Multivariable Generalized Estimating Equations Research Articles

Prevalence of Hemoplasma spp. positivity in potential feline blood donors and study of the association with selected clinical variables.

Hemotropic mycoplasmas, hemoplasmas, are epi-erythrocytic parasitic bacteria that can be transmitted through blood transfusion. To study the prevalence of hemoplasma infection of potential feline blood donors and investigate the association between Hemoplasma spp. quantitative polymerase chain reaction (qPCR) positivity in blood units and selected variables. Seven thousand five hundred seventy-three blood units from 4121 privately-owned potential donor cats. Retrospective observational cross-sectional study. The Banco Sangue Animal (BSA)-Animal Blood Bank medical database was reviewed for all feline donations performed in 2022 in Portugal, Spain, and Belgium. Baseline characteristics and results of blood-borne pathogens screening tests were extracted from the medical records. Two hundred twelve of 4034 Portuguese donor cats and 2 of 70 Spanish donor cats tested positive for Hemoplasma spp. qPCR in 2022 leading to an overall estimated prevalence of 5.2% (95% CI: 4.5%-5.9%) in potential blood donors. Using multivariable generalized estimation equation models, Hemoplasma spp. qPCR was more often positive among blood units issued from male cats (OR = 1.9, 95% CI: 1.4-2.6, P < .0001), units positive for FeLV (OR = 2.8, 95% CI: 1.4-5.6, P = .0023), and units collected in winter months (OR = 2.5, 95% CI: 1.7-3.6, P < .0001). This study underscores the importance of Hemoplasma spp. and other relevant blood-borne pathogens screening at every donation. Implementing stringent screening protocols is crucial to mitigate the risk of hemoplasma transmission via blood transfusions, thereby safeguarding the health and welfare of cats receiving transfusions.

Nurse Staffing, Work Hours, Mandatory Overtime, and Turnover in Acute Care Hospitals Affect Nurse Job Satisfaction, Intent to Leave, and Burnout: A Cross-Sectional Study.

Objectives: This study examined the impact of nurse staffing, working hours, mandatory overtime, and turnover on nurse outcomes in acute care hospitals. Previous studies have focused on the single characteristics of sub-optimal nurse staffing but have not considered them comprehensively. Methods: Data were collected in July-September 2022 using convenience sampling and an online survey (N = 397). For the analysis, 264 nurses working as staff nurses at 28 hospitals met the inclusion criteria. Univariate analysis and multivariable generalized estimating equation (GEE) were performed. Results: Both nurse staffing (β = -0.036, standard error [SE] = 0.011) and turnover (β = -0.006, SE = 0.003) were significant factors affecting job satisfaction. In the multivariable GEE, only mandatory overtime (β = 0.395, SE = 0.116) was significantly related to intent to leave. Nurse staffing, work hours, mandatory overtime, and turnover were not significantly related to burnout. Subjective health status and workload were significantly associated with burnout. Conclusion: Nurse staffing policies and improvement programs in hospitals should be implemented to improve nurses' job satisfaction. Labor policy should ban mandatory overtime.

Complications during Adolescence Predict Mortality in Young Adults with Childhood Onset Type 1 Diabetes

Objective. Microvascular complications increase the risk of cardiovascular disease and premature death in adults with type 1 diabetes. We examined the association between microvascular complications during adolescence, including cardiac autonomic nerve dysfunction and subsequent mortality. Research Design and Methods. We undertook data linkage with the Australian National Death Index in a cohort of 409 adolescents (diagnosed between 1973 and 1993), 48% male, median age at final complications assessment 17.4 years (interquartile range: 16.0–18.9), followed longitudinally for median 22.3 years (21.0–23.4) from diagnosis. Generalized estimating equations (GEE) were used to examine associations between mortality and adolescent complications. Mortality risk was calculated as standardized mortality ratio (SMR). Results. At final adolescent visit, 20% had CAN abnormality, 30% abnormal pupillary response, 20% albuminuria, 40% early elevation of albumin excretion rate (AER) and 45% retinopathy. Data linkage 8–13 years later showed 14 were deceased (3% of cohort), 57% male, median age 28.3 years (24.8–32.9). Acute or chronic diabetes complications accounted for 25% of deaths. In multivariable GEE, elevated AER (OR 4.54, 1.23–16.80, p=0.030), pupillary abnormality (OR 4.27, 1.20–15.22, p=0.023), systolic blood pressure SDS (OR 2.17, 1.26–3.74, p=0.005) and CAN (OR 4.65, 1.03–21.0, p=0.045) predicted mortality. HbA1c was not significant. SMR was 2.5 (1.4–4.2) and was higher in females (SMR 3.5, 1.3–7.8) but not in males (SMR 2.1, 0.9–4.0). Conclusion. Mortality in young adults with type 1 diabetes is predicted by subclinical markers of autonomic neuropathy and elevated AER during adolescence, but not glycemia. Mortality was over twice that of the background population in females but not in males.

