more likely to experience surgical menopause overall and had elevated risk of earlier surgical menopause until age 43 years but experienced no differences in the timing of natural menopause. Infertility is experienced by 12-25% of women and is thought to reveal a propensity for poor health outcomes, such as chronic illness, later in life. However, little is known about whether infertility is linked with characteristics of the menopausal transition as women age, despite possible shared underlying pathways involving ovarian function and gynecologic disease. Secondary analysis of a prospective cohort study of 13 243 midlife females recruited in Phase 1 of the Alberta's Tomorrow Project (Alberta, Canada) and followed approximately every 4 years (2000-2022). Data were collected through standardized self-report questionnaires. History of infertility, defined as ever trying to become pregnant for more than 1 year without conceiving, was measured at baseline. Menopause characteristics were measured at each study follow-up. Menopause type was defined as premenopause, natural menopause, surgical menopause (bilateral oophorectomy), or indeterminate menopause (premenopausal hysterectomy with ovarian conservation). Timing of natural menopause was defined as the age at 1 full year after the final menstrual period, and timing of surgical and indeterminate menopause was defined as the age at the time of surgery. We used flexible parametric survival analysis for the outcome of menopause timing with age as the underlying time scale and multinomial logistic regression for the outcome of menopause type. Multivariable models controlled for race/ethnicity, education, parity, previous pregnancy loss, and smoking. Sensitivity analyses additionally accounted for birth history, menopausal hormone therapy, body mass index, chronic medical conditions, and age at baseline. Overall, 18.2% of women reported a history of infertility. Past infertility was associated with earlier timing of surgical menopause exclusively before age 43 years (age 35: adjusted hazard ratio 3.13, 95% CI 1.95-5.02; age 40: adjusted hazard ratio 1.83, 95% CI 1.40-2.40; age 45: adjusted hazard ratio 1.13, 95% CI 0.87-1.46) as well as greater odds of experiencing surgical menopause compared to natural menopause (adjusted odds ratio 1.40, 95% CI 1.18-1.66). Infertility was not associated with the timing of natural or indeterminate menopause. Information on the underlying cause of infertility and related interventions was not collected, which precluded us from disentangling whether associations differed by infertility cause and treatment. Residual confounding is possible given that some covariates were measured at baseline and may not have temporally preceded infertility. Women with a history of infertility were more likely to experience early surgical menopause and may therefore benefit from preemptive screening and treatment for gynecologic diseases to reduce bilateral oophorectomy, where clinically appropriate, and its associated health risks in midlife. Moreover, the lack of association between infertility and timing of natural menopause adds to the emerging knowledge that diminishing ovarian reserve does not appear to be a primary biological mechanism of infertility nor its downstream implications for women's health. Alberta's Tomorrow Project is only possible due to the commitment of its research participants, its staff and its funders: Alberta Health, Alberta Cancer Foundation, Canadian Partnership Against Cancer and Health Canada, and substantial in-kind funding from Alberta Health Services. The views expressed herein represent the views of the author(s) and not of Alberta's Tomorrow Project or any of its funders. This secondary analysis is funded by Project Grant Priority Funding in Women's Health Research from the Canadian Institutes of Health Research (Grant no. 491439). N.V.S. is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research. H.K.B. is supported by the Canada Research Chairs Program. E.A.B. is supported by an Early Career Investigator Award in Maternal, Reproductive, Child and Youth Health from the Canadian Institutes of Health Research. A.K.S. has received honoraria from Pfizer, Lupin, Bio-Syent, and Eisai and has received grant funding from Pfizer. N.V.S., H.K.B., and E.A.B. have no conflicts of interest to report. N/A.

Can bank branch establishment help SMEs survive? Evidence from China

In this study, we trace the survival of 18,118,907 Chinese SMEs from 2000 to 2010. We use flexible parametric survival analysis, the Cox model, the Kaplan-Meier survival function, and IV-Tobit to assess the policy effects of Chinese financial reforms that rely on the establishment of more bank branches to impact the survival of SMEs. According to the findings, SMEs in China face a severe survival dilemma, with more than 50% failing in their first year of existence and approximately 80% not surviving more than 10 years. However, the establishment of more bank branches does help improve this phenomenon. The survival hazard of SMEs decreases as the number of branches around them increases. Nonetheless, here are certain necessary conditions for the policy to be effective. From the standpoint of financial supply, the establishment of bank branches is only beneficial to the survival of SMEs when the banks and firms are geographically close or the branches are small- or medium-sized. From the standpoint of financial demand, the establishment of bank branches is beneficial to the survival of larger and eastern-based SMEs.

