Multivariate Cox Proportional Hazards Regression Research Articles

Acne Relapse and Isotretinoin Retrial in Patients With Acne

Isotretinoin is the only medical acne treatment capable of inducing acne remission; however, some patients experience acne relapse and require retrials of isotretinoin. There is a need to understand who is most at risk and how daily dose and cumulative dosage can influence outcomes. To assess rates of acne relapse and isotretinoin retrial and to identify associated factors among patients with acne who received an isotretinoin treatment course. This cohort study used data from the MarketScan commercial claims database from January 1, 2017, to December 31, 2020, to identify patients with acne who were 12 years or older and had received isotretinoin for 4 months or longer, with at least 1 year of continuous enrollment after completion of isotretinoin. Data analyses were performed from June 30, 2024, to August 1, 2024. Multivariable Cox proportional hazards regression was used to quantify associations of patient demographic and treatment characteristics with acne relapse and isotretinoin retrial. A total of 19 907 patients (mean [SD] age, 20.6 [7.8] years; 10 504 females [52.8%]) were included, among whom 4482 (22.5%) had acne relapse and 1639 (8.2%) had isotretinoin retrial. Female sex (hazard ratio [HR], 1.43; 95% CI, 1.35-1.52) was significantly associated with increased rates of acne relapse, and isotretinoin cumulative dosage (mg/kg) was associated with a decreased rate of acne relapse (HR, 0.996; 95% CI, 0.995-0.997). Furthermore, daily dose was not associated with decreased risk of acne relapse or isotretinoin retrial among those with conventional and high cumulative dosages. Female sex (HR, 0.68; 95% CI, 0.62-0.76) and isotretinoin cumulative dosage (HR, 0.99; 95% CI, 0.98-0.99) were associated with decreased rates of isotretinoin retrial. Stratification by cumulative dosage indicated that higher cumulative dosage was associated with decreased rates of retrial among patients with low (<120 mg/kg) and conventional (120-220 mg/kg), but not high (>220 mg/kg) cumulative dosage. Maximum daily dose (mg/kg/d) was not negatively associated with acne relapse or isotretinoin retrial in patients with cumulative dosage of 120 mg/kg or more. The findings of this cohort study suggest that higher cumulative dosage may potentially reduce risk of acne relapse and isotretinoin retrial. Furthermore, daily dose was not associated with decreased risk of the outcomes for conventional and high cumulative dosage; therefore, daily dosing could be individualized to patient goals and preferences.

Return to work of major trauma survivors from a private level 1 trauma centre in South Africa

PurposeTrauma is known as a leading cause of mortality and injury related disability globally. In South Africa (SA) the socioeconomic burden of trauma is magnified as the working age is most affected. The aim of this study was to describe the proportion of major trauma survivors who returned to work (RTW) during a 6-month period post hospital discharge and to identify the factors associated with the RTW outcome.MethodsThis was a prospective observational cohort study involving major trauma survivors from a private level 1 trauma centre intensive care unit in SA between January and September 2022. RTW status was assessed using the Employment Questionnaire. Univariate and multivariable Cox proportional hazards regression was used in analysis.ResultsSixty-four of the 86 participants (74.4%) RTW at six months post hospital discharge. RTW had a median time of 16 weeks. After adjusting and backwards analysis, Chelsea Critical Care Physical assessment tool scores (adjusted hazard ratio (AHR), 1.06, 95% CI 1.01–1.10, p = 0.007), and not having applied/received any form of grants (AHR 2.26, 95% CI 1.35–3.77, p = 0.002) were the only factors that were associated with the RTW outcome.ConclusionThe cumulative probability of no RTW was 25.6% among participants after 24 weeks. Higher physical function at ICU discharge and not seeking any form of compensation was associated with a higher probability of RTW. This study has highlighted the complexities of RTW and the socioeconomic burden following major trauma. There is therefore a need for further studies on RTW following major trauma in SA.

Diabetes and Untoward Outcomes after ACL Reconstruction

Background Diabetes affects approximately 536.6 million adults worldwide and 32.2 million in the United States. Prior studies across multiple specialties have reported the presence of diabetes is associated with adverse outcomes following surgical operations. While several studies have identified diabetes as a risk factor for adverse outcomes following ACL reconstruction (ACLR), literature evaluating the relationship between diabetes status and outcomes after ACLR is lacking. Purpose We aimed to study surgical outcomes following primary ACLR among patients with diabetes compared to those without diabetes. Study Design Retrospective Cohort Study Methods We conducted a cohort study using data from an integrated healthcare system’s ACLR registry. Patients aged ≥12 receiving a primary unilateral ACLR were included (2005–2020). Preoperative diabetes status was the exposure of interest. The two primary outcomes were revision surgery and ipsilateral reoperation following primary ACLR, modeled using multivariable Cox proportional hazards regression that followed patients until an adverse event or loss to follow up. We also examined hospital readmission within 90 days post-surgery, modeled using logistic regression. All models compared patients with diabetes to those without diabetes, adjusting for age, gender, race, smoking status, body mass index, American Society of Anesthesiologist’s score, comorbid conditions, education level, income level, exercise, and graft type. Results There were 18,797 primary ACLR in the study sample with 383 (2.0%) occurring in patients with diabetes. The diabetes group exercised about 90 minutes less per week than the non-diabetes group. In unadjusted bivariate descriptive analyses, patients with diabetes had a lower rate of revision surgery (1.6% vs. 3.6%, p = 0.037) but a higher rate of ipsilateral reoperation (10.7% vs. 8.0%, p = 0.051). The 90-day readmission rate was higher among patients with diabetes compared to those without diabetes (1.8% vs. 0.7%, p = 0.016). However, after adjusting for covariates, these associations were no longer statistically significant. Conclusion After controlling for patient characteristics and other risk factors, the presence of diabetes was not associated with a higher risk of adverse events following primary ACLR.

