Medical imaging utilization and associated radiation exposure in children with down syndrome.

OBJECTIVE: To evaluate the frequency of medical imaging or estimated associated radiation exposure in children with Down syndrome. METHODS: This retrospective cohort study included 4,348,226 children enrolled in six U.S. integrated healthcare systems from 1996-2016, 3,095 of whom were diagnosed with Down syndrome. We calculated imaging rates per 100 person years and associated red bone marrow dose (mGy). Relative rates (RR) of imaging in children with versus without Down syndrome were estimated using overdispersed Poisson regression. RESULTS: Compared to other children, children with Down syndrome received imaging using ionizing radiation at 9.5 times (95% confidence interval[CI] = 8.2-10.9) the rate when age <1 year and 2.3 times (95% CI = 2.0-2.5) between ages 1-18 years. Imaging rates by modality in children <1 year with Down syndrome compared with other children were: computed tomography (6.6 vs. 2.0, RR = 3.1[95%CI = 1.8-5.1]), fluoroscopy (37.1 vs. 3.1, RR 11.9[95%CI 9.5-14.8]), angiography (7.6 vs. 0.2, RR = 35.8[95%CI = 20.6-62.2]), nuclear medicine (6.0 vs. 0.6, RR = 8.2[95% CI = 5.3-12.7]), radiography (419.7 vs. 36.9, RR = 11.3[95%CI = 10.0-12.9], magnetic resonance imaging(7.3 vs. 1.5, RR = 4.2[95% CI = 3.1-5.8]), and ultrasound (231.2 vs. 16.4, RR = 12.6[95% CI = 9.9-15.9]). Mean cumulative red bone marrow dose from imaging over a mean of 4.2 years was 2-fold higher in children with Down syndrome compared with other children (4.7 vs. 1.9mGy). CONCLUSIONS: Children with Down syndrome experienced more medical imaging and higher radiation exposure than other children, especially at young ages when they are more vulnerable to radiation. Clinicians should consider incorporating strategic management decisions when imaging this high-risk population.

Changes in Cervical Cytology Results and Human Papillomavirus Types Among Persons Screened for Cervical Cancer, 2007 and 2015-2017.

OBJECTIVES: Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015-2017 compared with 2007. MATERIALS AND METHODS: Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015-2017. RESULTS: Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015-2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015-2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups. CONCLUSIONS: Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015-2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement.

Endocrine therapy initiation among women with stage I-III invasive, hormone receptor-positive breast cancer from 2001-2016.

PURPOSE: This retrospective cohort study examined patterns of endocrine therapy initiation over time and by demographic, tumor, and treatment characteristics. METHODS: We included 7777 women from three U.S. integrated healthcare systems diagnosed with incident stage I-III hormone receptor-positive breast cancer between 2001 and 2016. We extracted endocrine therapy from pharmacy dispensings, defining initiation as dispensings within 12 months of diagnosis. Demographic, tumor, and treatment characteristics were collected from electronic health records. Using generalized linear models with a log link and Poisson distribution, we estimated initiation of any endocrine therapy, tamoxifen, and aromatase inhibitors (AI) over time with relative risks (RR) and 95% confidence intervals (CI) adjusted for age, tumor characteristics, diagnosis year, other treatment, and study site. RESULTS: Among women aged 20+ (mean 62 years), 6329 (81.4%) initiated any endocrine therapy, and 1448 (18.6%) did not initiate endocrine therapy. Tamoxifen initiation declined from 67 to 15% between 2001 and 2016. AI initiation increased from 6 to 69% between 2001 and 2016 in women aged ≥ 55 years. The proportion of women who did not initiate endocrine therapy decreased from 19 to 12% between 2002 and 2014 then increased to 17% by 2016. After adjustment, women least likely to initiate endocrine therapy were older (RR = 0.81, 95% CI 0.77-0.85 for age 75+ vs. 55-64), Black (RR = 0.93, 95% CI 0.87-1.00 vs. white), and had stage I disease (RR = 0.88, 95% CI 0.85-0.91 vs. stage III). CONCLUSIONS: Despite an increase in AI use over time, at least one in six eligible women did not initiate endocrine therapy, highlighting opportunities for improving endocrine therapy uptake in breast cancer survivors.

