Mixed-effects Cox Models Research Articles

The association of a low-inflammatory diet with the trajectory of multimorbidity: a large community-based longitudinal study

BackgroundA proinflammatory diet has been associated with a risk of individual chronic diseases, however, evidence on the association between inflammatory dietary patterns and the trajectory of chronic disease multimorbidity is sparse. ObjectivesWe aimed to investigate the associations of a low-inflammatory diet with the multimorbidity trajectory. MethodsWithin the UK Biobank, 102,424 chronic disease-free participants (mean age 54.7 ± 7.9 y, 54.8% female) were followed up to detect multimorbidity trajectory (annual change in the number of 59 chronic diseases). Baseline inflammatory diet index (IDI) and empirical dietary inflammatory pattern (EDIP) were separately calculated from the weighted sum of 32 posteriori-derived (15 anti-inflammatory) and 18 prior-defined (9 anti-inflammatory) food groups, and tertiled as low-, moderate-, and high-inflammatory diet. Data were analyzed using linear mixed effects model, Cox model, and Laplace regression with adjustment for potential confounders. ResultsDuring the follow-up (median 10.23 y), 15,672 and 35,801 participants developed 1 and 2+ chronic conditions, respectively. Adherence to a low-inflammatory diet was associated with decreased multimorbidity risk (hazard ratio [HRIDI] = 0.84, 95% confidence interval [CI]: 0.81, 0.86; HREDIP = 0.91, 95% CI: 0.89, 0.94) and a slower multimorbidity accumulation (βIDI = −0.033, 95% CI: −0.036, −0.029; βEDIP = −0.006, 95% CI: −0.010, −0.003) compared with a high-inflammatory diet, especially in participants aged > 60 y (βIDI = −0.051, 95% CI: −0.059, −0.042; βEDIP = −0.020, 95% CI: −0.029, −0.012; both P-interactions < 0.05). The 50th percentile difference (95% CI) of chronic disease-free survival time was prolonged by 0.81 (0.64, 0.97) and 0.49 (0.34, 0.64) y for participants with a low IDI and EDIP, respectively. Higher IDI and EDIP were associated with the development of 4 and 3 multimorbidity clusters (especially for cardiometabolic diseases), respectively. ConclusionsA low-inflammatory diet is associated with a lower risk and slower accumulation of multimorbidity (especially in participants aged > 60 y). A low-inflammatory diet may prolong chronic disease-free survival time.

Longevity of acrylic and cobalt-chromium removable partial dentures–A ten-year retrospective survival analysis of 1246 denture-wearing patients

Objectivesto assess the survival rates of removable partial dentures (RPDs) and identify factors impacting their longevity. Methodselectronic health records were retrieved of patients aged ≥18 who received RPDs between 2010 – 2021 with a follow-up of ≥ three months. Data extracted included demographics, medical history, dental charting, periodontal screening and recording scores, prostheses details and related interventions, including new dentures/denture remakes, and maintenance. Multivariate Mixed-Effect Cox regression was performed to identify potential RPD survival risk factors. Reduced model selection was reached using a backward step-down by comparing the performance of these multivariable models using the ANOVA test. Results1893 RPDs from 1246 patients were included, with a median follow-up of 21.8 months (range from 3 to 131.3 months). Three hundred and twelve patients received a maxillary RPD, 460 received a mandibular RPD, and the remaining 474 patients received both maxillary and mandibular RPDs. Metal-based RPDs had a median survival of 73 months (95%CI: 70 – 82) versus 45 months (95% CI: 37-67) for acrylic ones. Multivariable mixed effects Cox model showed that the lifespans of RPDs were longer amongst patients receiving more maintenance care within three months [Hazards Ratio (HR)=0.89 (0.83, 0.96)] and after three months [HR=0.53 (0.46, 0.61)] of denture delivery, patients wearing both maxillary and mandibular RPDs [HR=0.67 (0.52, 0.87)], and patients receiving metal-based RPDs [HR=0.31 (0.23, 0.42)]. ConclusionsMetal-based dentures, dual arch restoration, and increased maintenance positively impact the survival of RPDs. Clinical significanceAdapting consent and warranty practices is advised to reflect RPD performance variations.

Factors Associated With the Discontinuation of Two Short-Course Tuberculosis Preventive Therapies in Programmatic Settings in the United States.

