Mortality and Causes of Death Among Individuals With Keratoconus.

PURPOSE: The purpose of this study was to determine whether there is an increased risk of mortality among individuals with keratoconus. METHODS: This was a retrospective, case-control study using the Utah Population Database. Cases were defined as individuals diagnosed with keratoconus from 1996 to 2020 and were matched 5:1 with controls on birth year, sex, whether born in Utah, and follow-up time in Utah. Individuals diagnosed with trisomy 21 or connective tissue disease were excluded. Main outcome measures were the all-cause and cause-specific mortality among keratoconus cases compared with matched controls. Cox regression models were used, additionally adjusting for race and ethnicity. RESULTS: A total of 7847 keratoconus cases and 38,597 controls were studied in the final analyses. The mean age at index diagnosis was 43 ± 17 years, and mean age at last follow-up was 54 ± 17 years for both cases and controls. At last follow-up, 92% of cases were living compared with 91% of controls. After adjusting for covariates, there were no significant differences in all-cause mortality (P = 0.161), mortality from natural causes (0.222), or mortality from unnatural causes (P = 0.494) between cases and controls. When analyzed according to specific causes of death, keratoconus cases had a higher mortality risk from diseases of the nervous system and sense organs compared with their matching controls (hazard ratio 1.59; 95% confidence interval, 1.19-2.11; P = 0.002). CONCLUSIONS: There was no evidence of an increased risk of mortality among individuals with keratoconus. There may be an increased risk of death due to diseases of the nervous system and sense organs among individuals with keratoconus.

Healthcare Burden and Resource Utilization After Pediatric Acute Respiratory Distress Syndrome: A Secondary Analysis of the Collaborative Pediatric Critical Care Research Network Acute Respiratory Distress Syndrome Study.

OBJECTIVES: To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months. DESIGN: Secondary analysis of a prospective multisite cohort study. SETTING: Eight academic PICUs in the United States (2019-2020). PATIENTS: Critically ill children with ARDS and follow-up survey data collected at 3 and/or 9 months after the event. INTERVENTIONS: None. METHODS AND MEASUREMENT: We evaluated family healthcare burden, a measure of healthcare provided by families at home, and child health resource use including medication use and emergency department (ED) and hospital readmissions during the initial 3- and 9-month post-ARDS using proxy-report. Using multivariable logistic regression, we evaluated patient characteristics associated with family healthcare burden at 3 months. MAIN RESULTS: Of 109 eligible patients, 74 (68%) and 63 patients (58%) had follow-up at 3- and 9-month post-ARDS. At 3 months, 46 families (62%) reported healthcare burden including (22%) with unmet care coordination needs. At 9 months, 33 families (52%) reported healthcare burden including 10 families (16%) with unmet care coordination needs. At month 3, 61 patients (82%) required prescription medications, 13 patients (18%) had ED visits and 16 patients (22%) required hospital readmission. At month 9, 41 patients (65%) required prescription medications, 19 patients (30%) had ED visits, and 16 (25%) required hospital readmission were reported. Medication use was associated with family healthcare burden at both 3 and 9 months. In a multivariable analysis, preillness functional status and chronic conditions were associated with healthcare burden at month 3 but illness characteristics were not. CONCLUSIONS: Pediatric ARDS survivors report high rates of healthcare burden and health resource utilization at 3- and 9-month post-ARDS. Future studies should assess the impact of improved care coordination to simplify care (e.g., medication management) and improve family burden.

Mortality risk following end-of-life caregiving: A population-based analysis of hospice users and their families.