Low-Demand Cemented Femoral Stem Designs and Revision Risk Following the Hemiarthroplasty Treatment of Geriatric Hip Fracture.

Cemented fixation is recommended in the hemiarthroplasty treatment of geriatric femoral neck fractures. Certain cemented stems have similarly designed "low-demand" counterparts, but it is unclear whether they yield comparable clinical outcomes. The purpose of this study was to evaluate the revision risk associated with two low-demand stems, Summit Basic (DePuy Synthes) and Versys LD/Fx (Zimmer Biomet), in comparison to their standard counterparts, Summit (DePuy Synthes) and Versys Advocate (Zimmer Biomet). Using our U.S. integrated healthcare system's Hip Fracture Registry, we identified patients aged ≥60 years who were treated with one of these four cemented hemiarthroplasty devices (2009-2022). Low-demand stems were compared with standard stems on the basis of aseptic revision rates (primary outcome measure) as well as periprosthetic fracture and 90-day complications (secondary outcome measures). Multivariable Cox proportional hazards regression was used to adjust for potential confounders. Overall, there were 9,828 cemented hemiarthroplasties (69.0% female, 78.9% White), including 3,713 low-demand stems and 6,115 standard stems. In the adjusted analysis, low-demand stems were associated with a higher risk of aseptic revision compared with standard designs (hazard ratio [HR] 1.53, 95%CI 1.06-2.22, P = 0.024). This difference was driven primarily by a higher risk of periprosthetic fracture in the low-demand stems (HR 3.40, 95%CI 1.54-7.51, P = 0.003). Similar findings were observed when separately comparing Summit Basic with Summit and Versys LD/Fx to Versys Advocate, and when restricting to procedures performed by experienced total hip arthroplasty surgeons. In this study of 9,828 hip fracture patients treated with cemented hemiarthroplasty, low-demand stems were associated with a higher risk of aseptic revision as compared with their standard counterparts. Further research is required to determine the features of the low-demand stems which could be contributing to this finding, as well as the circumstances under which usage of low-demand stems could still be justified based on cost.

Comparison of BCG Tokyo172 Strain Induction Therapy Between Low Dose and Standard Dose for Non-Muscle Invasive Bladder Cancer: Intravesical Instillation of BCG Tokyo172 Strain.

The aim of this study was to identify factors that predict recurrence by comparing low-dose and standard-dose Bacillus Calmette-Guérin (BCG) induction therapy in patients with non-muscle invasive bladder cancer (NMIBC). A total of 273 consecutive NMIBC patients who received low-dose (40 mg) or standard-dose (80 mg) BCG intravesical instillation therapy between January 2004 and December 2023 were analyzed. Recurrence-free survival (RFS) rates were assessed using the Kaplan-Meier method with the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors of recurrence based on the Club Urológico Español de Tratamiento Oncológico (CUETO) criteria. The log-rank test showed that older age, low BCG dose, number of tumors, and a history of recurrence increased the risk of recurrence significantly. Regarding older patients, recurrence rates were similar between the two dose groups. However, younger patients had significantly lower recurrence rates with standard-dose BCG compared to low-dose BCG. Multiple Cox regression analysis confirmed that older age, low-dose BCG, greater than three tumors, and a history of recurrence were significant predictors of recurrence. In this study, we found that low-dose BCG induction therapy was associated with higher relapse rates compared with standard doses, especially in younger patients. Age-related differences in the immune response to BCG may influence these relapse patterns.

Proteomics-based aging clocks in midlife and late-life and risk of dementia.

