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Introduction: Risk of gastric and small intestinal cancer in Lynch syndrome (LS) remains poorly understood. We investigated the risk of gastric and small intestinal cancer in patients with LS in a large, community-based population., Methods: This retrospective cohort study included all patients diagnosed with LS between January 1, 1997, and December 31, 2020, at Kaiser Permanente Northern California. Cumulative incidence of gastric cancer and small intestinal cancer was calculated using competing risk methodology., Results: Among 1,106 patients with LS with a median follow-up of 19.3 years (interquartile range [IQR] 9.4-24.0 years), 11 developed gastric cancer (8 MSH2 , 2 MLH1 and 1 PMS2 ) with a median diagnosis age of 56 years (IQR 42-63 years) and 11 developed small intestinal cancer (6 MSH2 , 3 MLH1 , 1 MSH6 and 1 PMS2 ) with a median diagnosis age of 57 years (IQR 50-66 years). Cumulative incidence by age 80 years was 7.26% (95% confidence internal [CI], 1.80-18.03%) for men and 3.43% (95% CI, 0.50-11.71%) for women for gastric cancer and 7.28% (95% CI, 3.19-13.63%) for men and 2.21% (95% CI, 0.23-9.19%) for women for small intestinal cancer. Pathogenic variant carriers of MSH2 and MLH1 had the highest risk of gastric and small intestinal cancer. History of Helicobacter pylori infection was associated with increased risk of gastric cancer (adjusted odds ratio 5.52; 95% CI, 1.72-17.75)., Discussion: Patients with LS, particularly MSH2 and MLH1 pathogenic variant carriers, had significantly increased lifetime risk of gastric and small intestinal cancer. Testing and treatment of H. pylori infection should be considered for all patients with LS., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Consensus guidelines regarding the amount and necessity of post-operative imaging in thoracic surgery are lacking. The efficacy of daily chest radiographs (CXR) following video-assisted (VATS) and robotic-assisted (RATS) thoracoscopic surgery in directing management has not been previously studied. We hypothesize that abnormal clinical findings, rather than abnormal imaging findings, better predict post-operative complications in patients undergoing VATS/RATS lobectomies., Methods: A retrospective review of VATS and RATS lobectomy patients were performed at a tertiary referral center from 1/1/2019-12/31/2021. Demographics, hospital course, and imaging were evaluated. Descriptive statistics, Chi-Square test, Fisher's exact, Wilcoxon rank sum, and multivariable logistic regression were performed. Our outcomes were post-operative complications requiring a procedure and extended length of stay (LOS) (>2 days post-operatively)., Results: Out of 362 VATS/RATS lobectomy patients, 15 patients had post-operative complications requiring a procedure. Almost all patients who required a procedure had abnormal clinical signs and symptoms (14/15; p  < 0.001) while 70 % had expected post-operative day (POD) one CXR findings (11/15; p  = 0.463). Multivariable logistic regression demonstrated clinical signs and symptoms independently predicted procedural requirement (odds ratio [OR] = 48, 95 % Confidence Interval [CI]:8.5-267) while abnormal POD one imaging did not. For extended LOS, a positive smoking history (OR = 4.4, 95 % CI:1.4-14.1), number of CXRs (OR = 2.4, 95 % CI:1.8-3.2) and thoracostomy tubes (OR = 5.3, 95 % CI:1.0-27.3) were independent predictors while clinical signs and symptoms was not., Conclusion: Abnormal clinical findings may guide management more predictably than abnormal CXRs after VATS/RATS. Routine CXR in the post-operative setting may be unnecessary in those without clinical signs or symptoms., Key Message: There are no consensus guidelines regarding the efficacy of routine, post-operative diagnostic studies after major thoracic lobar resections. The presence of abnormal signs or symptoms after minimally invasive lobectomies may better predict those who will require additional procedures better than the presence of abnormal routine, post-operative chest radiographs., Competing Interests: All authors have no declaration of interests or disclosures to report. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (© 2024 The Authors.)

