Effect of Health Service Area on Primary Care Physician Provision of Low-Value Cancer Screening.

BACKGROUND: Using a health systems approach to investigate low-value care (LVC) may provide insights into structural drivers of this pervasive problem. OBJECTIVE: To evaluate the influence of service area practice patterns on low-value mammography and prostate-specific antigen (PSA) testing. DESIGN: Retrospective study analyzing LVC rates between 2008 and 2018, leveraging physician relocation in 3-year intervals of matched physician and patient groups. SETTING: U.S. Medicare claims data. PARTICIPANTS: 8254 physicians and 56 467 patients aged 75 years or older. MEASUREMENTS: LVC rates for physicians staying in their original service area and those relocating to new areas. RESULTS: Physicians relocating from higher-LVC areas to low-LVC areas were more likely to provide lower rates of LVC. For mammography, physicians staying in high-LVC areas (LVC rate, 10.1% [95% CI, 8.8% to 12.2%]) or medium-LVC areas (LVC rate, 10.3% [CI, 9.0% to 12.4%]) provided LVC at a higher rate than physicians relocating from those areas to low-LVC areas (LVC rates, 6.0% [CI, 4.4% to 7.5%] [difference, -4.1 percentage points {CI, -6.7 to -2.3 percentage points}] and 5.9% [CI, 4.6% to 7.8%] [difference, -4.4 percentage points {CI, -6.7 to -2.4 percentage points}], respectively). For PSA testing, physicians staying in high- or moderate-LVC service areas provided LVC at a rate of 17.5% (CI, 14.9% to 20.7%) or 10.6% (CI, 9.6% to 13.2%), respectively, compared with those relocating from those areas to low-LVC areas (LVC rates, 9.9% [CI, 7.5% to 13.2%] [difference, -7.6 percentage points {CI, -10.9 to -3.8 percentage points}] and 6.2% [CI, 3.5% to 9.8%] [difference, -4.4 percentage points {CI, -7.6 to -2.2 percentage points}], respectively). Physicians relocating from lower- to higher-LVC service areas were not more likely to provide LVC at a higher rate. LIMITATION: Use of retrospective observational data, possible unmeasured confounding, and potential for relocating physicians to practice differently from those who stay. CONCLUSION: Physicians relocating to service areas with lower rates of LVC provided less LVC than physicians who stayed in areas with higher rates of LVC. Systemic structures may contribute to LVC. Understanding which factors are contributing may present opportunities for policy and interventions to broadly improve care. PRIMARY FUNDING SOURCE: National Cancer Institute of the National Institutes of Health.

Familial Associations of Prevalence and Cause-Specific Mortality for Thoracic Aortic Disease and Bicuspid Aortic Valve in a Large-Population Database.

BACKGROUND: Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database. METHODS: In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands. RESULTS: The study population included 3 812 588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62-8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80-6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25-5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68-4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93-5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82-13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44-3.29]) compared with controls. CONCLUSIONS: Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. This study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection.

Describing patterns of familial cancer risk in subfertile men using population pedigree data.

