Cox Proportional Hazards Regression Research Articles

Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma.

Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour. This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers. Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location. Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.

Association of serum gamma-glutamyl transferase levels with cardiovascular disease risk in type 2 diabetes patients: a prospective cohort study

To investigate the associations of serum gamma-glutamyl transferase (GGT) levels with the risk of cardiovascular disease (CVD) and its subtypes in patients with type 2 diabetes mellitus (T2DM) in Jiangsu Province. Methods: The participants were enrolled in the Comprehensive Research project regarding 'Prevention and Control of Diabetes' in Jiangsu Province. The baseline survey was conducted from 2013 to 2014, and follow-up until December 31, 2021. After excluding the participants who self-reported with chronic liver disease/stroke/coronary heart disease at baseline survey and those with incomplete information on GGT, a total of 16 147 T2DM patients were included in the final analysis. Cox proportional hazard regression models were used to calculate the hazard ratio (HR) and their 95%CI of GGT for CVD, myocardial infarction, and stroke. Restricted cubic spline models were applied to analyze the dose-response relationship between GGT and the risk of CVD and its subtypes. Results: During the median follow-up time of 8.02 years, 2 860 CVD cases were registered, including 196 cases of myocardial infarction and 2 730 cases of stroke. Multivariate Cox proportional risk regression model indicated that compared to the lowest serum GGT level group, the highest GGT level group had a 24% increased risk of CVD (HR=1.24, 95%CI: 1.09-1.41) and a 23% increased risk of stroke (HR=1.23, 95%CI: 1.08-1.40). The restricted cubic spline model showed a nonlinear dose-response relationship between GGT and the risk of CVD, myocardial infarction, and stroke in T2DM patients. Conclusions: High levels of GGT may be associated with an increased risk of cardiovascular disease in T2DM patients, which needs further exploration and validation in future clinical practice.

Survival status and influencing factors of death risk of HIV-infected patients in Hangzhou, 2004-2023

Objective: To analyze the survival status and death factors of confirmed HIV-infected patients in Hangzhou to provide a basis for the formulation of AIDS prevention and treatment strategies. Methods: A retrospective cohort study was conducted. The data were from the HIV/AIDS Comprehensive Response Information Management System of the Chinese Disease Control and Prevention Information System.Epidemiological characteristics of HIV-infected patients were comparied in Hangzhou City from 2004 to 2023 by using chi-square Test. The survival rate of HIV-infected patients in Hangzhou was calculated by the life table method, the survival curves of different subgroups were described by the Kaplan-Meier method, and the Cox proportional hazard regression model was used to analyze the influencing factors of death risk. The SPSS 26.0 software was used for statistical analysis. Results: Among the 9 457 subjects, the total follow-up time was 58 004.18 person-years, 494 patients died, fatality rate of all-cause cases was 0.85 per 100 person-years.The average survival time was 18.59 (95%CI:18.40-18.78) years. Malignant neoplasms and pneumocystis pneumonia were the first (14.37%,71/494) and second (10.73%, 53/494) causes of death, respectively. Death within 6 months after diagnosis accounted for 42.51% (210/494), and suicide accounted for 4.25% (21/494). Multivariate Cox regression analysis showed that compared with those who received antiviral treatment (ART) within 3 months of diagnosis, those who received ART outside 3 months and those who did not receive ART had a 1.65 (95%CI:1.25-2.19) and 20.68 (95%CI:15.80-27.06) times risk of death, respectively. The HIV-infected patients with high CD4+T lymphocytes (CD4) counts for the first time had a lower risk of death. The risk of death of patients with baseline CD4 counts of 200-349 cells/µl, 350-499 cells/µl, and ≥500 cells/µl was 0.38 (95%CI:0.29-0.49), 0.26 (95%CI:0.19-0.36), 0.21 (95%CI:0.14-0.31) times higher than that of baseline CD4 counts <200 cells/µl, respectively. Conclusions: The overall survival of the HIV-infected patients was good in Hangzhou from 2004 to 2023. Early detection of HIV infection and timely mobilization to participate in ART was the key to improving the survival rate of patients. At the same time, given the suicide problem of HIV-infected patients, suicide surveillance and depression and anxiety screening of HIV-infected patients should be further strengthened, and targeted psychological intervention policies should be implemented.