Background: Biological age can be quantified by composite proteomic scores, called aging clocks. We investigated whether biological age acceleration (a discrepancy between chronological and biological age) in midlife and late-life is associated with cognitive function and risk of dementia. Methods: We used two population-based cohort studies: Atherosclerosis Risk in Communities (ARIC) Study and Multi-Ethnic Study of Atherosclerosis (MESA). Proteomics-based aging clocks (PACs) were created in ARIC at midlife (mean age: 58 years, n=11,758) and late-life (mean age: 77 years, n=4,934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third of participants. Age acceleration (AA) was calculated as residuals after regressing PACs on chronological age. We validated the midlife PAC in the MESA cohort (mean age: 62 years, n=5,829). We used multivariable linear and Cox proportional hazards regression to assess the association of AA with cognitive function and dementia incidence, respectively. Results: In ARIC, every five years AA was associated with lower global cognitive function: difference: -0.11, 95% confidence interval (CI): -0.16, -0.06) using midlife AA and difference: -0.17, CI: -0.23, -0.12 using late-life AA. Consistently, midlife AA was associated with higher risk of dementia (hazard ratio [HR]: 1.20 [CI: 1.04, 1.36]) and more prominently when using late-life AA (HR: 2.14 [CI:1.67, 2.73]). Similar findings were observed in the MESA study: every five years AA was associated with lower global cognitive function (difference: -0.08 [CI: -0.14, -0.03]) and higher risk of dementia (HR:1.23 [CI: 1.04, 1.46]). Conclusion: Accelerated biological age - as defined by the plasma proteome - is associated with lower cognitive function and predicts a higher risk of dementia in midlife and more prominently in late-life.

Association Between Chewing Capacity and Mortality Risk: The Role of Diet and Ageing.

Masticatory dysfunction due to tooth loss is a potentially modifiable risk for mortality, but the pathway behind that remains to be investigated. This prospective study aimed to examine the role of diet and ageing in the associations between chewing capacity and long-term mortality. Data were obtained from participants (aged ≥ 20) in the National Health Nutritional and Health Survey (NHANES 1999-2010, n = 22,900). The mortality follow-up ended on 31 December 2019. Chewing capacity was determined by the number of functional tooth units (FTUs). Diet information in NHANES was collected using a 24-h-recall questionnaire, and diet quality was measured by three index-based dietary patterns, namely the nutrition index (NI), energy-adjusted dietary inflammatory index (E-DII) and healthy eating index-2015 (HEI-2015). The biological ageing process was reflected using phenotypic age acceleration (PhenoAgeAccel) and frailty index. Mediation analyses were conducted to assess the role of diet quality in the association between FTUs and ageing, as well as the role of ageing in the association between impaired chewing capacity (ICC) and mortality. Participants with more FTUs were found to have a slower biological ageing process. Diet quality scores were estimated to mediate 9.0%-23.0% of the association between chewing capacity and biological ageing. Multivariable Cox proportional hazards regression models found a positive association between ICC and all-cause mortality (hazard ratio = 1.282 [95% confidence interval: 1.189-1.382]). Also, ICC was significantly associated with a 28.9% higher risk of mortality due to cardiovascular disease (CVD) and a 32.7% higher risk of mortality due to cancer. Mediation analyses indicated that PhenoAgeAccel mediated the effect of ICC on all-cause, CVD and cancer mortality with proportions of 18.1%, 17.3% and 12.5%, respectively. Similar mediating proportions were observed in the frailty index (range: 11.6%-23.5%). ICC was associated with poorer diet quality and accelerated ageing, resulting in higher mortality risk. Therefore, it is plausible that dietary interventions and oral rehabilitation would promote healthy longevity, although further investigations are needed.

Long-term mortality outcomes among immunotherapy recipients treated with dupilumab for the management of cutaneous immune-related adverse events.

Dupilumab has been added to National Cancer Comprehensive Network (NCCN) guidelines as a therapeutic strategy for managing certain cutaneous immune-related adverse events (cirAEs) from immune checkpoint inhibitor (ICI) therapy. However, little is known about the implications of dupilumab for cancer outcomes in this population. In this multi-institutional study, we evaluate the impact of dupilumab treatment on survival among ICI recipients. We conducted a muti-institutional retrospective cohort study of ICI recipients from the Mass General Brigham Healthcare System and Dana-Farber Cancer Institute. The dupilumab group was compared to two control groups who did not receive dupilumab: with and without cirAEs (control groups 1 and 2, respectively) that were 1:2 matched on sex, race, age at ICI initiation, Charlson Comorbidity Score, year of ICI initiation, and ICI type. Manual chart review was performed to obtain cirAE characteristics, systemic glucocorticoid use, dupilumab treatment, vital status, and last contact date. Time-varying multivariable Cox proportional hazards regressions were used to evaluate the impact of dupilumab on overall survival, adjusted for sex, race, age at ICI initiation, ICI type, Charlson Comorbidity Index score, cancer type, cancer stage at ICI initiation, and systemic glucocorticoid use. A total of 53 cirAE patients treated with dupilumab were compared to two control groups of 106 patients each. Most patients receiving dupilumab demonstrated either complete or partial resolution of their cirAE (88.7%). In multivariable modeling, the overall survival of the dupilumab group was not significantly different from control group 1 (HR=0.74, 95% CI:0.35-1.60, p=0.5) or control group 2 (HR=0.70, 95% CI:0.32-1.51, p=0.4). However, the use of systemic glucocorticoids within two years after ICI initiation was associated with poorer overall survival when comparing the dupilumab group to control group 1 (HR=2.03, 95% CI:1.04-3.96, p=0.039) and control group 2 (HR=2.21, 95% CI:1.25-3.91, p=0.006). This study suggests that dupilumab is an effective therapeutic option for recalcitrant cirAEs and does not adversely impact mortality. Due to the observed detrimental effects of systemic glucocorticoid therapy, this study supports the need to shift away from systemic glucocorticoid immunosuppression and towards targeted immune modulators for irAE management that are less detrimental to ICI response. Current guidelines recommend the use of dupilumab in the treatment of certain moderate to severe cutaneous immune related adverse events (cirAE) and systemic glucocorticoids for others. Previous studies have shown dupilumab to be effective for steroid refractory cirAEs; 1 however, the impact dupilumab on survival outcomes among recipients of immune checkpoint inhibitor therapy (ICI) remains under studied. This study concludes that dupilumab is an effective modality to treat cirAEs, with 88.7% of patients responding to treatment. Additionally, this study demonstrates a 206-day average delay from cirAE onset to dupilumab treatment suggesting the need for more timely consideration of this therapeutic option. Finally, our results demonstrated that dupilumab does not increase mortality among ICI recipients. The results of this study suggest that use of dupilumab in the treatment of cirAEs is effective and does not adversely impact mortality in the cancer population. Based on these findings, clinicians should consider dupilumab treatment for cirAEs in the appropriate clinical setting. Moreover, this study provides further evidence for the use of targeted immune modulators as preferred over more commonly utilized broad-based glucocorticoid immunosuppression for the management of immune related adverse events in the setting of ICI therapy.

