Hazard Ratio Estimates Research Articles

Overall survival of breast cancer patients in association with ESR1 polymorphism

Breast cancer (BC) is the most common carcinoma in women. Genetic polymorphism in estrogen receptor-α (ESR1) gene is involved in alteration in receptor expression, function and evolving as important determinant of breast cancer susceptibility. The present study aimed to evaluate single nucleotide polymorphism (SNP) in breast carcinoma to find out co-relation with overall survival (OS) of breast carcinoma patients. In present study, overall survival of two hundred breast cancer patients with single nucleotide polymorphism was studied in detail. OS was evaluated by Kaplan-Meier method and then analysed with the log-rank test. The cox regression method was used for analyzing data of survival, hazard ratio estimation and its confidence interval value. The significant association of OS was observed with AG genotype of rs9340799 and rs373404617 (Log-rank χ2 = 18.1658, DF = 2, p = 0.0351; χ2 = 5.7632, DF = 2, p = 0.0560 respectively). The genotypes of ESR1 SNP rs9340799 and rs373404617 were predictive of good outcomes of breast cancer. This study suggests that overall survival studies are helpful in investigating progression or regression of the disease which is required for perfect management of breast carcinoma. Future directions include genetic and proteomic-based approaches for breast carcinoma development and progress.

Self-measured home blood pressure highlights cardiovascular risk in women: the HOMED-BP study.

No studies examined sex differences in relation to the prognostic significance of self-measured home blood pressure (HBP). We compared the predictive power for the risk of cardiovascular events in 1547 women and 1516 men with hypertension using HBP captured at treatment-free baseline and during on-treatment follow-up, based on the Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study. To express the change in risk for the composite cardiovascular endpoint associated with a 1-SD increase in HBP at baseline or on treatment, we derived multivariable-adjusted hazard ratios (HR) based on a Cox regression model. Over a median follow-up of 7.3 years, 100 composite events occurred, including 40 events in women. In women, systolic HBP both at baseline and on-treatment showed significant risk increment (at baseline: HR per 1-SD increment, 1.62; 95% confidence interval [CI], 1.17-2.24. on-treatment: HR, 1.74; 95% CI, 1.32-2.29). However, systolic HBP at baseline did not predict cardiovascular events in men (P = 0.25). On-treatment HBP was significantly associated with cardiovascular risk (P ≤ 0.012) irrespective of sex. Nevertheless, the point estimate of HR for systolic HBP in men (1.33) was less than that in women (1.74), and the interaction of sex with 1 SD-increase in systolic HBP in cardiovascular risk was significant irrespective of baseline (P = 0.039) or follow-up (P = 0.040) measurement when they were mutually adjusted. The increase in cardiovascular risk with the systolic HBP was steeper in women than in men for both baseline and on-treatment. The current findings unveil the importance of the control of systolic HBP, especially in women. Clinical Trial Registration: UMIN Clinical Trial Registry ( http://www.umin.ac.jp/ctr ), Unique identifier: C000000137.

Association between depression and risk of type 2 diabetes and its sociodemographic factors modifications: A prospective cohort study in southwest China.

Depression may be associated with the risk of developing type 2 diabetes. The goal of this study was to explore the association of severe of depression with the risk of type 2 diabetes in adults in Guizhou, China. A 10-year prospective cohort study of 7158 nondiabetes adults aged 18 years or older was conducted in Guizhou, southwest China from 2010 to 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to measure the prevalence of depression. Cox proportional hazard models were used to estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) of depression and incident type 2 diabetes. A quantile regression (QR) analytical approach were applied to evaluate the associations of PHQ-9 score with plasma glucose values. A total of 739 type 2 diabetes cases were identified during a median follow-up of 6.59 years. The HR (95% CI) per 1-SD increase for baseline PHQ-9 score was 1.051 (1.021, 1.082) after multivariable adjustment. Compared with participants without depression, those with mild or more advanced depression had a higher risk of incident type 2 diabetes (HR:1.440 [95% CI, 1.095, 1.894]). Associations between depression with type 2 diabetes were suggested to be even stronger among women or participants aged ≥45 years (p < .05). There are significant positive associations of PHQ-9 score with 2-h oral glucose tolerance test blood glucose levels. Depression significantly increased the risk of incident type 2 diabetes, especially in women, participants aged ≥45 years, Han ethnicity, and urban residents. These findings highlighted the importance and urgency of depression health care.