Association of solid fuel use for heating and smoking with respiratory diseases: a prospective cohort study

Objective: To investigate the association between solid fuel use for heating, smoking, and respiratory diseases. Methods: This study is based on the Qingdao project of the China Kadoorie Biobank. After screening, 26 165 individuals were included in the study. We employed Cox proportional hazards regression models, stratified by risk age (in 5-year intervals) and sex while adjusting for confounding variables such as occupation and physical activity level to analyze the association between solid fuel use for heating, smoking, and increased risk of respiratory diseases. Results: Among the 26 165 participants, the average age of those using solid fuel for heating was (52.57±10.31) years, with females constituting 58.04% and former/current smokers accounting for 65.38%. The results indicated that both the solid fuel group and the former/current smoking group had a higher risk of respiratory diseases, with hazard ratios (HR) (95%CI) of 1.21 (1.04-1.41) and 1.41 (1.16-1.71), respectively. For the duration of solid fuel use, the HR (95%CI) for 20 years or more, it was 1.27 (1.07-1.51). The multiplicative interaction term between solid fuel use and smoking was statistically significant. Conclusions: The use of solid fuel for heating and smoking significantly increases the risk of respiratory diseases, and there may be a multiplicative interaction between solid fuel use and smoking.

Prognostic Prediction and Immune Microenvironment Characterization in Uveal Melanoma: A Novel Mitochondrial Metabolism-Related Gene Signature.

Uveal Melanoma (UM), a highly aggressive and metastatic intraocular cancer with a strong propensity for liver metastasis, presents limited therapeutic alternatives and unfavorable survival outcomes. Despite its low incidence, the underlying mechanisms of UM pathogenesis and the precise role of mitochondrial metabolism in UM remain inadequately understood. Utilizing Cox proportional hazards regression analysis was used to assess prognostic relevance, and consensus clustering was employed for molecular subtyping. A risk signature was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression. We further conducted comparative analyses on clinicopathological characteristics, somatic mutation profiles, drug sensitivity, gene expression patterns, and tumor microenvironment features across different molecular subtypes. Moreover, a nomogram was developed and evaluated. Among 1234 mitochondria metabolism-related genes (MMRGs), 343 were identified as significantly associated with the prognosis of UM. These prognosis-associated MMRGs facilitated the classification of UM into two distinct molecular subtypes, which displayed notable differences in prognosis and pathological staging. Furthermore, an index termed the MMRGs-derived index (MMI) was derived from eight MMRGs, serving as a quantitative measure for poor prognosis risk in UM. MMI demonstrated significant associations with clinicopathological characteristics, somatic mutations, drug responsiveness, and the tumor microenvironment, where higher MMI levels corresponded to worse prognosis, advanced pathological stages, and increased immune cell infiltration. The nomogram built upon MMI provided a potential tool for clinical prognosis assessment in UM patients. This study demonstrated the potential value of MMRGs in predicting prognosis and molecular stratification within UM; however, additional clinical and basic research is warranted to validate their applicability and elucidate the related mechanisms.

Prognostic modeling of hepatocellular carcinoma based on T-cell proliferation regulators: a bioinformatics approach.

The prognostic value and immune significance of T-cell proliferation regulators (TCRs) in hepatocellular carcinoma (HCC) have not been previously reported. This study aimed to develop a new prognostic model based on TCRs in patients with HCC. This study used The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and International Cancer Genome Consortium-Liver Cancer-Riken, Japan (ICGC-LIRI-JP) datasets along with TCRs. Differentially expressed TCRs (DE-TCRs) were identified by intersecting TCRs and differentially expressed genes between HCC and non-cancerous samples. Prognostic genes were determined using Cox regression analysis and were used to construct a risk model for HCC. Kaplan-Meier survival analysis was performed to assess the difference in survival between high-risk and low-risk groups. Receiver operating characteristic curve was used to assess the validity of risk model, as well as for testing in the ICGC-LIRI-JP dataset. Additionally, independent prognostic factors were identified using multivariate Cox regression analysis and proportional hazards assumption, and they were used to construct a nomogram model. TCGA-LIHC dataset was subjected to tumor microenvironment analysis, drug sensitivity analysis, gene set variation analysis, and immune correlation analysis. The prognostic genes were analyzed using consensus clustering analysis, mutation analysis, copy number variation analysis, gene set enrichment analysis, and molecular prediction analysis. Among the 18 DE-TCRs, six genes (DCLRE1B, RAN, HOMER1, ADA, CDK1, and IL1RN) could predict the prognosis of HCC. A risk model that can accurately predict HCC prognosis was established based on these genes. An efficient nomogram model was also developed using clinical traits and risk scores. Immune-related analyses revealed that 39 immune checkpoints exhibited differential expression between the high-risk and low-risk groups. The rate of immunotherapy response was low in patients belonging to the high-risk group. Patients with HCC were further divided into cluster 1 and cluster 2 based on prognostic genes. Mutation analysis revealed that HOMER1 and CDK1 harbored missense mutations. DCLRE1B exhibited an increased copy number, whereas RAN exhibited a decreased copy number. The prognostic genes were significantly enriched in tryptophan metabolism pathways. This bioinformatics analysis identified six TCR genes associated with HCC prognosis that can serve as diagnostic markers and therapeutic targets for HCC.