The Impact of Pre-Operative Anaemia on One Year Amputation Free Survival and Re-Admissions in Patients Undergoing Vascular Surgery for Peripheral Arterial Disease: a National Vascular Registry Study

Anaemia is common among patients undergoing surgery, but its association with post-operative outcomes in patients with peripheral arterial disease (PAD) is unclear. The aim of this observational population based study was to examine the association between pre-operative anaemia and one year outcomes after surgical revascularisation for PAD. This study used data from the National Vascular Registry, linked with an administrative database (Hospital Episode Statistics), to identify patients who underwent open surgical lower limb revascularisation for PAD in English NHS hospitals between January 2016 and December 2019. The primary outcome was one year amputation free survival. Secondary outcomes were one year re-admission rate, 30 day re-intervention rate, 30 day ipsilateral major amputation rate and 30 day death. Flexible parametric survival analysis and generalised linear regression were performed to assess the effect of anaemia on one year outcomes. The analysis included 13 641 patients, 57.9% of whom had no anaemia, 23.8% mild, and 18.3% moderate or severe anaemia. At one year follow up, 80.6% of patients were alive and amputation free. The risk of one year amputation or death was elevated in patients with mild anaemia (adjusted HR 1.3; 95% CI 1.15 - 1.41) and moderate or severe anaemia (aHR 1.5; 1.33 - 1.67). Patients with moderate or severe anaemia experienced more re-admissions over one year (adjusted IRR 1.31; 1.26 - 1.37) and had higher odds of 30 day re-interventions (aOR 1.22; 1.04 - 1.45), 30 day ipsilateral major amputation (aOR 1.53; 1.17 - 2.01), and 30 day death (aOR 1.39; 1.03 - 1.88) compared with patients with no anaemia. Pre-operative anaemia is associated with lower one year amputation free survival and higher one year re-admission rates following surgical revascularisation in patients with PAD. Research is required to evaluate whether interventions to correct anaemia improve outcomes after lower limb revascularisation.

Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS)

SummaryWe investigated the association between bisphosphonate and denosumab use and risk of hip fracture in Norway. These drugs protect against fractures in clinical trials, but their population-level effect is unknown. Our results showed lowered risk of hip fracture for treated women. Treatment of high-risk individuals could prevent future hip fractures.PurposeTo investigate whether bisphosphonates and denosumab reduced the risk of first-time hip fracture in Norwegian women when adjusting for a medication-based comorbidity index.MethodsNorwegian women aged 50–89 in 2005–2016 were included. The Norwegian prescription database (NorPD) supplied data on exposures to bisphosphonates, denosumab, and other drugs for the calculation of the Rx-Risk Comorbidity Index. Information on all hip fractures treated in hospitals in Norway was available. Flexible parametric survival analysis was used with age as time scale and with time-varying exposure to bisphosphonates and denosumab. Individuals were followed until hip fracture or censoring (death, emigration, age 90 years), or 31 December 2016, whichever occurred first. Rx-Risk score was included as a time-varying covariate. Other covariates were marital status, education, and time-varying use of bisphosphonates or denosumab with other indications than osteoporosis.ResultsOf 1,044,661 women 77,755 (7.2%) were ever-exposed to bisphosphonate and 4483 (0.4%) to denosumab. The fully adjusted hazard ratios (HR) were 0.95 (95% confidence interval (CI): 0.91–0.99) for bisphosphonate use and 0.60 (95% CI: 0.47–0.76) for denosumab use. Bisphosphonate treatment gave a significantly reduced risk of hip fracture compared with the population after 3 years and denosumab after 6 months. Fracture risk was lowest in denosumab users who had previously used bisphosphonate: HR 0.42 (95% CI: 0.29–0.61) compared with the unexposed population.ConclusionsIn population-wide real-world data, women exposed to bisphosphonates and denosumab had a lower hip fracture risk than the unexposed population after adjusting for comorbidity. Treatment duration and treatment history impacted fracture risk.

Venous Thromboembolism in Surgically Treated Esophageal Cancer Patients: A Provincial Population-Based Study.