Experiencing the death of a family member and providing end-of-life caregiving can be stressful on families - this is well-documented in both the caregiving and bereavement literatures. Adopting a linked-lived theoretical perspective, exposure to the death and dying of one family member could be conceptualized as a significant life stressor that produces short and long-term health consequences for surviving family members. This study uses familial-linked administrative records from the Utah Population Database to assess how variations in family hospice experiences affect mortality risk for surviving spouses and children. A cohort of hospice decedents living in Utah between 1998 and 2016 linked to their spouses and adult children (n = 37,271 pairs) provides an ideal study population because 1) hospice typically involves family members in the planning and delivery of end-of-life care, and 2) hospice admission represents a conscious awareness and acknowledgment that the decedent is entering an end-of-life experience. Thus, hospice duration (measured as the time between admission and death) is a precise measure of the family's exposure to an end-of-life stressor. Linking medical records, vital statistics, and other administrative microdata to describe decedent-kin pairs, event-history models assessed how hospice duration and characteristics of the family, including familial network size and coresidence with the decedent, were associated with long-term mortality risk of surviving daughters, sons, wives (widows), and husbands (widowers). Longer hospice duration increased mortality risk for daughters and husbands, but not sons or wives. Having other family members in the state was protective, and living in the same household as the decedent prior to death was a risk factor for sons. We conclude that relationship type and sex likely modify the how of end-of-life stressors (i.e., potential caregiving demands and bereavement experiences) affect health because of normative gender roles. Furthermore, exposure to dementia deaths may be particularly stressful, especially for women.

Disparities in Provider Ordering Practices of Image-Guided Interventions and Surgery for Patients With Low Back Pain: A Cohort Study.

OBJECTIVE: To assess individual- and neighborhood-level sociodemographic factors associating with providers' ordering of nonpharmacologic treatments for patients with low back pain (LBP), specifically physical therapy, image-guided interventions, and lumbar surgery. METHODS: Our cohort included all patients diagnosed with LBP from 2000 to 2017 in a statewide database of all hospitals and ambulatory surgical facilities within Utah. We compared sociodemographic and clinical characteristics of (1) patients with LBP who received any treatment with those who received none and (2) patients with LBP who received invasive LBP treatments with those who only received noninvasive LBP treatments using the Student's t test, Wilcoxon's rank-sum tests, and Pearson's χ2 tests, as applicable, and two separate multivariate logistic regression models: (1) to determine whether sociodemographic characteristics were risk factors for receiving any LBP treatments and (2) risk factors for receiving invasive LBP treatments. RESULTS: Individuals in the most disadvantaged neighborhoods were less likely to receive any nonpharmacologic treatment orders (odds ratio [OR] 0.74 for most disadvantaged, P < .001) and received fewer invasive therapies (0.92, P = .018). Individual-level characteristics correlating with lower rates of treatment orders were female sex, Native Hawaiian or other Pacific Islander race (OR 0.50, P < .001), Hispanic ethnicity (OR 0.77, P < .001), single or unmarried status (OR 0.69, P < .001), and no insurance or self-pay (OR 0.07, P < .001). CONCLUSION: Neighborhood and individual sociodemographic variables associated with treatment orders for LBP with Area Deprivation Index, sex, race or ethnicity, insurance, and marital status associating with receipt of any treatment, as well as more invasive image-guided interventions and surgery.

Analysis of acute extremity compartment syndrome using a genealogic population database.

INTRODUCTION: Acute extremity compartment syndrome ("CS") is an under-researched, highly morbid condition affecting trauma populations. The purpose of this study was to analyze incidence rates and risk factors for extremity compartment syndrome using a high-quality population database. Additionally, we evaluated heritable risk for CS using available genealogic data. We hypothesized that diagnosis of extremity compartment syndrome would demonstrate heritability. MATERIALS AND METHODS: Adult patients with fractures of the tibia, femur, and upper extremity were retrospectively identified by ICD-9, ICD-10, and CPT codes from 1996 to 2020 in a statewide hospital database. Exposed and unexposed cohorts were created based on a diagnosis of CS. Available demographic data were analyzed to determine risk factors for compartment syndrome using logistic regression. Mortality risk at the final follow-up was evaluated using Cox proportional hazard modeling. Patients with a diagnosis of CS were matched with those without a diagnosis for heritability analysis. RESULTS: Of 158,624 fractures, 931 patients were diagnosed with CS. Incidence of CS was 0.59% (tibia 0.83%, femur 0.31%, upper extremity 0.27%). Male sex (78.1% vs. 46.4%; p < 0.001; RR = 3.24), younger age at fracture (38.8 vs. 48.0 years; p < 0.001; RR = 0.74), Medicaid enrollment (13.2% vs. 9.3%; p < 0.001; RR = 1.58), and smoking (41.1% vs. 31.1%; p < 0.001; RR 1.67) were significant risk factors for CS. CS was associated with mortality (RR 1.61, p < 0.001) at mean follow-up 8.9 years in the CS cohort. No significant heritable risk was found for diagnosis of CS. CONCLUSIONS: Without isolating high-risk fractures, rates of CS are lower than previously reported in the literature. Male sex, younger age, smoking, and Medicaid enrollment were independent risk factors for CS. CS increased mortality risk at long-term follow-up. No heritable risk was found for CS. LEVEL OF EVIDENCE: III.