Positive predictive value and sensitivity of ICD-9-CM codes for identifying pediatric leukemia.

BACKGROUND: To facilitate community-based epidemiologic studies of pediatric leukemia, we validated use of ICD-9-CM diagnosis codes to identify pediatric leukemia cases in electronic medical records of six U.S. integrated health plans from 1996-2015 and evaluated the additional contributions of procedure codes for diagnosis/treatment. PROCEDURES: Subjects (N = 408) were children and adolescents born in the health systems and enrolled for at least 120 days after the date of the first leukemia ICD-9-CM code or tumor registry diagnosis. The gold standard was the health system tumor registry and/or medical record review. We calculated positive predictive value (PPV) and sensitivity by number of ICD-9-CM codes received in the 120-day period following and including the first code. We evaluated whether adding chemotherapy and/or bone marrow biopsy/aspiration procedure codes improved PPV and/or sensitivity. RESULTS: Requiring receipt of one or more codes resulted in 99% sensitivity (95% confidence interval [CI]: 98-100%) but poor PPV (70%; 95% CI: 66-75%). Receipt of two or more codes improved PPV to 90% (95% CI: 86-93%) with 96% sensitivity (95% CI: 93-98%). Requiring at least four codes maximized PPV (95%; 95% CI: 92-98%) without sacrificing sensitivity (93%; 95% CI: 89-95%). Across health plans, PPV for four codes ranged from 84-100% and sensitivity ranged from 83-95%. Including at least one code for a bone marrow procedure or chemotherapy treatment had minimal impact on PPV or sensitivity. CONCLUSIONS: The use of diagnosis codes from the electronic health record has high PPV and sensitivity for identifying leukemia in children and adolescents if more than one code is required.

Long-term medical imaging use in children with central nervous system tumors.

BACKGROUND: Children with central nervous system (CNS) tumors undergo frequent imaging for diagnosis and follow-up, but few studies have characterized longitudinal imaging patterns. We described medical imaging in children before and after malignant CNS tumor diagnosis. PROCEDURE: We conducted a retrospective cohort study of children aged 0-20 years diagnosed with CNS tumors between 1996-2016 at six U.S. integrated healthcare systems and Ontario, Canada. We collected computed topography (CT), magnetic resonance imaging (MRI), radiography, ultrasound, nuclear medicine examinations from 12 months before through 10 years after CNS diagnosis censoring six months before death or a subsequent cancer diagnosis, disenrollment from the health system, age 21 years, or December 31, 2016. We calculated imaging rates per child per month stratified by modality, country, diagnosis age, calendar year, time since diagnosis, and tumor grade. RESULTS: We observed 1,879 children with median four years follow-up post-diagnosis in the U.S. and seven years in Ontario, Canada. During the diagnosis period (±15 days of diagnosis), children averaged 1.10 CTs (95% confidence interval [CI] 1.09-1.13) and 2.14 MRIs (95%CI 2.12-2.16) in the U.S., and 1.67 CTs (95%CI 1.65-1.68) and 1.86 MRIs (95%CI 1.85-1.88) in Ontario. Within one year after diagnosis, 19% of children had ≥5 CTs and 45% had ≥5 MRIs. By nine years after diagnosis, children averaged one MRI and one radiograph per year with little use of other imaging modalities. CONCLUSIONS: MRI and CT are commonly used for CNS tumor diagnosis, whereas MRI is the primary modality used during surveillance of children with CNS tumors.

Incidence of herpes zoster among varicella-vaccinated children, by number of vaccine doses and simultaneous administration of measles, mumps, and rubella vaccine.

INTRODUCTION: Children may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration. METHODS: In six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003-2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR. RESULTS: Among 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups. CONCLUSIONS: HZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.

Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier.