Open reduction with internal fixation (ORIF) of Lisfranc injuries are associated with an increased risk for secondary surgery including hardware removal and salvage arthrodesis. In the current literature, rates of salvage arthrodesis vary due to small sample sizes and a low incidence of Lisfranc injuries. There is little evidence to identify specific surgical and patient-related variables that may result in later arthrodesis. The purpose of this study is to determine the rate of tarsometatarsal joint arthrodesis following Lisfranc ORIF in a relatively large sample size. This retrospective review included patients who underwent ORIF for a Lisfranc injury between January 2007 and December 2012. A total of 146 patients met our criteria. Trans-articular fixation was used in 109 (74.6%) patients, 33 (22.6%) received percutaneous fixation and 4 (2.7%) extraarticular fixation. Five out of 120 (4.2%) patients required a salvage arthrodesis for post-traumatic arthritis that had a follow-up greater than 5 y but up to 10 y. The mean age of patients who underwent arthrodesis after ORIF was 24.5 ± 11.95 (16-48) y compared to 40.9 ± 15.8 (16-85) y. Patients who required an arthrodesis also had earlier hardware removal than patients who did not have an arthrodesis, 71.2 ± 28.3 (38-100) days and 131.4 ±101.2 (37-606) days, respectively. Patients who required salvage arthrodesis tended to be younger and hardware was removed earlier compared to those patients who did not require an arthrodesis. Four of the 5 patients who underwent a secondary arthrodesis had a loss of correction after hardware removal., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The authors examined recent trends in incidence of psychotic disorders, demographic characteristics, and comorbid psychiatric and medical conditions among six racial/ethnic groups., Method: A retrospective cohort study design was used to examine the incidence of psychotic disorders across race/ethnicity groups and comorbid psychiatric and medical conditions among members of Kaiser Permanente Northern California from 2009 to 2019 (N=5,994,758). Poisson regression was used to assess changes in annual incidence, and Cox proportional hazards and logistic regression models adjusted for age and sex were used to test correlates and consequences., Results: Overall, the incidence of nonaffective psychotic disorders decreased slightly over the study period. Compared with White members, the risk of nonaffective psychosis diagnosis was higher among Black (hazard ratio=2.13, 95% CI=2.02-2.24) and American Indian or Alaskan Native (AIAN) (hazard ratio=1.85, 95% CI=1.53-2.23) members and lower among Asian (hazard ratio=0.72, 95% CI=0.68-0.76) and Hispanic (hazard ratio=0.91, 95% CI=0.87-0.96) members, as well as those whose race/ethnicity was categorized as "other" (hazard ratio=0.92, 95% CI=0.86-0.99). Compared with White members, the risk of affective psychosis diagnosis adjusted for age and sex was higher among Black (hazard ratio=1.76, 95% CI=1.62-1.91), Hispanic (hazard ratio=1.09, 95% CI=1.02-1.16), and AIAN (hazard ratio=1.38, 95% CI=1.00-1.90) members and lower among Asian (hazard ratio=0.77, 95% CI=0.71-0.83), Native Hawaiian or other Pacific Islander (hazard ratio=0.69, 95% CI=0.48-0.99), and "other" (hazard ratio=0.86, 95% CI=0.77-0.96) members. Psychotic disorders were associated with significantly higher odds of suicide (odds ratio=2.65, 95% CI=2.15-3.28), premature death (odds ratio=1.30, 95% CI=1.22-1.39), and stroke (odds ratio=1.64, 95% CI=1.55-1.72) and lower odds of health care utilization (odds ratio=0.44, 95% CI=0.42-0.47)., Conclusions: This study demonstrates racial and ethnic variation in incident psychotic disorder diagnoses in the United States, compared with non-Hispanic Whites. Individuals diagnosed with psychosis face a greater burden of other negative health outcomes and lower odds of health care utilization, reflecting personal and economic impacts. Identifying risk factors for elevated rates and protective influences in subgroups can inform strategies for prevention and interventions to ameliorate severe consequences of psychotic syndromes., Competing Interests: The authors report no financial relationships with commercial interests.