STUDY QUESTION: Can we simultaneously assess risk for multiple cancers to identify familial multicancer patterns in families of azoospermic and severely oligozoospermic men? SUMMARY ANSWER: Distinct familial cancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in familial cancer risk by both type of subfertility and within subfertility type. WHAT IS KNOWN ALREADY: Subfertile men and their relatives show increased risk for certain cancers including testicular, thyroid, and pediatric. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of subfertile men (N = 786) was identified and matched to fertile population controls (N = 5674). Family members out to third-degree relatives were identified for both subfertile men and fertile population controls (N = 337 754). The study period was 1966-2017. Individuals were censored at death or loss to follow-up, loss to follow-up occurred if they left Utah during the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Azoospermic (0 × 106/mL) and severely oligozoospermic (<1.5 × 106/mL) men were identified in the Subfertility Health and Assisted Reproduction and the Environment cohort (SHARE). Subfertile men were age- and sex-matched 5:1 to fertile population controls and family members out to third-degree relatives were identified using the Utah Population Database (UPDB). Cancer diagnoses were identified through the Utah Cancer Registry. Families containing ≥10 members with ≥1 year of follow-up 1966-2017 were included (azoospermic: N = 426 families, 21 361 individuals; oligozoospermic: N = 360 families, 18 818 individuals). Unsupervised clustering based on standardized incidence ratios for 34 cancer phenotypes in the families was used to identify familial multicancer patterns; azoospermia and severe oligospermia families were assessed separately. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to control families, significant increases in cancer risks were observed in the azoospermia cohort for five cancer types: bone and joint cancers hazard ratio (HR) = 2.56 (95% CI = 1.48-4.42), soft tissue cancers HR = 1.56 (95% CI = 1.01-2.39), uterine cancers HR = 1.27 (95% CI = 1.03-1.56), Hodgkin lymphomas HR = 1.60 (95% CI = 1.07-2.39), and thyroid cancer HR = 1.54 (95% CI = 1.21-1.97). Among severe oligozoospermia families, increased risk was seen for three cancer types: colon cancer HR = 1.16 (95% CI = 1.01-1.32), bone and joint cancers HR = 2.43 (95% CI = 1.30-4.54), and testis cancer HR = 2.34 (95% CI = 1.60-3.42) along with a significant decrease in esophageal cancer risk HR = 0.39 (95% CI = 0.16-0.97). Thirteen clusters of familial multicancer patterns were identified in families of azoospermic men, 66% of families in the azoospermia cohort showed population-level cancer risks, however, the remaining 12 clusters showed elevated risk for 2-7 cancer types. Several of the clusters with elevated cancer risks also showed increased odds of cancer diagnoses at young ages with six clusters showing increased odds of adolescent and young adult (AYA) diagnosis [odds ratio (OR) = 1.96-2.88] and two clusters showing increased odds of pediatric cancer diagnosis (OR = 3.64-12.63). Within the severe oligozoospermia cohort, 12 distinct familial multicancer clusters were identified. All 12 clusters showed elevated risk for 1-3 cancer types. An increase in odds of cancer diagnoses at young ages was also seen in five of the severe oligozoospermia familial multicancer clusters, three clusters showed increased odds of AYA diagnosis (OR = 2.19-2.78) with an additional two clusters showing increased odds of a pediatric diagnosis (OR = 3.84-9.32). LIMITATIONS, REASONS FOR CAUTION: Although this study has many strengths, including population data for family structure, cancer diagnoses and subfertility, there are limitations. First, semen measures are not available for the sample of fertile men. Second, there is no information on medical comorbidities or lifestyle risk factors such as smoking status, BMI, or environmental exposures. Third, all of the subfertile men included in this study were seen at a fertility clinic for evaluation. These men were therefore a subset of the overall population experiencing fertility problems and likely represent those with the socioeconomic means for evaluation by a physician. WIDER IMPLICATIONS OF THE FINDINGS: This analysis leveraged unique population-level data resources, SHARE and the UPDB, to describe novel multicancer clusters among the families of azoospermic and severely oligozoospermic men. Distinct overall multicancer risk and familial multicancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in cancer risk by type of subfertility and within subfertility type. Describing families with similar cancer risk patterns provides a new avenue to increase homogeneity for focused gene discovery and environmental risk factor studies. Such discoveries will lead to more accurate risk predictions and improved counseling for patients and their families. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): R01 HD106112). The authors have no conflicts of interest relevant to this work. TRIAL REGISTRATION NUMBER: N/A.

Evaluating county-level lung cancer incidence from environmental radiation exposure, PM2.5, and other exposures with regression and machine learning models.

Characterizing the interplay between exposures shaping the human exposome is vital for uncovering the etiology of complex diseases. For example, cancer risk is modified by a range of multifactorial external environmental exposures. Environmental, socioeconomic, and lifestyle factors all shape lung cancer risk. However, epidemiological studies of radon aimed at identifying populations at high risk for lung cancer often fail to consider multiple exposures simultaneously. For example, moderating factors, such as PM2.5, may affect the transport of radon progeny to lung tissue. This ecological analysis leveraged a population-level dataset from the National Cancer Institute's Surveillance, Epidemiology, and End-Results data (2013-17) to simultaneously investigate the effect of multiple sources of low-dose radiation (gross [Formula: see text] activity and indoor radon) and PM2.5 on lung cancer incidence rates in the USA. County-level factors (environmental, sociodemographic, lifestyle) were controlled for, and Poisson regression and random forest models were used to assess the association between radon exposure and lung and bronchus cancer incidence rates. Tree-based machine learning (ML) method perform better than traditional regression: Poisson regression: 6.29/7.13 (mean absolute percentage error, MAPE), 12.70/12.77 (root mean square error, RMSE); Poisson random forest regression: 1.22/1.16 (MAPE), 8.01/8.15 (RMSE). The effect of PM2.5 increased with the concentration of environmental radon, thereby confirming findings from previous studies that investigated the possible synergistic effect of radon and PM2.5 on health outcomes. In summary, the results demonstrated (1) a need to consider multiple environmental exposures when assessing radon exposure's association with lung cancer risk, thereby highlighting (1) the importance of an exposomics framework and (2) that employing ML models may capture the complex interplay between environmental exposures and health, as in the case of indoor radon exposure and lung cancer incidence.

A population-wide analysis of the familial risk of suicide in Utah, USA.

BACKGROUND: The degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives. METHODS: A population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (<25 v. ⩾25 years) was examined. RESULTS: Significantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12-3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02-1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99-12.25) in mothers, 6.39 in sisters (95% CI 3.78-10.82), and 5.65 (95% CI 3.38-9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49-5.26). CONCLUSIONS: Elevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed - namely suicidal young adults and women with a strong family history of suicide.

