Time-dependent Cox Regression Models Research Articles

Hormone therapy use and the risk of acute kidney injury in patients with prostate cancer: a population-based cohort study

BackgroundHormone therapy is widely used in prostate cancer. However, studies have raised concerns that hormone therapy, particularly the use of gonadotropin-releasing hormone agonists, could increase the risk of acute kidney injury.MethodsMen newly diagnosed with non-metastatic prostate cancer, from 2012 to 2017, were identified from the Scottish Cancer Registry. A matched comparison cohort of prostate cancer-free men was also identified. Hormone therapy use was determined from the Prescribing Information System in Scotland. The primary outcome was hospitalisations with acute kidney injury taken from Scottish hospital records (SMR01) up to June 2019. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for acute kidney injury by hormone therapy use.ResultsThe prostate cancer cohort contained 10,751 patients followed for 41,997 person years, during which there were 618 hospitalisations with acute kidney injury. Prostate cancer patients had higher rates of acute kidney injury compared with cancer-free controls (adjusted HR = 1.47 95% CI 1.29, 1.69). However, prostate cancer patients currently using hormone therapy (adjusted HR = 1.14 95% CI 0.92, 1.41), including gonadotropin-releasing hormone (GnRH) agonists (adjusted HR = 1.13 95% CI 0.90, 1.40), did not appear to have a marked increase in acute kidney injury compared with prostate cancer patients not using hormone therapy after adjusting for potential confounders.ConclusionsIn our cohort, there was little evidence that gonadotropin-releasing hormone agonists were associated with marked increases in acute kidney injury.

Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales

BackgroundHormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality.MethodsThe study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts.DiscussionOur study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.

Recurrent heart failure hospitalizations increase the risk of cardiovascular and all‐cause mortality in patients with heart failure in Sweden: a real‐world study

AimsHeart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality. We examined the impact of recurrent HF hospitalizations (HFHs) on cardiovascular (CV) mortality among patients with HF in Sweden.Methods and resultsAdults with incident HF were identified from linked national health registers and electronic medical records from 01 January 2005 to 31 December 2013 for Uppsala and until 31 December 2014 for Västerbotten. CV mortality and all‐cause mortality were evaluated. A time‐dependent Cox regression model was used to estimate relative CV mortality rates for recurrent HFHs. Assessment was also done for ejection fraction‐based HF phenotypes and for comorbid atrial fibrillation, diabetes, or chronic renal impairment. Overall, 3878 patients with HF having an index hospitalization were included, providing 9691.9 patient‐years of follow‐up. Patients were relatively old (median age: 80 years) and were more frequently male (55.5%). Compared with patients without recurrent HFHs, the adjusted hazard ratio (HR [95% confidence interval; CI]) for CV mortality and all‐cause mortality were statistically significant for patients with one, two, three, and four or more recurrent HFHs. The risk of CV mortality and all‐cause mortality increased approximately six‐fold in patients with four or more recurrent HFHs vs. those without any HFHs (HR [95% CI]: 6.26 [5.24–7.48] and 5.59 [4.70–6.64], respectively). Similar patterns were observed across the HF phenotypes and patients with comorbidities.ConclusionsThere is a strong association between recurrent HFHs and CV and all‐cause mortality, with the risk increasing progressively with each recurrent HFH.

Comparative assessment of mortality risk factors between admission and follow-up models among patients hospitalized with COVID-19

ObjectivesThis study aimed to compare differences in mortality risk factors between admission and follow-up incorporated models. MethodsA retrospective cohort study of 524 patients with confirmed COVID-19 infection admitted to a tertiary medical center in São Paulo, Brazil from 13 March to 30 April 2020. Data were collected on admission, and the third, eighth and fourteenth days of hospitalization. The hazard ratio (HR) was calculated and 28-day in-hospital mortality risk factors were compared between admission and follow-up models using a time-dependent Cox regression model. ResultsOf 524 patients, 50.4% needed mechanical ventilation. The 28-day mortality rate was 32.8%. Compared with follow-up, admission models under-estimated the mortality HR for peripheral oxygen saturation <92% (1.21 versus 2.09), heart rate >100 bpm (1.19 versus 2.04), respiratory rate >24/min (1.01 versus 1.82) and mechanical ventilation (1.92 versus 12.93). Low oxygen saturation, higher oxygen support and more biomarkers–including lactate dehydrogenase, C-reactive protein, neutrophil-lymphocyte ratio, and urea remained associated with mortality after adjustment for clinical factors at follow-up compared with only urea and oxygen support at admission. ConclusionsThe inclusion of follow-up measurements changed mortality hazards of clinical signs and biomarkers. Low oxygen saturation, higher oxygen support, lactate dehydrogenase, C-reactive protein, neutrophil-lymphocyte ratio, and urea could help with prognosis of patients during follow-up.