The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations.

Effects of socioeconomic status (SES) and healthcare resource (HCR) availability on survival in Black patients (pts) versus (vs) White pts with multiple myeloma (MM): A SEER Medicare analysis.

e13678 Background: In MM, disparities exist for overall survival (OS) by race, and many factors may contribute to these differences. This study evaluates whether SES and HCR availability impacts OS in older pts with newly diagnosed MM (NDMM) based on race. Methods: This retrospective study used linked SEER-Medicare claims (diagnosis [Dx] 6/1/2013–12/31/2017) and Area Health Resource Files (AHRFs; from 2018) to identify non-Hispanic White and non-Hispanic Black pts aged ≥66 years with NDMM. AHRFs included county-level HCR availability data (e.g. number of long-term hospital beds, medical doctors [MDs]). Continuous Medicare A and B enrollment until 12/31/2019 or preceding death was required. Pts with other cancers, Dx from death data, missing county information and enrollment in health maintenance organizations or clinical trials were excluded. Kaplan-Meier was used for unadjusted median OS and Cox proportional hazards for OS risk by race. Age, sex, race, Charlson Comorbidity Index (CCI), poverty, education, and HCR availability were included in the adjusted mixed effects Cox model. Results: We identified 6,609 pts with NDMM; 15.6% were Black. For Black pts vs White pts, median age at Dx was 76 vs 77 years, 57.1% vs 46.0% were female, and mean CCI was 2.1 vs 1.4 (p&lt;.001 for all). Within census tracts, mean percentage of pts living under the poverty line and received &lt;12 years of education was 21.2% vs 11.3% (p&lt;.001) and 19.0% vs 11.3% (p&lt;.001) for Black pts vs White pts, respectively. Unadjusted median OS for Black pts vs White pts was 2.76 vs 3.01 years (hazard ratio [HR]: 1.08; p=.063). In the adjusted model, several SES and HCR availability factors were significant. OS HR by race reversed directionality when adjusted for demographics, SES and HCR availability, but this was not significant (HR: 0.92; p=.12; Table). Conclusions: We found that Black pts with NDMM in SEER-Medicare claims were younger, had higher CCI, completed less education, and were more likely to live in census tracts with higher poverty percentages vs White pts. Several factors relating to SES and HCR availability significantly influenced OS and may drive disparities in care. Further research on larger datasets is needed to better understand these disparities. [Table: see text]

Automated digital oncologic data review for breast cancer research: AI-enabled mCODE and field-of-interest extraction framework.

e12647 Background: Enhancing outcomes in cancer care and research can be optimally achieved by accelerating data extraction from unstructured electronic health resources. Understanding the association between treatment response markers and long-term outcomes is crucial for refining cancer therapeutic approaches and improving patient prognosis. In this study, we explore the association of oncologic outcomes with pathologic complete response (pCR) in high-risk early-stage breast cancer treated with neoadjuvant chemotherapy (NACT) using automated oncologic data extraction framework. Methods: Patients with primary stage I-III breast cancer who received NACT followed by mastectomy, with or without immediate breast reconstruction from January 2010 to August 2023 were retrospectively analyzed. We extracted pCR results and data on clinical and pathological stage, tumor subtype, grade, and treatment regimens and factors affecting postoperative complications from electronic medical records based on the AI enabled-mCODE (Minimal Common Oncology Data Elements) and fields of interest extraction framework. Employing mixed-effects Cox models, we explored the association between pCR and event-free survival (EFS), distant recurrence free Survival (DRFS) and overall survival (OS). Survival curves of patients were estimated using Kaplan-Meier method. Multivariate analysis was performed to evaluate the predictive factors for pCR. Results: Overall, 2725 patients were analyzed. The median age was 50.6 years. The median follow-up was 67 months. pCR was achieved in 31.0%. Hazard ratio for pCR vs. non-pCR were 0.34 for EFS (95% CI, 0.25-0.45), 0.32 for DRFS (95% CI, 0.23-0.43), 0.21 for OS (95% CI, 0.13-0.34), varying from 0.13 to 0.56 for EFS, 0.12 to 0.48 for DRFS and 0.07 to 0.40 for OS. The presence of pCR remained prognostic for event-free survival in multivariate models adjusted for age, tumor size, and nodal status at baseline. Conclusions: This study confirms that patients achieving pCR after NACT have better long-term survival outcomes that patients who do not. Oncologic data extraction from unstructured electronic medical records using AI-enabled extraction framework can be expected to enhance robust cancer research and generate valuable insights from real-world practice settings for tailored therapeutic decision-making. [Table: see text]

Risk of early revision in total hip arthroplasty: the relative contribution of the surgeon versus the hospital.