The Association Between Family History and Diverticulitis Recurrence: A Population-Based Study.

BACKGROUND: After initial nonoperative management of diverticulitis, individuals with a family history of diverticulitis may have increased risk of recurrent disease. OBJECTIVE: This study measured the association between family history and recurrent diverticulitis in a population-based cohort. DESIGN: This is a retrospective, population-based cohort study. SETTINGS: The cohort was identified from the Utah Population Database, a statewide resource linking hospital and genealogy records. PATIENTS: Individuals evaluated in an emergency department or hospitalized between 1998 and 2018 for nonoperatively managed diverticulitis were included. INTERVENTION: The primary predictor was a positive family history of diverticulitis, defined as diverticulitis in a first-, second-, or third-degree relative. MAIN OUTCOME MEASURES: This study measured the adjusted association between family history and the primary outcome of recurrent diverticulitis. A secondary outcome was elective surgery for diverticulitis. Additional analyses evaluated risk by degree of relation of the affected family member. RESULTS: The cohort included 4426 individuals followed for a median of 71 months. Median age was 64 years and 45% were male; 17% had complicated disease, 11% had recurrence, and 15% underwent elective surgery. After adjustment, individuals with a family history of diverticulitis had a similar risk of recurrence when compared to those without a family history (HR 1.0; 95% CI 0.8-1.2). However, individuals with a family history of diverticulitis were more likely to undergo elective surgery (HR 1.4; 95% CI 1.1-1.6). This effect was most pronounced in those with an affected first-degree family member (HR 1.7; 95% CI 1.4-2.2). LIMITATIONS: The use of state-specific data may limit generalizability. CONCLUSIONS: In this population-based analysis, individuals with a family history of diverticulitis were more likely to undergo elective surgery than those without a family history, despite similar risks of recurrence and complicated diverticulitis. Further work is necessary to understand the complex social, environmental, and genetic factors that influence diverticulitis treatment and outcomes. See Video Abstract at http://links.lww.com/DCR/B876 . ASOCIACIN ENTRE LOS ANTECEDENTES FAMILIARES Y LA RECURRENCIA DE LA DIVERTICULITIS UN ESTUDIO POBLACIONAL: ANTECEDENTES:Después del tratamiento inicial no quirúrgico de la diverticulitis, las personas con antecedentes familiares de diverticulitis pueden tener un mayor riesgo de enfermedad recurrente.OBJETIVO:Este estudio midió la asociación entre antecedentes familiares y diverticulitis recurrente en una cohorte poblacional.DISEÑO:Este es un estudio de cohorte retrospectivo de la población.ENTORNO CLÍNICO:La cohorte se identificó a partir de la Base de datos de población de Utah, un recurso estatal que vincula los registros hospitalarios y genealógicos.PACIENTES:Se incluyeron individuos evaluados en un departamento de emergencias u hospitalizados entre 1998 y 2018 por diverticulitis manejada de forma no quirúrgica.INTERVENCIÓN:El predictor principal fue un historial familiar positivo de diverticulitis, definida como diverticulitis en un familiar de primer, segundo o tercer grado.PRINCIPALES MEDIDAS DE VALORACIÓN:Este estudio midió la asociación ajustada entre los antecedentes familiares y el resultado primario de diverticulitis recurrente. Un resultado secundario fue la cirugía electiva por diverticulitis. Análisis adicionales evaluaron el riesgo por grado de parentesco del familiar afectado.RESULTADOS:La cohorte incluyó a 4.426 individuos seguidos durante una mediana de 71 meses. La mediana de edad fue de 64 años y el 45% eran varones. El 17% tenía enfermedad complicada, el 11% recidiva y el 15% se sometió a cirugía electiva. Después del ajuste, los individuos con antecedentes familiares de diverticulitis tenían un riesgo similar de recurrencia en comparación con aquellos sin antecedentes familiares (HR 1,0; IC del 95%: 0,8-1,2). Sin embargo, las personas con antecedentes familiares de diverticulitis tenían más probabilidades de someterse a una cirugía electiva (HR 1,4; IC del 95%: 1,1-1,6). Este efecto fue más pronunciado en aquellos con un familiar de primer grado afectado (HR 1,7; IC del 95%: 1,4-2,2).LIMITACIONES:El uso de datos específicos del estado puede limitar la generalización.CONCLUSIONES:En este análisis poblacional, los individuos con antecedentes familiares de diverticulitis tenían más probabilidades de someterse a una cirugía electiva que aquellos sin antecedentes familiares, a pesar de riesgos similares de recurrencia y diverticulitis complicada. Es necesario seguir trabajando para comprender los complejos factores sociales, ambientales y genéticos que influyen en el tratamiento y los resultados de la diverticulitis. Consulte Video Resumen en http://links.lww.com/DCR/B876 . (Traducción-Dr. Ingrid Melo ).

