Risk Factors for Postoperative Fever and Systemic Inflammatory Response Syndrome After Ureteroscopy for Stone Disease.

Introduction: Infectious complications after ureteroscopy (URS) for stone disease lead to emergency department visits, hospitalizations, and other costly health care utilization. The objective of our study was to identify risk factors for postoperative fever (POF) and systemic inflammatory response syndrome (SIRS) after URS for stone disease. Materials and Methods: We performed a retrospective cohort study on 2746 patients who underwent 3298 URS for stone disease at Geisinger from 2008 to 2016. A univariate analysis tested the associations between candidate demographic, preoperative, and intraoperative predictors and the primary outcome of POF (temperature >100.4°F) or SIRS. Variables with a p-value of <0.05 on univariate comparisons were entered into a random-effects logistic regression model. The final model used backward elimination random-effects logistic regression to identify predictors most predictive of POF/SIRS. Results: Overall, 229 (6.9%) of 3298 URS had POF/SIRS. On univariate analysis, individuals with POF/SIRS were older, had higher mean body mass index, higher Charlson Comorbidity Index (CCI), bilateral and larger stones, stone location in the kidney, positive preoperative urine culture, pre-stented, and longer surgical times. In the final model, female gender (adjusted odds ratio [OR] 1.6, 95% confidence interval [CI] 1.19-2.15), surgical time (adjusted OR 1.01, 95% CI 1.0-1.01), CCI ≥2 (adjusted OR 1.86, 95% CI 1.29-2.67), and positive preoperative urine culture (adjusted OR 1.53, 95% CI 1.06-2.22) were the most significant predictors of POF/SIRS. Conclusions: Female gender, longer surgical time, medical complexity, and positive preoperative urine culture are associated with POF/SIRS after URS. These data may be used to identify and counsel high-risk individuals.

Exome Sequencing-Based Screening for BRCA1/2 Expected Pathogenic Variants Among Adult Biobank Participants.

Importance: Detection of disease-associated variants in the BRCA1 and BRCA2 (BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals. Objectives: To identify pathogenic and likely pathogenic (P/LP) BRCA1/2 variants in an unselected research cohort, and to characterize the features associated with P/LP variants. Design, Setting, and Participants: This is a cross-sectional study of adult volunteers (n = 50 726) who underwent exome sequencing at a single health care system (Geisinger Health System, Danville, Pennsylvania) from January 1, 2014, to March 1, 2016. Participants are part of the DiscovEHR cohort and were identified through the Geisinger MyCode Community Health Initiative. They consented to a research protocol that included sequencing and return of actionable test results. Clinical data from electronic health records and clinical visits were correlated with variants. Comparisons were made between those with (cases) and those without (controls) P/LP variants in BRCA1/2. Main Outcomes: Prevalence of P/LP BRCA1/2 variants in cohort, proportion of variant carriers not previously ascertained through clinical testing, and personal and family history of relevant cancers among BRCA1/2 variant carriers and noncarriers. Results: Of the 50 726 health system patients who underwent exome sequencing, 50 459 (99.5%) had no expected pathogenic BRCA1/2 variants and 267 (0.5%) were BRCA1/2 carriers. Of the 267 cases (148 [55.4%] were women and 119 [44.6%] were men with a mean [range] age of 58.9 [23-90] years), 183 (68.5%) received clinically confirmed results in their electronic health record. Among the 267 participants with P/LP BRCA1/2 variants, 219 (82.0%) had no prior clinical testing, 95 (35.6%) had BRCA1 variants, and 172 (64.4%) had BRCA2 variants. Syndromic cancer diagnoses were present in 11 (47.8%) of the 23 deceased BRCA1/2 carriers and in 56 (20.9%) of all 267 BRCA1/2 carriers. Among women, 31 (20.9%) of 148 variant carriers had a personal history of breast cancer, compared with 1554 (5.2%) of 29 880 noncarriers (odds ratio [OR], 5.95; 95% CI, 3.88-9.13; P < .001). Ovarian cancer history was present in 15 (10.1%) of 148 variant carriers and in 195 (0.6%) of 29 880 variant noncarriers (OR, 18.30; 95% CI, 10.48-31.4; P < .001). Among 89 BRCA1/2 carriers without prior testing but with comprehensive personal and family history data, 44 (49.4%) did not meet published guidelines for clinical testing. Conclusions and Relevance: This study found that compared with previous clinical care, exome sequencing-based screening identified 5 times as many individuals with P/LP BRCA1/2 variants. These findings suggest that genomic screening may identify BRCA1/2-associated cancer risk that might otherwise remain undetected within health care systems and may provide opportunities to reduce morbidity and mortality in patients.

Burden of Multiple Chronic Conditions among Patients with Urological Cancer.

PURPOSE: We describe age, multiple chronic condition profiles and health system contact in patients with urological cancer. MATERIALS AND METHODS: Using Geisinger Health System electronic health records we identified adult primary care patients and a subset with at least 1 urology encounter between 2001 and 2015. The Agency for Health Care Research and Quality Chronic Condition Indicator and Clinical Classifications Software tools were applied to ICD-9 codes to identify chronic conditions. Multiple chronic conditions were defined as 2 or more chronic conditions. Patients with urological cancer were identified using ICD-9 codes for prostate, bladder, kidney, testis and penile cancer. Inpatient and outpatient visits in the year prior to the most recent encounter were counted to document health system contact. RESULTS: We identified 357,100 primary care and 33,079 urology patients, of whom 4,023 had urological cancer. Patients with urological cancer were older than primary care patients (71 vs 46 years) and they had more median chronic conditions (7 vs 4). Kidney and bladder cancer were the most common chronic conditions (median 8 patients each). Coronary artery disease and chronic kidney disease were common in urological cancer cases compared to mental health conditions in primary care cases. Patients with urological cancer who had multiple chronic conditions had the most health system contact, including 32% with at least 1 hospitalization and 68% with more than 5 outpatient visits during 1 year. CONCLUSIONS: Urology patients are older and more medically complex, especially those with urological cancer than primary care patients. These data may inform care redesign to reduce the treatment burden and improve care coordination in urological cancer cases.

Patient-reported quality of life recovery curves after robotic prostatectomy are similar across body mass index categories.

PURPOSE: To assess the impact of body mass index (BMI) on postoperative recovery curve of urinary and sexual function after robotic-assisted laparoscopic prostatectomy (RALP). We hypothesized that overweight and obese men have different recovery curves than normal weight men. MATERIALS AND METHODS: We reviewed preoperative and postoperative surveys from 691 men who underwent RALP from 2004-2014 in an integrated healthcare delivery system. Survey instruments included: sexual health inventory for men (SHIM), urinary behavior, leakage, and incontinence impact questionnaire (IIQ). A repeated measures analysis with autoregressive covariance structure was employed with linear splines with 2 knots for the time factor. We fit unadjusted and adjusted models and stratified by BMI (under/normal weight, overweight, and obese). Adjusted models included age, race/ethnicity, smoking status, diabetes, operation length, prostate-specific antigen, pathologic stage, nerve-sparing status, and surgery year. RESULTS: Mean age was 59 years. Most men were overweight (43%) and obese (42%). There were no significant differences in mean baseline SHIM, urinary behavior, leakage, and IIQ scores by BMI category. All groups had initial steep declines in urinary and sexual function in the first 3 months after RALP. There were no significant differences in postoperative urinary and sexual function score curves by BMI category. CONCLUSIONS: The pattern of urinary and sexual function recovery was similar across all BMI categories. Overweight and obese men may be counseled that urinary and sexual function recovery curves after surgery is similar to that of normal weight men.

Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study.

The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery.