Markers of kidney function, genetic variation related to cognitive function, and cognitive performance in the UK Biobank.

BACKGROUND: Chronic kidney disease has been linked to worse cognition. However, this association may be dependent on the marker of kidney function used, and studies assessing modification by genetics are lacking. This study examined associations between multiple measures of kidney function and assessed effect modification by a polygenic score for general cognitive function. METHODS: In this cross-sectional study of up to 341,208 European ancestry participants from the UK Biobank study, we examined associations between albuminuria and estimated glomerular filtration rate based on creatinine (eGFRcre) or cystatin C (eGFRcys) with cognitive performance on tests of verbal-numeric reasoning, reaction time and visual memory. Adjustment for confounding factors was performed using multivariate regression and propensity-score matching. Interaction between kidney function markers and a polygenic risk score for general cognitive function was also assessed. RESULTS: Albuminuria was associated with worse performance on tasks of verbal-numeric reasoning (ß(points) = -0.09, p < 0.001), reaction time (ß(milliseconds) = 7.06, p < 0.001) and visual memory (ß(log errors) = 0.013, p = 0.01). A polygenic score for cognitive function modified the association between albuminuria and verbal-numeric reasoning with significantly lower scores in those with albuminuria and a lower polygenic score (p = 0.009). Compared to participants with eGFRcre ≥ 60 ml/min, those with eGFRcre < 60 ml/min had lower verbal-numeric reasoning scores and slower mean reaction times (verbal numeric reasoning ß = -0.11, p < 0.001 and reaction time ß = 6.08, p < 0.001 for eGFRcre < 60 vs eGFRcre ≥ 60). Associations were stronger using cystatin C-based eGFR than creatinine-based eGFR (verbal numeric reasoning ß = -0.21, p < 0.001 and reaction time ß = 11.21, p < 0.001 for eGFRcys < 60 vs eGFRcys ≥ 60). CONCLUSIONS: Increased urine albumin is associated with worse cognition, but this may depend on genetic risk. Cystatin C-based eGFR may better predict cognitive performance than creatinine-based estimates.

Biomarkers of kidney function and cognitive ability: A Mendelian randomization study.

BACKGROUND: Estimated glomerular filtration rate (eGFR), albuminuria and serum uric acid (SUA) are markers of kidney function that have been associated with cognitive ability. However, whether these associations are causal is unclear. METHODS: We performed one-sample Mendelian randomization (MR) to estimate the effects of kidney function markers on cognitive performance using data from the UK Biobank. Polygenic scores for SUA, urine albumin to creatinine ratio (ACR), estimated glomerular filtration rate based on serum creatinine (eGFRcre) and serum cystatin C (eGFRcys) were used as instrumental variables, and cognitive function outcomes included tests of verbal-numeric reasoning, reaction time, visual memory, and numeric memory. RESULTS: We found no evidence of a causal effect of genetically determined SUA, eGFRcre or eGFRcys on cognitive function outcomes. There was no association between a polygenic score for ACR and verbal-numeric reasoning or numeric memory. However, there was suggestive evidence of a relationship between genetically increased ACR and slower reaction time and worse visual memory. ACR was no longer significantly associated with visual memory in analyses using an unweighted polygenic score and in analyses stratified by sex and age category. Pleiotropy adjusted estimates were directionally consistent with those of the principal analysis but overlapped with the null. CONCLUSIONS: This MR study does not support causal effects of SUA, eGFRcre or eGFRcys on cognitive performance. Genetically increased ACR was associated with slower processing speed and visual memory, but results need confirmation in independent samples.

Prevalence and correlates of obstructive lung disease among people who inject drugs, San Diego, California.