Social inequities in neighborhood health amenities over time in the Wasatch Front Region of Utah: Historical inequities, population selection, or differential investment?

Socially disadvantaged groups generally are more likely to reside in areas with less desirable conditions. We examined longitudinal relationships between neighborhood resident characteristics and amenities from 1990 to 2010 in an urban area of Utah, U.S. Four temporal patterns of social inequities are described using mixed-effects models: historical inequities; differential selection into amenity-rich tracts; differential investment in amenities; and simultaneous twenty-year change. Results indicate historical differences by neighborhood socioeconomic status, with lower status tracts having fewer green/natural amenities and higher air pollution in 1990 but also greater walkability and more food stores. Differences in amenities by neighborhood socioeconomic status widened over time as aggregate socioeconomic status disproportionately increased in tracts with more green/natural amenities, less air pollution, and lower walkability in 1990, consistent with differential selection. Tract percentage non-Hispanic White did not predict historical differences, but tracts that were less walkable and had fewer healthy food stores in 1990 experienced larger subsequent increases in racial/ethnic diversity. Tracts with higher relative to lower percentage non-Hispanic White in 1990 had larger decreases in air pollution but declining green/natural amenities. This study shows how social inequities in neighborhood amenities change over time, providing evidence of historical socioeconomic differences increasing from differential resident selection.

Disparities and determinants of place of death: Insights from the Utah Population Database.

To better understand determinants and potential disparities in end of life, we model decedents' place of death with explanatory variables describing familial, social, and economic resources. A retrospective cohort of 204,041 decedents and their family members are drawn from the Utah Population Database family caregiving dataset. Using multinomial regression, we model place of death, categorized as at home, in a hospital, in another location, or unknown. The model includes family relationship variables, sex, race and ethnicity, and a socioeconomic status score, with control variables for age at death and death year. We identified the effect of a family network of multiple caregivers, with 3+ daughters decreasing odds of a hospital death by 17 percent (OR: 0.83 [0.79, 0.87], p < 0.001). Place of death also varies significantly by race and ethnicity, with most nonwhite groups more likely to die in a hospital. These determinants may contribute to disparities in end of life.

Long-term cancer outcomes after bariatric surgery.

OBJECTIVE: Obesity is associated with increased cancer risk. Because of the substantial and sustained weight loss following bariatric surgery, postsurgical patients are ideal to study the association of weight loss and cancer. METHODS: Retrospectively (1982-2019), 21,837 bariatric surgery patients (surgery, 1982-2018) were matched 1:1 by age, sex, and BMI with a nonsurgical comparison group. Procedures included gastric bypass, gastric banding, sleeve gastrectomy, and duodenal switch. Primary outcomes included cancer incidence and mortality, stratified by obesity- and non-obesity-related cancers, sex, cancer stage, and procedure. RESULTS: Bariatric surgery patients had a 25% lower risk of developing any cancers compared with a nonsurgical comparison group (hazard ratio [HR] 0.75; 95% CI 0.69-0.81; p < 0.001). Cancer incidence was lower among female (HR 0.67; 95% CI 0.62-0.74; p < 0.001) but not male surgery patients, with the HR lower for females than for males (p < 0.001). Female surgery patients had a 41% lower risk for obesity-related cancers (i.e., breast, ovarian, uterine, and colon) compared with nonsurgical females (HR 0.59; 95% CI 0.52-0.66; p < 0.001). Cancer mortality was significantly lower after surgery in females (HR 0.53; 95% CI 0.44-0.64; p < 0.001). CONCLUSIONS: Bariatric surgery was associated with lower all-cancer and obesity-related cancer incidence among female patients. Cancer mortality was significantly lower among females in the surgical group versus the nonsurgical group.