Objective Venous thromboembolism (VTE) is a major cause of morbidity and mortality in surgical patients. Surgery for esophageal cancer carries a high risk of VTE. This study identifies the risk factors and associated mortality of thrombotic complications among patients undergoing esophageal cancer surgery. Methods All patients in the province of Ontario undergoing esophageal cancer surgery from 2007 to 2017 were identified. Logistic regression identified VTE risk factors at 90 days and 1 year postoperatively. A flexible parametric survival analysis compared mortality and survival up to 5 years after surgery for patients with and without a postoperative VTE. Results Overall 9,876 patients with esophageal cancer were identified; 2,536 (25.7%) underwent surgery. VTE incidence at 90 days and 1 year postoperatively were 4.1 and 6.3%, respectively. Patient factors including age, sex, performance status, and comorbidities were not associated with VTE risk. VTE risk peaked at 1 month after surgery, with a subsequent decline, plateauing after 6 months. Adenocarcinoma was strongly associated with VTE risk compared with squamous cell carcinoma (SCC) (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.38–4.63, p = 0.003). VTE risk decreased with adjuvant chemotherapy (OR = 0.58, 95% CI 0.36–0.94, p = 0.028). Postoperative VTE was associated with decreased survival at 1 and 5 years (hazard ratio = 1.57, 95% CI 1.23–2.00, p < 0.001). Conclusion Esophageal cancer patients with postoperative VTE have worse long-term survival compared with those without thrombotic complications. Adenocarcinoma carries a higher VTE risk compared with SCC. Strategies to reduce VTE risk should be considered to reduce the negative impacts on survival conferred by thrombotic events.

Venous Thromboembolism in Surgical Lung Cancer Patients: A Provincial Population-Based Study

BackgroundVenous thromboembolism (VTE) is a significant cause of morbidity and mortality in surgical patients. Thoracic surgery patients are at increased risk due to inherent technical and disease-specific factors. Other surgical specialties have adopted postdischarge extended VTE prophylaxis; however evidence is scarce in thoracic surgery. This study aims to identify VTE risk factors and associated mortality among surgical lung cancer patients. MethodsUsing administrative databases all patients in the province of Ontario undergoing lung cancer surgery from 2007 to 2017 were identified. Logistic regression identified VTE risk factors at 90 days and 1 year postoperatively. A flexible parametric survival analysis compared mortality and survival up to 5 years after surgery between patients with and without VTE. ResultsOf 65,513 patients diagnosed with lung cancer, 12,626 (19.3%) underwent surgery. VTE incidence at 90 days and 1 year postoperatively was 1.3% and 2.7%, respectively. Open and more extensive resections carried an increased VTE risk, with pneumonectomy conferring the highest risk (odds ratio, 2.36; P < .001). Stage III and IV disease carried a 3.19 and 4.97 times higher risk of VTE, respectively, compared with stage I (P < .001). The hazard ratio for mortality at 1 year for patients with VTE was 2.01 (P < .001). Patients suffering a VTE had reduced 5-year survival. ConclusionsPatients undergoing pneumonectomy and those with advanced stage have an increased VTE risk. Patients suffering a thrombotic complication have an increased risk of mortality and decreased 5-year survival. Accordingly strategies to reduce VTE risk should be considered in patients undergoing high-risk operations to reduce the mortality of VTEs.

Socioeconomic gaps over time in colorectal cancer survival in England: flexible parametric survival analysis

BackgroundDespite persistent reports of socioeconomic inequalities in colorectal cancer survival in England, the magnitude of survival differences has not been fully evaluated.MethodsPatients diagnosed with colon cancer (n=68 169) and rectal...

Unemployment Insurance and Mortality Among the Long-Term Unemployed: A Population-Based Matched-Cohort Study.

Unemployment insurance is hypothesized to play an important role in mitigating the adverse health consequences of job loss. In this prospective cohort study, we examined whether receiving unemployment benefits is associated with lower mortality among the long-term unemployed. Census records from the 2006 Canadian Census Health and Environment Cohort (n=2,105,595) were linked to mortality data from 2006-2016. Flexible parametric survival analysis and propensity score matching were used to model time-varying relationships between long-term unemployment (≥20 weeks), unemployment-benefit recipiency, and all-cause mortality. Mortality was consistently lower among unemployed individuals who reported receiving unemployment benefits, relative to matched nonrecipients. For example, mortality at 2 years of follow-up was 18% lower (95% confidence interval (CI): 9, 26) among men receiving benefits and 30% lower (95% CI: 18, 40) among women receiving benefits. After 10 years of follow-up, unemployment-benefit recipiency was associated with 890 (95% CI: 560, 1,230) fewer deaths per 100,000 men and 1,070 (95% CI: 810, 1,320) fewer deaths per 100,000 women. Our findings indicate that receiving unemployment benefits is associated with lower mortality among the long-term unemployed. Expanding access to unemployment insurance may improve population health and reduce health inequalities associated with job loss.