Early revision for total hip arthroplasty is a serious adverse outcome. There are multiple contributing risk factors for early revision. Risk factors can exist at the level of the surgeon and the level of the institution. The primary research question of this study was to determine the relative contribution of surgeon-level and hospital-level variance to rates of early revision (overall and for infection) after primary total hip arthroplasty. This is a registry-based study from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). Data for the most commonly used stem (Exeter V40) were used to reduce prosthesis variation from the analysis. A mixed effects Cox Model (also known as a frailty model) with crossed random effects for surgeon and hospital was used. Outcomes were early revision (within 2 years) for all causes and for infection. This model allowed for the risk of early revision to be explained by the variability at the surgeon level or hospital level. There were 32 031 procedures performed by 735 surgeons across 250 hospitals between 1 January 2015 and 31 December 2019. Surgeon variability significantly contributed to overall variation in revision for any cause and revision for infection (P < 0.0001). There was no significant contribution of hospital-level variation to overall revision or for infection. Surgeon-level factors play a more important role than institution-level factors in early revision after primary total hip arthroplasty. If surgeons are identified as having a higher risk of revision, there is potential for surgeon-level practice change to reduce the risk of early revision.

Association between arterial oxygen and mortality across critically ill patients with hematologic malignancies: results from an international collaborative network.

Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies. Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100mmHg) on day-28 mortality. 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]). In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer.

Detection of circulating tumor DNA (ctDNA) in patients who have completed treatment for early-stage breast cancer is associated with a high risk of relapse, yet the optimal assay for ctDNA detection is unknown. The cTRAK-TN clinical trial prospectively used tumor-informed digital PCR (dPCR) assays for ctDNA molecular residual disease (MRD) detection in early-stage triple-negative breast cancer. We compared tumor-informed dPCR assays with tumor-informed personalized multimutation sequencing assays in 141 patients from cTRAK-TN. MRD was first detected by personalized sequencing in 47.9% of patients, 0% first detected by dPCR, and 52.1% with both assays simultaneously (P < 0.001; Fisher exact test). The median lead time from ctDNA detection to relapse was 6.1 months with personalized sequencing and 3.9 months with dPCR (P = 0.004, mixed-effects Cox model). Detection of MRD at the first time point was associated with a shorter time to relapse compared with detection at subsequent time points (median lead time 4.2 vs. 7.1 months; P = 0.02). Personalized multimutation sequencing assays have potential clinically important improvements in clinical outcome in the early detection of MRD.

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

P-059 Sperm DNA fragmentation (SDF) after cryopreservation and sperm selection: implications for clinical pregnancies and live births after intrauterine insemination with donor sperm