Socioeconomic inequalities associated with mortality for COVID-19 in Colombia: a cohort nationwide study

BackgroundAfter 8 months of the COVID-19 pandemic, Latin American countries have some of the highest rates in COVID-19 mortality. Despite being one of the most unequal regions of the world,...

Predictors of death after receiving a modified Blalock-Taussig shunt in cyanotic heart children: A competing risk analysis.

ObjectiveTo determine risk factors affecting time-to-death ≤90 and >90 days in children who underwent a modified Blalock-Taussig shunt (MBTS).MethodsData from a retrospective cohort study were obtained from children aged 0–3 years who experienced MBTS between 2005 and 2016. Time-to-death (prior to Glenn/repair), time-to-alive up until December 2017 without repair, and time-to-progression to Glenn/repair following MBTS were presented using competing risks survival analysis. Demographic, surgical and anesthesia-related factors were recorded. Time-to-death ≤90 days and >90 days was analyzed using multivariate time-dependent Cox regression models to identify independent predictors and presented by adjusted hazard ratios (HR) and 95% confidence intervals (CI).ResultsOf 380 children, 119 died, 122 survived and 139 progressed to Glenn/repair. Time-to-death probability (95% CI) within 90 days was 0.18 (0.14–0.22). Predictors of time-to-death ≤90 days (n = 63) were low weight (<3 kg) (HR 7.6, 95% CI:2.8–20.4), preoperative ventilator support (HR 2.7, 95% CI:1.3–5.6), postoperative shunt thrombosis (HR 5.0, 95% CI:2.4–10.4), bleeding (HR 4.5, 95% CI:2.1–9.4) and renal failure (HR 4.1, 95% CI:1.5–10.9). Predictors of time-to-death >90 days (n = 56) were children diagnosed with pulmonary atresia with ventricular septal defect and single ventricle (compared to tetralogy of fallot) (HR 3.2, 95% CI:1.2–7.7 and HR 3.1, 95% CI:1.3–7.6, respectively), shunt size/weight ratio >1.1 vs <0.65 (HR 6.8, 95% CI:1.4–32.6) and longer duration of mechanical ventilator (HR 1.002, 95% CI:1.001–1.004). Shunt size/weight ratio ≥1.0 (vs <1.0) and ≥0.65 (vs <0.65) were predictors for overall time-to-death in neonates and toddlers, respectively (HR 13.1, 95% CI:2.8–61.4 and HR 7.8, 95% CI:1.7–34.8, respectively).ConclusionsPerioperative factors were associated with time-to-death ≤90 days, whereas particular cardiac defect, larger shunt size/weight ratio, and longer mechanical ventilation were associated with time-to-death >90 days after receiving MBTS. Larger shunt size/weight ratio should be reevaluated within 90 days to minimize the risk of shunt over flow.

COVID-19 and death of older adults in the Northeast region of Brazil: a survival analysis

Objective: to analyze survival and factors associated with increased risk of death for older adults diagnosed with COVID-19, living in the Northeast region of Brazil. Method: retrospective observational study developed with secondary data provided by the Brazilian Ministry of Health, between June 14 and December 26, 2020. The Kaplan-Meyer method, the time-dependent cox regression model was used, including covariates (age, sex, skin color, comorbidities, admission to the ICU, ventilatory support). Results: out of 9,306 individuals analyzed, 55.9% died and 44.1% survived. The highest risk of death was observed for those aged 80-89 (HR=1.95), brown-skinned (HR=1.99), with immunodeficiency (HR=1.259) or kidney disease (HR=1.147), admitted to the ICU (HR=1,795) and in use of ventilatory support (HR=1606). Conclusion: among older adults residing in the Northeast region of Brazil, there was a higher risk of death from COVID-19 for octogenarians, brown-skinned, with comorbidities, hospitalization in the ICU, followed by the use of ventilatory support. The creation of health prevention strategies that identify older adults with these profiles is suggested to prevent deaths in future pandemic situations.