Sugar-sweetened or artificially sweetened beverage consumption, physical activity and risk of type 2 diabetes in US adults.

A positive association between sugar-sweetened beverages (SSBs) and diabetes risk has been shown, with inconsistent evidence between artificially sweetened beverages (ASBs) and diabetes. Moreover, it is uncertain if physical activity can mitigate the negative effects of these beverages on diabetes development. Therefore, we aimed to evaluate the independent and joint associations between SSB or ASB consumption and physical activity on the risk of type 2 diabetes. We followed 64,029 women in the Nurses' Health Study (1980-2016), 88,340 women in the Nurses' Health Study II (1991-2017) and 39,436 men in the Health Professionals Follow-up Study (1986-2016). SSB and ASB consumption was calculated from food-frequency questionnaires administered every 4 years, while physical activity data were collected biennially. A validated supplementary questionnaire on diabetes symptoms, diagnostic tests and treatment confirmed type 2 diabetes cases. Multivariable Cox proportional hazards regression models were used to calculate HRs and 95% CIs for developing type 2 diabetes. During 5,105,351 person-years of follow-up, we recorded 19,940 new cases of type 2 diabetes. Compared with those who never or rarely consumed SSBs or ASBs, those who consumed ≥2 servings/day had a 41% (HR 1.41 [95% CI 1.33, 1.50]) and 11% (HR 1.11 [95% CI 1.07, 1.16]) higher risk of type 2 diabetes, respectively. For participants meeting physical activity guidelines (≥7.5 metabolic equivalent of task [MET] h/week) and consuming ≥2 servings/week of SSBs or ASBs, the risk was 22% (HR 1.22 [95% CI 1.15, 1.29]) and 7% (HR 1.07 [95% CI 1.02, 1.12]) higher, respectively, compared with those who met physical activity guidelines and never or rarely (<1 serving/month) consumed these beverages. For participants meeting the physical activity guidelines and consuming 1-4 servings/month of SSBs, there was a 9% (HR 1.09 [95% CI 1.02, 1.15]) higher risk of type 2 diabetes. Compared with the reference group (those who met physical activity guidelines and consumed <1 SSB serving/month), adults who did not meet physical activity guidelines (<7.5 MET h/week) and who never or rarely (<1 serving/month) consumed SSBs, had 1-4 SSB servings/month, or had ≥2 SSB servings/week, the HRs (95% CIs) were 1.22 (1.13, 1.31), 1.28 (1.20, 1.37), and 1.51 (1.43, 1.61), respectively. Similarly, for ASB consumption, adults who did not meet physical activity guidelines and who never or rarely (<1 serving/month) consumed ASBs, had 1-4 servings/month, or had ≥2 servings/week, the HRs (95% CIs) were 1.21 (1.14, 1.28), 1.21 (1.13, 1.30), and 1.30 (1.23, 1.37) compared with the reference group (who met physical activity guidelines and consumed <1 ASB serving/month). Even when individuals were physically active, a higher consumption of SSBs or ASBs was associated with a higher risk of type 2 diabetes. Meeting physical activity guidelines reduced the impact of SSB and ASB consumption on diabetes risk, underscoring the need to promote physical activity as part of lifestyle modifications to lower diabetes incidence.

Quadrant, necrosis, and infection criteria for the risk stratification of walled-off necrosis: external validation using multi-institutional data.