BACKGROUND: Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date. METHODS: A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score. RESULTS: Over a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19-1.50, p < 0.001), while age, serum PSA, biopsy GG, and clinical T-stage were not (all p > 0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19-1.48, p < 0.001) and GC high-risk (vs low-risk, HR: 2.95, 95% CI: 1.79-4.87, p < 0.001) were significantly associated with metastasis. The addition of GC score to regression models based on NCCN risk group improved model AUC from 0.46 to 0.67, and CAPRA from 0.59 to 0.71. CONCLUSIONS: Among men with high-risk prostate cancer, conventional clinico-pathologic data had poor discrimination to risk stratify development of metastatic disease. GC score was a significant and independent predictor of metastasis and may help identify men best suited for treatment intensification/de-escalation.

External validation of the EORTC and NCCN bladder cancer recurrence and progression risk calculators in a U.S. community-based health system.

OBJECTIVES: To externally validate the European Organization for the Research and Treatment of Cancer (EORTC) risk calculator and National Comprehensive Cancer Network (NCCN) guidelines in a contemporary population of U.S. non-muscle-invasive bladder cancer (NMIBC) patients treated in a community-based setting and compare our findings to those from another U.S. health system. MATERIALS AND METHODS: We identified 1,491 NMIBC patients with a median follow-up of 2.1 years (recurrence) and 4.1 years (progression). We calculated NCCN risk groupings and EORTC prognostic index for recurrence and progression. We followed Royston and Altman's guidelines for the external validation of prognostic calculators. RESULTS: For predicting recurrence using the EORTC framework, Harrell's C (a measure of discrimination) was smaller in our sample (0.66) than in the European Association of Urology sample (0.61), whereas for progression, Harrell's C was larger in our sample (0.78 vs. 0.75). The EORTC calculator overestimated progression risk in the highest stratum for our sample; calibration and discrimination were adequate for all groups except the highest risk group. For NCCN risk groupings, Harrell's C was 0.54 for recurrence and 0.62 for progression, suggesting poor to fair discrimination in our sample. The NCCN framework had slightly better performance for predicting progression vs. recurrence. CONCLUSIONS: Existing NMIBC risk-stratification frameworks have acceptable accuracy to predict outcomes. However, further innovation in NMIBC care will require predictive tools with more granularity to reflect the differential risks of subgroups of NMIBC recurrence, prior treatment histories, and other prognostic variables.

Bariatric Surgery is Associated With Reduced Risk of Breast Cancer in Both Premenopausal and Postmenopausal Women.

OBJECTIVE: This retrospective cohort study examined whether bariatric surgery is associated with reduced risk of breast cancer among pre- and postmenopausal women. BACKGROUND: Obesity is associated with increased risk of breast cancer, but the impact of weight loss on breast cancer risk has been difficult to quantify. METHODS: The cohort included obese (body mass index ≥35 kg/m) patients enrolled in an integrated health care delivery system between 2005 and 2012 (with follow-up through 2014). Female bariatric surgery patients (N = 17,998) were matched on body mass index, age, study site, and comorbidity index to 53,889 women with no bariatric surgery. Kaplan-Meier curves and Cox proportional hazards models were used to examine incident breast cancer up to 10 years after bariatric surgery. Pre- and postmenopausal women were examined separately, and further classified by estrogen receptor (ER) status. RESULTS: The analysis included 301 premenopausal and 399 postmenopausal breast cancer cases. In multivariable adjusted models, bariatric surgery was associated with a reduced risk of both premenopausal (HR = 0.72, 95% CI, 0.54-0.94) and postmenopausal (HR = 0.55, 95% CI, 0.42-0.72) breast cancer. Among premenopausal women, the effect of bariatric surgery was more pronounced among ER-negative cases (HR = 0.36, 95% CI, 0.16-0.79). Among postmenopausal women, the effect was more pronounced in ER-positive cases (HR = 0.52, 95% CI, 0.39-0.70). CONCLUSIONS: Bariatric surgery was associated with a reduced risk of breast cancer among severely obese women. These findings have significant public health relevance because the prevalence of obesity continues to rise, and few modifiable breast cancer risk factors have been identified, especially for premenopausal women.

Trends in Medical Imaging During Pregnancy in the United States and Ontario, Canada, 1996 to 2016.

Importance: The use of medical imaging has sharply increased over the last 2 decades. Imaging rates during pregnancy have not been quantified in a large, multisite study setting. Objective: To evaluate patterns of medical imaging during pregnancy. Design, Setting, and Participants: A retrospective cohort study was performed at 6 US integrated health care systems and in Ontario, Canada. Participants included pregnant women who gave birth to a live neonate of at least 24 weeks' gestation between January 1, 1996, and December 31, 2016, and who were enrolled in the health care system for the entire pregnancy. Exposures: Computed tomography (CT), magnetic resonance imaging, conventional radiography, angiography and fluoroscopy, and nuclear medicine. Main Outcomes and Measures: Imaging rates per pregnancy stratified by country and year of child's birth. Results: A total of 3 497 603 pregnancies in 2 211 789 women were included. Overall, 26% of pregnancies were from US sites. Most (92%) were in women aged 20 to 39 years, and 85% resulted in full-term births. Computed tomography imaging rates in the United States increased from 2.0 examinations/1000 pregnancies in 1996 to 11.4/1000 pregnancies in 2007, remained stable through 2010, and decreased to 9.3/1000 pregnancies by 2016, for an overall increase of 3.7-fold. Computed tomography rates in Ontario, Canada, increased more gradually by 2.0-fold, from 2.0/1000 pregnancies in 1996 to 6.2/1000 pregnancies in 2016, which was 33% lower than in the United States. Overall, 5.3% of pregnant women in US sites and 3.6% in Ontario underwent imaging with ionizing radiation, and 0.8% of women at US sites and 0.4% in Ontario underwent CT. Magnetic resonance imaging rates increased steadily from 1.0/1000 pregnancies in 1996 to 11.9/1000 pregnancies in 2016 in the United States and from 0.5/1000 pregnancies in 1996 to 9.8/1000 pregnancies in 2016 in Ontario, surpassing CT rates in 2013 in the United States and in 2007 in Ontario. In the United States, radiography rates doubled from 34.5/1000 pregnancies in 1996 to 72.6/1000 pregnancies in 1999 and then decreased to 47.6/1000 pregnancies in 2016; rates in Ontario slowly increased from 36.2/1000 pregnancies in 1996 to 44.7/1000 pregnancies in 2016. Angiography and fluoroscopy and nuclear medicine use rates were low (5.2/1000 pregnancies), but in most years, higher in Ontario than the United States. Imaging rates were highest for women who were younger than 20 years or aged 40 years or older, gave birth preterm, or were black, Native American, or Hispanic (US data only). Considering advanced imaging only, chest imaging of pregnant women was more likely to use CT in the United States and nuclear medicine imaging in Ontario. Conclusions and Relevance: The use of CT during pregnancy substantially increased in the United States and Ontario over the past 2 decades. Imaging rates during pregnancy should be monitored to avoid unnecessary exposure of women and fetuses to ionizing radiation.

Incidence of Herpes Zoster Among Children: 2003-2014.

BACKGROUND AND OBJECTIVES: After the 1996 introduction of routine varicella vaccination in the United States, most studies evaluating pediatric herpes zoster (HZ) incidence reported lower incidence over time, with varying degrees of decline. Using the combined databases of 6 integrated health care organizations, we examined HZ incidence in children over a 12-year period in the varicella vaccine era. METHODS: This study included children aged 0 through 17 years from 2003 through 2014. Using electronic medical records, we identified HZ cases through International Classification of Diseases, Ninth Revision diagnosis code 053. We calculated HZ incidence rates per 100 000 person years of health plan membership for all children and among children who were vaccinated versus unvaccinated. We calculated rates for the 12-year period and examined temporal trends. Among children who were vaccinated, we compared HZ rates by month and year of age at vaccination. RESULTS: The study included 6 372 067 children with ≥1 month of health plan membership. For the 12-year period, the crude HZ incidence rate for all subjects was 74 per 100 000 person years, and the rate among children who were vaccinated was 38 per 100 000 person years, which was 78% lower than that among children who were unvaccinated (170 per 100 000 person years; P < .0001). Overall HZ incidence declined by 72% (P < .0001) from 2003 through 2014. Annual rates in children who were vaccinated were consistently lower than in children who were unvaccinated. CONCLUSIONS: With this population-based study, we confirm the decline in pediatric HZ incidence and the significantly lower incidence among children who are vaccinated, reinforcing the benefit of routine varicella vaccination to prevent pediatric HZ.