Background: We compared the results of hereditary cancer multigene panel testing among patients ≤ 45 years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in a large integrated health care system., Methods: A retrospective cohort study of hereditary cancer gene testing among women ≤ 45 years of age diagnosed with DCIS or IBC at Kaiser Permanente Northern California between September 2019 and August 2020 was performed. During the study period, institutional guidelines recommended the above population be referred to genetic counselors for pretesting counseling and testing., Results: A total of 61 DCIS and 485 IBC patients were identified. Genetic counselors met with 95% of both groups, and 86.4% of DCIS patients and 93.9% of IBC patients (p = 0.0339) underwent gene testing. Testing differed by race/ethnicity (p = 0.0372). Among those tested, 11.76% (n = 6) of DCIS patients and 16.71% (n = 72) of IBC patients had a pathogenic variant (PV) or likely pathogenic variant (LPV) based on the 36-gene panel (p = 0.3650). Similar trends were seen in 13 breast cancer (BC)-related genes (p = 0.0553). Family history of cancer was significantly associated with both BC-related and non-BC-related PVs in IBC, but not DCIS., Conclusion: In our study, 95% of patients were seen by a genetic counselor when age was used as an eligibility criterion for referral. While larger studies are needed to further compare the prevalence of PVs/LPVs among DCIS and IBC patients, our data suggest that even in younger patients, the prevalence of PVs/LPVs in BC-related genes is lower in DCIS patients., (© 2023. Society of Surgical Oncology.)

Background & Aims: High-quality data regarding the effect of Helicobacter pylori eradication on the risk of noncardia gastric adenocarcinoma (NCGA) remain limited in the United States. We investigated the incidence of NCGA after H pylori eradication therapy in a large, community-based US population., Methods: We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent testing and/or treatment for H pylori between 1997 and 2015 and were followed through December 31, 2018. The risk of NCGA was evaluated using the Fine-Gray subdistribution hazard model and standardized incidence ratios., Results: Among 716,567 individuals with a history of H pylori testing and/or treatment, the adjusted subdistribution hazard ratios and 95% confidence intervals of NCGA for H pylori-positive/untreated and H pylori-positive/treated individuals were 6.07 (4.20-8.76) and 2.68 (1.86-3.86), respectively, compared with H pylori-negative individuals. When compared directly with H pylori-positive/untreated individuals, subdistribution hazard ratios for NCGA in H pylori-positive/treated were 0.95 (0.47-1.92) at <8 years and 0.37 (0.14-0.97) ≥8 years of follow-up. Compared with the Kaiser Permanente Northern California general population, standardized incidence ratios (95% confidence interval) of NCGA steadily decreased after H pylori treatment: 2.00 (1.79-2.24) ≥1 year, 1.01 (0.85-1.19) ≥4 years, 0.68 (0.54-0.85) ≥7 years, and 0.51 (0.38-0.68) ≥10 years., Conclusion: In a large, diverse, community-based population, H pylori eradication therapy was associated with a significantly reduced incidence of NCGA after 8 years compared with no treatment. The risk among treated individuals became lower than the general population after 7 to 10 years of follow-up. The findings support the potential for substantial gastric cancer prevention in the United States through H pylori eradication., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening form of pulmonary hypertension and the only potentially curable form of the World Health Organization Pulmonary Hypertension classes. Thus, the prompt and accurate diagnosis of this condition is imperative. Despite widespread chronic symptoms following acute pulmonary embolism (PE), the condition is rarely considered, and an externally validated inexpensive diagnostic algorithm is lacking., Methods: A long-term, retrospective cohort study was conducted to assess the incidence of CTEPH following acute PE in a real-world study population. Additional data were collected regarding the practice patterns of diagnostic testing and imaging, particularly in patients with persistent or recurrent symptoms. Amongst diagnosed CTEPH patients, previously established risk factors were evaluated for degree of risk and commonly used diagnostic tests (electrocardiogram [ECG] right ventricular hypertrophy [RVH] pattern, B-type natriuretic peptide [BNP] elevations) employed during this period were evaluated and assessed for feasibility as screening tests. The study population was obtained from the MAPLE study cohort, comprised of