Missed opportunities for treatment of inflammatory arthritis and factors associated with non-treatment: An observational cohort study in United States Veterans with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis

ObjectiveTo identify factors associated with non-treatment with biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs) during the 12 months after initial inflammatory arthritis (IA) diagnosis. MethodsWe identified Veterans with incident IA diagnosed in 2007–2019. We assessed time to treatment with Kaplan-Meier curves. We identified associations between non-treatment and factors relating to patients, providers, and the health system with multivariate Generalized Estimation Equation (GEE) log-Poisson. Subgroup analyses included IA subtypes (rheumatoid arthritis [RA], psoriatic arthritis [PsA], and ankylosing spondylitis [AS]) and timeframes of the initial IA diagnosis (2007–11, 2012–15, and 2016–19). ResultsOf 18,318 study patients, 40.7 % did not receive treatment within 12 months after diagnosis. In all patients, factors associated with non-treatment included Black race (hazard ratio, 95 % confidence interval: 1.13, 1.08–1.19), Hispanic ethnicity (1.14, 1.07–1.22), Charlson Comorbidity Index ≥2, (1.15, 1.11–1.20), and opiate use (1.09, 1.05–1.13). Factors associated with higher frequency of DMARD treatment included married status (0.86, 0.81–0.91); erosion in joint imaging report (HR: 0.86, 0.81–0.91); female diagnosing provider (0.90, CI: 0.85–0.96), gender concordance between patient and provider (0.91, CI: 0.86–0.97), and diagnosing provider specialty of rheumatology (0.53, CI: 0.49–0.56). ConclusionA high proportion of Veterans with IA were not treated with a biologic or non-biologic DMARD within one year after their initial diagnosis. A wide range of factors were associated with non-treatment of IA that may represent missed opportunities for improving the quality of care through early initiation of DMARDs.

The Impact of an Unsanctioned Compassion Club on Non-Fatal Overdose

In 2022, the Drug User Liberation Front opened an unsanctioned compassion club in Vancouver where members could purchase illicit drugs that had been rigorously tested to ensure quality and a lack of potentially fatal contaminants. We sought to evaluate the impact of access to this novel safer supply intervention on non-fatal overdose. Data were obtained from 47 club members via surveys completed at 3-month intervals between August 2022 and October 2023. We conducted multivariable generalized estimating equations (GEE) analyses to examine the association between club enrolment and the outcomes of: (1) any non-fatal overdose; and (2) any non-fatal overdose involving naloxone administration. The final sample, including 47 study participants, contributed a total of 225 observations and 44.4 person-years of follow-up during the study, and a median follow-up duration of 12.2 months (quartile 1 - 3: 10.4 - 14.7) per participant. In multivariable GEE analyses, enrolment in the compassion club was associated with reduced likelihood of non-fatal overdose (Adjusted Odds Ratio [AOR] = 0.51, 95% Confidence Interval (CI): 0.26 - 0.99) and non-fatal overdose involving naloxone administration (AOR = 0.37, 95% CI: 0.16 - 0.84) after adjusting for potential confounders. In this study, enrolment in an unsanctioned compassion club was found to be associated with reductions in any type of non-fatal overdose and non-fatal overdose involving naloxone administration. These findings highlight the need for ongoing research on safer supply interventions, as well as the potential of non-medicalized compassion clubs to complement existing safer supply programming and reduce overdose events.

Effect of nutrition education integrating the health belief model and theory of planned behavior on dietary diversity of pregnant women in Southeast Ethiopia: a cluster randomized controlled trial

BackgroundMaternal anemia, miscarriage, low birth weight (LBW), preterm birth (PTB), intrauterine growth restriction (IUGR), prenatal and infant mortality, morbidity, and the risk of chronic disease later in life are all increased by a lack of dietary diversity during pregnancy. However, evidence for the effect of nutrition education on the dietary diversity score (DDS) among pregnant women was sparse in Ethiopia, particularly in the study areas. This study aimed to assess the effect of nutrition education on dietary diversity among pregnant women in urban settings in Southeast Ethiopia.MethodsA community-based two-arm parallel cluster randomized controlled trial was conducted among 447 randomly selected pregnant women attending antenatal care (224 intervention group and 223 control group) at health facilities from February to December 2021. A multistage cluster sampling technique, followed by systematic sampling, was used to select the pregnant women. Pregnant women who participated in the interventions were given nutrition education starting at 16 weeks of gestation and continuing for 6 months. We used a pre-tested, interviewer-administered, structured questionnaire to collect the data. A 24-hour qualitative dietary recall was used to calculate the dietary diversity score (DDS). A multivariable generalized estimating equation (GEE) model was conducted to evaluate the intervention effect.ResultsAfter the intervention, the proportion of adequate dietary diversity was 14.15% higher in the intervention arm compared to the control group (45.09% versus 30.94%, P = 0.002). The overall difference in adequate dietary diversity between the two groups was 8.5%. After adjusting for background characteristics, the multivariable GEE binary logistic model revealed that having received intervention [(AOR = 1.89, 95% CI: 1.27, 2.79)], being literate [(AOR = 3.41, 95% CI: 1.13, 10.23)], and having high wealth [(AOR = 1.60, 95% CI: 1.09, 2.35)] significantly improved adequate dietary diversity.ConclusionThe findings indicated that having received the intervention, being literate, and having a high level of wealth significantly improved maternal dietary diversity. Efforts should be made to increase nutrition education using the health belief model (HBM) and the theory of planned behavior (TPB). Moreover, there is a need to improve literacy and economic empowerment through income-generating activities to enhance adequate dietary diversification during pregnancy.Trial registrationClinicaltrials.gov (PACTR202201731802989, Retrospectively registered on 24 January 2022).