Factors That Influence Selectionof Urinary Diversion Among Bladder Cancer Patients in 3 Community-based Integrated Health Care Systems.

OBJECTIVE: To assess the relative contributions of patient and surgeon factors for predicting selection of ileal conduit (IC), neobladder (NB), or continent pouch (CP) urinary diversions (UD) for patients diagnosed with muscle-invasive/high-risk nonmuscle invasive bladder cancer. This information is needed to enhance research comparing cancer survivors' outcomes across different surgical treatment options. METHODS: Bladder cancer patients' age ≥21 years with cystectomy/UD performed from January 2010 to June 2015 in 3 Kaiser Permanente regions were included. All patient and surgeon data were obtained from electronic health records. A mixed effects logistic regression model was used treating surgeon as a random effect and region as a fixed effect. RESULTS: Of 991 eligible patients, 794 (80%) received IC. One hundred sixty-nine surgeons performed the surgeries and accounted for a sizeable proportion of the variability in patient receipt of UD (intraclass correlation coefficient = 0.26). The multilevel model with only patient factors showed good fit (area under the curve = 0.93, Hosmer-Lemeshow test P = .44), and older age, female sex, estimated glomerular filtration rate <45, 4+ comorbidity index score, and stage III/IV tumors were associated with higher odds of receiving an IC vs neobladder/continent pouch. However, including surgeon factors (annual cystectomy volume, specialty training, clinical tenure) had no association (P = .29). CONCLUSION: In this community setting, patient factors were major predictors of UD received. Surgeons also played a substantial role, yet clinical training and experience were not major predictors. Surgeon factors such as beliefs about UD options and outcomes should be explored.

Bariatric Surgery and the Risk of Cancer in a Large Multisite Cohort.

OBJECTIVE: To determine whether bariatric surgery is associated with a lower risk of cancer. BACKGROUND: Obesity is strongly associated with many types of cancer. Few studies have examined the relationship between bariatric surgery and cancer risk. METHODS: We conducted a retrospective cohort study of patients undergoing bariatric surgery between 2005 and 2012 with follow-up through 2014 using data from a large integrated health insurance and care delivery systems with 5 study sites. The study included 22,198 subjects who had bariatric surgery and 66,427 nonsurgical subjects matched on sex, age, study site, body mass index, and Elixhauser comorbidity index. Multivariable Cox proportional-hazards models were used to examine incident cancer up to 10 years after bariatric surgery compared to the matched nonsurgical patients. RESULTS: After a mean follow-up of 3.5 years, we identified 2543 incident cancers. Patients undergoing bariatric surgery had a 33% lower hazard of developing any cancer during follow-up [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.60, 0.74, P < 0.001) compared with matched patients with severe obesity who did not undergo bariatric surgery, and results were even stronger when the outcome was restricted to obesity-associated cancers (HR 0.59, 95% CI 0.51, 0.69, P < 0.001). Among the obesity-associated cancers, the risk of postmenopausal breast cancer (HR 0.58, 95% CI 0.44, 0.77, P < 0.001), colon cancer (HR 0.59, 95% CI 0.36, 0.97, P = 0.04), endometrial cancer (HR 0.50, 95% CI 0.37, 0.67, P < 0.001), and pancreatic cancer (HR 0.46, 95% CI 0.22, 0.97, P = 0.04) was each statistically significantly lower among those who had undergone bariatric surgery compared with matched nonsurgical patients. CONCLUSIONS: In this large, multisite cohort of patients with severe obesity, bariatric surgery was associated with a lower risk of incident cancer, particularly obesity-associated cancers, such as postmenopausal breast cancer, endometrial cancer, and colon cancer. More research is needed to clarify the specific mechanisms through which bariatric surgery lowers cancer risk.