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.

Geographic Proximity of Family Members and Healthcare Utilization After Complex Surgical Procedures.

OBJECTIVE: We sought to determine the relationship between a patient's proximal familial social support, defined as the geographic proximity of family members, and healthcare utilization after complex cardiovascular and oncologic procedures. BACKGROUND: Social support mechanisms are increasingly identified as modifiable risk factors for healthcare utilization. METHODS: We performed a retrospective cohort study of 60,895 patients undergoing complex cardiovascular procedures or oncologic procedures. We defined healthcare utilization outcomes as 30-day all-cause readmission unplanned readmission, nonindex hospital readmission, index hospital length of stay, and home discharge disposition. For each patient, we aggregated the number of first-degree relatives (FDR) living within 30 miles of the patient's home address at the time of the surgical procedure into the following categories: 0 to 1, 2 to 3, 4 to 5, 6+ FDRs. We developed hierarchical multivariable regression models to determine the relationship between the number of FDR living within 30 miles of the patient and the healthcare utilization outcomes. RESULTS: Compared with patients with 0 to 1 FDRs, patients with 6+ FDRs living in close proximity had significantly lower rates of all-cause readmission (12.1% vs 13.5%, P <0.001), unplanned readmission (10.9% vs 12.0%, P =0.001), nonindex readmission (2.6% vs 3.2%, P =0.003); higher rates of home discharge (88.0% vs 85.3%, P <0.001); and shorter length of stay (7.3 vs 7.5 days, P =0.02). After multivariable adjustment, a larger number of FDRs living within 30 miles of the patient was significantly associated with a lower likelihood of all-cause readmission ( P <0.001 for trend), 30-day unplanned readmission ( P <0.001), nonindex readmission ( P <0.001); higher likelihood of home discharge ( P <0.001); and shorter index length of stay ( P <0.001). CONCLUSIONS: The geographic proximity of family members is significantly associated with decreased healthcare utilization after complex cardiovascular and oncologic surgical procedures.

Nephrectomy Is Not Associated with Increased Risk of Mortality or Acute Kidney Injury after High-Grade Renal Trauma: A Propensity Score Analysis of the Trauma Quality Improvement Program (TQIP).

PURPOSE: Patients with high-grade renal trauma (HGRT) undergoing nephrectomy may be at higher risk for mortality compared to those treated conservatively. However, no study has controlled for degree of hemorrhage as a measure of shock. We hypothesized that after controlling for blood transfusions and other factors, nephrectomy after HGRT would be associated with increased mortality and acute kidney injury (AKI). MATERIALS AND METHODS: We identified adult patients with HGRT (American Association for the Surgery of Trauma grade III-V) in TQIP (2013-2017). Propensity scoring was used to adjust for the probability of nephrectomy. Conditional logistic regression was used to analyze the association between nephrectomy and mortality and AKI. We adjusted for patient characteristics, injury specifics, and physiological factors including blood transfusions. RESULTS: There were 12,780 patients with HGRT, and 1,014 (7.9%) underwent nephrectomy. Mortality was 10.6% and 4.2% in the nephrectomy and nonnephrectomy groups, respectively (p <0.001). In nephrectomy patients, 8.6% experienced AKI vs 2.4% of nonnephrectomy patients (p <0.001). In the adjusted analysis, there was no association between nephrectomy and mortality (OR=0.367, 95% CI 0.09-1.497, p=0.162). There was also no association between nephrectomy and AKI. Increasing age, nonCaucasian race, increasing Injury Severity Score, decreasing Glasgow Coma Score and blood transfusions were associated with higher mortality. For AKI, independent predictors included increasing age, male sex, and blood transfusions. CONCLUSIONS: After adjusting for volume of blood transfused in the first 24 hours, nephrectomy after HGRT was not associated with increased mortality or AKI. As a clinical principle, trauma nephrectomy should be avoided when possible.

Seasonal variation in semen quality is not associated with fecundity in the Utah Population Database.

We determine whether a suspected seasonal variability in semen quality affect subsequent live birth rates. This is a retrospective, cohort analysis of men who provided semen analyses as part of fertility workup through a large andrology lab between 1996 and 2013 and corresponding birth rates using the Utah Population Database (UPDB). Semen parameters were analysed including total motile count (TMC), total sperm count, sperm concentration and progressive motility. Corresponding live births reflect those born in the state of Utah and were derived from birth certificate data available in the UPDB. Descriptive statistics were reported along with linear regression analysis with mixed effected models to test for an interaction between seasonal variation in semen quality and birth rates, accounting for age at the time of the semen analysis and abstinence time. A total of 11,929 patients and 14,765 semen samples were included. Only 3597 men (39% of men) had one or more values outside the World Health Organization reference range for their semen parameters. Linear regression demonstrated a consistent U-shaped relationship between TMC, total sperm count, and sperm concentration and season, with spring and winter yielding the highest values with a decline in the summer and fall. 7319 of these males had recorded live births for a total of 13,502 live births during the study period after a median follow-up of 7.2 years (IQR: 3.9-11.0). We did not find a significant interaction between specific semen parameters for a specific season and subsequent live births. Semen quality was the highest in the spring and winter, however there was no interaction between seasonal variability in semen quality and subsequent births. This is one of the largest studies describing seasonal variation in semen quality in humans.