The Impact of Same-Day Antiretroviral Therapy Initiation Under the World Health Organization Treat-All Policy.

Rapid initiation of antiretroviral therapy (ART) is recommended for people living with human immunodeficiency virus (HIV), with the option to start treatment on the day of diagnosis (same-day ART). However, the effect of same-day ART remains unknown in realistic public sector settings. We established a cohort of ≥16-year-old patients who initiated first-line ART under a treat-all policy in Nhlangano (Eswatini) during 2014–2016, either on the day of HIV care enrollment (same-day ART) or 1–14 days thereafter (early ART). Directed acyclic graphs, flexible parametric survival analysis, and targeted maximum likelihood estimation (TMLE) were used to estimate the effect of same-day-ART initiation on a composite unfavorable treatment outcome (loss to follow-up, death, viral failure, treatment switch). Of 1,328 patients, 839 (63.2%) initiated same-day ART. The adjusted hazard ratio of the unfavorable outcome was higher, 1.48 (95% confidence interval: 1.16, 1.89), for same-day ART compared with early ART. TMLE suggested that after 1 year, 28.9% of patients would experience the unfavorable outcome under same-day ART compared with 21.2% under early ART (difference: 7.7%; 1.3%–14.1%). This estimate was driven by loss to follow-up and varied over time, with a higher hazard during the first year after HIV care enrollment and a similar hazard thereafter. We found an increased risk with same-day ART. A limitation was that possible silent transfers that were not captured.

Predicting Survival in Thai Patients After Low Impact Hip Fracture Using Flexible Parametric Modelling: A Retrospective Cohort Study

Predictive post-hip fracture mortality models have been presented for specific time points (in-hospital, 30-days or 1-year) and most provide marginal predictions based on the patient's risk group. However, the predictive model for individual survival probability following hip fracture is not available. This study aimed to develop a flexible parametric model for predicting individual survival probability for hip fracture patients. In this retrospective study, the medical charts of 765 Thai patients admitted to hospital with a hip fracture resulting from low-impact injury from January 2014 to December 2018 were reviewed. Predictors for all-cause mortality were identified using flexible parametric survival analysis and were used to develop the predictive model. The model was calibrated using a calibration graph and discrimination performance was evaluated using the C-statistic. Internal validity was assessed using bootstrapping. The overall mortality rate of the hip fracture patients was 14%. Predictors significantly associated with survival after hip fracture were age, active malignancy, dementia or Alzheimer's disease, chronic obstructive pulmonary disorder, diabetes mellitus, hemoglobin concentration, eGFR<30 mL/min/1.73m2 and operative treatments. The model-predicted survival was similar to that actually observed in the very low survival group in the first year after hip fracture. In bootstrapping, the apparent C-statistic and the test C-statistic of the reduced model were 0.79 (95% CI 0.77–0.81) and 0.79 (95% CI 0.78–0.80), respectively. The flexible survival model provides good predictive power for individual survival probability at any given time point within the first year after hip fracture and would be an easy to use tool in clinical practice.

Increased Mortality in Hip Fracture Patients Living Alone: A NOREPOS Study.

Hip fracture is associated with excess mortality, persisting for many years after the fracture. Several factors may affect survival; however, the role of social support has been less studied. Living situation could be an indicator of a person's social support, which predicts mortality in the general population. In this longitudinal cohort study, we considered whether living alone was a risk factor for post-hip fracture mortality compared with living with a partner. Information on hip fractures from all hospitals in Norway from 2002 to 2013 was combined with the 2001 National Population and Housing Census. The association between living situation and mortality during 12.8 years of follow-up in 12,770 men and 22,067 women aged 50 to 79 years at fracture was investigated using flexible parametric survival analysis. We also estimated relative survival of hip fracture patients compared with that of the non-fractured background population in the same living situation (alone or with a partner). Higher mortality after hip fracture was found in both men and women living alone versus with a partner (hazard ratio [HR] men = 1.37, 95% confidence interval [CI] 1.29-1.44; HR women = 1.23, 95% CI 1.18-1.28, adjusting for age, education level, urbanization degree, and number of children). We demonstrated the strongest association in male hip fracture patients aged <60 years (long-term mortality HR = 3.29, 95% CI 2.25-6.49). Compared with the general population, relative survival 8 years after a hip fracture was 43% in men and 61% in women living alone, whereas relative survival in those living with a partner was 51% in men and 67% in women. In conclusion, hip fracture patients who lived alone had higher mortality than those living with a partner and lower survival relative to the general population. © 2021 American Society for Bone and Mineral Research (ASBMR).