The Use of 5-Alpha Reductase Inhibitors to Manage Benign Prostatic Hyperplasia and the Risk of All-cause Mortality.

OBJECTIVE: To compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. METHODS: We employed a retrospective matched cohort study in 4 regions of an integrated healthcare system. Men aged 50 years and older who initiated pharmaceutical treatment for BPH and/or lower urinary tract symptoms between 1992 and 2008 and had at least 3 consecutive prescriptions that were eligible and followed through 2010 (N = 174,895). Adjusted hazard ratios were used to estimate the risk of mortality due to all-causes associated with 5ARI use (with or without concomitant ABs) as compared to AB use. RESULTS: In this large and diverse sample with 543,523 person-years of follow-up, 35,266 men died during the study period, 18.9% of the 5ARI users and 20.4% of the AB users. After adjustment for age, medication initiation year, race, region, prior AB history, Charlson score, and comorbidities, 5ARI use was not associated with an increased risk of mortality when compared to AB use (Adjusted hazard ratios: 0.64, 95% confidence interval: 0.62, 0.66). CONCLUSION: Among men receiving medications for BPH in community practice settings, 5ARI use was not associated with an increased risk of mortality when compared to AB use. These data provide reassurance about the safety of using 5ARIs in general practice to manage BPH and/or lower urinary tract symptoms.

Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

Association Between Weight Loss and the Risk of Cancer after Bariatric Surgery.

OBJECTIVE: The goal of this study was to determine whether the reduction in cancer risk after bariatric surgery is due to weight loss. METHODS: A retrospective matched cohort study of patients undergoing bariatric surgery was conducted using data from a large integrated health insurance and care delivery system with five sites in four states. The study included 18,355 bariatric surgery subjects and 40,524 nonsurgical subjects matched on age, sex, BMI, site, and Elixhauser comorbidity index. Multivariable Cox proportional hazards models examined the relationship between weight loss at 1 year and incident cancer during up to 10 years of follow-up. RESULTS: The study identified 1,196 cases of incident cancer. The average 1-year postsurgical weight loss was 27% among patients undergoing bariatric surgery versus 1% in matched nonsurgical patients. Percent weight loss at 1 year was significantly associated with a reduced risk of any cancer in adjusted models (HR 0.897, 95% CI: 0.832-0.968, P = 0.005 for every 10% weight loss) while bariatric surgery was not a significant independent predictor of cancer incidence. CONCLUSIONS: Weight loss after bariatric surgery was associated with a lower risk of incident cancer. There was no apparent independent effect of the bariatric surgery itself on cancer risk that was independent of weight loss.

Pregnancy Outcomes after Treatment for Cervical Cancer Precursor Lesions: An Observational Study.

