Publications

Inguinal hernia repair is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop inguinal hernias. We perform a genome-wide association analysis of surgically confirmed inguinal hernias in 72,805 subjects (5,295 cases and 67,510 controls) and confirm top associations in an independent cohort of 92,444 subjects with self-reported hernia repair surgeries (9,701 cases and 82,743 controls). We identify four novel inguinal hernia susceptibility loci in the regions of EFEMP1, WT1, EBF2 and ADAMTS6. Moreover, we observe expression of all four genes in mouse connective tissue and network analyses show an important role for two of these genes (EFEMP1 and WT1) in connective tissue maintenance/homoeostasis. Our findings provide insight into the aetiology of hernia development and highlight genetic pathways for studies of hernia development and its treatment.

BACKGROUND

Access to specialty care remains a challenge for primary care providers and patients. Implementation of electronic referral and/or consultation (eCR) systems provides an opportunity for innovations in the delivery of specialty care. We conducted key informant interviews to identify drivers, facilitators, barriers and evaluation metrics of diverse eCR systems to inform widespread implementation of this model of specialty care delivery.

METHODS

Interviews were conducted with leaders of 16 diverse health care delivery organizations between January 2013 and April 2014. A limited snowball sampling approach was used for recruitment. Content analysis was used to examine key informant interview transcripts.

RESULTS

Electronic referral systems, which provide referral management and triage by specialists, were developed to enhance tracking and operational efficiency. Electronic consultation systems, which encourage bi-directional communication between primary care and specialist providers facilitating longitudinal virtual co-management, were developed to improve access to specialty expertise. Integrated eCR systems leverage both functionalities to enhance the delivery of coordinated, specialty care at the population level. Elements of successful eCR system implementation included executive and clinician leadership, established funding models for specialist clinician reimbursement, and a commitment to optimizing clinician workflows.

CONCLUSIONS

eCR systems have great potential to streamline access to and enhance the coordination of specialty care delivery. While different eCR models help solve different organizational challenges, all require institutional investments for successful implementation, such as funding for program management, leadership and clinician incentives.

OBJECTIVE

To determine whether greater emotional and instrumental support during childhood is associated with less dysregulation across multiple physiological systems in midlife.

METHODS

Data are from participants in the second wave of the Midlife in the United States study (2004-2005) who participated in a clinic-based assessment of health status. Emotional and instrumental support was measured using a seven-item scale (α=0.89) based on participant retrospective self-report. Biological dysregulation was assessed using an allostatic load (AL) score constructed from 24 measures across seven physiological systems (N=1236, aged 34-84 years).

RESULTS

Emotional and instrumental support in childhood was associated with lower AL in a monotonic fashion: compared to individuals in the lowest quartile of support, respondents in the second, third, and fourth quartiles had -0.08 (standard deviation (SD)=0.08), -0.13 (SD=0.08) and -0.21 (SD=0.08) units lower AL, adjusting for age, sex, and race. This pattern was maintained after adjustment for reporting bias, childhood socioeconomic disadvantage, past-year depression, and physician-diagnosed cardiovascular disease or diabetes (p≤0.01). The inflammation and metabolic-lipid subscales showed the strongest associations.

CONCLUSIONS

Greater emotional and instrumental support in childhood was associated with less biological dysregulation in midlife, even after accounting for socioeconomic disadvantage in childhood and other potential confounders.

In COPD, body composition studies have focused primarily on low BMI. We examined obesity (BMI ≥ 30 kg/m(2)) as a risk factor for poor function and longitudinal functional decline. Data from a longitudinal cohort of adults with COPD (n = 1096) and an age- and sex-matched comparison group collected in two in-person visits ∼49 months apart were analyzed. Two measures of functioning were examined: six-minute walk distance (6MWD) and Short Physical Performance Battery (SPPB). Multivariate regression analyses examined relationships of obesity with functioning. Secondary analyses stratified by GOLD classification (GOLD-0/1, GOLD-2, GOLD-3/4). Obesity (53% of COPD cohort) was associated cross-sectionally with 6MWD and SPPB in COPD, and only with 6MWD in the comparison group. Obesity predicted significant functional decline in 6MWD for individuals with COPD (odds ratio (OR) for decline [95% CI] 1.8 [1.1, 2.9]), but not the comparison group. Secondary analyses revealed that the risk of decline was significant only in those with more severe COPD (GOLD 3/4, OR = 2.3 [1.0, 5.4]). Obesity was highly prevalent and was associated with poor function concurrently and with subsequent decline in 6MWD in COPD. Obesity in COPD should be considered a risk not only for more co-morbidities and greater health care use, but also for functional decline.