Higher CD4+ T Cell Counts after CAR-T in Large B-Cell Lymphomas Are Significantly Associated with Better Overall Survival

Introduction Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of large B-cell lymphomas (LBCL), demonstrating remarkable efficacy. However, CAR-T therapy is also associated with significant toxicities, some arising from relative immunologic incompetence after treatment. A key knowledge gap persists regarding how the immune landscape changes post-CAR-T, defined as immune reconstitution (IR), and the influence of IR on patient outcomes. In this study, we set out to describe patterns and determinants of IR following CAR-T as well as impacts of IR on outcomes. Methods Adult patients with primary or transformed LBCL treated with CD19-CAR-T cells, namely axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), between 2017 and 2022 were included in this single center retrospective study. Immune cell levels were measured at various timepoints after CAR-T. Median cell counts and interquartile range (IQR) at pre-specified time windows (using the first available observation) were used to describe temporal IR patterns. Multivariable generalized estimating equation (GEE) models with cubic time variables were used to investigate the association between cell count trajectory and baseline characteristics. A multivariable Cox model with longitudinal cell count as a time-varying covariate was utilized to assess the association between IR and overall survival (OS), adjusted for confounding factors. Kaplan-Meier (KM) curves were generated for visualization. Results A total of 210 patients were included, of whom 153 had at least one CD4+ T cell measurement from time of CAR-T. The median age was 65 (range 20-86) and most were male (65.7%) and diagnosed with diffuse large B-cell lymphoma (79.5%). Axi-cel (49.5%) was the most common product, followed by tisa-cel (28.6%) and liso-cel (21.9%). Lymphodepletion was mostly cyclophosphamide and fludarabine (82.4%). Of the 210 patients, 58.1% achieved a complete response (CR) and 17.1% a partial response by 100 days after CAR-T. Following CAR-T, CD3+ T cells were the most abundant circulating lymphocyte. By 30 days (±15 days) after CAR-T, median (IQR) values of CD3+ T cells, B cells, and NK cells were 445 (162-776), 0 (0-0), and 90 cells/ul (57-146), respectively; by 60 days (±15 days), median (IQR) values were 498 (220-706), 0 (0-0), and 104 cells/ul (69-169), respectively. Proportions of CD4+ and CD8+ T cells remained similar through one year after CAR-T, with CCR7-45RA+ TEMRA and CCR7-45RA- effector memory cells dominating among CD8's, and CCR7-45RA- effector memory cells being the most abundant among CD4's. Regulatory T cells (CD25+CD127-) comprised about 10% of the CD4+ T cell lymphocyte population, with a median (IQR) of 9 cells/ul (4.5-15.5) by day 30 (±15 days) after CAR-T. Finally, receipt of tisa-cel was associated with greater levels of CD4+ EM T cells compared with axi-cel and liso-cel (median [IQR]: 253 [158-406] vs 81 [51-138] and 113 cells/ul [88-154], respectively), by 30 days (±15 days) after CAR-T. According to a multivariable GEE model, patients receiving tisa-cel had significantly higher CD4+ count trajectories compared to those receiving axi-cel or liso-cel ( p&amp;lt;0.001 for both) ( Figure A). In addition, patients with more extensive pre-treatment (i.e., 6+ prior lines) had significantly lower CD4+ count trajectories compared to those who received 2-3 or 4-5 prior lines ( p=0.015 and p=0.004, respectively). A multivariable Cox model, moreover, indicated that a higher CD4+ count (in units of 50 cells/ul) was significantly associated with better OS (adjusted HR: 0.845; 95% CI, 0.745-0.960; p=0.010), adjusted for product and prior lines of therapy. KM curves by patients above or below the median of the last observed CD4+ count further demonstrated this significant association between longitudinal IR and OS ( Figure B). Conclusion In this single-center retrospective study, we extensively characterized the immune environment at time of and following CAR-T. To the best of our knowledge, this is the largest study of its kind. Additionally, we identified several factors that impact IR, which in turn shapes OS. In doing so, we show that CD4+ T lymphocytes are key players in disease response post-CAR-T and suggest that tracking CD4+ recovery following CAR-T may provide both diagnostic and therapeutic benefit.