OBJECTIVE: To examine whether surgical procedures involving the uterine cervix were associated with pregnancy outcomes, including preterm birth, low birth weight, cesarean delivery and pregnancy loss. DESIGN: Population-based observational study nested in retrospective matched cohort. SETTING: Kaiser Permanente Northwest integrated health plan in Oregon/Washington, U.S.A. POPULATION: Female health plan members age 14-53 years with documented pregnancies from 1998-2009. Women with prior excisional and ablative cervical surgical procedures (N = 322) were compared to women unexposed to cervical procedures (N = 4,307) and, separately, to those having undergone only diagnostic/biopsy procedures (N = 847). METHODS: Using log-linear regression models, we examined risk of adverse pregnancy outcomes in relation to prior excisional or ablative cervical surgical procedures. We stratified excisional procedures by excision thickness. We evaluated for confounding by age, body mass index, race, smoking history, previous preterm birth, and parity. RESULTS: We found a positive association between excisional treatment > = 1.0 cm and the outcomes preterm birth and low birth weight (preterm birth unadjusted risk ratio [RR] = 2.15, 95% confidence interval [CI] 1.16-3.98 for excisions ≥1.0 cm compared to unexposed women), particularly in women who delivered within one year of surgery (RR = 3.26, 95% CI 1.41-7.53). There was no clear association between excisional treatment and cesarean delivery, and treated women did not have a substantially higher risk of dysfunctional labor. Ablative treatment was not associated with low birth weight, preterm birth, or cesarean delivery but was associated with pregnancy loss (RR = 1.43, 95% CI 1.05-1.93 vs. unexposed women). Analyses using the diagnostic procedures comparison group produced similar results. CONCLUSION: Women with > = 1.0 cm excisional treatment had elevated risk of preterm birth and low birth weight when compared to unexposed women and women with cervical diagnostic procedures. This suggests that increased risk derives from the treatment itself, not from other characteristics. The observed association between pregnancy loss and ablative surgical treatment requires further investigation.

Harms of cervical cancer screening in the United States and the Netherlands.

We studied harms related to cervical cancer screening and management of screen-positive women in the United States (US) and the Netherlands. We utilized data from four US integrated health care systems (SEARCH), the US National Health Interview Survey, New Mexico state, the Netherlands national histopathology registry, and included studies on adverse health effects of cervical screening. We compared the number of Papanicolaou (Pap) smear tests, abnormal test results, punch biopsies, treatments, health problems (anxiety, pain, bleeding and discharge) and preterm births associated with excisional treatments. Results were age-standardized to the 2007 US population. Based on SEARCH, an estimated 36 million Pap tests were performed in 2007 for 91 million US women aged 21-65 years, leading to 2.3 million abnormal Pap tests, 1.5 million punch biopsies, 0.3 million treatments for precancerous lesions, 5 thousand preterm births and over 8 million health problems. Under the Netherlands screening practice, fewer Pap tests (58%), abnormal test results (64%), punch biopsies (75%), treatment procedures (40%), preterm births (60%) and health problems (63%) would have occurred. The SEARCH data did not differ much from other US data for 2007 or from more recent data up to 2013. Thus compared to the less intensive screening practice in the Netherlands, US practice of cervical cancer screening may have resulted in two- to threefold higher harms, while the effects on cervical cancer incidence and mortality are similar. The results are also of high relevance in making recommendations for HPV screening. Systematic collection of harms data is needed for monitoring and for better incorporation of harms in making screening recommendations.

Occupational exposures and chronic obstructive pulmonary disease (COPD): comparison of a COPD-specific job exposure matrix and expert-evaluated occupational exposures.

OBJECTIVES: To compare the occupational exposure levels assigned by our National Institute for Occupational Safety and Health chronic obstructive pulmonary disease-specific job exposure matrix (NIOSH COPD JEM) and by expert evaluation of detailed occupational information for various jobs held by members of an integrated health plan in the Northwest USA. METHODS: We analysed data from a prior study examining COPD and occupational exposures. Jobs were assigned exposure levels using 2 methods: (1) the COPD JEM and (2) expert evaluation. Agreement (Cohen's κ coefficients), sensitivity and specificity were calculated to compare exposure levels assigned by the 2 methods for 8 exposure categories. RESULTS: κ indicated slight to moderate agreement (0.19-0.51) between the 2 methods and was highest for organic dust and overall exposure. Sensitivity of the matrix ranged from 33.9% to 68.5% and was highest for sensitisers, diesel exhaust and overall exposure. Specificity ranged from 74.7% to 97.1% and was highest for fumes, organic dust and mineral dust. CONCLUSIONS: This COPD JEM was compared with exposures assigned by experts and offers a generalisable approach to assigning occupational exposure.

5-Alpha Reductase Inhibitors and the Risk of Prostate Cancer Mortality in Men Treated for Benign Prostatic Hyperplasia.

OBJECTIVE: To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. PATIENTS AND METHODS: A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. RESULTS: In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). CONCLUSION: Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.