Association between beta‐blocker atenolol use and prostate cancer upgrading in active surveillance1

AbstractObjectivesThe objective of this study is to investigate the association between the use of beta‐adrenergic antagonist atenolol and risk of pathologic upgrade in patients on active surveillance, considering growing literature implicating adrenergic innervation with disease progression mediated through beta‐adrenergic signalling.Patients and MethodsMen with low‐risk or favourable intermediate‐risk prostate cancer who were placed on an active surveillance protocol between 2006 and 2020 across three diverse urban hospitals were included. Exposure was duration of atenolol use, and outcome was pathologic grade group upgrading (to GG ≥ 3) on final prostate biopsy. Cox proportional hazard regression models were used to determine the associations between atenolol use and risk of upgrading with time, on a per‐examination basis.ResultsA total of 467 men with initial GG ≤ 2 were included. Postdiagnosis atenolol use was associated with a decreased risk of pathologic upgrade to GG ≥ 3 on final repeat biopsy (HR 0.81, 95% CI 0.39–0.98). Longer duration of postdiagnosis atenolol use (&gt;2 years) and greater cumulative atenolol dose (&gt;730 defined daily doses) were associated with a more pronounced decreased risk of upgrade to GG ≥ 3 (HR 0.41, 95% CI 0.05–0.88, and HR 0.32, 95% CI 0.15–0.99, respectively). Initiation of atenolol use prior to prostate cancer diagnosis had a slightly greater protective effect than drug initiation postdiagnosis (HR 0.79, 95% CI 0.43–0.98, and HR 0.83, 95% CI 0.30–0.99, respectively).ConclusionsBeta‐adrenergic blockade with atenolol use in men on active surveillance is associated with a reduced risk for clinically significant grade group pathologic upgrade.

Development and validation of a prediction model for people with mild chronic kidney disease in Japanese individuals

BackgroundChronic kidney disease (CKD) poses significant health risks due to its asymptomatic nature in early stages and its association with increased cardiovascular and kidney events. Early detection and management are critical for improving outcomes.ObjectiveThis study aimed to develop and validate a prediction model for hospitalization for ischemic heart disease (IHD) or cerebrovascular disease (CVD) and major kidney events in Japanese individuals with mild CKD using readily available health check and prescription data.MethodsA retrospective cohort study was conducted using data from approximately 850,000 individuals in the PREVENT Inc. database, collected between April 2013 and April 2023. Cox proportional hazard regression models were utilized to derive and validate risk scores for hospitalization for IHD/CVD and major kidney events, incorporating traditional risk factors and CKD-specific variables. Model performance was assessed using the concordance index (c-index) and 5-fold cross-validation.ResultsA total of 40,351 individuals were included. Key predictors included age, sex, diabetes, hypertension, and lipid levels for hospitalization for IHD/CVD and major kidney events. Age significantly increased the risk score for both hospitalization for IHD/CVD and major kidney events. The baseline 5-year survival rates are 0.99 for hospitalization for IHD/CVD and major kidney events are 0.99. The developed risk models demonstrated predictive ability, with mean c-indexes of 0.75 for hospitalization for IHD/CVD and 0.69 for major kidney events.ConclusionsThis prediction model offers a practical tool for early identification of Japanese individuals with mild CKD at risk for hospitalization for IHD/CVD and major kidney events, facilitating timely interventions to improve patient outcomes and reduce healthcare costs. The models stratified patients into risk categories, enabling identification of those at higher risk for adverse events. Further clinical validation is required.