Familial Analysis of Nonunion in a Genealogic Population Database Demonstrates No Evidence of Heritable Risk.

OBJECTIVE: To determine whether there is evidence of heritable risk for nonunion using a large, state-wide population database. DESIGN: Database. SETTING: Level 1 Trauma Center. POPULATION: All Utah residents from 1996 to 2021 who sustained a long bone fracture and their family members were included. OUTCOMES: The primary outcome was nonunion and the prevalence of nonunion among the patients' first-, second-, and third-degree relatives. The secondary objective was to identify demographic, injury, and socioeconomic risk factors associated with nonunion. RESULTS: In total, 150,263 fractures and 6577 nonunions (4.4%) were identified. This was highly refined to a 1:3 matched cohort of 4667 nonunions of 13,981 fractures for familial clustering analysis. Cox proportional hazards did not demonstrate excessive risk of nonunion among first- ( P = 0.863), second- ( P = 0.509), and third-degree relatives ( P = 0.252). Further analysis of the entire cohort demonstrated that male sex (relative risk [RR] = 1.15; P < 0.001), Medicaid enrollment (RR = 2.64; P < 0.001), open fracture (RR = 2.53; P < 0.001), age group 41-60 years (RR = 1.43; P < 0.001), and a history of obesity (RR = 1.20; P < 0.001) were independent risk factors for nonunion. CONCLUSIONS: Our results demonstrate no evidence of heritable risk for nonunion. Independent risk factors for nonunion were male sex, Medicaid enrollment, open fracture, middle age, and a history of obesity. Although it is important to identify modifiable and nonmodifiable risk factors, these results continue to support that the risk of nonunion is multifactorial, relating to injury characteristics, operative techniques, and patient-specific risk factors. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Lean legacy, heavy heritage: family history of diabetes and its association with young adult body mass index.

Substantial intergenerational transmission of diabetes mellitus (DM) risk exists. However, less is known regarding whether parental DM and DM among extended family members relate to adult offspring's body mass index (BMI), and whether any of these associations vary by sex. Using data from the National Longitudinal Study of Youth 1997 cohort (NLSY97), we assess the sex-specific relationship between DM present in first-degree parents and second-degree relatives and BMI among the parents' young adult offspring.Multivariate regressions reveal a positive relationship between parental DM and young adults' BMI for both daughters and sons, and the magnitude of coefficients is somewhat larger for the same-sex parent. Further, we observe that the link between parental DM and young adults' BMI is strongest when both parents have diagnosed diabetes. In contrast, the relationship between second-degree relatives with DM and the respondent's BMI is weaker and appears to be sex-specific, through same-sex parent and respondent. Logistic regressions show the association is especially strong when assessing how parental DM status relates to young adults' obesity risk. These results generally persist when controlling for parental BMI. The findings of this study point to the need to better distinguish the role of shared family environments (e.g., eating and physical activity patterns) from shared genes in order to understand factors that may influence young adults' BMI. Young adult offspring of parents with diabetes should be targeted for obesity prevention efforts in order to reduce their risks of obesity and perhaps diabetes.

Long-term maternal mortality risk following spontaneous preterm birth: A retrospective cohort study.