Higher dietary advanced glycation products intake is associated with increased risk of dementia, independent from genetic predisposition

Dietary advanced glycation end products (AGEs) might exert adverse effects on cognition. The associations between dietary AGEs and long-term risk of dementia are yet to be assessed in large population studies. We aimed to explore whether elevated dietary AGEs intake is associated with increased risk of dementia, and whether this association might be affected by genetic risk. A prospective cohort study, which included a total of 93,830 participants (aged≥ 50 years) free from dementia at baseline of the UK Biobank study (2006-2010) and had at least two 24-h dietary assessments and were followed up until 2021. Dietary AGEs, including Nε-(1-Carboxyethyl)-l-lysine (CEL), Nε-(carboxymethyl) lysine (CML), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated via averaged data from the multiple 24-h food assessments according to the ultra-performance LC-tandem MS based dAGEs database. Incidence of all-cause dementia was ascertained through hospital inpatient and mortality records. Multivariable Cox regression models were utilized to estimate hazards ratios (HRs) and 95% confidence interval (CI) of dementia risk associated with dietary AGEs. During a median follow-up of 11.9 years, 728 participants developed dementia. In multivariable adjusted model, when comparing the highest with the lowest tertile of intake level, HRs (95% CI) of dementia were 1.43 (1.16, 1.76) for total AGEs Z score, 1.53 (1.25, 1.89) for CEL, 1.27 (1.03, 1.56) for CML and 1.24 (1.02, 1.52) for MG-H1 (all P trend<0.01). There was no significant interaction between dietary AGEs intake, genetic risk and APOE ε4 carrier status for dementia. Higher intakes of dietary AGEs including CEL, CML and MG-H1 were associated with a higher risk of dementia, independent from genetic risk, highlighting the significance of dietary AGEs restriction for dementia prevention.

Symptom Clusters in Patients With Advanced Cancer: A Prospective Longitudinal Cohort Study to Examine Their Stability and Prognostic Significance.

This study's purpose was to assess symptom cluster (SC) stability during disease progression and determine their strength of association with survival in patients with advanced cancer . Consecutively eligible patients with advanced cancer not receiving cancer-specific treatment and referred to a Tertiary Palliative Care Clinic were enrolled in a prospective cohort study. At first consultation (D0) and in subsequent consultations at day 15 (D15) and day 30 (D30), patients rated 9 symptoms through the Edmonton Symptom Assessment System scale (0-10) and 10 others using a Likert scale (1-5). Principal components factor analysis with varimax rotation was used to determine SCs at each consultation. Of 318 patients with advanced cancer, 301 met eligibility criteria with a median age of 69 years (range 37-94). Three SCs were identified: neuro-psycho-metabolic (NPM), gastrointestinal, and sleep impairment, with some variations in their constitution over time. Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter median survival was observed continuously for NPM cluster (D0 23 vs. 58 days, P < .001; D15 41 vs. 104 days, P=.004; D30 46 vs. 114 days, P = .002), although the presence of 2 or more SCs on D0 and D15 also had prognostic significance (D0: 21 vs. 45 days, P = .005; D30: 50 vs. 96 days, P = .040). In a multivariable model, NPM cluster (D0 hazard ratio estimate: HR 1.64; 95%CI, 1.17-2.31; P = .005; D15 HR: 2.51; 95%CI, 1.25-5.05; P = .009; D30 HR: 3.9; 95%CI, 1.54-9.86; P = .004) and hospitalization (D0 HR: 2.27; 95%CI, 1.47-3.51; P < .001; D15 HR: 2.43; 95%CI, 1.18-5.01; P = .016; D30 HR: 3.41; 95%CI, 1.35-8.62; P = .009) were independently and significantly associated with worse survival. Three clinically relevant SCs were identified, and their constitution had small variations, maintaining a stable set of nuclear symptoms through disease progression. Presence of the NPM cluster and hospitalization maintained their prognostic value over time.

Expression and prognostic role of STAT5a across cancer types.

Studies examining the role of signal transducer and activator of transcription 5 (STAT5) in various cancers have produced controversial results. To address this controversy, we examined the prognostic role of STAT5a in cancer patients across multiple cancers. Transcription levels of STAT5a between tumors and normal tissues, obtained from public databases, were analyzed for statistical differences using Cox regression analysis with the outcome as overall survival and covariate of interest as high STAT5a expression. Meta-analysis was then conducted to summarize the hazard ratio estimate from the Cox regression analyses. We found that STAT5a was significantly under-expressed in breast, lung, and ovarian cancers, while STAT5a was significantly overexpressed in lymphoid neoplasm diffuse large B-cell lymphoma, glioblastoma, and glioma. High STAT5a expression was significantly associated with favorable survival in bladder cancer (lnHR = -0.8689 [-1.4087, -0.3292], P-value = 0.0016), breast cancer (lnHR = -0.7805 [-1.1394, -0.4215], P-value < 0.0001) and lung cancer (lnHR = -0.3255 [-0.6427, -0.0083], P-value = 0.0443). After adjusting for clinicopathological factors, high STAT5a expression remained significantly associated with favorable survival in breast cancer (lnHR = -0.6091 [-1.0810, -0.1372], P-value = 0.0114). These results suggest that higher STAT5a expression is associated with favorable overall survival in breast cancer, and therefore might have protective effects, and that STAT5a expression could be a potential prognostic biomarker, especially in breast cancer. However, the prognostic role of STAT5a is dependent on cancer type.