Association of RAAS inhibitors on osteoporosis and fracture risk in the hypertensive population–A prospective population-based cohort study in Lanzhou, China

BackgroundRenin-angiotensin-aldosterone system (RAAS) inhibitors appear to benefit bone tissue in antihypertensive treatment. However, the association between RAAS inhibitors and bone metabolism was inconsistent.Methods and study designBased on the study of Risk Evaluation of Cancers in Chinese Diabetic Individuals(REACTION) conducted in 2011, We followed 6,252 Lanzhou residents aged 40–75 years from 2014 to 2016. Finally, 1,625 hypertension cases with complete data were included in the analysis. The study subjects were divided into four groups according to the type of antihypertensive drugs. We employed logistic or multivariate Cox proportional hazards regression to estimate the association between different antihypertensive drug use and osteoporosis, the risk of fracture, and the change in bone mineral density (BMD) level. The association of osteoporosis or the fracture risk by cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated.ResultsThe cross-sectional study showed that there was no significant association between baseline antihypertensive drugs (angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB)) use and osteoporosis and fracture. During a mean follow-up of 3.4 years in the longitudinal study, there were 478 new osteoporosis cases and 76 fractures. Compared with patients without antihypertensive drug use, the hazard ratios (HRs) [95% confidence interval (CI)] for the risk of osteoporosis were 1.005(0.651,1.552) and 1.077(0.793,1.462) in ACEI or ARB use (p > 0.05). ACEI or ARB use was also not significantly associated with fracture risk (HR 1.102(0.326,3.726), 0.735(0.251,2.148), p > 0.05). Further analysis showed that the use of ACEI (HR 1.078(0.146,7.950)) or ARB (HR 1.169(0.347,3.939)) was not significantly associated with the improvement of osteoporosis (p > 0.05). In addition, the duration of RAAS inhibitors used showed no apparent correlation with the risk of osteoporosis (≤ 3 years: HR 0.872 (0.516, 1.474), > 3 years: HR 1.151 (0.574, 2.308)), nor with the improvement of osteoporosis and the risk of fracture. Meanwhile, the association mentioned above did not change compared to different RAAS inhibitors.ConclusionsThe use of RAAS inhibitors, including ACEIs and ARBs, was not significantly associated with osteoporosis, risk of fracture, or BMD change.

Combined Methylphenidate and Selective Serotonin Reuptake Inhibitors in Adults With Attention-Deficit/Hyperactivity Disorder.

Depression is a common comorbidity of adult attention-deficit/hyperactivity disorder (ADHD), and the combination of methylphenidate and selective serotonin reuptake inhibitors (SSRIs) is a frequently prescribed treatment. However, there is limited clinical evidence on the safety of this medication combination in adults with ADHD. To evaluate the safety of administering a combination of SSRI and methylphenidate in adults with ADHD and comorbid depression. This cohort study obtained data from a nationwide claims database in South Korea from January 2016 to February 2021. Participants were adults aged 18 years or older with a diagnosis of ADHD and depressive disorder who were prescribed methylphenidate. Comparisons of 4 groups who received prescriptions were conducted: (1) SSRI plus methylphenidate (hereafter, SSRI) group vs methylphenidate-only group and (2) methylphenidate plus fluoxetine (hereafter, fluoxetine) group vs methylphenidate plus escitalopram (hereafter, escitalopram) group (compared to find a preferable treatment option). Data analysis was conducted between July and December 2023. New users of the methylphenidate and SSRI combination among adults with both ADHD and depressive disorder. A total of 17 primary and secondary outcomes, including neuropsychiatric and other events, were assessed, with respiratory tract infection used as a control outcome. Groups were matched at a 1:1 ratio using a propensity score to balance confounders. A Cox proportional hazards regression model was used to calculate hazard ratio (HRs) and 95% CIs. Subgroup analysis by sex and sensitivity analyses in varying epidemiologic settings were conducted. The study included 17 234 adults with ADHD (mean [SD] age at study entry, 29.4 [10.8] years; 9079 females [52.7%]). There was no difference in the risk of outcomes between the methylphenidate-only and SSRI groups, except for a lower risk of headache in the SSRI group (HR, 0.50; 95% CI, 0.24-0.99). In sensitivity analyses of fluoxetine vs escitalopram, the risk of hypertension (HR: 1:n matching, 0.26; 95% CI, 0.08-0.67) and hyperlipidemia (HR: 1:n matching, 0.23; 95% CI, 0.04-0.81) was lower in the fluoxetine group than in the escitalopram group. Results of this study revealed no significant increase in adverse event risk associated with use of SSRI plus methylphenidate vs methylphenidate alone in adults with ADHD and comorbid depression. Instead, the combination was associated with a lower risk of headache.

Genetic Susceptibility to Hidradenitis Suppurativa and Predisposition to Cardiometabolic Disease.