BACKGROUND: Pulmonary tissue damage leading to obstructive lung disease (OLD) could result from intravenous administration of insoluble particles found in illicit drugs. This study described the prevalence and identified correlates of OLD among people who inject drugs (PWID). METHODS: In 2012-2016, a community-based cohort of PWID who had injected within the past month were enrolled in a study to assess HIV, hepatitis C virus (HCV) andMycobacterium tuberculosis (Mtb) infections and their related risk factors. Data were obtained through face-to-face interviews, serological testing and spirometry. Baseline data were used for a cross-sectional analysis of the prevalence and correlates of OLD, defined as FEV1/FVC < 0.7. Univariate and multivariable logistic regression were used to identify factors associated with OLD. RESULTS: Among 516 participants who had complete spirometry and interview results, the mean age was 43.3 years, 73.6 % were male, 9.5 % were Black, 91.1 % smoked cigarettes and 18.2 % had OLD. Few (9.6 %) PWID with OLD reported a previous diagnosis of COPD although many (44.7 %) reported related symptoms. Black race (AOR = 2.66, 95 %CI: 1.37, 5.17), pack-years smoked (AOR = 1.06/5 years, 95 %CI: 1.01, 1.12), and duration of injection drug use (AOR = 1.13, 95 %CI: 1.01, 1.27) were independently associated with OLD after controlling for age. CONCLUSIONS: The prevalence of OLD was high in this cohort and associated with Black race and cigarette smoking-known risk factors. In addition, OLD prevalence increased with greater duration of injection drug use, suggesting a link between cumulative exposure to injected insoluble particles and OLD. Further examination of these adulterants and lung pathology are needed.

Association of Race and Major Adverse Cardiac Events (MACE): The Atherosclerosis Risk in Communities (ARIC) Cohort.

BACKGROUND AND AIMS: To evaluate the association of self-reported race with major adverse cardiac events (MACE) and modification of this association by paraoxonase gene (PON1, PON2, and PON3) single nucleotide polymorphisms (SNPs). METHODS: Included in this longitudinal study were 12,770 black or white participants from the Atherosclerosis Risk in Communities (ARIC) cohort who completed a baseline visit (1987-1989) with PON genotyping. Demographic, behavioral, and health information was obtained at baseline. MACE was defined as first occurrence of myocardial infarction, stroke, or CHD-related death through 2004. Cox proportional hazards regression was used to evaluate the association between race and MACE after adjustment for age, gender, and other demographic and cardiovascular risk factors such as diabetes and hypertension. Modification of the association between PON SNPs and MACE was also assessed. RESULTS: Blacks comprised 24.6% of the ARIC cohort; overall, 14.0% of participants developed MACE. Compared with whites, blacks had 1.24 times greater hazard of MACE (OR = 1.24,95%CI = 1.10,1.39) than whites after adjusting for age, gender, BMI, cigarette and alcohol use, educational and marital status, and aspirin use. This association became nonsignificant after further adjustment for high cholesterol, diabetes, and hypertension. None of the evaluated SNPs met the significance level (p < 0.001) after Bonferroni correction for multiple comparisons. CONCLUSIONS: No association between race and MACE was identified after adjusting for high cholesterol, diabetes, and hypertension, suggesting that comorbidities are major determinants of MACE; medical intervention with focus on lifestyle and health management could ameliorate the development of MACE. Further studies are needed to confirm this observation.

Rehabilitation After Total Knee Arthroplasty: Do Racial Disparities Exist?

BACKGROUND: Racial disparities in functional outcomes after total knee arthroplasty (TKA) exist. Whether differences in rehabilitation utilization contribute to these disparities remains to be investigated. METHODS: Among 8349 women enrolled in the prospective Women's Health Initiative cohort who underwent primary TKA between 2006 and 2013, rehabilitation utilization was determined through linked Medicare claims data. Postacute discharge destination (home, skilled nursing facility, and inpatient rehabilitation facility), facility length of stay, and number of home health physical therapy (HHPT) and outpatient physical therapy (OPPT) sessions were compared between racial groups. RESULTS: Non-Hispanic black women had worse physical function (median score, 65 vs 70) and higher likelihood of disability (13.2% vs 6.9%) than non-Hispanic white women before surgery. After TKA, black women were more likely to be discharged postacutely to an institutional facility (64.3% vs 54.5%) than white women, were more likely to receive HHPT services (52.6% vs 47.8%), and received more HHPT and OPPT sessions. After stratification by postacute discharge setting, the likelihood of receipt of HHPT or OPPT services was similar between racial groups. No significant difference in receipt of HHPT or OPPT services was found after use of propensity score weighting to balance health and medical characteristics indicating severity of need for physical therapy services. CONCLUSION: Rehabilitation utilization was generally comparable between black and white women who received TKA when accounting for need. There was no evidence of underutilization of post-TKA rehabilitation services, and thus disparities in post-TKA functional outcomes do not appear to be a result of inequitable receipt of rehabilitation care.