Lower female partner live birth rate in male cancer survivors: An age-matched cohort analysis of the Utah Population Database.

We determine the time to first live birth for female partners of males after a cancer diagnosis. Our group performed a retrospective, population-based, age-matched cohort study of Utah male residents diagnosed with cancer at age 18 years or later between 1956 and 2013 (exposed) matched to male Utah residents without cancer diagnosis (unexposed). Using stratified Cox proportional hazard models, we adjusted for race, ethnicity and number of live births prior to cancer diagnosis, to estimate the effect of time to a partner live birth following cancer diagnosis. Our study cohort included 19,303 men diagnosed with cancer (exposed) and 93,608 age-matched men without cancer diagnoses (unexposed). Exposed men were less likely to have a live birth prior to first cancer diagnosis (60.7% vs. 65.4%, p < 0.001) and after first cancer diagnosis (10.9% vs. 12.2%, p < 0.001) compared to unexposed men. Exposed men had a fertility hazard rate that was 31% lower after cancer diagnosis date than unexposed men (HR: 0.69; 95% CI: 0.65-0.72). This was most profound for men aged 18-30 years (HR: 0.59, 95% CI: 0.55-0.63). Male cancer survivors have a 31% lower female partner live birth rate after cancer diagnosis. These findings are important for patient counselling regarding fertility preservation at the time of cancer diagnosis.

Decision fatigue in low-value prostate cancer screening.

BACKGROUND: Low-value prostate-specific antigen (PSA) testing is common yet contributes substantial waste and downstream patient harm. Decision fatigue may represent an actionable target to reduce low-value urologic care. The objective of this study was to determine whether low-value PSA testing patterns by outpatient clinicians are consistent with decision fatigue. METHODS: Outpatient appointments for adult men without prostate cancer were identified at a large academic health system from 2011 through 2018. The authors assessed the association of appointment time with the likelihood of PSA testing, stratified by patient age and appropriateness of testing based on clinical guidelines. Appointments included those scheduled between 8:00 am and 4:59 pm, with noon omitted. Urologists were examined separately from other clinicians. RESULTS: In 1,581,826 outpatient appointments identified, the median patient age was 54 years (interquartile range, 37-66 years), 1,256,152 participants (79.4%) were White, and 133,693 (8.5%) had family history of prostate cancer. PSA testing would have been appropriate in 36.8% of appointments. Clinicians ordered testing in 3.6% of appropriate appointments and in 1.8% of low-value appointments. Appropriate testing was most likely at 8:00 am (reference group). PSA testing declined through 11:00 am (odds ratio [OR], 0.57; 95% CI, 0.50-0.64) and remained depressed through 4:00 pm (P < .001). Low-value testing was overall less likely (P < .001) and followed a similar trend, declining steadily from 8:00 am (OR, 0.48; 95% CI, 0.42-0.56) through 4:00 pm (P < .001; OR, 0.23; 95% CI, 0.18-0.30). Testing patterns in urologists were noticeably different. CONCLUSIONS: Among most clinicians, outpatient PSA testing behaviors appear to be consistent with decision fatigue. These findings establish decision fatigue as a promising, actionable target for reducing wasteful and low-value practices in routine urologic care. LAY SUMMARY: Decision fatigue causes poorer choices to be made with repetitive decision making. This study used medical records to investigate whether decision fatigue influenced clinicians' likelihood of ordering a low-value screening test (prostate-specific antigen [PSA]) for prostate cancer. In more than 1.5 million outpatient appointments by adult men without prostate cancer, the chances of both appropriate and low-value PSA testing declined as the clinic day progressed, with a larger decline for appropriate testing. Testing patterns in urologists were different from those reported by other clinicians. The authors conclude that outpatient PSA testing behaviors appear to be consistent with decision fatigue among most clinicians, and interventions may reduce wasteful testing and downstream patient harms.

Nephrectomy is Associated with Increased Mortality after Renal Trauma: An Analysis of the National Trauma Data Bank from 2007-2016.