patients presenting with acute PE in 21 community medical centers across the Kaiser Permanente Northern California system from January 2013 to April 2015. Diagnosis of CTEPH was confirmed via pulmonary vascular imaging (ventilation/perfusion [V/Q] scanning, computed tomography angiography, pulmonary angiography) and diagnostic right heart catheterization (RHC). Probable diagnoses were defined as a combination of suggestive echocardiographic and RHC findings. Additional inclusion criteria included age (≥18 years) with at least 2 years follow up and no previous diagnosis of CTEPH or PE during the prior 30 days., Results: There were 1973 patients who met inclusion criteria (mean age 62.4 years). Despite 75 % of patients developing symptoms consistent with CTEPH >3 months following acute PE, only 5.6 % of these symptomatic patients underwent V/Q scanning. There was overall a very low cumulative incidence of CTEPH (2.3 %), which was significantly higher amongst patients with symptoms compared to those without symptoms. When controlled for confounding in the multivariate analysis, only recurrent PE (HR 19.3, P < 0.001) and pulmonary artery systolic pressure >50 mmHg (HR 10.4, P < 0.001) were statistically significant predictors of CTEPH. Of the non-invasive diagnostic tests, ECG criteria for RVH were found to be poorly sensitive (2.6 %), but very specific (98.8 %) for CTEPH. Elevated levels of BNP alone were more sensitive than RVH ECG criteria (76.3 %) but poorly specific (44.4 %)., Conclusions: The diagnosis of CTEPH is uncommonly made following acute PE. Despite the frequency of persistent symptoms consistent with CTEPH following acute PE, the appropriate diagnostic work-up is rarely undertaken as evidenced in this cohort. This suggests that CTEPH is underappreciated and rarely considered, likely underestimating the true incidence in this cohort. Future studies are needed to elucidate the true prevalence of CTEPH and further investigate both the optimal diagnostic tools and timing of appropriate screening. These discoveries may help guide future development of diagnostic algorithms that can effectively rule out and accurately identify this potentially curable disease in a timely manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Despite studies showing improved safety, efficacy, and cost-effectiveness of endoscopic resection for nonmalignant colorectal polyps, colectomy rates for nonmalignant colorectal polyps have been increasing in the United States and Europe. Given this alarming trend, we aimed to investigate whether colectomy rates for nonmalignant colorectal polyps are increasing or declining in a large, integrated, community-based healthcare system with access to advanced endoscopic resection procedures., Methods: We identified all individuals aged 50-85 years who underwent a colonoscopy between 2008 and 2018 and were diagnosed with a nonmalignant colorectal polyp(s) at the Kaiser Permanente Northern California integrated healthcare system. Among these individuals, we identified those who underwent a colectomy for nonmalignant colorectal polyps within 12 months after the colonoscopy. We calculated annual colectomy rates for nonmalignant colorectal polyps and stratified rates by age, sex, and race and ethnicity. Changes in rates over time were tested by the Cochran-Armitage test for a linear trend., Results: Among 229,730 patients who were diagnosed with nonmalignant colorectal polyps between 2008 and 2018, 1,611 patients underwent a colectomy. Colectomy rates for nonmalignant colorectal polyps decreased significantly from 125 per 10,000 patients with nonmalignant polyps in 2008 to 12 per 10,000 patients with nonmalignant polyps in 2018 (P < 0.001 for trend). When stratified by age, sex, and race and ethnicity, colectomy rates for nonmalignant colorectal polyps also significantly declined from 2008 to 2018., Discussion: In a large, ethnically diverse, community-based population in the United States, we found that colectomy rates for nonmalignant colorectal polyps declined significantly over the past decade likely because of the establishment of advanced endoscopy centers, improved care coordination, and an organized colorectal cancer screening program., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Importance: Standard diabetic ketoacidosis care in the US includes intravenous insulin treatment in the intensive care unit. Subcutaneous (SQ) insulin could decrease intensive care unit need, but the data are limited., Objective: To assess outcomes after implementation of an SQ insulin protocol for treating diabetic ketoacidosis., Design, Setting, and Participants: This cohort study is a retrospective evaluation