Endoscopic ultrasound-guided peripancreatic fluid drainage (EUS-PFD) with on-demand endoscopic necrosectomy, increasingly utilized to manage walled-off necrosis (WON), is associated with substantial morbidity and mortality. This multicenter study aimed to externally validate recently developed quadrant (an abdominal quadrant distribution), necrosis, and infection (QNI) criteria for risk stratification in this setting. Of 423 patients with pancreatic fluid collections treated in a large multi-institutional cohort between 2010 and 2020, 212 with available preprocedural computed tomography images were included. Clinical outcomes between high- and low-risk groups defined according to QNI criteria were compared. The clinical success rate did not differ significantly between the QNI-high and QNI-low groups (74.4% vs. 83.5%, respectively; P = 0.12). Time to clinical success was longer in the QNI-high group compared with the QNI-low group (median, 68 vs. 46 days, respectively; P = 0.0016). Compared with the QNI-low group, the QNI-high group was associated with higher rates of percutaneous interventions, direct endoscopic necrosectomy, mortality, and adverse events. The QNI-high group was independently associated with time to clinical success (hazard ratio 0.64, 95% confidence interval 0.46-0.87; P =0.005) in multivariable Cox proportional hazards regression analysis, and with the risk of ≥grade III adverse events (odds ratio 2.93, 95% confidence interval 1.04-8.20; P = 0.04) in multivariable logistic regression analysis. The QNI criteria effectively stratified time to clinical success and the risk of adverse outcomes for patients receiving EUS-PFD of WON. Further investigations could elucidate appropriate management strategies based on QNI-based risk stratification.

Association between HALP (hemoglobin, albumin, lymphocyte, and platelet) score and poor outcomes in acute ischemic stroke patients with type 2 diabetes mellitus: a study from the Third China National Stroke Registry.

The combined index (HALP) of hemoglobin, albumin, lymphocytes, and platelets is considered a novel scoring system that reflects systemic inflammation and nutritional status. This study aimed to investigate the relationship between HALP scores and poor outcomes in acute ischemic stroke (AIS) patients with type 2 diabetes mellitus (DM). Patients with AIS and type 2 DM were screened from the Third China National Stroke Registry (CNSR-III) and divided into quartiles based on their HALP scores at admission. Clinical outcomes were adverse functional outcomes (modified Rankin scale [mRS] score of 3-6 or 2-6) and all-cause mortality at 3 months and 1 year. The association of HALP with the risk of poor functional outcome and all-cause mortality were analyzed by multivariable logistic regression and Cox proportional hazards regression. A total of 3,603 patients were included in this study. After adjusting for confounders, it was found that patients in the highest HALP score quartile had lower mRS scores of 2-6 (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.51-0.80) and 3-6 (OR, 0.53; 95% CI, 0.51-0.82) at the 3-month follow-up. At the 1-year follow-up, a significant correlation was observed between HALP scores and mRS scores of 2-6 (OR, 0.65; 95%CI, 0.57-0.81) and 3-6 (OR, 0.64; 95%CI, 0.47-0.86). Additionally, the highest HALP score quartile was associated with a reduced risk of all-cause mortality at the 3-month follow-up (hazard ratio [HR], 0.35; 95%CI, 0.13-0.93). Similar results were observed at the 1-year follow-up (HR, 0.34; 95%CI, 0.18-0.63). At 3 months of AIS patients with type 2 diabetes and 1-year follow-up, lower HALP scores were associated with poorer functional outcomes and all-cause mortality.

Composite dietary antioxidant index is inversely and nonlinearly associated with cardiovascular disease, atherosclerotic cardiovascular disease, and cardiovascular mortality in people with dyslipidemia: evidence from NHANES 2001-2018.

Dyslipidemia is a major risk factor for cardiovascular disease (CVD) and atherosclerotic CVD (ASCVD). The composite dietary antioxidant index (CDAI), an emerging measure of combined dietary antioxidant exposure, may provide insights into the relationship between diet and CVD/ASCVD outcomes. We aimed to explore the association between CDAI and the prevalence of CVD/ASCVD, as well as CVD mortality in individuals with dyslipidemia. CDAI was assessed by integrating dietary vitamins A, C, E, zinc, selenium, and carotenoids. Dyslipidemia was diagnosed according to widely established criteria. Data on CVD/ASCVD were obtained through self-reports, while CVD mortality was obtained through prospective matching participant records with the National Death Index database. Multivariate logistic regression analysis and Cox proportional hazards regression analysis were used to explore these associations and to calculate odds ratios [OR], hazard ratios [HR], and 95% confidence intervals [CI], respectively. A total of 23,126 participants with dyslipidemia from NHANES 2001-2018 were included. After adjusting for potential confounders, CDAI was inversely associated with the prevalence of both CVD and ASCVD in dyslipidemia populations (OR and 95% CI 0.979 (0.964, 0.995) and 0.977 (0.961, 0.993), respectively). Similar associations were observed between CDAI and specific types of CVD. CDAI was also inversely associated with CVD mortality in dyslipidemia participants (HR = 0.957, 95% CI = 0.939-0.976, p < 0.0001). Restricted cubic spline and threshold effects analyses indicated that CDAI was nonlinearly associated with CVD/ASCVD, with significant associations occurring only when CDAI≤0; however, the association of CDAI with CVD mortality was observed only when CDAI > -2. Furthermore, age, sex, and drinking were found to modify the association of CDAI with CVD/ASCVD, while body mass index influenced the relationship between CDAI and CVD mortality. CDAI was inversely and nonlinearly associated with both CVD/ASCVD events and CVD mortality in dyslipidemic populations. These findings highlight the potential of antioxidant dietary patterns to alleviate the CVD burden in these populations and underscore the importance of personalized strategies.