Oral Candidiasis in Patients with Rheumatoid Arthritis: A Hospital-Based Cohort Study

Background: Rheumatoid (RA) arthritis is a chronic autoimmune disease characterized by symmetric polyarthritis and systemic inflammation. Systemic complications due to RA and its treatment may affect oral health. Objective: To assess the prevalence and predisposing factors for oral candidiasis in Rheumatoid Arthritis patients treated at a rheumatology referral hospital. Methods: This is a longitudinal study of a panel of repeated measures performed on patients attending the Rheumatology and Oral Diagnosis Outpatient Clinic of the General Hospital of Cuiabá. Patients were followed up between 2018 and 2019, with the information recorded in the medical records and subsequently extracted. A generalized estimation equation model was used to assess the association between oral candidiasis and RA. Results: In the final model, in crude (bivariate) analysis, the use of prednisone (OR 8.3) and tocilizumab (OR 3.7) were significantly associated with oral candidiasis. In the multivariate generalized estimation equation model, the use of prednisone (OR 9.9) and the presence of hyposalivation in male patients (OR 1.8) were the variables that remained statistically associated with oral candidiasis. Conclusion: The use of immunosuppressive drugs and the low rate of salivary flow in male patients increase the risk of oral candidiasis in patients with rheumatoid arthritis, reinforcing the importance of stomatological monitoring, a preventive approach and early diagnosis of this pathology.

A cross-sectional study for prevalence and risk factors of peri-implant marginal bone loss

Progressive peri-implant marginal bone loss and peri-implantitis have become a growing problem, but cross-sectional studies on their prevalence and risk factors are sparse. The purpose of this cross-sectional clinical study was to investigate the prevalence of peri-implant marginal bone loss (MBL) and to identify systemic and local risk factors. All adult patients who had received dental implants at the National Taiwan University Hospital (NTUH) during 2009 or 2010 were included. Their medical records were collected from the NTUH-integrative Medical Database. Consecutive follow-up radiographs were accessed for severity of MBL. The influence of each factor on MBL was estimated by using generalized estimating equations (GEEs). A total of 732 participants with 1873 implants were analyzed (mean follow-up: 5.30 years). The prevalence of MBL was 59.15% at the individual level and 49.55% at the implant level. The risk indicators identified for the presence of MBL were follow-up period of more than 2 years, diagnosis of diabetes within 12 months, radiation therapy (2 years after implant placement), implant location at maxillary canine (compared with mandibular molar), and implants from the Nobel Biocare brands (Brånemark System and NobelActive). A second multivariate GEE model confirmed the association of progressive MBL with implant location at the maxillary canine and mandibular incisor and implant brand or design. The identified risk indicators for MBL were longer follow-up period, diagnosis of diabetes, radiation therapy, implant location at maxillary canine, and implant brand or design.

Association between institutional volume of out-of-hospital cardiac arrest cases and short term outcomes

BackgroundOut-of-hospital cardiac arrest (OHCA) is a serious condition. The volume-outcome relationship and various post–cardiac arrest care elements are believed to be associated with improved neurological outcomes. Although previous studies have investigated the volume–outcome relationship, adjusting for post-cardiac arrest care, intra-class correlation for each institution, and other covariates may have been insufficient. ObjectiveTo investigate the volume-outcome relationships and favorable neurological outcomes among OHCA cases in each institution. MethodsWe conducted a prospective observational study of adult patients with non-traumatic OHCA using the OHCA registry in Japan. The primary outcome was 30-day favorable neurological outcomes, and the secondary outcome was 30-day survival. We set the cutoff values to trisect the number of patients as equally as possible and classified institutions into high-, middle-, and low-volume. Generalized estimating equations (GEE) were performed to adjust for covariates and within-hospital clustering.1Department of Emergency Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8606, Japan ResultsAmong the 9909 registry patients, 7857 were included. These patients were transported to either low- (2679), middle- (2657), or high- (2521) volume institutions. The median number of eligible patients per institution in 19 months of study periods was 82 (range, 1–207), 252 (range, 210–353), and 463 (range, 390–701), respectively. After multivariable GEE using the low-volume institution as a reference, no significant difference in odds ratios and 95% confidence intervals were noted for 30-day favorable neurological outcomes for middle volume [1.22 (0.69–2.17)] and high volume [0.80 (0.47–1.37)] institutions. Moreover, there was no significant difference for 30-day survival for middle volume [1.02 (0.51–2.02)] and high volume [1.09 (0.53–2.23)] institutions. ConclusionThe patient volume of each institution was not associated with 30-day favorable neurological outcomes. Although this result needs to be evaluated more comprehensively, there may be no need to set strict requirements for the type of institution when selecting a destination for OHCA cases.