PURPOSE: The majority of high grade renal trauma can be managed conservatively. However, nephrectomy is still common for acute management. We hypothesized that when controlling for multiple injury severity measures, nephrectomy would be associated with increased mortality. MATERIALS AND METHODS: We identified high grade renal trauma patients from the National Trauma Data Bank® from 2007-2016. Exclusion criteria were age <18 years, severe head injury and death within 4 hours of admission. We performed conditional logistic regression analysis to determine if nephrectomy was independently associated with mortality, controlling for age, gender, race/ethnicity, mechanism of injury, shock, blood transfusion, Glasgow Coma Scale, Revised Trauma Score and Injury Severity Score. Interaction was measured for mechanism of injury and shock with mortality. RESULTS: We identified 42,898 patients with high grade renal trauma (grade III-V), of whom 3,204 (7.5%) underwent nephrectomy. Unadjusted mortality was 16.6% in nephrectomy vs 5.7% in nonnephrectomy patients. In multivariable logistic regression, nephrectomy was associated with 82% increased odds of death (OR 1.82, 95% CI 1.63-2.03, p <0.001). Other significant associations with death included age, nonWhite race, penetrating mechanism, hypotension, blood transfusion, lower Glasgow Coma Scale, lower Revised Trauma Score and higher Injury Severity Score. The association between nephrectomy and death did not differ by mechanism of injury. However, it was slightly attenuated in patients presenting in shock. CONCLUSIONS: In the National Trauma Data Bank, nephrectomy is independently associated with increased risk of mortality after adjusting for patient demographics, injury characteristics and multiple measures of overall injury severity. Nephrectomy may impact overall survival and must be avoided when possible.

Semen parameter thresholds and time-to-conception in subfertile couples: how high is high enough?

STUDY QUESTION: What thresholds for total sperm count, sperm concentration, progressive motility, and total progressive motile sperm count (TPMC) are associated with earlier time-to-conception in couples undergoing fertility evaluation? SUMMARY ANSWER: Values well above the World Health Organization (WHO) references for total sperm count, concentration, and progressive motility, and values up to 100 million for TPMC were consistently associated with earlier time-to-conception and higher conception rates. WHAT IS KNOWN ALREADY: Although individual semen parameters are generally not able to distinguish between fertile and infertile men, they can provide clinically useful information on time-to-pregnancy for counseling patients seeking fertility treatment. Compared to the conventional semen parameters, TPMC might be a better index for evaluating the severity of male infertility. STUDY DESIGN, SIZE, DURATION: We used data from a longitudinal cohort study on subfertile men from 2002 to 2017 and included 6061 men with initial semen analysis (SA) in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men from subfertile couples who underwent a SA within the study period were included, and 5-year follow-up data were collected to capture conception data. Couples were further categorized into two subgroups: natural conception (n = 5126), after separating those who achieved conception using ART or IUI; natural conception without major female factor (n = 3753), after separating those with severe female factor infertility diagnoses. TPMC was calculated by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm (%). Cox proportional hazard models were used to report hazard ratios (HRs) with 95% CIs before and after adjusting for male age, the number of previous children before the first SA, and income. Using the regression tree method, we calculated thresholds for total sperm count, sperm concentration, progressive motility, and TPMC to best differentiate those who were more likely to conceive within 5 years after first SA from those less likely to conceive. We also plotted continuous values of semen parameters in predicting 5-year conception rates and time-to-conception. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, the median time to conception was 22 months (95% CI: 21-23). A total of 3957 (65%) couples were known to have achieved conception within 5 years of the first SA. These patients were younger and had higher values of sperm concentration, progressive motility, and TPMC. In the overall cohort, a TPMC of 50 million best differentiated men who were more likely to father a child within 5 years. Partners of men with TPMC ≥50 million had a 45% greater chance of conception within 5 years in the adjusted model (HR: 1.45; 95% CI: 1.34-1.58) and achieved pregnancy earlier compared to those men with TPMC < 50 million (median 19 months (95% CI: 18-20) versus 36 months (95% CI: 32-41)). Similar results were observed in the natural conception cohort. For the natural conception cohort without major female factor, the TPMC cut-off was 20 million. In the visual assessment of the graphs for the continuous semen parameter values, 5-year conception rates and time-to-conception consistently plateaued at higher values of sperm concentration, total sperm count, progressive motility, and TPMC compared to the WHO reference levels and our calculated thresholds. For TPMC, values up to 100-150 million were still associated with a better conception rate and time-to-conception in the visual assessment of the curves. LIMITATIONS, REASONS FOR CAUTION: There was limited information on female partners and potential for inaccuracies in capturing less severe female infertility diagnoses. Also we lacked details on assisted pregnancies achieved outside of our healthcare network (with possible miscoding as 'natural conception' in our cohort). We only used the initial SA and sperm morphology, another potentially important parameter, was not included in the analyses. We had no information on continuity of pregnancy attempts/intention, which could affect the time-to-conception data. Finally, most couples had been attempting conception for >12 months prior to initiating fertility treatment, so it is likely that we are underestimating time to conception. Importantly, our data might lack the generalizability to other populations. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that a TPMC threshold of 50 million sperm provided the best predictive power to estimate earlier time-to-conception in couples evaluated for male factor infertility. Higher values of sperm count, concentration and progressive motility beyond the WHO references were still associated with better conception rates and time-to-conception. This provides an opportunity to optimize semen parameters in those with semen values that are low but not abnormal according to the WHO reference values. These data can be used to better inform patients regarding their chances of conception per year when SA results are used for patient counseling. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Are paternal or grandmaternal age associated with higher probability of trisomy 21 in offspring? A population-based, matched case-control study, 1995-2015.