The Relationship Between Asthma and Cardiovascular Disease: An Examination of the Framingham Offspring Study

Although asthma has been suggested as a risk factor for cardiovascular disease (CVD), robust longitudinal evidence of this relationship is limited. Using Framingham Offspring Cohort data, the goal of this study was to longitudinally examine the association between asthma and lifetime risk of CVD while controlling for cardiovascular risk factors included in the Framingham Risk Score. Data were analyzed from a prospective population-based cohort of 3,612 individuals, ages 17 to 77 years, who participated in Framingham Offspring Study examinations from 1979 to 2014. Asthma was defined based on physician diagnosis during study interviews. Incident CVD included myocardial infarction, angina, coronary insufficiency, stroke, transient ischemic attack, and heart failure. Time-dependent Cox regression models were used to evaluate the relationship between asthma and CVD incidence. Overall, 533 (15%) participants had a diagnosis of asthma and 897 (25%) developed CVD during the course of the study. Unadjusted analyses revealed that asthma was associated with increased CVD incidence (hazard ratio, 1.40; 95%CI, 1.17-1.68). Cox regression also showed an adjusted association between asthma and CVD incidence (hazard ratio, 1.28; 95%CI, 1.07-1.54) after controlling for established cardiovascular risk factors. This prospective analysis with > 35 years of follow-up shows that asthma is a risk factor for CVD after adjusting for potential confounders. When assessing risk of cardiovascular disease, asthma should be evaluated and managed as a risk factor contributing to morbidity and mortality.

Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study.

We conducted a multicenter cohort study to determine the effect of drug therapies on survival in mechanically ventilated patients with coronavirus disease 2019. All consecutive adult patients admitted to ICU for coronavirus disease 2019 from March 1, 2020, to April 25, 2020, and under invasive mechanical ventilation for more than 24 hours were included. Out of 2,003 patients hospitalized for coronavirus disease 2019, 361 were admitted to ICU, 257 were ventilated for more than 24 hours, and 247 were included in the study. Simple and multiple time-dependent Cox regression models were used to assess the effects of factors on survival. Methylprednisolone administration during the first week of mechanical ventilation was associated with a decrease in mortality rate from 48% to 34% (p = 0.01). Mortality was significantly associated with older age, higher creatinine, lower lymphocyte count, and mean arterial pressure lower than 70 mm Hg on the day of admission.

Analysis of lens opacity and its influencing factors of medical radiation workers

Objective: To explore the association between long-term low-dose radiation exposure and other influencing factors with the risk of lens opacity on medical radiation workers. Methods: In July 2019, a retrospective cohort study was conducted by collecting the basic demographic information, dose data and health inspection result of 2708 radiologists in 22 hospitals of Guangzhou from the Occupational Health Inspection Information System and the Personal Dose Monitoring System of the Guangdong Prevention and Treatment Center for Occupational Disease between 2010 to 2018. The association between the average annual effective dose and lens opacity risk was calculated by using Time-Dependent Cox Regression Model. Results: From 2010 to 2018, the incidence density of lens opacity was 185.90/10000 person years. Compared with the radiation workers in the age <30 years group (93.74%) , the 5-year normal rate of lens in the age ≥50 years group (72.51%) was lower (P<0.01) ; Compared with the radiation workers in the exposure age <10 years group (92.69%) , the 5-year normal rate of lens in more than 20 years exposed group (83.05%) was lower (P<0.01) . Multifactor analysis showed that age was an independent influencing factor for lens opacity in medical radiation workers (HR=14.485, P<0.01) . The risk of lens opacification increased by 4.9%, 10.1% and 15.5% in 30-, 40- and 50-years group, respectively. Gender, cigarette, alchol, type of work, length of service and annual effective dose had no significant effect on lens opacity (P>0.05) . Conclusion: Age is the main influencing factor of lens opacification in medical radiation workers, their radiation working time and intensity should be strictly controlled and radiation protection should be done.