Age at Menopause and Development of Type 2 Diabetes in Korea

There is limited evidence regarding the association between age at menopause and incident type 2 diabetes (T2D). To investigate whether age at menopause and premature menopause are associated with T2D incidence in postmenopausal Korean women. This population-based cohort study was conducted among a nationally representative sample from the Korean National Health Insurance Service database of 1 125 378 postmenopausal women without T2D who enrolled in 2009. The median (IQR) follow-up was 8.4 (8.1-8.7) years. Data were analyzed in March 2024. Age at menopause and premature menopause (menopause onset at age <40 years). The primary outcome was incident T2D. Multivariable Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% CIs for incident T2D by age at menopause, adjusting for potential confounders. Of 1 125 378 participants (mean [SD] age at enrollment, 61.2 [8.4] years), 113 864 individuals (10.1%) were diagnosed with T2D at least 1 year after enrollment. Women with menopause onset at ages younger than 40 years (premature menopause; HR, 1.13; 95% CI, 1.08-1.18) and ages 40 to 44 years (HR, 1.03; 95% CI, 1.00-1.06) had increased risk of T2D compared with those with onset at age 50 years or older, with adjustment for sociodemographic, lifestyle, cardiometabolic, psychiatric, and reproductive factors; a younger age at menopause was associated with increased risk of developing T2D (P for trend <.001). Body mass index, depressive disorder, and prediabetes modified the association in subgroup analyses; for example, for individuals with premature menopause vs those with menopause at ages 50 years or older, HRs were 1.54 (95% CI, 1.14-2.06) for a BMI less than 18.5 and 1.14 (95% CI, 1.00-1.30) for a BMI of 30 or greater (P < .001), 1.28 (95% CI, 1.12-1.45) for individuals with depression and 1.11 (95% CI, 1.07-1.16) for those without depression (P = .01), and 1.25 (95% CI, 1.18-1.33) for individuals who were not prediabetic and 1.04 (95% CI, 0.99-1.11) those who were prediabetic (P < .001). In this study, premature and early menopause were associated with a higher risk of T2D, highlighting the need for targeted public health strategies aimed at preventing or delaying T2D among postmenopausal women.

Association Between Running Characteristics and Lower Extremity Musculoskeletal Injuries in United States Military Academy Cadets.

Running-related overuse injuries are common among recreational runners; however, there is currently little prospective research investigating the role of running characteristics on overuse injury development. To investigate the relationship between running characteristics and lower extremity musculoskeletal injury (MSKI). Cohort study; Level of evidence, 2. The study included 827 incoming cadets of the class of 2020 at the United States Military Academy. Before cadet basic training, running spatiotemporal parameters (stride length, ground contact time, and cadence) were recorded for each participant, and foot-strike pattern was analyzed. Demographic data were recorded and analyzed as potential covariates. Lower extremity MSKIs sustained over the 9 weeks of cadet basic training were documented. Kaplan-Meier survival curves were estimated, with time to incident lower extremity MSKI as the primary outcome, by level of the independent predictor variables. Risk factors or potential covariates were carried forward into multivariate Cox proportional hazards regression models. Approximately 18.1% of participants incurred a lower extremity MSKI resulting in ≥3 days of activity limitation during cadet basic training. Univariate analysis indicated that participants with the shortest stride length (<133.0 cm) were 39% more likely to incur any lower extremity MSKI and 45% more likely to incur an overuse MSKI than those with the longest stride length (>158.5 cm), and that participants with the longest ground contact time (>0.42 seconds) were twice as likely to incur any MSKI than those with the shortest contact time (<0.28 seconds). After adjusting for sex, weekly distance running 3 months before cadet basic training, and history of injury, multivariate regression analysis indicated that participants with the longest contact times were significantly more likely to incur overuse lower extremity MSKI than those with the shortest contact times (hazard ratio, 2.15; 95% CI, 1.06-4.37). There was no significant difference in risk of MSKI associated with foot-strike pattern or cadence. Study participants running with the longest ground contact times were 2.15 times more likely to incur an overuse lower extremity MSKI during cadet basic training than those with the shortest contact times. Also, study participants with the shortest stride length were 45% more likely to incur an overuse MSKI than those with the longest stride length.

Incense Use and the Risk of Chronic Limb-Threatening Ischemia Among Middle-Aged and Older Adults in the Singapore Chinese Health Study.