SAT397 A Low Dose Cyproterone Acetate In Feminizing Hormone Treatment

Abstract Disclosure: S. Korpaisarn: None. J. Arunakul: None. K. Chaisuksombat: None. T. Rattananukrom: None. Background: A feminizing hormone therapy (FHT) for transgender women (TW) who have not undergone gonadectomy consists of estrogens and antiandrogens. Cyproterone acetate (CPA) is the most common antiandrogen used in Thailand. A standard dose of CPA is 25-50 mg/day. Recent data showed that a low-dose CPA might be effective in testosterone suppression. However, the result was limited due to the small number of subjects. Our recent survey showed that CPA 12.5 mg/day was commonly used among Thai TW. This study aimed to evaluate the effectiveness of CPA 12.5 mg/day in testosterone suppression. Methods: The retrospective cohort chart review was done on all TW receiving FHT in a transgender clinic at Ramathibodi Hospital between January 2014-July 2022. Among the TW who initiated FHT during the study period, the effectiveness and safety of CPA 12.5 mg/day were compared with the standard dose of CPA. Only TW with information at 3-month follow-up were analyzed for a median time of achieving the T level at the goal (&amp;lt;50 ng/dL) using a Cox regression analysis and a proportion of TW achieving T level at goal at 3 months using risk ratio regression model. All TW who initiated CPA were analyzed for changes in laboratory measurements using a generalized estimating equation (GEE). Results: A total of 89 transwomen were initially reviewed. Forty-one TW initiated CPA, and 37 TW had information at the 3-month follow-up visit. Among the latter, 22 TW (59.5%) started with CPA 12.5 mg. The median age of FHT initiation were 19 years (IQR 15-23) in CPA 12.5 mg group and 20 years (IQR 17-27) in the standard CPA dose group (p-value=0.504). Median follow-up time was 7.5 months (IQR 3-12) and 9 months (IQR 6-12), respectively (p-value=0.402). Baseline T levels were not different, with the median level at 518 ng/dL (IQR 173-787) in CPA 12.5 mg and 752 ng/dL (IQR 56-957) in control (p-value =0.653). In terms of effectiveness, the median time when T levels were suppressed at goal (&amp;lt;50 ng/dL) was 3 months in both groups. The proportion of TW who achieved targeted testosterone level within 3 months was 72.7% in CPA 12.5 mg and 86.7% in control with the risk ratio (RR) of 0.84 (95%CI 0.60-1.17, p-value= 0.295) for univariable analysis. The multivariable analysis showed an adjusted RR of 0.85 (95% CI 0.46-1.57, p-value=0.606). The multivariable GEE showed no difference between testosterone level changes. Only the LDL levels was significantly lower in the CPA 12.5 mg dose group with the difference of -13.72 mg/dL (95%CI (-25.86) – (-1.58), p-value=0.027). Other laboratories were not different among the 2 groups. There was no report of cardiovascular disease or new-onset depression in both groups.Conclusion: A CPA of 12.5 mg/day is effective in testosterone suppression as the standard dose of CPA in a FHT for TW with a comparable safety profile. This low-dose CPA regimen could be used as a FHT since it has a 50% cost reduction with equivalent effectiveness. Presentation: Saturday, June 17, 2023

Association of Medicaid expansion with 2-year survival and time to treatment initiation in gastrointestinal cancer patients: A National Cancer Database study.

We evaluated whether Medicaid expansion (ME) was associated with improved 2-year survival and time to treatment initiation (TTI) among patients with gastrointestinal (GI) cancer. GI cancer patients diagnosed 40-64 years were queried from the National Cancer Database. Those diagnosed from 2010 to 2012 were considered pre-expansion; those diagnosed from 2014 to 2016 were considered post-expansion. Cox models estimated hazard ratios and 95% confidence intervals (CIs) for 2-year overall survival. Generalized estimating equations (GEE) estimated odds ratios (OR) and 95% CI of TTI within 30- and 90 days. Multivariable Difference-in-Difference models were used to compare expansion/nonexpansion cohorts pre-/post-expansion, adjusting for patient, clinical, and hospital factors. 377,063 patients were included. No significant difference in 2-year survival was demonstrated across ME and non-ME states overall or in site-based subgroup analysis. In stage-based subgroup analysis, 2-year survival significantly improved among stage II cancer, with an 8% decreased hazard of death at 2 years (0.92; 0.87-0.97). Those with stage IV had a 4% increased hazard of death at 2 years (1.04; 1.01-1.07). Multivariable GEE models showed increased TTI within 30 days (1.12; 1.09-1.16) and 90 days (1.22; 1.17-1.27). Site-based subgroup analyses indicated increased likelihood of TTI within 30and 90 days among colon, liver, pancreas, rectum, and stomach cancers, by 30 days for small intestinal cancer, and by 90 days for esophageal cancer. In subgroup analyses, all stages experienced improved odds of TTI within 30 and 90 days. ME was not associated with significant improvement in 2-year survival for those with GI cancer. Although TTI increased after ME for both cohorts, the 30- and 90-day odds of TTI was higher for those from ME compared with non-ME states. Our findings add to growing evidence of associations with ME for those diagnosed with GI cancer.