of a prospectively implemented SQ insulin protocol. The study was conducted at an integrated health care system in Northern California. Participants included hospitalized patients with diabetic ketoacidosis at 21 hospitals between January 1, 2010, and December 31, 2019. The preimplementation phase was 2010 to 2015, and the postimplementation phase was 2017 to 2019. Data analysis was performed from October 2020 to January 2022., Exposure: An SQ insulin treatment protocol for diabetic ketoacidosis., Main Outcomes and Measures: Difference-in-differences evaluation of the need for intensive care, mortality, readmission, and length of stay at a single intervention site using an SQ insulin protocol from 2017 onward compared with 20 control hospitals using standard care., Results: A total of 7989 hospitalizations for diabetic ketoacidosis occurred, with 4739 (59.3%) occurring before and 3250 (40.7%) occurring after implementation. The overall mean (SD) age was 42.3 (17.7) years, with 4137 hospitalizations (51.8%) occurring among female patients. Before implementation, SQ insulin was the first insulin used in 40 intervention (13.4%) and 651 control (14.7%) hospitalizations. After implementation, 98 hospitalizations (80.3%) received SQ insulin first at the intervention site compared with 402 hospitalizations (12.8%) at control sites. The adjusted rate ratio for intensive care unit admission was 0.43 (95% CI, 0.33-0.56) at the intervention sites, a 57% reduction compared with control sites, and was 0.50 (95% CI, 0.25-0.99) for 30-day hospital readmission, a 50% reduction. There were no significant changes in hospital length of stay and rates of death., Conclusions and Relevance: These findings suggest that a protocol based on SQ insulin for diabetic ketoacidosis treatment was associated with significant decreases in intensive care unit need and readmission, with no evidence of increases in adverse events.

Objective: Existing evidence demonstrates some benefit of regionalization on early postoperative outcomes following lung cancer resection, but data regarding the persistence of this effect in long-term mortality are lacking. We investigated whether previously reported improvements in short-term outcomes translated to long-term survival benefit., Methods: We retrospectively reviewed patients undergoing major pulmonary resection (lobectomy, bilobectomy, or pneumonectomy) for cancer within our integrated health care system before (2011-2013; n = 782) and after (2015-2017; n = 845) thoracic surgery regionalization. Overall survival was compared by Kaplan-Meier analysis, and 1- and 3-year mortality was compared by the by χ 2 or Fisher exact test. Multivariable Cox regression models evaluated the effect of regionalization on mortality adjusted for relevant factors., Results: Kaplan-Meier curves showed that overall survival was better among patients undergoing surgery postregionalization (log-rank test, P < .0001). Both 1- and 3-year mortality were decreased after regionalization: to 5.7% from 11.1% (P < .0001) for 1 year and to 17.0% from 25.5% (P = .0002) for 3 years. The multivariable adjusted Cox regression analysis revealed that only regionalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.42-0.76), age (HR, 1.03; 95% CI, 1.02-1.04), cancer stage (HR, 1.72, 1.83, and 2.56 for stages II, III, and IV, respectively), and Charlson comorbidity index (HR, 1.80 for 1-2; 2.05 for ≥3) were independent predictors of mortality., Conclusions: We found that overall mortality as well as 1- and 3-year mortality for lung cancer resection were lower after thoracic surgery regionalization. The association between regionalization and reduced mortality was significant even after adjusting for other related factors in a multivariable Cox analysis. Notably, surgeon volume, facility volume, surgeon specialty, neoadjuvant treatment, and video-assisted thoracoscopic surgery approach did not significantly affect mortality in the adjusted model., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Hip fracture is common in the elderly, many of whom are on anticoagulation. However, data are limited on outcomes with anticoagulation reversal in patients undergoing hip fracture surgery., Methods: Adults ≥60 years old on oral anticoagulation who underwent hip fracture surgery at 21 hospitals in Northern California from 2006 to 2016 were identified through electronic databases. Outcomes were compared among patients treated and untreated with anticoagulation reversal preoperatively., Results: Of 1984 patients on oral anticoagulation who underwent hip fracture surgery, 1943 (97.9%) were on warfarin and 41 (2.1%) were on direct oral anticoagulants. Reversal