Corticosteroid therapy for coronavirus disease 2019-related acute respiratory distress syndrome: a cohort study with propensity score analysis

BackgroundThe impact of corticosteroid therapy on outcomes of patients with coronavirus disease 2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without.MethodsIn this single-center retrospective observational study, patients with ARDS caused by COVID-19 between January 20, 2020, and February 24, 2020, were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality.ResultsA total of 382 patients [60.7 ± 14.1 years old (mean ± SD), 61.3% males] were analyzed. The median of sequential organ failure assessment (SOFA) score was 2.0 (IQR 2.0–3.0). Of these cases, 94 (24.6%) patients had invasive mechanical ventilation. The number of patients received systemic corticosteroids was 226 (59.2%), and 156 (40.8%) received standard treatment. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days after adjusting for age, sex, SOFA score at hospital admission, propensity score of corticosteroid treatment, comorbidities, antiviral treatment, and respiratory supports (HR 0.42; 95% CI 0.21, 0.85; p = 0.0160). Corticosteroids were not associated with delayed viral RNA clearance in our cohort.ConclusionIn this clinical practice setting, low-dose corticosteroid treatment was associated with reduced risk of in-hospital death within 60 days in COVID-19 patients who developed ARDS.

Prenatal Exposure to Ambient Air Temperature and Risk of Early Delivery

Background:Preterm birth is a major determinant of adverse health consequences. Often, the specific cause of preterm birth is unclear. However, there are known genetic, behavioral, socioeconomic and environmental risk factors. Considering climate change, temperature is an important factor to consider. Several studies have focused on associations of ambient air temperature (Ta) with risk of preterm birth. Climates studied and methods used varied and results have been inconsistent. Few studies included early-term births.Aims:To investigate the association of prenatal exposure to Ta with preterm and early-term birth in a semi-arid climate in Israel.Methods:All singleton deliveries at the Soroka Medical Center, Be’er Sheva, Israel, with estimated conception dates between May 2004 and March 2013 (N=62,547) were linked to prenatal Ta estimates from a spatiotemporally resolved model, with daily 1 km resolution. We used time-dependent Cox regression models with weekly mean Ta throughout gestation, adjusted for calendar month and year of conception, ethnicity, SES and population density. Effect modification by fetal sex and ethnicity was examined using interaction terms and stratified.Results:Ta was positively associated with late preterm birth (31+0/7 - 36+6/7 weeks of gestation), with increased risk in the upper Ta quintile as compared to the middle Ta quintile, hazard ratio (HR) = 1.31, 95% CI = 1.11 - 1.56. Ta was also associated with early term birth (37+0/6 - 38+6/7 of gestation), with increased risk in the upper Ta quintile as compared to the middle Ta quintile, HR = 1.24, 95% CI = 1.13 - 1.36. Ta was more strongly associated with late preterm birth for female fetuses than for male fetuses (HR = 1.50, 95% CI = 1.17-1.94 and HR = 1.17, 95% CI = 0.97-1.41, respectively).Conclusion:Prenatal exposure to high Ta is associated with a higher risk of early delivery in southern Israel.

Risk factors associated with delay in diagnosis and mortality in patients with COVID-19 in the city of Rio de Janeiro, Brazil

We investigated the predictors of delay in the diagnosis and mortality of patients with COVID-19 in Rio de Janeiro, Brazil. A cohort of 3,656 patients were evaluated (Feb-Apr 2020) and patients' sociodemographic characteristics, and social development index (SDI) were used as determinant factors of diagnosis delays and mortality. Kaplan-Meier survival analyses, time-dependent Cox regression models, and multivariate logistic regression analyses were conducted. The median time from symptoms onset to diagnosis was eight days (interquartile range [IQR] 7.23-8.99 days). Half of the patients recovered during the evaluated period, and 8.3% died. Mortality rates were higher in men. Delays in diagnosis were associated with male gender (p = 0.015) and patients living in low SDI areas (p < 0.001). The age groups statistically associated with death were: 70-79 years, 80-89 years, and 90-99 years. Delays to diagnosis greater than eight days were also risk factors for death. Delays in diagnosis and risk factors for death from COVID-19 were associated with male gender, age under 60 years, and patients living in regions with lower SDI. Delays superior to eight days to diagnosis increased mortality rates.

Chronic Opioid Use and Risk of Cancer in Patients with Chronic Noncancer Pain: A Nationwide Historical Cohort Study.