A comparison of revision rates for stemmed and stemless primary anatomic shoulder arthroplasty with all-polyethylene glenoid components: analysis from the Australian Orthopaedic Association National Joint Replacement Registry

We compared the rate of all-cause revision of 2 classes of primary anatomic shoulder arthroplasty, stemmed (stTSA) and stemless (slTSA), undertaken with cemented all-polyethylene glenoid components. A large national arthroplasty registry identified 2 cohort groups for comparison, stTSA and l undertaken for all diagnoses between January 1, 2011, and December 31, 2021. A subanalysis from January 1, 2017, allowed capturing of additional patient demographics including American Society of Anesthesiologists score, body mass index, and glenoid morphology. The cumulative percent revision (CPR) was determined using Kaplan-Meier estimates of survivorship and hazard ratios (HR) from Cox proportional hazard models adjusted for age and gender. Of the 7995 stTSA procedures, the CPR at 9 years was 5.6% (95% confidence interval [CI]: 5.0, 6.4), and for 3156 slTSA procedures, the CPR was 4.4% (95% CI: 3.6, 5.5). There was no significant difference in the rate of revision between the study groups (HR=0.76 [95% CI: 0.51, 1.14], P=.189, adjusted for age, gender, humeral head size, humeral fixation, bearing surface, glenoid design, and mean surgeon volume [MSV]). There was an increased rate of revision for stTSA and slTSA undertaken with humeral head sizes <44 mm (stTSA <44 mm vs. 44-50 mm, HR=1.56 [CI: 1.18, 2.08], P=.001; slTSA <44 mm vs. 44-50 mm, HR=2.08 [CI: 1.32, 3.33], P=.001). MSV as a continuous predictor was not a revision risk to stTSA vs. slTSA, but categorically, a low MSV (<10 stTSA+slTSA cases per annum) was associated with a higher revision rate for stTSA (10-20 cases/yr vs.<10 cases/yr, HR=0.72 [CI: 0.55, 0.95], P=.019) but was not in slTSA. Revision rates were increased for stTSA with non-crosslinked polyethylene (XLPE) glenoids vs. XPLE after 2 years (HR=2.20 [CI: 1.57, 3.08], P<.001) but did not significantly differ for slTSA. Metal/XPLE (humeral/glenoid) bearing surface of stTSA rate of revision was not different from each combination of slTSA bearing surface. Instability/dislocation was a revision risk for slTSA vs. stTSA (HR=1.93 [CI: 1.28, 2.91], P=.001), but from 2017, neither of American Society of Anesthesiologists score, body mass index, and glenoid morphology changed the rate of revision. Revision rates of stTSA and slTSA did not significantly differ and were associated with humeral head size but not patient characteristics. Surgeon inexperience of anatomic shoulder arthroplasty and non-XLPE glenoids were risk factors for stTSA revision but not slTSA. The metal/XLPE stTSA rate of revision was not found to differ significantly from slTSA regardless of polyethylene or humeral head bearing type. Revision for instability/dislocation was more common for slTSA.

Pregnancy Loss and the Risk of Myocardial Infarction, Stroke, and All-Cause Mortality: A Nationwide Partner Comparison Cohort Study.

Background Pregnancy loss has been associated with myocardial infarction, stroke, and all-cause mortality in women through unknown mechanisms. The aim of this study was to examine these associations in women and their male partners. Methods and Results In this register-based cohort study, all people born between 1957 and 1997, residing in Denmark between 1977 and 2017, and with a registered partner of the opposite sex were eligible for inclusion. Male partners through cohabitation, marriage, or paternity constituted the male cohort. Exposure to pregnancy loss was categorized as follows: 0, 1, 2, or ≥3 pregnancy losses. The outcomes of interest were myocardial infarction, stroke, and all-cause mortality. The Cox proportional hazards model estimated hazard ratios (HRs), adjusted for age, calendar year, parity, and parental history of myocardial infarction or stroke. During follow-up, 1 112 507 women experienced 4463 events of myocardial infarction compared with 13 838 events among 1 120 029 male partners. With the no pregnancy loss group as reference, the adjusted HRs of myocardial infarction in the female cohort after 1, 2, and ≥3 pregnancy losses were as follows: 1.1 (95% CI, 1.0-1.2), 1.3 (95% CI, 1.1-1.5), and 1.4 (95% CI, 1.1-1.8), respectively. In the male partner cohort, the corresponding estimates were 1.0 (95% CI, 1.0-1.1), 1.1 (95% CI, 1.0-1.2), and 1.0 (95% CI, 0.8-1.2), respectively. The outcome of stroke showed similar results. Pregnancy loss was not significantly associated with increased mortality in either sex. Conclusions Pregnancy loss or stillbirth was significantly associated with myocardial infarction and stroke in women but not their male partners. Pregnancy loss or stillbirth was not significantly associated with all-cause mortality in women or male partners.