OBJECTIVE: To determine whether women with spontaneous preterm birth (PTB) have increased risks for long-term mortality. DESIGN: Retrospective cohort. SETTING: Births in Utah between 1939 and 1977. POPULATION: We included women with a singleton live birth ≥20 weeks who survived at least 1 year following delivery. We excluded those who had never lived in Utah, had improbable birthweight/gestational age combinations, underwent induction (except for preterm membrane rupture) or had another diagnosis likely to cause PTB. METHODS: Exposed women had ≥1 spontaneous PTB between 20+0 weeks and 37+0 weeks. Women with >1 spontaneous PTB were included only once. Unexposed women had all deliveries at or beyond 38+0 weeks. Exposed women were matched to unexposed women by birth year, infant sex, maternal age group and infant birth order. Included women were followed up to 39 years after index delivery. MAIN OUTCOME MEASURES: Overall and cause-specific mortality risks were compared using Cox regression. RESULTS: We included 29 048 exposed and 57 992 matched unexposed women. There were 3551 deaths among exposed (12.2%) and 6013 deaths among unexposed women (10.4%). Spontaneous PTB was associated with all-cause mortality (adjusted hazard ratio [aHR] 1.26, 95% confidence interval [CI] 1.21-1.31), death from neoplasms (aHR 1.10, 95% CI 1.02-1.18), circulatory disease (aHR 1.35, 95% CI 1.25-1.46), respiratory disease (aHR 1.73, 95% CI 1.46-2.06), digestive disease (aHR 1.33, 95% CI 1.12-1.58), genito-urinary disease (aHR 1.60, 95% CI 1.15-2.23) and external causes (aHR 1.39, 95% CI 1.22-1.58). CONCLUSIONS: Spontaneous PTB is associated with modestly increased risks for all-cause and some cause-specific mortality.

Hypertensive disorders of pregnancy and subsequent risk of Alzheimer's disease and other dementias.

Introduction: Women with hypertensive disorders of pregnancy (HDP) have an increased risk of cardiovascular disease. Whether HDP is also associated with later-life dementia has not been fully explored. Methods: Using the Utah Population Database, we performed an 80-year retrospective cohort study of 59,668 parous women. Results: Women with, versus without, HDP, had a 1.37 higher risk of all-cause dementia (95% confidence interval [CI]: 1.26, 1.50) after adjustment for maternal age at index birth, birth year, and parity. HDP was associated with a 1.64 higher risk of vascular dementia (95% CI: 1.19, 2.26) and 1.49 higher risk of other dementia (95% CI: 1.34, 1.65) but not Alzheimer's disease dementia (adjusted hazard ratio = 1.04; 95% CI: 0.87, 1.24). Gestational hypertension and preeclampsia/eclampsia showed similar increased dementia risk. Nine mid-life cardiometabolic and mental health conditions explained 61% of HDP's effect on subsequent dementia risk. Discussion: Improved HDP and mid-life care could reduce the risk of dementia.

The changing food environment and neighborhood prevalence of type 2 diabetes.

In this ecological study, we used longitudinal data to assess if changes in neighborhood food environments were associated with type 2 diabetes mellitus (T2DM) prevalence, controlling for a host of neighborhood characteristics and spatial error correlation. We found that the population-adjusted prevalence of fast-food and pizza restaurants, grocery stores, and full-service restaurants along with changes in their numbers from 1990 to 2010 were associated with 2015 T2DM prevalence. The results suggested that neighborhoods where fast-food restaurants have increased and neighborhoods where full-service restaurants have decreased over time may be especially important targets for educational campaigns or other public health-related T2DM interventions.

Long-term all-cause and cause-specific mortality for four bariatric surgery procedures.