Abstract Study question Can SDF assessment pre-cryopreservation, post-thaw and after post-thaw sperm selection predict clinical outcome in a heterologous intra-uterine donor insemination program (IUI)? Summary answer SDF increased post-cryopreservation in donor sperm and after post-thaw density gradient without affecting clinical pregnancy, live birth and miscarriage rates. What is known already Sperm cryopreservation is effective for preservation of male fertility and facilitates the storage of donor semen, while infectious disease screening can be completed and confirmed negative. Sperm viability and motility are the most vulnerable parameters during the freeze-thaw process. Inherent reactive oxygen species may induce SDF via oxidative stress. Controversial results are reported regarding induction of SDF after cryopreservation due to differences in cryo tolerance, methods of cryopreservation and methods used to evaluate SDF. Sperm selection post-thaw is indispensable to select a normal motile fraction for insemination. Again, results are controversial regarding influence on SDF levels after sperm selection post-thaw. Study design, size, duration This was a prospective, observational study. Between March 2015 and March 2019, eighteen potential sperm donors were screened via a three step plan – semen assessment, medical assessment and serological blood tests. In accordance with the Belgian legislation (2007), a sperm donor was matched to obtain a maximum of 6 pregnancies in acceptor women/couples, allowing for more than one offspring/woman or couple. A total of 106 acceptors were matched for heterologous intra-uterine insemination. Participants/materials, setting, methods Semen samples were collected after 2-7 days abstinence and standard semen parameters analyzed within 60 mins after ejaculation. Within the same time frame SDF test was performed using TUNEL assay both before and after cryopreservation and after a two-step discontinuous density gradient centrifugation post-thaw. Samples were cryopreserved by the conventional slow freezing method using sperm freeze solution. A yield of ≥ 2 M progressive spermatozoa post-thaw after selection was sufficient to contemplate IUI. Main results and the role of chance Mean female age at first cycle was 33.9 ± 4.1 years and donor age 28.5 ± 5.6 years. Out of 429 cycles, 100 (23.3%) resulted in clinical pregnancy. Excluding three ongoing pregnancies, we counted 75 live births (17.6% of cycles or 77.3% of pregnancies), while 21 pregnancies ended in miscarriage (4.9% of cycles or 21.6% of pregnancies) and 1 resulted in stillbirth. Progressive motility (59.3 ± 12.5%) decreased significantly after cryopreservation (30.0 ± 13.2%; p &amp;lt; 0.001), but increased post-thaw after density gradient centrifugation (61.6 ± 16.0%; p &amp;lt; 0.001). On the contrary, SDF (12.0 ± 5.9%) increased post-cryopreservation (26.3 ± 14.5%; p &amp;lt; 0.001) and further increased after sperm selection (34.9 ± 22.1%; p = 0.04). Using multilevel mixed-effects logistic regression (Odds ratio [95%CI]), we found that female age significantly influenced clinical pregnancy (0.911 [0.847-0.981]; p = 0.01), live birth (0.894 [0.834-0.959]; p = 0.002) and miscarriage rates (1.180 [1.033-1.347]; p = 0.015). There was no significant age-adjusted effect of SDF post-thaw after density gradient selection on clinical pregnancy (1.007 [0.994-1.021]; p = 0.30), live birth (1.001 [0.988-1.014]; p = 0.84) or miscarriage (1.021 [0.997-1.046]; p = 0.08). Median time-to-live birth was 4 cycles. Analyses of time-to-live birth with mixed-effects Cox models revealed no significant association with progressive motility; SDF before or after cryopreservation and after sperm selection post-thaw. Limitations, reasons for caution Results concern a small donor population, with high normal semen parameters and should therefore be extrapolated cautiously to subfertile men with normal and subnormal semen parameters. Wider implications of the findings In a donor IUI program with strict selection on conventional sperm parameters, differences in SDF before and after cryopreservation and gradient centrifugation do not change IUI outcomes, although cryopreservation and centrifugation increase SDF. Findings could be useful for the optimization of sperm freezing and selection in different assisted reproductive procedures. Trial registration number not applicable

Dietary Polyphenol Intake and Risk of Hypertension: An 18-y Nationwide Cohort Study in China

BackgroundAlthough increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still lacking. ObjectivesThis study aimed to investigate the association between dietary polyphenol and hypertension risk in the China Health and Nutrition Survey (N = 11,056). MethodsFood intake was assessed using 3-d, 24-h dietary recalls and household weighing method; polyphenol intake was calculated by multiplying consumption of each food and its polyphenol content. Hypertension was defined as BP ≥ 140/90 mmHg, physicians’ diagnosis, or taking antihypertension medications. HR and 95% CI were estimated using mixed-effects Cox models. ResultsDuring 91,561 person-years of follow-up, a total of 3866 participants developed hypertension (35%). The lowest multivariable-adjusted HR (95% CI) of hypertension risk occurred in the third quartile intake, which was 0.63 (0.57, 0.70) for total polyphenol, 0.61 (0.55, 0.68) for flavonoid, 0.62 (0.56, 0.69) for phenolic acid, 0.46 (0.42, 0.51) for lignan, and 0.58 (0.52, 0.64) for stilbene, compared with the lowest quartile. The polyphenol-hypertension associations were nonlinear (all Pnonlinearity < 0.001), and different patterns were observed. U-shaped relations with hypertension were observed for total polyphenol, flavonoid, and phenolic acid, whereas L-shaped associations were observed for lignan and stilbene. Moreover, higher fiber intake strengthened the polyphenol-hypertension association, especially for lignan (P-interaction = 0.002) and stilbene (P-interaction = 0.004). Polyphenol-containing food, particularly vegetables and fruits rich in lignan and stilbene, were significantly associated with lower hypertension risk. ConclusionsThis study demonstrated an inverse and nonlinear association between dietary polyphenol, especially lignan and stilbene, and hypertension risk. The findings provide implications for hypertension prevention.