Associations of military divorce with mental, behavioral, and physical health outcomes.

BACKGROUND: Divorce has been linked with poor physical and mental health outcomes among civilians. Given the unique stressors experienced by U.S. service members, including lengthy and/or multiple deployments, this study aimed to examine the associations of recent divorce on health and military outcomes among a cohort of U.S. service members. METHODS: Millennium Cohort participants from the first enrollment panel, married at baseline (2001-2003), and married or divorced at follow-up (2004-2006), (N = 29,314). Those divorced were compared to those who remained married for mental, behavioral, physical health, and military outcomes using logistic regression models. RESULTS: Compared to those who remained married, recently divorced participants were significantly more likely to screen positive for new-onset posttraumatic stress disorder, depression, smoking initiation, binge drinking, alcohol-related problems, and experience moderate weight gain. However, they were also more likely be in the highest 15(th) percentile of physical functioning, and be able to deploy within the subsequent 3-year period after divorce. CONCLUSIONS: Recent divorce among military members was associated with adverse mental health outcomes and risky behaviors, but was also associated with higher odds of subsequent deployment. Attention should be given to those recently divorced regarding mental health and substance abuse treatment and prevention strategies.

Serum 25-hydroxyvitamin D and breast cancer in the military: a case-control study utilizing pre-diagnostic serum.

PURPOSE: The objective of this study was to ascertain whether a relationship exists between pre-diagnostic serum levels of 25-hydroxyvitamin D (25(OH)D) and risk of breast cancer in young women. METHODS: About 600 incident cases of breast cancer were matched to 600 controls as part of a nested case-control study that utilized pre-diagnostic sera. Logistic regression was used to assess the relationship between serum 25(OH)D concentration and breast cancer risk, controlling for race and age. RESULTS: According to the conditional logistic regression for all subjects, odds ratios for breast cancer by quintile of serum 25(OH)D from lowest to highest were 1.2, 1.0, 0.9, 1.1, and 1.0 (reference) (p trend = 0.72). After multivariate regression for subjects whose blood had been collected within 90 days preceding diagnosis, odds ratios for breast cancer by quintile of serum 25(OH)D from lowest to highest were 3.3, 1.9, 1.7, 2.6, and 1.0 (reference) (p trend = 0.09). CONCLUSIONS: An inverse association between serum 25(OH)D concentration and risk of breast cancer was not present in the principal analysis, although an inverse association was present in a small subgroup analysis of subjects whose blood had been collected within 90 days preceding diagnosis. Further prospective studies of 25(OH)D and breast cancer risk are needed.

Does the evidence for an inverse relationship between serum vitamin D status and breast cancer risk satisfy the Hill criteria?

A wide range of epidemiologic and laboratory studies combined provide compelling evidence of a protective role of vitamin D on risk of breast cancer. This review evaluates the scientific evidence for such a role in the context of the A.B. Hill criteria for causality, in order to assess the presence of a causal, inverse relationship, between vitamin D status and breast cancer risk. After evaluation of this evidence in the context of Hill's criteria, it was found that the criteria for a causal relationship were largely satisfied. Studies in human populations and the laboratory have consistently demonstrated that vitamin D plays an important role in the prevention of breast cancer. Vitamin D supplementation is an urgently needed, low cost, effective, and safe intervention strategy for breast cancer prevention that should be implemented without delay. In the meantime, randomized controlled trials of high doses of vitamin D(3) for prevention of breast cancer should be undertaken to provide the necessary evidence to guide national health policy.