Epidemiologic studies have shown that daily exposure to incense smoke is associated with greater risk of cardiovascular mortality, which suggests that chronic exposure to incense could be linked to atherosclerosis. We studied the association between home incense use and the risk of chronic limb-threatening ischemia (CLTI), the most severe outcome of peripheral arterial disease. We used data from the Singapore Chinese Health Study, which recruited 63,257 Chinese participants 45-74 years old from 1993-1998. Data were collected via in-person interviews conducted at the participants' homes by trained interviewers. Linkage to the nationwide hospital discharge database was used to determine incident cases, defined as participants who underwent revascularization or lower extremity amputation for CLTI. Association between use of incense and risk of CLTI was examined using multivariable Cox proportional hazards regression models, adjusted for demographics and cardiovascular risk factors. In this cohort, 76.9% were current users of incense at recruitment, and 92.6% of those used incense daily at home. During a mean 18.8 years of follow-up, 1,097 participants developed CLTI. Compared to never or former users, current users had a 22% higher risk of CLTI [hazard ratio ; 95% confidence interval (CI): 1.04, 1.43]. The risk was greater with chronicity of use, and the HR was highest and statistically significant in participants who had used incense daily for years [ (95% CI: 1.06, 1.46)]. The results did not differ by sex, history of diabetes, or smoking status. Daily exposure to incense in the home environment for more than 40 years was associated with a greater risk of developing CLTI. https://doi.org/10.1289/EHP14674.

Association between Daily Sesame Consumption and the Risk of Sarcopenia in Elderly Adults: The Tianjin Chronic Low-Grade Systemic Inflammation and Health Cohort Study.

Sarcopenia is an age-related, progressive, and systemic skeletal muscle disorder that can lead to numerous adverse outcomes. Animal studies have shown that sesame can enhance skeletal muscle blood flow and improve physical performance. However, no studies have yet explored the association between sesame consumption and the incidence of sarcopenia in the general population. This study aimed to clarify the association between daily sesame consumption and the risk of sarcopenia in a cohort of Chinese elderly aged 60 y and over. This cohort study was conducted in Tianjin, China, involving 3017 elderly participants (1270 men). Sesame consumption frequency was assessed using a validated self-administered food frequency questionnaire. Sarcopenia was defined according to the consensus of the Asian Working Group for Sarcopenia. Multivariable Cox proportional hazards regression models were used to evaluate the association between daily sesame consumption and the risk of sarcopenia. After adjusting for potential confounders (age, BMI, smoking status, alcohol consumption, physical activity, marital status, educational level, personal history of diseases, depressive state, total energy intake, and dietary patterns), the multivariable hazard ratios and 95% confidence interval for sarcopenia among the elderly with different levels of daily sesame consumption were as follows: almost never consuming sesame (reference value), ≤1 time/wk: 1.06 (0.81, 1.39), and ≥2-3 times/wk: 0.62 (0.46, 0.84), respectively (P values <0.01). This study indicates that daily sesame consumption in the elderly aged 60 y and over is associated with a reduced risk of sarcopenia. Further research is needed to explore the causal mechanisms underlying this association.

Association of blood cadmium and physical activity with mortality: A prospective cohort study.

Physical activity (PA) may be considered an alternative method to ameliorate the elevated mortality risks associated with cadmium exposure. In this prospective cohort study, a total of 20,253 participants (weighted mean age, 47.79 years), including 10,247 men (weighted prevalence: 50.1 %), aged 18 years or older, were selected from the National Health and Nutrition Examination Survey from 2007 to 2018. Multivariable Cox proportional hazards regression models were utilized to evaluate the associations between blood cadmium levels, PA, and the risks of mortality. Restricted cubic spline analyses were employed to investigate the nonlinear relationships between blood cadmium and PA levels and mortality risks. During a median follow-up of 7.6 years, a total of 2002 (9.89 %) all-cause deaths occurred, of which 581 (2.87 %) participants were due to cardiovascular disease (CVD) and 498 (2.46 %) died of cancer. J-shaped associations were observed for blood cadmium with risks of mortality (all Poverall < 0.001; all Pnonlinearity < 0.001). Blood cadmium and PA had multiplicative interactions on mortality risk (all Pinteraction < 0.05). Compared with the subgroup with the lowest quartile of blood cadmium and recommended PA, the combination of the highest quartile of blood cadmium and without recommended PA was associated with the highest risks of all-cause and cancer mortality, followed by those meeting recommended PA but in the highest quartile of blood cadmium (hazard ratios, 2.43; 95 % confidence interval, 1.95-3.02). Achieving recommended PA significantly attenuated the detrimental effects of blood cadmium on all-cause, CVD, and cancer mortality risks.

Survival and Its Predictors Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma in Ethiopia: A 6-Year Follow-Up Study.

To analyze survival and its predictors among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) in Ethiopia. We conducted a retrospective cohort study among patients who received TACE for HCC at MCM Hospital from December 1, 2016, to December 31, 2022. Data were extracted from patients' medical records, and vital status was ascertained from the patients' charts or by phone call to the next of kin. We used Kaplan-Meier estimator to determine survival functions and log-rank test to compare the survival functions in different groups. Predictors of survival were identified using a multivariable Cox proportional hazards regression model as expressed by adjusted hazard ratio (aHR). Of the total 257 patients included in the study, 68.9% were male, with a mean age of 56.5 (±14.06) years, and 86% were diagnosed at the advanced stage of the cancer (Barcelona Clinic Liver Cancer-C). The median overall survival was 12.7 months (95% CI, 10.57 to 14.85), and the overall survival rate at 1 year, 2 years, 3 years, 4 years, 5 years, and 6 years was found to be 58.0% (95% CI, 51.8% to 63.8%), 24.1% (95% CI, 19.1% to 29.6%), 8.2% (95% CI, 5.1% to 11.7%), 7.0% (95% CI, 3.9% to 10.1%), 1.6% (95% CI, 0.4% to 3.1%), and 1.2% (95% CI, 0.1% to 2.7%), respectively. The probability of death was significantly increased by alpha-fetoprotein level <400 ng/mL (aHR, 5.72 [95% CI, 1.52 to 21.51]), albumin level (aHR, 5.03 [95% CI, 1.41 to 18.01]), and bilobar distribution (aHR, 5.67 [95% CI, 1.40 to 23.04]). The findings of the study underscore the need for the expansion of preventive measures and treatment facilities to address the overwhelming burden of HCC in Ethiopia.

Risk and Prognosis of Hepatocellular Carcinoma in Mexican Americans with Type 2 Diabetes Mellitus.

Hepatocellular carcinoma (HCC) disproportionately affects Hispanic persons with higher age-specific incidence and increased mortality rates compared to non-Hispanic Whites. These high rates of incidence and mortality may be explained by the variation in risk factors. Given the high prevalence of type 2 diabetes mellitus (DM) among the Hispanic population, we aimed to assess the risk and prognosis of HCC in Mexican Americans with type 2 DM with consideration of treatment for DM. A case-control study of 241 Mexican American HCC patients and 500healthy controls in Texas was conducted. Multivariable logistic regression analysis was performed to determine the association between type 2 DM and HCC risk while adjusting for other risk factors. Also, a restricted analysis of patients with type 2 DM was conducted to determine the effects of age at onset and duration of DM on HCC risk. Interactions among DM, heavy alcohol consumption, and viral hepatitis infection were examined. Overall survival was examined, and multivariable Cox proportional hazards regression analysis was performed for HCC patients with type 2 DM. The adjusted odds ratio (AOR) for DM was 2.74 (P < 0.01). Compared with patients who had DM for 2-10 years, those who had it for at least 20 years had an AOR of 4.60 (P = 0.04). Metformin use was associated with a reduced risk of death in HCC cases with type 2 DM, with a hazard ratio of 0.72 (P = 0.01) as compared with non-users. Our results demonstrate that type 2 DM was independently associated with increased risk of HCC among Mexican Americans. Metformin use was associated with improved survival among HCC patients with type 2 DM. Type 2 DM significantly increased the risk of HCC alone and in conjunction with other parameters of metabolic syndrome in the Mexican American population after adjusting for other risk factors.

Clinical significance of the estimation of pulmonary-right ventricular uncoupling in patients with transthyretin amyloid cardiomyopathy.

There are few data on the prognostic impact of pulmonary-right ventricular (RV) uncoupling in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Among the 174 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from 2002 to 2021, 143 patients who met the current Japanese guideline and had sufficient information for two-dimensional speckle tracking echocardiography were retrospectively analysed. During a median follow-up of 1209 days, 39 cardiac deaths occurred. Compared with patients in the non-event group, those in the cardiac death group were significantly older (79.3 ± 6.7 vs. 76.4 ± 6.2, respectively; P < 0.05). Additionally, RV global longitudinal strain (RV-GLS)/systolic pulmonary artery pressure (sPAP), an index of pulmonary-RV uncoupling, was significantly lower in patients in the cardiac death group vs. the non-event group [0.29 (0.18-0.35) vs. 0.40 (0.29-0.57), P < 0.01]. Multivariate Cox proportional hazards regression analysis demonstrated that RV-GLS/sPAP was significantly associated with cardiac death after adjusting for tricuspid annular plane systolic excursion/sPAP (P < 0.01), sPAP (P < 0.05), and conventional prognostic factors including age and hospitalization for heart failure (<0.01), laboratory finding including high-sensitivity cardiac troponin T, and B-type natriuretic peptide (P < 0.01). Receiver operating characteristic analysis showed that the area under the curve for RV-GLS/sPAP for cardiac death was 0.72 and that the best cut off value for RV-GLS/sPAP was 0.34 (sensitivity, 76%; specificity, 65%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low vs. high RV-GLS/sPAP (cut-off value 0.34) had a significantly higher probability of cardiac death (P < 0.01). Pulmonary-RV uncoupling has significantly higher prognostic value compared with conventional prognostic factors in ATTRwt-CM.