OBJECTIVE: This retrospective study incorporated long-term mortality results after different bariatric surgery procedures and for multiple age at surgery groups. METHODS: Participants with bariatric surgery (surgery) and without (non-surgery) were matched (1:1) for age, sex, BMI, and surgery date with a driver license application/renewal date. Mortality rates were compared by Cox regression, stratified by sex, surgery type, and age at surgery. RESULTS: Participants included 21,837 matched surgery and non-surgery pairs. Follow-up was up to 40 years (mean [SD], 13.2 [9.5] years). All-cause mortality was 16% lower in surgery compared with non-surgery groups (hazard ratio, 0.84; 95% CI: 0.79-0.90; p < 0.001). Significantly lower mortality after bariatric surgery was observed for both females and males. Mortality after surgery versus non-surgery decreased significantly by 29%, 43%, and 72% for cardiovascular disease, cancer, and diabetes, respectively. The hazard ratio for suicide was 2.4 times higher in surgery compared with non-surgery participants (95% CI: 1.57-3.68; p < 0.001), primarily in participants with ages at surgery between 18 and 34 years. CONCLUSIONS: Reduced all-cause mortality was durable for multiple decades, for multiple bariatric surgical procedures, for females and males, and for greater than age 34 years at surgery. Rate of death from suicide was significantly higher in surgery versus non-surgery participants only in the youngest age at surgery participants.

Tobacco use increases the risk of chronic rhinosinusitis among patients undergoing endoscopic sinus surgery.

BACKGROUND: Although it has been postulated that tobacco use, as well as other environmental exposures, may contribute to chronic rhinosinusitis (CRS), the data remain limited. Here, we utilised a large state population database to assess the association between tobacco use and CRS prevalence among patients undergoing endoscopic sinus surgery (ESS). METHODS: Employing a case-control study design, the Utah Population Database was queried for patients age >18 with a diagnosis of CRS and tobacco use who underwent ESS between 1996 and 2018. Smoking status was compared between patients with CRS (n = 34 350) and random population controls matched 5:1 on sex, birth year, birthplace, time residing in Utah, and pedigree (i.e., familial) information (n = 166 020). Conditional logistic regression models were used for comparisons between CRS patients and their matched controls. All analyses were repeated, additionally adjusting for race, ethnicity, tobacco use, asthma history, and interaction between tobacco use and asthma history. RESULTS: A total of 200 370 patients were included in the final analysis. Patients with CRS were significantly more likely to demonstrate a history of tobacco use than controls (19.6% vs. 15.0%; p < .001), with an adjusted odds ratio (aOR) of 1.42, 95% confidence interval 1.37-1.47; p < .001. More patients with CRS and comorbid asthma used tobacco (19.5%) than controls with asthma (15.0%; p < .001). CONCLUSION: History of tobacco use may portend increased risk for the development of CRS among patients undergoing ESS compared to healthy controls.

Familial risk of epithelial ovarian cancer after accounting for gynaecological surgery: a population-based study.

BACKGROUND: Uptake of risk-reducing surgery has increased among women at high risk of epithelial ovarian cancer. We sought to characterise familial risk of epithelial ovarian cancer histotypes in a population-based study after accounting for gynaecological surgeries, including bilateral oophorectomy. METHODS: We compared risk of epithelial ovarian cancer in relatives of 3536 epithelial ovarian cancer cases diagnosed in 1966-2016 and relatives of 35 326 matched controls. We used Cox competing risk models, incorporating bilateral oophorectomy as a competing risk, to estimate the relative risk of ovarian cancer in first-degree (FDR), second-degree (SDR) and third-degree (TDR) relatives from 1966 to 2016. We also estimated relative risks in time periods before (1966-1994, 1995-2004) and after (2005-2016) formal recommendations were made for prophylactic oophorectomy among women with pathogenic variants in BRCA1/2. RESULTS: The relative risks of epithelial ovarian cancer in FDRs, SDRs and TDRs of cases versus controls were 1.68 (95% CI 1.39 to 2.04), 1.51 (95% CI 1.30 to 1.75) and 1.34 (95% CI 1.20 to 1.48), respectively. Relative risks were greatest for high-grade serous, mucinous and 'other epithelial' histotypes. Relative risks were attenuated for case FDRs, but not for SDRs or TDRs, from 2005 onwards, consistent with the timing of recommendations for prophylactic surgery. CONCLUSION: Familial risk of epithelial ovarian cancer extends to TDRs, especially for high-grade serous and mucinous histotypes. Distant relatives share genes but minimal environment, highlighting the importance of germline inherited genetics in ovarian cancer aetiology. Increased ovarian cancer risk in distant relatives has implications for counselling and recommendations for prophylactic surgeries that, from our data, appear only to reach FDRs.