BACKGROUND: Fetal aneuploidy risk increases with maternal age, but the majority of pregnancies complicated by trisomy 21 occur in younger women. It has been suggested that grandmaternal and/or paternal age may also play a role. OBJECTIVES: To assess the association between grandmaternal and paternal age and trisomy 21. METHODS: For the grandmaternal assessments, we included all offspring with trisomy 21 in a statewide birth defects surveillance system (1995-2015) that could be linked to 3-generation matrilineal pedigrees in the Utah Population Database. Ten sex/birth year-matched controls were selected for each case (770 cases and 7700 controls). For the paternal assessments, our cohort included all trisomy 21 cases (1995-2015) where both the mother and father resided in Utah at the time of birth (1409 cases and 14 090 controls). Ages were categorised by 5-year intervals (reference: 25-29 years). Conditional logistic regression, adjusting for potential confounding factors, was used to model the association between grandmaternal and paternal age and trisomy 21. RESULTS: No association between grandmaternal age and trisomy 21 was detected, whether age was assessed continuously (adjusted odds ratio [OR] 1.01, 95% confidence interval [CI] 0.98, 1.03) or categorically after adjusting for grandmaternal and grandpaternal race/ethnicity and grandpaternal age. Compared to fathers aged 20-29 years, fathers <20 years (OR 3.15, 95% CI 1.99, 4.98) and 20-24 years (OR 1.39, 95% CI 1.11, 1.73) had increased odds of trisomy 21 offspring, after adjusting for maternal and paternal race/ethnicity and maternal age. Results were consistent after excluding stillbirths, multiples, and trisomy 21 due to translocation or mosaicism. CONCLUSIONS: Maternal age is an important risk factor for trisomy 21 offspring; however, this population-based study shows that that young paternal age is also associated with trisomy 21, after taking into account maternal age and race/ethnicity.

Lower total motile count is associated with smaller historic intergenerational family size: a pedigree analysis from the Utah Population Database.

PURPOSE: To describe the association between contemporary total motile count (TMC), a measure of male factor infertility, and historic intergenerational family size. METHODS: This is a retrospective, population-based, cohort study of men who underwent semen analysis for infertility workup at University of Utah, with at least a single measure of TMC, who were linked to extensive genealogical data. Two thousand one hundred eighty-two pedigree branches of men with a measure of TMC within the UPDB were identified. We identified the average number of generations and offspring within each generation. Conditional logistic regression models were used to assess the association between the risk of having a TMC in the 5th or 25th percentile and intergenerational family size. Generalized estimating equations (GEE) were used to assess the association between interval-level TMC and the number of ancestral offspring. RESULTS: We found no association between intergenerational size and TMC within the 5th percentile (TMC < 4 million; RR = 0.97, 95% CI 0.93-1.01) or the 25th percentile (TMC < 62 million; RR = 1.00, 95% CI 0.97-1.03). When TMC was analyzed as a continuous variable, we found that lower TMC is associated with smaller intergenerational family size. For every additional child in their ancestral pedigree, we observed an increase in TMC of 1.88 million (p = 0.03). Men in the top quartile for intergenerational family size had a TMC that was 48 million higher than men in the bottom quartile (p = 0.047). CONCLUSIONS: We found an association between TMC and ancestral family size, suggesting that lower TMC is associated with smaller intergenerational family size.

Spatial clusters of cancer incidence: analyzing 1940 census data linked to 1966-2017 cancer records.

PURPOSE: A life course perspective to cancer incidence is important for understanding effects of the environment during early life on later cancer risk. We assessed spatial clusters of cancer incidence based on early life location defined as 1940 US Census Enumeration District (ED). METHODS: A cohort of 260,585 individuals aged 0-40 years in 1940 was selected. Individuals were followed from 1940 to cancer diagnosis, death, or last residence in Utah. We geocoded ED centroids in Utah for the 1940 Census. Spatial scan statistics with purely spatial elliptic scanning window were used to identify spatial clusters of EDs with excess cancer rates across 26 cancer types, assuming a discrete Poisson model. RESULTS: Cancer was diagnosed in 66,904 (25.67%) individuals during follow-up across 892 EDs. Average follow-up was 50.9 years. We detected 15 clusters of excess risk for bladder, breast, cervix, colon, lung, melanoma, oral, ovary, prostate, and soft tissue cancers. An urban area had dense overlap of multiple cancer types, including two EDs at increased risk for five cancer types each. CONCLUSIONS: Early environments may contribute to cancer risk later in life. Life course perspectives applied to the study of cancer incidence can provide insights for increasing understanding of cancer etiology.