Association Between the Healthy Lifestyle Index and Risk of Multimorbidity in the Women's Health Initiative.

Multimorbidity, defined as the presence of 2 or more chronic health conditions, is increasingly common among older adults. The combination of lifestyle characteristics such as diet quality, smoking status, alcohol intake, physical activity (PA), sleep duration, and body fat as assessed by body mass index (BMI) or waist circumference, and risk of multimorbidity are not well understood. We investigated the association between the healthy lifestyle index (HLI), generated by combining indicators of diet quality, smoking, alcohol, PA, sleep amount, and BMI, and risk of multimorbidity, a composite outcome that included cardiovascular disease (CVD), diabetes, cancer, and fracture. We studied 62 037 postmenopausal women aged 50-79 years at enrollment in the Women's Health Initiative, with no reported history of CVD, diabetes, cancer, or fracture at baseline. Lifestyle characteristics measured at baseline were categorized and a score (0-4) was assigned to each category. The combined HLI (0-24) was grouped into quintiles, with higher quintiles indicating a healthier lifestyle. Multivariable adjusted estimates of hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of developing multimorbidity were obtained using Cox proportional hazard models. Over an average follow-up period of 16.3 years, 5 656 women developed multimorbidity. There was an inverse association between the HLI levels and risk of multimorbidity (compared to the HLI_1st quintile: HR_2nd quintile = 0.81 95% CI 0.74-0.83, HR_3rd quintile = 0.77 95% CI 0.71-0.83, HR_4th quintile = 0.70 95% CI 0.64-0.76, and HR_5th quintile = 0.60 95% CI 0.54-0.66; p trend < .001). Similar associations were observed after stratification by age or BMI categories. Among postmenopausal women, higher levels of the HLI were associated with a reduced risk of developing multimorbidity.

Parathyroidectomy and the Risk of Major Cerebrovascular and Cardiovascular Events in the Elderly.

We aimed to determine the incidence of major cardiovascular and cerebrovascular events in elderly patients with primary hyperparathyroidism (pHPT) and the impact of parathyroidectomy. pHPT is underdiagnosed and undertreated in the United States. It is associated with increased cardiovascular disease risk, but its association with cerebrovascular disease risk is not well-established. It is also unknown if parathyroidectomy reduces these risks. The incidence of major cerebrovascular and cardiovascular events in 108,869 patients with pHPT diagnosed in the Medicare database between 2008 and 2018 and a matched comparison group of 1,088,690 Medicare subjects was prospectively evaluated. We estimated hazard ratios (HR) for the association of pHPT and parathyroidectomy for the risk of these outcomes from Cox proportional hazards models. Survival curves were calculated to obtain 5-year disease-free survival estimates. For patients with pHPT, five-year disease-free survival was lower, and HRs were higher than the comparison group for any outcome (75.9% vs. 78.4; HR 1.11, 95% confidence interval [CI] 1.09-1.13), major cerebrovascular events (84.5% vs. 86.3%; HR 1.14, 95% CI 1.12-1.17), and major cardiovascular events (87.7% vs. 88.8%; HR 1.06, 95% CI 1.03-1.08). However, in patients who had parathyroidectomy, the risks of major cerebrovascular and cardiovascular events did not differ from the comparison cohort. The lower risk in patients who had parathyroidectomy was maintained in subgroup analyses. Older patients with pHPT have an increased risk of major cerebrovascular and cardiovascular events compared with patients without the disease. Physicians treating older patients with primary hyperparathyroidism should consider parathyroidectomy.R.M.P. and N.N. contributed equally to the preparation of this manuscript.

Clinical Significance of Ascitic Fluid Polymorphonuclear Leukocyte Percentage in Patients With Cirrhosis Without Spontaneous Bacterial Peritonitis.