Hidradenitis suppurativa (HS) is associated with an increased prevalence of cardiovascular diseases compared with the general population. Any association between polygenic risk for HS, risk of incident cardiometabolic outcomes, and the plasma proteome is unclear. To investigate the genetic correlation between HS and cardiometabolic disease. This cohort study used a polygenic risk score (PRS) for HS to examine the risks of coronary artery disease (CAD) and diabetes and identify changes in the plasma proteome in individuals of European ancestry from the UK Biobank. Participants were enrolled from January 1, 2006, to December 31, 2010. End of follow-up was January 1, 2023. Correlations were assessed between HS susceptibility and cardiometabolic traits using linkage disequilibrium score regression. Odds ratios were assessed in logistic regressions. The risk of incident CAD and diabetes was estimated in cause-specific survival models designed as time-to-event analyses. The PRS for HS. Main outcomes were CAD and diabetes diagnosis measured by logistic regressions and incident disease measured by Cox proportional hazards regression models adjusted for sex, age, body mass index, and smoking status. The study included 391 481 individuals (median [IQR] age, 58 [51-64] years; 209 235 [53%] female). Genetic variants for HS correlated significantly with variants associated with CAD, diabetes, and plasma levels of high-density lipoprotein cholesterol, triglycerides, and C-reactive protein. Compared with the low-risk group, a high PRS for HS (≥75th percentile) conferred odds ratios of 1.09 (95% CI, 1.06-1.12; P < .001) for CAD and 1.13 (95% CI, 1.10-1.17; P < .001) for diabetes. Estimates remained consistent when examining only incident CAD and diabetes. The PRS for HS was significantly associated with altered expression of 58 plasma proteins. Integrating this proteomic profile and the PRS for HS in a machine learning model improved prediction of CAD and diabetes compared with a reference model based on sex, age, and body mass index. These findings suggest that a high genetic risk of HS is associated with increased risk of subsequent CAD and diabetes and altered composition of the plasma proteome. Additional investigation into the identified proteins and their potential roles as drug targets is warranted.

Survival analysis of primary molars following pulpectomy performed under dental general anesthesia: a five-year retrospective study

BackgroundCurrently, the indications for pulpectomy of primary molars performed under dental general anesthesia vary across countries. Therefore, we retrospectively investigated the five-year survival rate of primary molars following pulpectomy performed under dental general anesthesia and the impact of this treatment on permanent successors, assessed the risk factors related to overall survival and clarified the indications for pulpectomy.MethodsThe medical records of children receiving pulpectomy of primary molars under dental general anesthesia from August 1, 2013, to November 30, 2023, were reviewed. Potential risk factors, including gender, age, general health, tooth type, tooth location, endodontic diagnosis and quality of root filling, were assessed via univariate and multivariate Cox proportional hazards regression models, and the survival rate was examined via the Kaplan‒Meier technique. Moreover, the rate of resorption of the root canal filling materials, degree of resorption of the overfilled/over-extended root canal filling materials and development of permanent successors were assessed by clinical and radiographic examination.ResultsThe study included 320 teeth from 161 children (86 boys and 75 girls). The overall five-year survival rate was 38.2%, and the mean overall survival time was 54.2 months. Endodontic diagnosis was considered a significant risk factor (P < 0.05). In the first, second and third years, 57.4%, 81.8%, and 94.8%, respectively, of obturation materials in the root canals were resorbed at a faster rate than the roots. There was an altered eruption direction in 7 permanent teeth, and 4 permanent teeth were diagnosed with enamel hypoplasia.ConclusionsIn this study, the 60-month survival rate of primary molars treated by pulpectomy under dental general anesthesia was 38.32%. Operators should have an accurate assessment of the status of the pulp, have a strict grasp of the preoperative indications and select the appropriate treatment method according to the guidelines. Individual cases suggest overfilling, overextension and periapical periodontitis in primary molars have an impact on enamel hypoplasia and altered eruption direction in permanent teeth.

Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.

Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent. In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression. During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar. Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.

Validation of the Updated "LIfestyle for BRAin health" (LIBRA) Index in the English Longitudinal Study of Ageing and Maastricht Aging Study.