Interpregnancy Body Mass Index Change and Offspring Mortality Risk following the Second Pregnancy.

OBJECTIVE: The aim of the study is to examine the impact of maternal interpregnancy body mass index (BMI) change on subsequent offspring mortality risk. STUDY DESIGN: This is a retrospective cohort study of women who had two consecutive live singleton deliveries of at least 20 weeks' gestation from the Utah Population Database. Our exposure was defined as interpregnancy BMI change from the date of first delivery to the conception date of subsequent pregnancy. We categorized BMI change as: < - 1, -1 to 0, 0 to <1 (reference), 1 to 2, 2 to 4, ≥4 kg/m2. Our primary outcome was all-cause age-specific mortality during four time periods: neonatal (≤28 days), infant (29 days to <1 year old), childhood ((≥1 to <5 years old), and late childhood (5 to <18 years old). We also examined mortality specifically attributed to congenital anomalies. Analyses used Cox proportional hazard models stratified by full term (≥37 weeks) and preterm (<37 weeks) deliveries. All models were adjusted for relevant confounders. RESULTS: Of 266,752 women, among full-term deliveries, women with a BMI increase of 4 kg/m2 or more had an increased risk of neonatal mortality in their subsequent pregnancy (hazard ratio or HR = 1.72, 95% confidence interval or CI: 1.23-2.41) Women who lost 1 kg/m2 or more between deliveries also had increased neonatal mortality (HR = 1.46, 95% CI: 1.04-2.05). There were no differences in infant, early, or late childhood mortality by interpregnancy BMI change. Maternal interpregnancy interval weight loss of 1 kg/m2 or more and weight gain of ≥4 kg/m2 also had increased risk of mortality associated with congenital anomalies or conditions arising during the neonatal period following their subsequent delivery. CONCLUSION: Women with significant interpregnancy weight gain and modest weight loss have a significant increased risk of neonatal mortality following their subsequent pregnancy. KEY POINTS: · Significant weight gain between deliveries increases the risk of neonatal death.. · Modest weight loss between deliveries increases the risk of neonatal death.. · This risk may be partially explained by increased risk of congenital malformations..

Familial aggregation of stillbirth: A pedigree analysis of a matched case-control study.

OBJECTIVE: To determine whether stillbirth aggregates in families and quantify its familial risk using extended pedigrees. DESIGN: State-wide matched case-control study. SETTING: Utah, United States. POPULATION: Stillbirth cases (n = 9404) and live birth controls (18 808) between 1978 and 2019. METHODS: Using the Utah Population Database, a population-based genealogical resource linked with state fetal death and birth records, we identified high-risk pedigrees with excess familial aggregation of stillbirth using the Familial Standardised Incidence Ratio (FSIR). Stillbirth odds ratio (OR) for first-degree relatives (FDR), second-degree relatives (SDR) and third-degree relatives (TDR) of parents with a stillbirth (affected) and live birth (unaffected) were estimated using logistic regression models. MAIN OUTCOME MEASURES: Familial aggregation estimated using FSIR, and stillbirth OR estimated for FDR, SDR and TDR of affected and unaffected parents using logistic regression models. RESULTS: We identified 390 high-risk pedigrees with evidence for excess familial aggregation (FSIR ≥2.00; P-value <0.05). FDRs, SDRs and TDRs of affected parents had 1.14-fold (95% confidence interval [CI]: 1.04-1.26), 1.22-fold (95% CI 1.11-1.33) and 1.15-fold (95% CI 1.08-1.21) higher stillbirth odds compared with FDRs, SDRs and TDRs of unaffected parents, respectively. Parental sex-specific analyses showed male FDRs, SDRs and TDRs of affected fathers had 1.22-fold (95% CI 1.02-1.47), 1.38-fold (95% CI 1.17-1.62) and 1.17-fold (95% CI 1.05-1.30) higher stillbirth odds compared with those of unaffected fathers, respectively. FDRs, SDRs and TDRs of affected mothers had 1.12-fold (95% CI 0.98-1.28), 1.09-fold (95% CI 0.96-1.24) and 1.15-fold (95% CI 1.06-1.24) higher stillbirth odds compared with those of unaffected mothers, respectively. CONCLUSIONS: We provide evidence for familial aggregation of stillbirth. Our findings warrant investigation into genes associated with stillbirth and underscore the need to design large-scale studies to determine the genetic architecture of stillbirth.