Absolute polymorphonuclear leukocyte (PMN) count (PMN-C) ≥250 cells/mm 3 in ascites is the diagnostic hallmark of spontaneous bacterial peritonitis (SBP) and is associated with high morbidity and mortality. However, the clinical significance of ascitic PMN percentage (PMN-%) and PMN-C in the absence of SBP as additional biomarkers for mortality and future incidence of SBP has not been determined. This retrospective cohort included adults with cirrhosis undergoing first-recorded paracentesis with initial PMN-C < 250 cells/mm 3 at 2 tertiary medical centers between 2015 and 2020. Patients with prior SBP were excluded. Outcomes were death and SBP development. Cox regression estimated hazard ratios (HRs) for risk of death and SBP development and Akaike information criterion to compare model fit. Three hundred eighty-four adults (73% male, median age 58 years, 67% with alcohol-associated cirrhosis, median PMN-C 14 cells/mm 3 [interquartile range 5-34], and median PMN-% 10% [interquartile range 4-20]) were included in this study. Univariate risk of death increased 10% per 25-unit increase in PMN-C (95% confidence interval 1.01-1.21, P = 0.03) and 19% per 10-unit increase in PMN-% (95% confidence interval 1.06-1.33, P = 0.003) with PMN-% demonstrating better model fit in assessing mortality risk (Akaike information criterion: 1,044 vs 1,048, respectively). In models adjusted for age, chronic hepatitis C virus infection, and Model for End-Stage Liver Disease-Sodium, PMN-% was associated with risk of death (PMN-% 10%-29%, HR 1.17, P = 0.50; PMN-% ≥ 30% group, HR 1.94, P = 0.03; vs PMN-% < 10%) and SBP development (PMN-% 10%-29%, HR 1.68, P = 0.07; PMN-% ≥ 30%, HR 3.48, P < 0.001; vs PMN-% < 10%). Our results suggest PMN-% at first paracentesis represents a better biomarker compared with PMN-C for assessing risk of death and future SBP development in patients with PMN-C < 250 cells/mm 3 .

Paper 56: Dual Plate Fixation of Midshaft Clavicle Fractures May Reduce Reoperation Rates Compared to Single Plating with Anterior or Superior Fixation Techniques

Objectives: Dual plate fixation has been proposed as a solution to the high rates of reoperation secondary to operative management of displaced midshaft clavicle fractures. Previous studies have recommended dual plating for patients specifically at higher risk of reoperation. Therefore, the purpose of this study was to compare reoperation rates among patients who underwent single superior, single anterior, and dual plating while adjusting for risk factors including age, smoking status, and high-risk fracture morphology. We hypothesized lower rates of reoperation among patients who underwent dual plate fixation. Methods: This was a retrospective cohort study of all patients who presented with a midshaft clavicle fracture and underwent ORIF between 2007 and 2021 to our trauma/sports divisions. Patient demographics, fracture pattern, plating technique, postoperative complications, date of surgery, reoperation status, date of last follow up, and date of reoperation were documented. We report hazard ratio (HR) estimates using a multivariate multilevel mixed-effects parametric survival model, which accounted for patients with multiple reoperations and adjusted for covariates. Results: A cohort of 395 patients (mean age 38.5±14.4 years, 81.7% male) were identified with average follow-up of 5.5±8.6 months. There were 77 z-type, 157 transverse, and 161 oblique fractures. With regards to plating technique, 152 underwent single superior plating, 149 experienced single anterior plating, and 94 had dual plating. After initial operation, there were 8 total instances of non-union (2.0%), 0 in the dual plating cohort (0%), 4 in the superior plating cohort (2.6%), and 4 in the anterior plating cohort (2.7%) (p=0.35). A total of 28 reoperations took place among 19 patients (4.8%), with 6 patients experiencing multiple reoperations. Single plating with superior placement revealed the highest reoperation rate of 0.26 per person-years, followed by anterior placement with 0.17 per person-years, and finally dual plating with 0.02 per person-years ( Figure 1). Patients who underwent single plating (either anterior or superior placement) revealed a greater rate of reoperation when compared to patients who underwent dual plating (HR: 8.3, p=0.045). Patients who underwent single plating with superior placement had a rate of reoperation ten- times greater than patients who underwent dual plating (HR:10.1, p=0.03). Patients who underwent single plating with anterior placement had a rate of reoperation six-times greater than patients who underwent dual plating (HR: 6.4, p=0.09), although not statistically significant. Conclusions: Dual plate fixation of displaced midshaft clavicle fractures has an eight-fold lower risk of reoperation compared to single plate fixation, while accounting for age, smoking, and high-risk fracture morphology. More specifically, dual plating had lower rates of reoperation than both single plating with anterior and superior placement. When operative management is indicated for a midshaft clavicle fracture, dual plating may be an excellent treatment alternative in patients at high risk for reoperation.

Preoperative factors influencing the rate and speed of available communication ability in prelingual paediatric cochlear implantation recipients

Background Few studies have assessed factors influencing the rate and speed of good outcomes in cochlear implantation (CI) children. Objective To analyse the factors influencing the rate and speed of available communication in CI children. Material and Methods The study involved 316 children. The categories of auditory performance (CAP) and speech intelligibility rating (SIR) were used to evaluate outcomes. Multivariable proportional Cox regression models were established to analyse the effect of preoperative factors. Results Five variables were entered into the three multivariable models of CAP ≥6, SIR ≥4 and concurrent CAP ≥6 and SIR ≥4. Older age at implantation was a significant poor factor in the three models with estimated hazard ratios (HRs) of .541, .629, and .554, respectively. Another negative factor was poor parental literacy for the three outcomes (HR .639, .638, and .542, respectively). More than 3 months of rehabilitation from institutes had a positive effect on CAP ≥6 and concurrent CAP ≥6 and SIR ≥4 (HR 1.626 and 1.667, respectively). Conclusions and Significance Older age at implantation and poor parental literacy were negative factors. Receiving regular rehabilitation from institutes pre-CI could help the children gain available communication ability earlier on.