To investigate whether chronic opioid therapy is associated with a higher risk of cancer among noncancer patients with chronic pain. A population-based historical cohort study of the South Korean adult population was conducted using data from the National Health Insurance Service. We included patients registered with a diagnostic code of M00-M99 (musculoskeletal system and connective tissue diseases) according to the International Classification of Diseases, 10th revision, in 2010. Patients prescribed a continuous supply of any opioid drug for ≥90 days were defined as chronic opioid users. A total of 351,701 patients were analyzed. Among them, 25,153 (7.2%) were chronic opioid users. Using a multivariate time-dependent Cox regression model, the risk of cancer in chronic opioid users was 1.20-fold higher than that in controls [HR, 1.20; 95% confidence interval (CI), 1.15-1.25; P < 0.001]. On subgroup analysis according to opioid potency, the cancer risk in chronic weak and strong opioid users was 1.18-fold (HR, 1.18; 95% CI, 1.13-1.23; P < 0.001) and 1.32-fold (HR, 1.32; 95% CI, 1.10-1.59; P = 0.003) higher than that in controls, respectively. Chronic opioid therapy was associated with an increased risk of cancer among noncancer patients with chronic pain. This association was more evident in chronic strong opioid users. However, as unmeasured and potential confounders may have affected the results, the relationship between chronic opioid use and cancer risk should be evaluated with caution. Chronic opioid therapy was associated with an increased risk of cancer among noncancer patients.

Association between nonsteroidal anti-inflammatory drug use and major adverse cardiovascular events in patients with end-stage renal disease: a population-based cohort study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for patients with end-stage renal disease (ESRD) despite clinical guideline recommendations that the use of NSAIDs be avoided in this population. However, the relationship between NSAID use and adverse cardiovascular events remains unclear. Thus, this study investigated the association between NSAID use and major adverse cardiovascular events (MACEs) in patients with ESRD. We used the Taiwan National Health Insurance Research Database to conduct this population-based cohort study of patients with newly diagnosed ESRD requiring long-term dialysis between 1998 and 2012. Clinical outcomes were evaluated until the end of 2013. Time-dependent Cox regression models were used to investigate the association between NSAID use and MACEs in patients with ESRD. Among 2349 patients with ESRD receiving dialysis, 1923 (82%) patients used NSAIDs during the follow-up period. Multivariable analysis revealed that compared with nonusers, NSAID users exhibited an increased risk of MACEs with an adjusted hazard ratio (HR) of 1.70 (95% confidence interval [CI] 1.22-2.36). Further analysis demonstrated a significant dose-response relationship between the cumulative use of NSAIDs and MACEs. Adjusted HRs for MACEs were 1.63 (95% CI 1.16-2.30), 1.86 (95% CI 1.22-2.83), and 1.99 (95% CI 1.24-3.20) for cumulative NSAID use of 1-30 defined daily doses (DDDs), 31-90 DDDs, and > 90 DDDs, respectively. The results of this study suggest that NSAID use may increase the risk of MACEs in patients with ESRD. Clinicians and patients with ESRD should be aware of the potential cardiovascular risks associated with NSAIDs.

Sex differences in the risk of diabetes mellitus among individuals with psoriasis: A retrospective cohort study in Québec, Canada

Sex differences in the risk of diabetes mellitus among individuals with psoriasis: A retrospective cohort study in Québec, Canada

Importance of previous hospital stays on the risk of hospital re-admission in older adults: a real-life analysis of the PAERPA study population

consideration of the first hospital re-admission only and failure to take account of previous hospital stays, which are the two significant limitations when studying risk factors for hospital re-admission. The objective of the study was to use appropriate statistical models to analyse the impact of previous hospital stays on the risk of hospital re-admission among older patients. an exhaustive analysis of hospital discharge and health insurance data for a cohort of patients participating in the PAERPA ('Care Pathways for Elderly People at Risk of Loss of Personal Independence') project in the Hauts de France region of France. All patients aged 75 or over were included. All data on hospital re-admissions via the emergency department were extracted. The risk of unplanned hospital re-admission was estimated by applying a semiparametric frailty model, the risk of death by applying a time-dependent semiparametric Cox regression model. a total of 24,500 patients (median [interquartile range] age: 81 [77-85]) were included between 1 January 2015 and 31 December 2017. In a multivariate analysis, the relative risk (95% confidence interval [CI]) of hospital re-admission rose progressively from 1.8 (1.7-1.9) after one previous hospital stay to 3.0 (2.6-3.5) after five previous hospital stays. The relative risk [95%CI] of death rose slowly from 1.1 (1.07-1.11) after one previous hospital stay to 1.3 (1.1-1.5) after five previous hospital stays. analyses of the risk of hospital re-admission in older adults must take account of the number of previous hospital stays. The risk of death should also be analysed.