The "LIfestyle for BRAin health" (LIBRA) index was recently updated with three new modifiable factors: hearing impairment, social contact, and sleep (LIBRA2), but has not yet been validated. Comparison of the performance of both LIBRA versions in predicting dementia risk. Longitudinal data from the English Longitudinal Study of Ageing (ELSA) and the Maastricht Aging Study (MAAS) were used. The weighted LIBRA (11/12 factors available) and LIBRA2 (14/15 factors available) scores were calculated, with higher scores representing an unhealthier lifestyle. Dementia diagnoses were based on self- or informant reported physician diagnosis, an informant-based cognitive screening tool, registry data or test data. Cox-proportional hazards regression was used to investigate the association between LIBRA(2) scores and dementia risk. Model fit and predictive accuracy were determined using the Akaike information criterion and Harrell's C index. Over an average follow-up of 8.3 years in ELSA and 17.9 years in MAAS, 346 (4.6%) and 120 (8.5%) individuals developed dementia, respectively. In ELSA, a one-point increase in LIBRA2 was associated with an 8% (1.06-1.11) higher dementia risk (LIBRA: 13%, 1.09-1.16). In MAAS, a one-point increase in LIBRA2 was associated with a 6% (1.01-1.12) higher dementia risk (LIBRA: 8%, 0.99-1.16). In ELSA, LIBRA (Harrell's C = 0.68) and LIBRA2 (Harrell's C = 0.67) performed similarly. In MAAS, LIBRA2 (Harrell's C = 0.62) performed better compared to LIBRA (Harrell's C = 0.52). LIBRA2 is a better model for identifying individuals at increased dementia risk and for public health initiatives aimed at dementia risk reduction.

Risk for Suicide Attempts Assessed Using the Patient Health Questionnaire–9 Modified for Teens

Suicide is a leading cause of death in US youths. To assess whether screening with supplemental items 10 to 13 on the Patient Health Questionnaire-9 modified for teens (PHQ-9M) improves prediction of youth suicide attempts beyond the information provided by the first 9 items alone (the PHQ-9). This retrospective cohort study used a retrospective cohort of adolescents aged 12 to 17 years who were screened for depression in outpatient facilities within a pediatric health care system between January 1, 2016, and December 31, 2022, with up to 1 year of follow-up to assess the occurrence of suicidal behavior. Follow-up was completed on December 31, 2023. Screening with the PHQ-9M. This study developed and compared prediction using 3 Cox proportional hazards regression models (CR-9, CR-13, and CR-3) of subsequent suicide attempts, determined by the hospital's electronic health records up to 1 year following the last PHQ-9M screening. The CR-9 model used the PHQ-9 and the CR-13 model used all 13 items of PHQ-9M. The CR-3 model used the 3 most impactful variables selected from the 13 PHQ-9M items and PHQ-9 total score. All models were evaluated across 4 prediction horizons (30, 90, 180, and 365 days) following PHQ-9M screenings. Evaluation metrics were the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPRC). Of 130 028 outpatients (65 520 [50.4%] male) with 272 402 PHQ-9M screenings, 549 (0.4%) had subsequent suicide attempts within 1 year following the PHQ-9M screening. The AUROC of the CR-9 model in the 365-day horizon was 0.77 (95% CI, 0.75-0.79); of the CR-13 model, 0.80 (95% CI, 0.78-0.82); and of the CR-3 model, 0.79 (95% CI, 0.76-0.81); the AUPRC of the CR-9 model was 0.02 (95% CI, 0.02-0.03); of the CR-13 model, 0.03 (95% CI, 0.02-0.03); and of the CR-3 model, 0.02 (95% CI, 0.02-0.03). The 3 most impactful items using adjusted hazard ratios were supplemental item 13 (lifetime suicide attempts; 3.06 [95% CI, 2.47-3.80]), supplemental item 10 (depressed mood severity in the past year; 2.99 [95% CI, 2.32-3.86]), and supplemental item 12 (serious suicidal ideation in the past month; 1.63 [95% CI, 1.25-2.12]). All of the models achieved higher AUROCs as prediction horizons shortened. In this cohort study of adolescent PHQ-9M screenings, the supplemental items on PHQ-9M screening improved prediction of youth suicide attempts compared with screening using the PHQ-9 across all prediction horizons, suggesting that PHQ-9M screening should be considered during outpatient visits to improve prediction of suicide attempts.

Air Pollution and Breast Cancer Incidence in the Multiethnic Cohort Study.