The mortality burden of cachexia in patients with non-small cell lung cancer: A meta-analysis.

e24075 Background: Cachexia and weight loss have been linked to poor outcomes in patients with cancer. This study’s aim was to conduct a meta-analysis to estimate the risk of mortality associated with cachexia in patients with non-small cell lung cancer (NSCLC) in studies identified through a systematic literature review (SLR). Methods: A feasibility assessment was undertaken to determine the suitability of conducting a meta-analysis evaluating the impact of cachexia, defined per International Consensus criteria (ICC) or previous weight loss (WL) ≥5% (without specifying a 6-month duration), on overall survival (OS) in patients with NSCLC. The meta-analysis was conducted using a random-effects model, considering variability across studies, and using the identified studies as base case. The impact of heterogeneity was evaluated through sensitivity and subgroup analyses. Standard measures of statistical heterogeneity were calculated for each meta-analysis. Results: Of the 40 NSCLC publications identified in the SLR, 20 (50%) used the ICC definition or reported WL ≥5%. Sixteen studies (80%, n = 6,225 patients, published in 2016 to 2021) met the criteria for inclusion in the meta-analysis: 11 (69%) studies per ICC and 5 (31%) studies per WL ≥5%. Combined criteria (ICC or WL ≥5%) were associated with 82% higher mortality risk versus no cachexia or WL &lt; 5% (pooled hazard ratio [95% CI]: 1.82 [1.47, 2.25]). A subgroup analysis of studies using the ICC definition (hazard ratio [95% CI]: 2.26 [1.80, 2.83]) or WL ≥5% (hazard ratio [95% CI]: 1.28 [1.12, 1.46]) showed consistent findings. Although high statistical heterogeneity (I-square = 88%) was observed across studies, this variability could be disregarded because effect estimates (hazard ratios) from included studies were directionally aligned with considerable overlap in CIs of individual studies. A meta-influence analysis did not identify any potential outliers. Results of the sensitivity and subgroup analyses were consistent with the base case analysis. Cumulative meta-analyses by publication year or data collection midpoint identified no time-varying effect, indicating results were robust to the differing timeframes of publication or data collection. No substantial publication bias, measured via funnel plot analysis, was identified in the meta-analysis. Conclusions: Based on thorough methodologic, clinical, and statistical heterogeneity assessments, the meta-analysis results are robust. ICC-defined cachexia or WL ≥5% were associated with inferior OS in patients with NSCLC. Identifying cachexia or WL ≥5% has important implications for prognosis and treatment of NSCLC.

Trial eligibility criteria (EC) and diversity among patients with advanced non small cell lung cancer (advNSCLC).

1566 Background: FDA guidance encourages using real world data in developing diversity plans for clinical trials. Diversity plans may incorporate more inclusive (or expanded) EC, which may increase enrollment of minoritized populations. Whether broadened EC affect the diversity of eligible participants is unknown. Methods: Using the nationwide Flatiron Health electronic health record-derived deidentified database, we included patients with advNSCLC from 1/1/17-11/30/22 with a line of therapy (LOT) (N=61596). EC were defined by FDA, NCI/CTEP, and ASCO/FoCR standards, and included ECOG, ALT, AST, ALP, bilirubin, eGFR, CrCl, HGB, ANC &amp; PLT -90 to +7 days from first LOT. Claims-linkage identified brain mets (BM), congestive heart failure (CHF), hepatitis C (HCV) &amp; B (HBV), HIV and myocardial infarction (MI) within 6 months of first LOT. Logistic regression estimated odds ratios (OR) for exclusion by criterion associated with gender, age, race/ethnicity and area-level socioeconomic status (SES). Adjusting for clinical characteristics, Cox regression estimated hazard ratios (HR) for real world overall survival (rwOS). Results: Female patients (vs male patients) had greater odds of exclusion by CrCl (OR 2.9), eGFR (OR 1.27) &amp; BM (OR 1.30). Compared to non-Latinx (NL) White patients, NL Black patients had greater odds of exclusion by ECOG (OR 1.17), CrCl (OR 1.33), eGFR (OR 1.61), HGB (OR 2.2), ANC (OR 1.71), HIV (OR 5.31), CHF (OR 1.31), HBV (OR 2.29) and HCV (OR 2.73); NL Asian patients by ALT (OR 1.64), ALP (OR 1.71), CrCl (OR 1.63), BM (OR 1.45) and HBV (OR 26.2); and Latinx patients by ALP (OR 1.56), HIV (OR 2.23) and HCV (OR 1.47). Compared to younger patients (18-49), older patients (75-84) had greater odds of exclusion by ECOG (OR 2.12), bilirubin (OR 1.53), CrCl (OR 41.9), eGFR (OR 9.54), CHF (OR 4.9) and MI (OR 4.7). Patients with the lowest (vs highest) quintile of SES had greater odds of exclusion by ECOG (OR 1.29) and HGB (OR 1.52). Among patients with complete data on all non-claims criteria (N=22117), the impact of expanding EC on diversity is shown, except SES which was similar. Compared to standard EC, the group with expanded EC had lower rwOS (adj HR 1.32; 95% CI 1.28-1.37). Conclusions: Expanding EC has the potential to increase the proportion and absolute number of Black, older, and female patients in advNSCLC trials. The resulting more diverse eligible population may have different clinical outcomes compared to a cohort defined by more restrictive EC. Future work will explore generalizability of findings to other clinical contexts.[Table: see text]