Serum 25-hydroxyvitamin D and prevention of breast cancer: pooled analysis.

BACKGROUND: Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been associated with a high risk of breast cancer. Since publication of the most current meta-analysis of 25(OH)D and breast cancer risk, two new nested case-control studies have emerged. MATERIALS AND METHODS: A PubMed search for all case-control studies on risk of breast cancer by 25(OH)D concentration identified 11 eligible studies. Data from all 11 studies were combined in order to calculate the pooled odds ratio of the highest vs. lowest quantile of 25(OH)D across all studies. RESULTS: The overall Peto odds ratio summarizing the estimated risk in the highest compared to the lowest quantile across all 11 studies was 0.61 (95% confidence interval 0.47, 0.80). CONCLUSION: This study supports the hypothesis that higher serum 25(OH)D levels reduce the risk of breast cancer. According to the review of observational studies, a serum 25(OH)D level of 47 ng/ml was associated with a 50% lower risk of breast cancer.

Haemangiomas and associated congenital malformations in a large population-based sample of infants.

Haemangiomas are common, benign, vascular tumours, observed in 4-12% of infants during the first year of life. Most cases progress without complication, yet a small proportion experience life-threatening complications. Concomitant congenital malformations have been reported in a small but significant proportion of haemangioma patients. This study aimed to describe haemangioma cases and to identify patterns of congenital malformations associated with these diagnoses in a large population. Diagnoses of haemangiomas and 21 congenital malformations were extracted from electronic medical records of 467 295 singleton infants born to US military families from 1998 to 2003. Cluster analysis was used to group cases according to these diagnoses. Multivariable logistic regression was used to further explore the associations of the 21 congenital malformations with the diagnosis of haemangioma and to assess the adjusted relationships between a number of characteristics of interest and diagnosis of haemangioma. Clusters found to be associated with haemangioma were characterised by anomalies of the cervix, vagina, and external female genitalia, anophthalmia or microphthalmia, hydrocephalus without spina bifida, and reduction deformities of the brain. Logistic regression identified three congenital malformations significantly associated with haemangioma diagnosis: spina bifida without anencephalus, hydrocephalus without spina bifida, and anomalies of the cervix, vagina and external female genitalia. Characteristics significantly associated with haemangioma included female gender, preterm birth, white non-Hispanic race/ethnicity and increasing maternal age. This exploratory study identified a number of important associations between haemangiomas and congenital malformations that may provide insight into the pathogenesis of these disorders and have possible implications for clinical care.

Environmental interventions for eating and physical activity: a randomized controlled trial in middle schools.

BACKGROUND: Our objective was to evaluate the effects of environmental, policy, and social marketing interventions on physical activity and fat intake of middle school students on campus. DESIGN: Twenty-four middle schools were randomly assigned to intervention or control conditions. Baseline measures were collected in spring 1997, and interventions were conducted during the 1997-1998 and 1998-1999 school years SETTING/PARTICIPATION: The schools had mean enrollments of 1109, with 44.5% nonwhite students. Over 2 years, physical activity interventions were designed to increase physical activity in physical education classes and throughout the school day. Nutrition interventions were designed to provide and market low-fat foods at all school food sources, including cafeteria breakfasts and lunches, a la carte sources, school stores, and bag lunches. School staff and students were engaged in policy change efforts, but there was no classroom health education. MAIN OUTCOMES MEASURES: Primary outcomes were measured by direct observation and existing records. RESULTS: Randomized regression models (N =24 schools) revealed a significant intervention effect for physical activity for the total group (p <0.009) and boys (p <0.001), but not girls (p <0.40). The intervention was not effective for total fat (p <0.91) or saturated fat (p <0.79). Survey data indicated that the interventions reduced reported body mass index for boys (p <0.05). CONCLUSIONS: Environmental and policy interventions were effective in increasing physical activity at school among boys but not girls. The interventions were not effective in reducing fat intake at school. School environmental and policy interventions have the potential to improve health behavior of the student population, but barriers to full implementation need to be better understood and overcome.