Recent studies suggested fine particulate matter (PM2.5) exposure increases the risk of breast cancer, but evidence among racially and ethnically diverse populations remains sparse. Among 58,358 California female participants of the Multiethnic Cohort (MEC) Study followed for an average of 19.3 years (1993-2018), we used Cox proportional hazards regression to examine associations of time-varying PM with invasive breast cancer risk (n = 3,524 cases; 70% African American and Latino females), adjusting for sociodemographics and lifestyle factors. Subgroup analyses were conducted for race and ethnicity, hormone receptor status, and breast cancer risk factors. Satellite-based PM2.5 was associated with a statistically significant increased incidence of breast cancer (hazard ratio [HR] per 10 μg/m3, 1.28 [95% CI, 1.08 to 1.51]). We found no evidence of heterogeneity in associations by race and ethnicity and hormone receptor status. Family history of breast cancer showed evidence of heterogeneity in PM2.5-associations (Pheterogeneity = .046). In a meta-analysis of the MEC and 10 other prospective cohorts, breast cancer incidence increased in association with exposure to PM2.5 (HR per 10 μg/m3 increase, 1.05 [95% CI, 1.00 to 1.10]; P = .064). Findings from this large multiethnic cohort with long-term air pollutant exposure and published prospective cohort studies support PM2.5 as a risk factor for breast cancer. As about half of breast cancer cannot be explained by established breast cancer risk factors and incidence is continuing to increase, particularly in low- and middle-income countries, our results highlight that breast cancer prevention should include not only individual-level behavior-centered approaches but also population-wide policies and regulations to curb PM2.5 exposure.

Pre-Transplant Dual-Energy X-ray Absorptiometry (DXA)-Derived Body Composition Measures as Predictors of Treatment Outcomes and Early Post-Transplant Complications in Patients with Multiple Myeloma (MM) Treated with Autologous Hematopoietic Stem Cell Transplantation (AutoHSCT).

Background/Objectives: Changes in muscle mass and bone density are common in multiple myeloma (MM) patients. Dual-energy X-ray absorptiometry (DXA) offers precise, non-invasive insights into a patient's physical condition before autologous stem cell transplantation (autoHSCT). This study examines how pre-transplant body composition impacts treatment outcomes and early complications in MM patients undergoing autoHSCT. Methods: This study is a single-center, retrospective analysis of patients with MM who were treated with first or second autoHSCT and underwent DXA pre-transplant between 11 August 2019 and 12 June 2024. Results: We conducted a study of pre-transplant body composition in 127 patients with MM. Among them, 108 (85%) qualified for first autoHSCT, while 19 (15%) qualified for a second. The median age of the patients was 64 years (range 50-73). In the Cox proportional hazards regression conducted in the group of women, Total Body %Fat was a statistically significant predictor for progression-free survival (PFS) (HR = 0.07, 95% CI = 0.01,0.6, p = 0.0157). In the Mann-Whitney U test conducted on males, Lean Mass/Height2 and Appen. Lean Height2 were statistically significant predictors of early infections after autoHSCT (Z = 1.98, p = 0.0473 and Z = 2.32, p = 0.0204, respectively). In males, Fat Mass/Height2 was a significant predictor of non-infectious toxicity related to treatment (Z = -1.98, p = 0.0476). Conclusions: In women, higher levels of adipose tissue initially appear to exert a protective effect; however, this benefit diminishes over time, with greater fat mass eventually correlating with an increased risk of disease progression. In men, muscle mass has been identified as a significant predictor of early infection risk post-autoHSCT. Furthermore, our findings indicate that an increased amount of adipose tissue in men is statistically associated with a higher risk of non-infectious treatment-related toxicity. These conclusions highlight the critical need for further investigation into the role of body composition.

Non-linear relationship between relative fat mass and diabetes risk in Japanese adults: a retrospective cohort study

Background: Relative fat mass (RFM) represents a newly developed sex-specific anthropometric formula to estimate total body fat percentage. Nonetheless, research examining the correlation between RFM and the risk of diabetes remains scarce. This research assessed the link between RFM and DM risk within the Japanese demographic. Methods: From 2004 to 2015, 15,462 Japanese individuals without diabetes underwent physical evaluations at Murakami Memorial Hospital. The relationship between RFM and the onset of diabetes was analyzed separately using Cox proportional-hazards regression models. This study employed Cox proportional hazards regression incorporating cubic spline functions and smooth curve fitting to detect non-linear associations between RFM and new cases of diabetes, categorized by sex. Sensitivity analyses were performed to confirm the robustness of the link between RFM and incident diabetes. Results: After controlling for confounding factors, a significant positive correlation between RFM and diabetes risk was found in women (HR: 1.13, 95%CI: 1.04–1.24, P = 0.0061), while the association in men was not statistically significant (HR: 1.05, 95%CI: 0.98–1.13, P = 0.1511). Additionally, a non-linear relationship between RFM and the incidence of diabetes was detected in both genders. The RFM threshold was identified at 39.23 for women and 23.08 for men. For women, HR was 1.11 (95%CI: 1.01–1.21) below the threshold and 1.39 (95%CI: 1.17–1.65) above it. In men, an RFM above 23.08 was positively related to diabetes risk (HR: 1.16, 95%CI: 1.06–1.28, P = 0.0012), whereas an RFM below this point did not show a significant association (HR: 0.98, 95%CI: 0.91–1.06, P = 0.5899). Conclusion: Our findings suggest a non-linear relationship and threshold effect between RFM and the risk of diabetes. These findings imply that maintaining RFM at lower levels may be beneficial in mitigating the onset of DM.