Familial Clustering and Genetic Analysis of Severe Thumb Carpometacarpal Joint Osteoarthritis in a Large Statewide Cohort.

PURPOSE: Our goals were to identify individuals who required surgery for thumb carpometacarpal (CMC) joint osteoarthritis (OA), determine if CMC joint OA clusters in families, define the magnitude of familial risk of CMC joint OA, identify risk factors associated with CMC joint OA, and identify rare genetic variants that segregate with familial CMC joint OA. METHODS: We searched the Utah Population Database to identify a cohort of CMC joint OA patients who required surgery. Affected individuals were mapped to pedigrees to identify high-risk families with excess clustering of CMC joint OA. Cox regression models were used to calculate familial risk of CMC joint OA in related individuals. Risk factors were evaluated using logistic regression models. Whole exome sequencing was used to identify rare coding variants associated with familial CMC joint OA. RESULTS: We identified 550 pedigrees with excess clustering of severe CMC joint OA. The relative risk of CMC joint OA requiring surgical treatment was elevated significantly in first- and third-degree relatives of affected individuals, and significant associations with advanced age, female sex, obesity, and tobacco use were observed. We discovered candidate genes that dominantly segregate with severe CMC joint OA in 4 independent families, including a rare variant in Chondroitin Sulfate Synthase 3 (CHSY3). CONCLUSIONS: Familial clustering of severe CMC joint OA was observed in a statewide population. Our data indicate that genetic and environmental factors contribute to the disease process, further highlighting the multifactorial nature of the disease. Genomic analyses suggest distinct biological processes are involved in CMC joint OA pathogenesis. CLINICAL RELEVANCE: Awareness of associated comorbidities may guide the diagnosis of CMC joint OA in at-risk populations and help identify individuals who may not do well with nonoperative treatment. Further pursuit of the genes associated with severe CMC joint OA may lead to assays for detection of early stages of disease and have therapeutic potential.

Tobacco Use Increases the Adjusted Risk of Revision Endoscopic Sinus Surgery in Patients With Chronic Rhinosinusitis.

BACKGROUND: Large epidemiologic studies have suggested that a history of tobacco use may be associated with an increased risk of developing chronic rhinosinusitis (CRS). The impact of tobacco use on revision rates of endoscopic sinus surgery (ESS), however, remains limited. OBJECTIVE: This study seeks to define the independent risk of tobacco use (active or prior) on revision rates of ESS among a large cohort of patients with CRS. METHODS: A state population database was queried for patients age ≥18 years with CRS who underwent at least one ESS between 1996 and 2018. Demographic characteristics, history of ESS, and tobacco use status were compared across patients with CRS, using t tests for continuous variables and χ2 tests for categorical variables. Unadjusted and adjusted logistic regression models were used to understand the impact of tobacco status on revision surgery. RESULTS: The final analysis included 34 350 patients (29 916 CRS with no revision surgery and 4434 CRS with revision surgery). Unadjusted regression analysis demonstrated an increased odds of undergoing revision ESS (OR 1.12, 95% CI: 1.00-1.25, P = .05) among males with a history of tobacco use and CRS. Adjusted regression analysis demonstrated that the risk of revision ESS among CRS patients with a history of asthma and tobacco use was 1.72-fold, while the risk among CRS patients who were tobacco users without asthma was 1.11-fold. CONCLUSION: History of tobacco use is an independent risk factor for revision ESS among patients with CRS.