Methylphenidate and mortality in children with attention-deficit hyperactivity disorder: population-based cohort study.

Little is known about methylphenidate (MPH) use and mortality outcomes. To investigate the association between MPH use and mortality among children with an attention-deficit hyperactivity disorder (ADHD) diagnosis. This population-based cohort study analysed data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 68 096 children and adolescents aged 4-17 years with an ADHD diagnosis and prescribed MPH between 2000 and 2010 were compared with 68 096 without an MPH prescription, matched on age, gender and year of first ADHD diagnosis. All participants were followed to death, migration, withdrawal from the National Health Insurance programme or 31 December 2013. MPH prescriptions were measured on a yearly basis during the study period, and the association between MPH use and mortality was analysed using a repeated-measures time-dependent Cox regression model. The outcome measures included all-cause, unnatural-cause (including suicide, accident and homicide) and natural-cause mortality, obtained from linkage to the National Mortality Register in Taiwan. The MPH group had lower unadjusted all-cause, natural-, unnatural- and accident-cause mortality than the comparison group. After controlling for potential confounders, MPH use was associated with a significantly lower all-cause mortality (adjusted hazard ratio AHR = 0.81, 95% CI 0.67-0.98, P = 0.027), delayed use of MPH was associated with higher mortality (AHR = 1.05, 95% CI 1.01-1.09) and longer MPH use was associated with lower mortality (AHR = 0.83, 95% CI 0.70-0.98). MPH use is associated with a reduced overall mortality in children with ADHD in this cohort study, but unmeasured confounding cannot be excluded absolutely.

Prenatal exposure to ambient air temperature and risk of early delivery

BackgroundPreterm birth is a major determinant of adverse health consequences, and early term births are also associated with increased risk of various outcomes. In light of climate change, the effect of ambient temperature on earlier delivery is an important factor to consider. Several studies have focused on associations of ambient air temperature (Ta) on preterm birth, but few have examined associations with early term births. AimsTo investigate the association of prenatal exposure to Ta with preterm birth (<37 completed gestation weeks) and with early-term birth (<39 completed gestation weeks) in a semi-arid climate. MethodsAll singleton deliveries at the Soroka Medical Center from the Southern district of Israel, with estimated conception dates between May 1, 2004 and March 31, 2013 (N = 62,547) were linked to prenatal Ta estimates from a spatiotemporally resolved model, with daily 1 km resolution. We used time-dependent Cox regression models with weekly mean Ta throughout gestation, adjusted for calendar month and year of conception, ethnicity, census-level socio-economic status and population density. ResultsTa was positively associated with late preterm birth (31 + 0/7 – 36 + 6/7 weeks), with increased risk in the upper Ta quintile as compared to the third quintile, hazard ratio (HR) = 1.31, 95% confidence interval (CI) = 1.11–1.56. Ta also associated with early term birth (37 + 0/6 – 38 + 6/7), with increased risk in the upper Ta quintile as compared to the third quintile, HR = 1.24, 95% CI = 1.13–1.36. ConclusionExposure to high ambient temperature during pregnancy is associated with a higher risk of preterm and early term birth in southern Israel.

Application of Cox and extended regression models on modeling the effect of time-updated exposures in cohort studies

One of the characteristics on cohort studies is that exposures may change over time. The full use of information related to time-updated exposures, time-dependent covariates and their relationships to estimate the association between exposures and outcomes has become the hotspot of research. In this paper, the Kailuan cohort is used as an example to explore the association between fasting blood-glucose and hepatocellular carcinoma, based on different Cox regression models. Cox or time-dependent Cox regression models can be used to estimate the impact of exposure at baseline or on the time-updated exposures. When time-dependent confounders exist, marginal structure model is recommended. We also summarize the basic principles, conditions of applications, effect estimates, and results interpretation for each model, in this paper.