Impact of prior SARS-COV-2 infection and vaccination on COVID-19 hospital admission and mortality amongst nursing home residents.

Nursing home residents (NHRs) have experienced disproportionately high risk of severe outcomes due to COVID-19 infection. We investigated the impact of COVID-19 vaccinations and previous SARS-CoV-2 episodes in preventing hospitalization and mortality in NHRs. Retrospective study of a cohort of all NHRs in our area who were alive at the start of the vaccination campaign. The first three doses of SARS-CoV-2 vaccine and prior COVID-19 infections were registered. The main outcomes were hospital admission and mortality during each follow up. Random effects time-varying Cox models adjusted for age, sex, and comorbidities were fitted to estimate hazard ratios (HRs) according to vaccination status. COVID-19 hospitalization and death rates for unvaccinated NHRs were respectively 2.39 and 1.42 per 10,000 person-days, falling after administration of the second dose (0.37 and 0.34) and rising with the third dose (1.08 and 0.8). Rates were much lower amongst people who had previously had COVID-19. Adjusted HRs indicated a significant decrease in hospital admission amongst those with a two- and three-dose status; those who had had a previous COVID-19 infection had even lower hospital admission rates. Death rates decreased as NHRs received two and three doses, and the probability of death was much lower among those who had previously had the infection. The effectiveness of current vaccines against severe COVID-19 disease in NHRs remains high and SARS-CoV-2 episodes prior to vaccination entail a major reduction in hospitalization and mortality rates. The protection conferred by vaccines appears to decline in the following months. ClinicalTrials.gov Identifier: NCT04463706.

0816 Actigraphy-Measured Sleep Timing and Risk of Breast Cancer in the UK Biobank

Abstract Introduction Shift work leading to circadian disruption is associated with increased breast cancer risk, but it remains unclear whether typical sleep timing variation in the general population that may cause less extreme disruption is also associated with increased risk. Prior studies relied on sleep timing assessed using self-report, but research using actigraphy is limited. Our goal was to characterize the association between sleep timing and breast cancer risk using actigraphy-based measures. Methods Our sample included 43,109 women without a history of breast cancer in the UK Biobank cohort who wore Axivity-AX3 accelerometers over 7 days. We estimated sleep midpoints, the median of sleep onset and waking. Social jetlag was estimated as the absolute difference in average weekend and weekday sleep midpoints. We used multivariable Cox models to estimate hazards ratios (HRs) and 95% confidence intervals (CI), adjusting for age, body mass index, participant characteristics, socioeconomic status, physical activity, menopause, parity, and oral contraceptive use. We conducted a sensitivity analysis excluding shift workers to control for potential strong confounding from shift work. Results Over 6.2 years of follow-up, there were 683 incident breast cancer cases. Earlier and later sleep midpoints were not associated with breast cancer (Early, &amp;lt; 4:00AM HR:1.08 [95%CI: 0.89-1.32]; Later, ≥5:00AM HR:1.24 [0.86-1.81]; vs. Reference 4:00-4:59 AM). Per-hour increases in social jetlag were suggestively associated with greater breast cancer risk (HR:1.09 [0.96-1.24]), but significantly higher risk was only noted at the highest levels of social jetlag comparing ≥2 hours to &amp;lt; 1 hour (HR:1.58 [1.13-2.20]). Results were unchanged when excluding shift workers. Conclusion Higher levels of social jetlag among UK women appeared to be associated with elevated breast cancer risk, possibly due to circadian disruption. While our results suggest that minimizing variation between weekday and weekend sleep timing may be related to lower breast cancer risk, replication of our findings in future studies using actigraphy-based measures and larger case numbers is needed. Support (if any) Supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health.