The prognostic significance of synchronous metastasis in glioblastoma multiforme patients: a propensity score-matched analysis using SEER data.

Glioblastoma multiforme (GBM) with synchronous metastasis(SM) is a rare occurrence. We extracted the data of GBM patients from the SEER database to look into the incidence of SM in GBM, determine the prognostic significance of SM in GBM, and assess therapeutic options for patients presenting with SM. From 2004 to 2015, information on GBM patients was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The propensity score matching (PSM) method was employed to mitigate confounding factors between SM and non-SM groups, subsequently investigating the prognostic significance of SM in patients with GBM. Multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic variables for GBM patients with SM. A forest plot was used to visualize the results. A cohort of 19,708 patients was obtained from the database, among which 272 (1.4%) had SM at the time of diagnosis. Following PSM at a 3:1 ratio, in both univariate and multivariate cox regression analysis, SM (HR = 1.27, 95% CI: 1.09-1.46) was found to be an independent predictive predictor for GBM patients. Furthermore, the Cox proportional hazard forest plot demonstrated that independent risk variables for GBM patients with SM included age (Old vs. Young, HR = 1.44, 95% CI: 1.11-1.88), surgery (biopsy vs. no surgery, HR = 0.67, 95% CI: 0.46-0.96;Subtotal resection vs. no surgery, HR = 0.47, 95% CI: 0.32-0.68;Gross total resection vs. no surgery, HR = 0.44, 95% CI: 0.31-0.62), radiotherapy (HR = 0.58, 95% CI: 0.41-0.83), and chemotherapy (HR = 0.51, 95% CI: 0.36-0.72). The predictive value of SM in GBM was determined by this propensity-matched analysis using data from the SEER database. Radiotherapy, chemotherapy, and surgery constitute an effective treatment regimen for patients with SM. A more positive approach toward the use of aggressive treatment for GBM patients with SM may be warranted.

Impact of bacterial co-isolation on treatment initiation and long-term prognosis of patients with nontuberculous mycobacterial pulmonary disease: analysis of a prospective cohort study.

Nontuberculous mycobacterial pulmonary disease (NTM-PD), a chronic respiratory condition, presents a growing challenge globally. Uncertainties exist regarding the impact of concurrent bacterial co-isolation on treatment initiation and long-term prognosis. This study analysed data from participants enrolled in an ongoing prospective observational cohort study on NTM-PD (NCT01616745) between 1 July 2011, and 31 December 2022, who provided sputum samples for bacterial culture at enrolment. Identification of potential pathogenic microorganisms (PPMs) was defined as a positive bacterial culture. Clinical characteristics were compared between NTM-PD patients with Pseudomonas, non-pseudomonal PPMs, and those without PPM co-isolation. Cox proportional hazard regression models were employed to assess the association of bacterial co-isolation with rates of NTM-PD treatment initiation and all-cause mortality. Overall, 453 patients (median age, 62 years; 30% male) were included in the analysis. PPMs were co-isolated in 77 patients (17%), including 13 with Pseudomonas species. Co-isolation of Pseudomonas was associated with a significantly higher erythrocyte sedimentation rate (P = 0.02) and St. George's Respiratory Questionnaire score (P = 0.01). Non-pseudomonal PPM co-isolation was significantly associated with a higher likelihood of NTM-PD treatment initiation (adjusted hazards ratio [aHR], 1.56, 95% confidence interval [CI], 1.03-2.36, P = 0.036), whereas co-isolation of Pseudomonas was independently correlated with increased all-cause mortality (aHR, 3.25, 95% CI, 1.08-9.84, P = 0.037). Our findings emphasize the importance of microbial surveillance, as bacterial co-isolation affects treatment initiation and prognosis in patients with NTM-PD.