Association of measures of socioeconomic deprivation with healthcare utilization in elderly patients enrolled in SWOG cancer clinical trials.

6527 Background: Reducing unplanned Emergency Room (ER) visits and hospitalizations is an important strategy for improving value. Patients enrolled in clinical trials are treated per protocol. While demographic factors have been associated with increased healthcare utilization, less is known about measures of socioeconomic deprivation (SD), which may be a proxy for structural barriers to access. We tested whether ER and hospital stays are more common among trials participants who live in areas of SD or have Medicaid insurance (MI). Methods: We examined ER visits and hospitalizations among cancer patients ≥65 years treated on SWOG clinical trials from 1999-2018 using trial data linked to Medicare claims. Neighborhood socioeconomic deprivation (NSD) was measured using patients’ zip code linked to the Area Deprivation Index (ADI), measured on a 0-100 scale and categorized into tertiles (T1-T3). Higher ADI (T3) denotes areas of higher deprivation. Type of insurance was classified as Medicare alone or with Commercial, versus Medicare + MI. Outcomes were ER visits, hospital stays, and costs, all in the first year. Demographic, clinical, and prognostic factors were captured from trial records. Generalized estimating equations (GEE) were used, accounting for clustering by cancer type. Regression models were adjusted for age, race, and a study-specific prognostic risk score, and stratified by study and treatment. ADI and Insurance were considered separately to reflect neighborhood-level and individual-level measures of SD. Results: In total, N = 3,027 participants from 27 trials in bladder, breast, colorectal, lung, myeloma, and prostate cancers were analyzed. Median age was 71 years, 3% had Medicare + Medicaid and 22.3% were in the Highest ADI tertile. In all, 983 (32%) patients experienced hospitalization, and 1094 (36%) visited the ER. In multivariate GEE, patients living in more deprived areas were more likely to experience hospitalization (OR for ADI T3 compared to T1: 1.36, 95% CI, 0.95-1.94, p=.09) and to visit an ER (OR for ADI T3 compared to T1: 1.33, 95% CI, 1.08-1.63, p=.008). Overall, patients from the most deprived areas had a 61% increase in risk of either ER visit or hospitalization (OR for ADI T3 compared to T1: 1.61, 95% CI, 1.23-2.10, p&lt;.001). Patients with MI were 86% more likely to visit an ER in the first year (OR 1.86, 95% CI, 1.49-2.33, p&lt;.001. No increased risk of hospitalization was observed. Conclusions: Despite participation in cancer clinical trials, patients living in areas with higher deprivation or those with Medicare + MI had an increased risk of unplanned ER visits. These findings suggest that neighborhood deprivation and economic disadvantage may increase ER visits for socioeconomically vulnerable older patients with cancer. Efforts are needed to ensure adequate resources to prevent unplanned use of acute care in vulnerable populations.

Hurricanes Irma and Maria and Diabetes incidence in Puerto Rico

ObjectiveTo evaluate the impact of Hurricanes Irma/Maria on diabetes incidence in Puerto Rico. Mortality increased substantially after the hurricanes, but morbidity was not assessed.MethodsWe recruited 364 participants from the San Juan Overweight Adults Longitudinal Study (SOALS) aged 40–65 years who completed a three-year follow-up and were free of diabetes. We conducted additional questionnaires 1.7–2.5 years after hurricanes. Glycosylated hemoglobin (HbA1c), fasting glucose and insulin were assessed at all three visits. We compared diabetes incidence between pre-hurricane visits and between visits spanning the hurricanes using Generalized Estimating Equation (GEE) adjusting for within person repeated measures, age, and body mass index (BMI).ResultsDiabetes incidence was significantly higher spanning the hurricanes than pre-hurricane (multivariate GEE model: IRR = 2.1; 95% CI: 1.4–3.1). There was a significantly higher increase spanning the hurricanes compared to pre-hurricanes for Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (median: 0.3 uIU/mL vs. 0.2 uIU/mL). HbA1c levels increased by 0.4% spanning the hurricanes.ConclusionIncreases in diabetes incidence, HOMA-IR and HbA1c were higher spanning the hurricanes compared to the pre-hurricanes period. The increase in diabetes incidence remains significant after adjusting for age and BMI.

Analysis of ancestry-specific polygenic risk score and diet composition in type 2 diabetes.