A retrospective cohort study investigating the comparative effectiveness of pneumococcal vaccines against hospitalisation with otitis media and pneumonia in New Zealand

BackgroundSince 2008 New Zealand has used three different formulations of pneumococcal vaccines on the national infant schedule, PCV7, PCV10 and PCV13, switching between PCV10 and PCV13 twice in 10 years. We have used New Zealand’s linkable, administrative health data to examine the comparative risk of otitis media (OM) and pneumonia hospitalisations among children receiving three different pneumococcal conjugate vaccines (PCV). MethodsThis was a retrospective cohort study using linked administrative data. Outcomes were otitis media, all cause pneumonia and bacterial pneumonia related hospitalisation for children in three cohorts representing periods where PCVs transitioned between PCV7, PCV10, PCV13 and back to PCV10 between 2011 and 2017. Cox’s proportional hazard regression was used to provide hazard ratio estimates to compare outcomes for children vaccinated with different vaccine formulations and to adjust for different sub population characteristics. ResultsEach observation period, where different vaccine formulations coincided, and therefore comparable with respect to age and the environment, included over fifty-thousand infants and children. PCV10 was associated with a reduced risk for OM compared with PCV7 (Adjusted HR 0.89, 95 %CI 0.82–0.97). There were no significant differences between PCV10 and PCV13 in risk of hospitalisation with either otitis media or all-cause pneumonia amongst the transition 2 cohort. In the 18 -month follow-up, after transition 3, PCV13 was associated with a marginally higher risk of all-cause pneumonia and otitis media compared to PCV10. ConclusionThese results should offer reassurance about the equivalence of these pneumococcal vaccines against the broader pneumococcal disease outcomes OM and pneumonia.

Social integration and risk of mortality among African-Americans: the Jackson heart study

ObjectiveEvidence suggests that greater social integration is related to lower mortality rates. However, studies among African-Americans are limited. We examined whether higher social integration was associated with lower mortality in 5306 African-Americans from the Jackson Heart Study, who completed the Berkman-Syme Social Network Index in 2000–2004 and were followed until 2018.MethodsWe estimated hazard ratios (HR) of mortality by categories of the Social Network Index (i.e., high social isolation, moderate social isolation [reference group], moderate social integration, high social integration) using Cox proportional hazard models. Covariates included baseline sociodemographics, depressive symptoms, health conditions, and health behaviors.ResultsCompared with moderate isolation, moderate integration was associated with an 11% lower mortality rate (HR = 0.89, 95% confidence interval [CI] 0.77, 1.03), and high integration was associated with a 25% lower mortality rate (HR = 0.75, 95% CI 0.64, 0.87), controlling for sociodemographics and depressive symptoms; compared with moderate isolation, high isolation was related to a 34% higher mortality rate (HR = 1.34, 95% CI 1.00, 1.79). Further adjustment of potential mediators (health conditions and health behaviors) only slightly attenuated HRs (e.g., HRmoderate integration = 0.90, 95% CI 0.78, 1.05; HRhigh integration = 0.77, 95% CI 0.66, 0.89).ConclusionSocial integration may be a psychosocial health asset with future work needed to identify biobehavioral processes underlying observed associations with mortality among African-Americans.

Clinical manifestations of cancer in patients with acute pulmonary embolism.

Neoplasmatic disease increases the risk of acute pulmonary embolism (APE) by different pathophysiological mechanisms that favor thrombosis in patients with cancer. Recently, the role of cancer (active and occult) in the prevalence of venous thromboembolism has been discussed more thoroughly in the subject literature. Medical records of 366 consecutive patients with a diagnosis of APE (aged: mean = 65.0 ± 16.6, median = 68, range = 19-94; men = 41%/women = 59%) were collected with a wide range of demographic data, medical history of coexisting diseases, computer examination, and laboratory tests. The APE patients were analyzed in two groups: negative cancer cases (83%), i.e. without concomitant active malignancy or a history of cancer, and positive ones (17%), i.e. those hospitalized with concomitant active cancer disease or a history of cancer within the past 5 years. Based on the application of the Student's t -test for independent samples and the χ2 test of independence, a statistically significant difference ( P < 0.05) between cancer (-) and cancer(+) groups of patients was calculated for the following selected risk factors: BMI, smoking status, hemoglobin, hematocrit, red blood cell, urea, glomerular filtration rate, high-sensitivity troponin T, C-reactive protein (CRP), D-dimer, and NT-proBNP. Using univariate Cox regression and a discrete-time hazard model, the estimated hazard ratios and odds ratios, respectively, for the risk of an earlier death from cancer as well as for a secondary APE episode in APE patients with malignancy are more than three times higher than in cancer-free patients and they are statistically significant ( P < 0.05). Moreover, the modeled discrete-time hazard curves show a constant excess risk of death and a secondary APE episode in patients diagnosed with malignancy over the period of observation. Cancer and APE seem to go 'hand in hand'. Attention should be paid to many factors, primarily clinical, differentiating patients with cancer from those with an APE incident. The patients with cancer after a primary APE should receive anticoagulants to prevent a secondary APE episode and to reduce the risk of mortality.