Risk factors differ for viable and low viable crushed piglets in free farrowing pens.

Newborn piglets have a high risk of being crushed by the sow, and this risk implies welfare and economic consequences. The aim of this study was to investigate the importance of differentiating between low viable (secondary crushing losses) and viable crushed (primary crushing losses) piglets for the evaluation of risk factors for crushing related to characteristics of the sow, the litter, and the environment. Eleven Swiss farmers recorded sows' production data (parity class, gestation length, numbers of live-born and stillborn piglets), data (age, sex, weight, cause of death, and signs of weakness) for every live-born piglet that died in the first week after birth (piglet loss), and ambient temperature. Piglet losses were assigned to five categorical events: piglet loss, subdivided into not crushed and crushed, the latter being further subdivided into low viable crushed and viable crushed. Piglets recorded by the farmer as crushed were assigned to the events low viable crushed and viable crushed based on the piglet's body weight and signs of weakness (diseases, malformations). Data of 9,543 live-born piglets from 740 litters were eventually used to statistically model the hazard of dying at any given time in the first week after birth due to one of these events (mixed-effects Cox model). Five potential risk factors were analyzed as co-variates: parity class, gestation length, number of live-born piglets, number of stillborn piglets, and daily number of hours with ambient temperature >30°C. We identified two risk factors for dying from the event viable crushed that were not identified as risk factors for low viable crushed, namely shorter gestation length and higher daily number of hours with ambient temperature > 30°C. Vice-versa, we identified additional live-born piglets in the litter as risk factor for low viable crushed, but not for viable crushed. Our results show the importance of differentiating between low viable and viable crushed piglets for the interpretation of risk factors for crushing losses. Therefore, we suggest that for breeding purposes and in research, this differentiation should be made.

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: We redefined mild relapses in MSBase as ‘non-disabling’, and moderate or severe relapses as ‘disabling’. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00–1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15–1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71–1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Effect of Digital Early Warning Scores on Hospital Vital Sign Observation Protocol Adherence: Stepped-Wedge Evaluation.

Early warning scores (EWS) are routinely used in hospitals to assess a patient's risk of deterioration. EWS are traditionally recorded on paper observation charts but are increasingly recorded digitally. In either case, evidence for the clinical effectiveness of such scores is mixed, and previous studies have not considered whether EWS leads to changes in how deteriorating patients are managed. This study aims to examine whether the introduction of a digital EWS system was associated with more frequent observation of patients with abnormal vital signs, a precursor to earlier clinical intervention. We conducted a 2-armed stepped-wedge study from February 2015 to December 2016, over 4 hospitals in 1 UK hospital trust. In the control arm, vital signs were recorded using paper observation charts. In the intervention arm, a digital EWS system was used. The primary outcome measure was time to next observation (TTNO), defined as the time between a patient's first elevated EWS (EWS ≥3) and subsequent observations set. Secondary outcomes were time to death in the hospital, length of stay, and time to unplanned intensive care unit admission. Differences between the 2 arms were analyzed using a mixed-effects Cox model. The usability of the system was assessed using the system usability score survey. We included 12,802 admissions, 1084 in the paper (control) arm and 11,718 in the digital EWS (intervention) arm. The system usability score was 77.6, indicating good usability. The median TTNO in the control and intervention arms were 128 (IQR 73-218) minutes and 131 (IQR 73-223) minutes, respectively. The corresponding hazard ratio for TTNO was 0.99 (95% CI 0.91-1.07; P=.73). We demonstrated strong clinical engagement with the system. We found no difference in any of the predefined patient outcomes, suggesting that the introduction of a highly usable electronic system can be achieved without impacting clinical care. Our findings contrast with previous claims that digital EWS systems are associated with improvement in clinical outcomes. Future research should investigate how digital EWS systems can be integrated with new clinical pathways adjusting staff behaviors to improve patient outcomes.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Probable Sarcopenia, Obesity, and Risk of All-Cause Mortality: A Pooled Analysis of 4,612 Participants