Carbohydrate and protein dietary proportions have been debated as to whether higher or lower levels are optimal for diabetes metabolic control. The objective of this study was to investigate the associations, interactions, and mediational relationships between a polygenic risk score (PRS), carbohydrate and protein intake, and physical activity level on type 2 diabetes (T2DM) by genetic ancestry, in European Americans and African Americans. A secondary objective examined the biological pathways associated with the PRS-linked genes and their relationships to dietary intake. We performed a cross-sectional study in 9,393 participants: 83.3% European Americans and 16.7% African Americans from 7-NHLBI Care studies obtained from the database of Genotypes and Phenotypes. The main outcome was T2DM. Carbohydrate and protein intake derived from food frequency questionnaires were calculated as percent calories. Data were analyzed using multivariable generalized estimation equation models to derive odds ratios (OR) and 95% confidence intervals (CI). Ancestry-specific PRSs were constructed using joint-effects Summary Best Linear Unbiased Estimation in the train dataset and replicated in the test dataset. Mediation analysis was performed using VanderWeele's method. The PRS in the highest tertile was associated with higher risk of T2DM in European Americans (OR = 1.25;CI = 1.03-1.51) and African Americans (OR = 1.54;1.14-2.09). High carbohydrate and low protein intake had lower risks of T2DM when combined with the PRS after adjusting for covariates. In African Americans, high physical activity combined with the high PRS and high protein diet was associated with a 28% lower incidence of T2DM when compared to low physical activity. In mediational models in African Americans, the PRS-T2DM association was mediated by protein intake in the highest tertile by 55%. The top PRS tertile had the highest magnitude of risks with metabolic factors that were significantly associated with T2DM, especially in European Americans. We found metabolic pathways associated with the PRS-linked genes that were related to insulin/IGF and ketogenesis/ketolysis that can be activated by moderate physical activity and intermittent fasting for better T2DM control. Clinicians may want to consider diets with a higher portion of carbohydrates than protein, especially when the burden of high-risk alleles is great in patients with T2DM. In addition, clinicians and other medical professionals may want to emphasize the addition of physical activity as part of treatment regimen especially for African Americans. Given the metabolic pathways we identified, moderate physical activity and intermittent fasting should be explored. Researchers may want to consider longitudinal or randomized clinical trials to determine the predictive ability of different dietary patterns to inhibit T2DM in the presence of obesity and an elevated PRS.

Characteristics, level of evidence, and impact of clinical studies on peri-implantitis: 2017 to 2021.

The level of evidence (LOE) is an important tool in current evidence-based practice and clinical research. However, in clinical studies on peri-implantitis, the present status of the LOE and its association with research impact remains to be determined. The present study aimed to gather the characteristics and LOE of clinical studies on peri-implantitis conducted from 2017 to 2021 and assess the association of the LOE with social and scientific impact. The PubMed database was searched to retrieve clinical studies that evaluated peri-implantitis-related healthcare interventions and were published between 2017 and 2021. A 4-level modified Oxford 2011 LOE tool was used to determine the LOE of these studies. Citation count and Altmetric Attention Scores (AAS) were derived from the Web of Science and Altmetric Explorer, respectively. Multivariate generalized estimation equation (GEE) analysis was conducted to explore relationships between the LOE and citation count, and between the LOE and AAS; the publication year was considered the grouping factor for adjusting for potential clustering effects. Two hundred and thirty-five studies were considered eligible. The percentages by level from Level-1 to Level-4 were 9.8%, 35.7%, 28.9%, and 25.5%. Multivariable GEE analyses revealed that studies with higher LOE ratings had significantly greater citation counts (p=0.008). However, no significant association (p=0.872) was observed between the LOE and AAS. From 2017 to 2021, more than 40% of studies published on peri-implantitis each year had high-LOE ratings. High-LOE studies showed a tendency to have greater scientific impact.

Sustained low functional impairment in axial spondyloarthritis (axSpA): which are the primary outcomes that should be targeted to achieve this?

ObjectivesTo (i) determine whether sustained disease activity states, as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), impact function, and (ii) evaluate characteristics predicting sustained low functional impairment in a prospective axial spondyloarthritis (axSpA) cohort.MethodsBiologic Treatment Registry Across Canada (BioTRAC) was a multi-center, prospective registry that collected real-world data on axSpA patients receiving infliximab or golimumab between 2006 and 2017. Generalized estimating equations (GEE) were used to test baseline characteristics, treatment, and duration (at 6 and 12 months vs. only at 6 or 12 months vs. neither) of low BASDAI (< 3), ASDAS-inactive disease (ID)(< 1.3), and ASDAS-low disease activity (LDA) in predicting sustained low Bath Ankylosing Spondylitis Functional Index (BASFI)(< 3) between 12 and 18 months. The adjusted impact of achieving low disease state at 6 and/or 12 months on BASFI at 18 months was analyzed by generalized linear models.ResultsEight hundred ten patients were enrolled. 33.7%, 13.4%, and 24.7% achieved sustained low BASDAI, ASDAS-ID, and ASDAS-LDA, respectively. In univariable GEE of baseline variables, age and baseline BASDAI, BASFI, and ASDAS significantly predicted sustained low BASFI. In multivariable GEE, sustained low BASDAI (p < 0.001), low BASDAI only at 6 or 12 months (p = 0.001), and baseline BASFI (p < 0.001) were the only predictors of sustained low BASFI. Sustained ASDAS-ID (p = 0.040) and ASDAS-LDA (p < 0.001) were also predictors when forced into the model. Similar results were obtained when evaluating the BASFI score at 18 months.ConclusionSustained BASDAI < 3 may be a valid and feasible target for a treat-to-target strategy in axSpA having function as treatment goal.