The Effects of Marital Status, Fertility, and Bereavement on Adult Mortality in Polygamous and Monogamous Households: Evidence From the Utah Population Database.

Although the associations among marital status, fertility, bereavement, and adult mortality have been widely studied, much less is known about these associations in polygamous households, which remain prevalent across much of the world. We use data from the Utah Population Database on 110,890 women and 106,979 men born up to 1900, with mortality follow-up into the twentieth century. We examine how the number of wife deaths affects male mortality in polygamous marriages, how sister wife deaths affect female mortality in polygamous marriages relative to the death of a husband, and how marriage order affects the mortality of women in polygamous marriages. We also examine how the number of children ever born and child deaths affect the mortality of men and women as well as variation across monogamous and polygamous unions. Our analyses of women show that the death of a husband and the death of a sister wife have similar effects on mortality. Marriage order does not play a role in the mortality of women in polygamous marriages. For men, the death of one wife in a polygamous marriage increases mortality to a lesser extent than it does for men in monogamous marriages. For polygamous men, losing additional wives has a dose-response effect. Both child deaths and lower fertility are associated with higher mortality. We consistently find that the presence of other kin in the household-whether a second wife, a sister wife, or children-mitigates the negative effects of bereavement.

Balancing revenue generation with capacity generation: case distribution, financial impact and hospital capacity changes from cancelling or resuming elective surgeries in the US during COVID-19.

BACKGROUND: To increase bed capacity and resources, hospitals have postponed elective surgeries, although the financial impact of this decision is unknown. We sought to report elective surgical case distribution, associated gross hospital revenue and regional hospital and intensive care unit (ICU) bed capacity as elective surgical cases are cancelled and then resumed under simulated trends of COVID-19 incidence. METHODS: A retrospective, cohort analysis was performed using insurance claims from 161 million enrollees from the MarketScan database from January 1, 2008 to December 31, 2017. COVID-19 cases were calculated using Institute for Health Metrics and Evaluation models. Centers for Disease Control (CDC) reports on the number of hospitalized and intensive care patients by age estimated the number of cases seen in the ICU, the reduction in elective surgeries and the financial impact of this from historic claims data, using a denominator of all inpatient revenue and outpatient surgeries. RESULTS: Assuming 5% infection prevalence, cancelling all elective procedures decreases ICU overcapacity from 160 to 130%, but these elective surgical cases contribute 78% (IQR 74, 80) (1.1 trillion (T) US dollars) to inpatient hospital plus outpatient surgical gross revenue per year. Musculoskeletal, circulatory and digestive category elective surgical cases compose 33% ($447B) of total revenue. CONCLUSIONS: Procedures involving the musculoskeletal, cardiovascular and digestive system account for the largest loss of hospital gross revenue when elective surgery is postponed. As hospital bed capacity increases following the COVID-19 pandemic, restoring volume of these elective cases will help maintain revenue. In these estimates, adopting universal masking would help to avoid overcapacity in all states.

The Relative Importance of Race Compared to Health Care and Social Factors in Predicting Prostate Cancer Mortality: A Random Forest Approach.

PURPOSE: There is a differential in prostate cancer mortality between black and white men. Advances in precision medicine have shifted the research focus toward underlying genetic differences. However, nonbiological factors may have a large role in these observed disparities. Therefore, we sought to measure the relative importance of race compared to health care and social factors on prostate cancer specific mortality. MATERIALS AND METHODS: Using the SEER (Surveillance, Epidemiology, and End Results) database we identified 514,878 men diagnosed with prostate cancer at age 40 years or greater between 2004 and 2012. We also selected a subset of black and white men matched by age, stage and birth year. We stratified patients by age 40 to 54, 55 to 69 and 70 years or older and disease stage, resulting in 18 groups. By applying random forest methods with variable importance measures we analyzed 15 variables and interactions across 4 categories of factors (tumor characteristics, race, and health care and social factors) and the relative importance for prostate cancer specific mortality. RESULTS: Tumor characteristics at diagnosis were the most important factors for prostate cancer mortality. Across all groups race was less than 5% as important as tumor characteristics and only more important than health care and social factors in 2 of the 18 groups. Although race had a significant impact, health care and social factors known to be associated with racial disparities had greater or similarly important effects across all ages and stages. CONCLUSIONS: Eradicating disparities in prostate cancer survival will require a multipronged approach, including advances in precision medicine. Disparities will persist unless health care access and social equality are achieved among all populations.