Introduction: Conflicting evidence exists concerning whether having sarcopenic obesity has additive mortality risk over having only sarcopenia or obesity. We examined the independent and combined associations of obesity and probable sarcopenia with all-cause mortality. Methods: The pooled analysis included three large, harmonized datasets (Health 2000 Survey; Health, Aging and Body Composition Study; Longitudinal Aging Study Amsterdam) with mortality follow-up data on individuals aged 70 years and over at baseline (n = 4,612). Obesity indicators included body mass index and waist circumference, and probable sarcopenia was defined based on grip strength. The mixed effects Cox model was used for statistical analyses, adjusting for age, sex, marital status, education, race, physical activity, alcohol consumption, smoking, and baseline diseases. Results: Risk of death increased for those having probable sarcopenia only (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.39–1.85) or probable sarcopenia with obesity (HR: 1.36, 95% CI: 1.13–1.64) but not for the obese-only group (HR: 0.92, 95% CI: 0.85–1.01), when compared to non-obese non-sarcopenic individuals. The results were similar regardless of adjustments for covariates or different obesity criteria applied. Conclusion: Probable sarcopenia, whether combined with obesity or not, is associated with increased mortality. Obesity did not increase mortality among older adults. Maintaining muscle strength and identifying older adults at risk of sarcopenia is important for the prevention of premature mortality.

Reduced injury risk links sociality to survival in a group-living primate

Sociality has been linked to a longer lifespan in many mammals, including humans. Yet, how sociality results in survival benefits remains unclear. Using 10 years of data and over 1,000 recorded injuries in rhesus macaques (Macaca mulatta), we tested two injury-related mechanisms by which social status and affiliative partners might influence survival. Injuries increased individual risk of death by 3-fold in this dataset. We found that sociality can affect individuals' survival by reducing their risk of injury but had no effect on the probability of injured individuals dying. Both males and females of high social status (measured as female matrilineal rank and male group tenure) and females with more affiliative partners (estimated using the number of female relatives) experienced fewer injuries and thus were less likely to die. Collectively, our results offer rare insights into one mechanism that can mediate the well-known benefits of sociality on an individual's fitness.

Acute and chronic maternal exposure to fine particulate matter and prelabor rupture of the fetal membranes: A nation-wide survey in China

BackgroundPrelabor rupture of the fetal membranes (PROM) is a major contributor to adverse perinatal outcomes. Some epidemiologic studies explored the association between maternal PM2.5 exposure and PROM but failed to treat the labor induction and prelabor cesarean section as censored observations. ObjectiveWe aimed to evaluated whether acute and chronic maternal ambient PM2.5 exposure may increase the risk of PROM in China. MethodsThis study was based on the China Labor and Delivery Survey, a nationwide multicenter investigation. Included in the current analysis were 45,879 singleton spontaneous births in 96 hospitals in mainland China from 2015 to 2017. Outcomes were PROM, preterm PROM (<37 weeks’ gestation) and term PROM (≥37 weeks’ gestation). Daily concentration of PM2.5 at 1 km spatial resolution was estimated by gap-filling model. Generalized linear mixed model and mixed effects Cox model were applied to assess the associations of acute (from 0 to 4 days before delivery) and chronic (average gestational and trimester-specific) ambient PM2.5 exposure with outcomes, respectively. ResultsSignificant associations were found between acute PM2.5 exposures (per interquartile range increase) and the risk of preterm PROM (OR = 1.11; 95 % CI: 1.03, 1.19 for PM2.5 on delivery day; OR = 1.10; 95 % CI: 1.02, 1.18 for PM2.5 1 day before delivery) but not for term PROM. An interquartile range increase in PM2.5 during the second trimester was associated with elevated risks of PROM (HR = 1.14; 95 % CI: 1.07, 1.22), preterm PROM (HR = 1.22; 95 % CI: 1.02, 1.45) and term PROM (HR = 1.13; 95 % CI: 1.06, 1.22), respectively. Women who were less educated, obese, or gave birth in a cold season appeared to be more sensitive to ambient PM2.5 exposure. ConclusionOur findings suggest that both acute and chronic maternal exposures to ambient PM2.5 during pregnancy are risk factors for PROM.

Regional heterogeneity of in-hospital mortality of COVID-19 in Brazil.