A multi-subgroup predictive model based on clinical parameters and laboratory biomarkers to predict in-hospital outcomes of plasma exchange-centered artificial liver treatment in patients with hepatitis B virus-related acute-on-chronic liver failure.

Postoperative risk stratification is challenging in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) who undergo artificial liver treatment. This study characterizes patients' clinical parameters and laboratory biomarkers with different in-hospital outcomes. The purpose was to establish a multi-subgroup combined predictive model and analyze its predictive capability. We enrolled HBV-ACLF patients who received plasma exchange (PE)-centered artificial liver support system (ALSS) therapy from May 6, 2017, to April 6, 2022. There were 110 patients who died (the death group) and 110 propensity score-matched patients who achieved satisfactory outcomes (the survivor group). We compared baseline, before ALSS, after ALSS, and change ratios of laboratory biomarkers. Outcome prediction models were established by generalized estimating equations (GEE). The discrimination was assessed using receiver operating characteristic analyses. Calibration plots compared the mean predicted probability and the mean observed outcome. We built a multi-subgroup predictive model (at admission; before ALSS; after ALSS; change ratio) to predict in-hospital outcomes of HBV-ACLF patients who received PE-centered ALSS. There were 110 patients with 363 ALSS sessions who survived and 110 who did not, and 363 ALSS sessions were analyzed. The univariate GEE models revealed that several parameters were independent risk factors. Clinical parameters and laboratory biomarkers were entered into the multivariate GEE model. The discriminative power of the multivariate GEE models was excellent, and calibration showed better agreement between the predicted and observed probabilities than the univariate models. The multi-subgroup combined predictive model generated accurate prognostic information for patients undergoing HBV-ACLF patients who received PE-centered ALSS.

Longitudinal impact of stressful life events on HIV-related risk and psychosocial problems among MSM in Chennai and Mumbai, India.

Studies show that stressful life events (SLE) (e.g., discrimination, financial problems) can lead to psychosocial problems and exacerbate condomless anal sex (CAS) without protection via pre-exposure prophylaxis (PrEP) among men who have sex with men. However, few studies have examined this relationship among men who have sex with men in India, and none have examined this longitudinally. As a part of an HIV-prevention intervention, 608 MSM from Chennai and Mumbai, India, completed behavioral surveys at baseline, 4, 8, and 12months. We used longitudinal generalized estimating equations (GEE) modeling to examine the relationship between SLE and its severity and subsequent psychosocial problems, CAS, and history of diagnosed sexually transmitted infection (STI). All models are adjusted for age, sexual identity, intervention arm, human immunodeficiency virus status, and recruitment city. The number of SLE and their corresponding perceived impact score remained consistent at each time point. In multivariable GEE models, the number of SLE was predictive of CAS, depression, and harmful drinking. Similarly, the ratio of the impact of SLE was predictive of CAS, depression, and diagnosed STI. However, harmful drinking was not predictive in this model. These findings provide evidence that can inform future interventions, which can be used to enhance self-acceptance, coping skills, and other forms of resiliency.

Associated Factors of Spontaneous Hemorrhage in Brain Metastases in Patients with Lung Adenocarcinoma.

Hemorrhage in brain metastases (BMs) from lung cancer is common and associated with a poor prognosis. Research on associated factors of spontaneous hemorrhage in patients with BMs is limited. This study aimed to investigate the predictive risk factors for BM hemorrhage and assess whether hemorrhage affects patient survival. We retrospectively evaluated 159 BMs from 80 patients with lung adenocarcinoma from January 2017 to May 2022. Patients were classified into hemorrhagic and non-hemorrhagic groups. Patient demographics, lung cancer molecular subtype, treatment type, and tumor-node-metastasis stage were compared between the groups. Multivariate generalized estimating equation (GEE) analysis and gradient boosting were performed. To determine whether BM hemorrhage can stratify overall survival after BM (OSBM), univariate survival analysis was performed. In the univariate analysis, hemorrhagic BMs were significantly larger and had a history of receiving combination therapy with tyrosine kinase inhibitor (TKI) and intracranial radiation (p < 0.05). Multivariate GEE showed that tumor size and combination therapy were independent risk factors for BM hemorrhage (p < 0.05). Gradient boosting demonstrated that the strongest predictor of BM hemorrhage was tumor size (variable importance: 49.83), followed by age (16.65) and TKI combined with intracranial radiation (13.81). There was no significant difference in OSBM between the two groups (p = 0.33). Hemorrhage in BMs from lung adenocarcinomas may be associated with BM tumor size and a combination of TKI and intracranial radiotherapy. BM hemorrhage did not affect OSBM.