BackgroundThe ongoing Coronavirus disease of 2019 (COVID-19) pandemic has hit Brazil hard in period of different dominant variants. Different COIVD-19 variants have swept through the region, resulting that the total number of cases in Brazil is the third highest in the world. This study is aimed at investigating the regional heterogeneity of in-hospital mortality of COVID-19 in Brazil and the effects of vaccination and social inequality.MethodsWe fitted a multivariate mixed-effects Cox model to a national database of inpatient data in Brazil who were admitted for COVID-19 from February 27, 2020 to March 15, 2022. The in-hospital mortality risks of vaccinated and unvaccinated patients were compared, with adjustment for age, state, ethnicity, education and comorbidities. And the effects of variables to in-hospital mortality were also compared. Stratified analysis was conducted across different age groups and vaccine types.ResultsBy fitting the multivariate mixed-effects Cox model, we concluded that age was the most important risk factor for death. With regards to educational level, illiterate patients (hazard ratio: 1.63, 95% CI: 1.56–1.70) had a higher risk than those with a university or college degree. Some common comorbidities were more dangerous for hospitalized patients, such as liver disease (HR: 1.46, 95% CI: 1.34–1.59) and immunosuppression (HR:1.32, 95% CI: 1.26–1.40). In addition, the states involving Sergipe (HR: 1.75, 95% CI: 1.46–2.11), Roraima (HR: 1.65, 95% CI: 1.43–1.92), Maranhão (HR: 1.57, 95% CI: 1.38–1.79), Acre (HR: 1.44, 95% CI: 1.12–1.86), and Rondônia (HR: 1.26, 95% CI: 1.10–1.44) in the north and the northeast region tended to have higher hazard ratios than other area. In terms of vaccine protection, vaccination did not significantly reduce mortality among hospitalized patients. Sinovac and AstraZeneca offered different protection in different regions, and no vaccine provided high protection in all regions.ConclusionThe study revealed the regional heterogeneity of in-hospital mortality of Covid-19 in Brazil and the effects of vaccination and social inequality. We found that ethnic concentrations were consistent with higher proportion of death cases relative to population size. White Brazilians had more frequent international travel opportunities. As race revealed the intersection of social connections, we speculated that uneven interactions with residential communities partially contribute to the spread of the epidemic. Additionally, the vaccine showed different protection in different regions. In the northern and northeastern regions, AstraZeneca was much more protective than Sinovac, while Sinovac was more protective for hospitalized patients with varying numbers of comorbidities in the Central-west, Southeast and South regions.

Alcohol use disorder, psychiatric comorbidities, marriage and divorce in a high-risk sample.

To examine associations between alcohol use disorder (AUD), its psychiatric comorbidities, and their interactions, with marital outcomes in a diverse high-risk, genetically informative sample. Participants included European ancestry (EA; n = 4,045) and African ancestry (AA; n = 1,550) individuals from the multigenerational Collaborative Study on the Genetics of Alcoholism (COGA) sample (56% female, Mage ∼ 41 years). Outcomes were lifetime marriage and divorce. Predictors included lifetime AUD, an alcohol problems polygenic score (PRS), and AUD comorbidities, including conduct or antisocial personality disorder (ASP), cannabis dependence/abuse (CAN), frequent tobacco use (TOB), and major depressive disorder (MDD). Mixed effect Cox models and generalized linear mixed effects models were fit. Among EA participants, those with AUD and CAN were less likely to marry (hazard ratios [HRs] 0.70-0.83, ps < 0.01). Among AA participants, those with AUD and TOB were less likely to marry (HRs 0.66-0.82, ps < 0.05) and those with MDD were more likely to marry (HR = 1.34, ps < 0.01). Among EA participants, AUD, CAN, TOB, and MDD were associated with higher odds of divorce (odds ratios [ORs] 1.59-2.21, ps < 0.01). Among AA participants, no predictors were significantly associated with divorce. Significant random effects indicated genetic and environmental influences on marriage, but only environmental factors on divorce. In a high-risk sample, AUD was associated with reduced likelihood of marriage in EA and AA individuals and increased risk of divorce in EA individuals. These associations were largely independent of comorbidities. Genetic and environmental background factors contributed to marriage, while only environmental background factors contributed to divorce. (PsycInfo Database Record (c) 2022 APA, all rights reserved).