agents were administered to 1635 (82.4%). Compared to a watch-and-wait strategy, patients receiving reversal agents were more likely to be white, male, comorbid, and with higher admission and preoperative international normalized ratios (P <0.001 for all comparisons). No difference for 30-day mortality was detected between reversal vs non-reversal (7.8% vs 6.0%, respectively; hazard ratio [HR], 1.30 [95% confidence interval (CI), 0.82-2.07]). For secondary outcomes, reversal was associated with higher risk of delirium (8.6% vs 4.9%, risk ratio [RR], 1.77 [95% CI, 1.08-2.89]) and increased mean length of stay (6.4 vs 5.8 days, P <0.05). After adjustment, associations were no longer significant for delirium (RR 1.60, 95% CI, 0.97-2.65) or length of stay (mean difference 0.08, 95% CI, -0.55-0.71). No associations were detected between reversal and other secondary outcomes., Conclusion: No significant associations were found between reversal agents and 30-day mortality or other outcomes in patients on oral anticoagulation who underwent hip fracture surgery. Further investigation is needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Current literature favors a volume-outcome relationship in pulmonary lobectomy that prompted centralization of these operations abroad, in national, single-payer health care settings. This study examined the impact of regionalization on outcomes after lung cancer resection within a US integrated health care system., Methods: This study retrospectively reviewed major pulmonary resections (lobectomy, bilobectomy, pneumonectomy) for lung cancer that were performed before (2011 to 2013; n = 782) and after (2015 to 2017; n = 845) thoracic surgery regionalization during 2014., Results: Case migration from 16 regionwide sites to 5 designated centers was complete by 2016. Facility volume increased from 17.4 to 48.3 cases/y (P = .002), and surgeon volume increased from 12.5 to 19.9 cases/y (P = .001). The postregionalization era was characterized by increased video-assisted thoracoscopic surgery (86% from 57%; P < .001), as well as decreased intensive care unit use (-1.0 days; P < .001) and hospital length of stay (-3.0 days; P < .001). Postregionalization patients experienced fewer total (26.2% from 38.6%; P < .001) and major (9.6% from 13.6%; P = .01) complications. The association between regionalization and decreased length of stay and morbidity was independent of surgical approach and case volume in mixed multivariate models., Conclusions: After the successful implementation of thoracic surgery regionalization in our US health care network, pulmonary resection volume increased, and practice shifted to majority video-assisted thoracoscopic surgery and minimum intensive care unit utilization. Regionalization was independently associated with significant reductions in length of stay and morbidity., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To estimate risks of incident type 2 diabetes (T2D) and stage 2 and greater hypertension associated with self-reported and accelerometer-determined moderate-vigorous physical activity (MVPA) separately and adjusted for each other., Methods: The sample included 2291 black and white men and women, ages 38-50 yr, in the Coronary Artery Risk Development in Young Adults (CARDIA) fitness study, conducted during the year 20 core CARDIA examination. Accelerometer-determined (Actigraph, LLC. model 7164) MVPA (MVPA-Acc), assessed at year 20, was defined as minutes per day of counts ≥2020 min. Self-reported MVPA (MVPA-SR) was assessed at year 20 using the CARDIA Physical Activity History. Incident T2D was ascertained at years 25 and 30 from fasting glucose, 2 h glucose tolerance test, HbA1c, or diabetes medication; incident hypertension was ascertained at those same times from measured blood pressure or use of antihypertensive medications. Modified Poisson regression models estimated relative risk (RR) of incident (years 25 and 30) T2D or hypertension, associated with middle and high tertiles of year 20 MVPA-Acc alone, year 20 MVPA-SR alone, and both, adjusted for each other, relative to bottom tertile., Results: In men, MVPA-Acc, but not MVPA-SR, was associated with a 37% to 67% decreased risk of incident T2D in a dose-response relation that persisted with adjustment for BMI, Similar associations were observed in women, although the risk reduction was similar in the second and third tertiles, relative to the bottom tertile. In both men and women, MVPA-Acc was marginally associated with reduced risk of incident stage 2 and greater hypertension, but only after adjustment for BMI, whereas MVPA-SR was not associated in either sex., Conclusions: Accelerometer-determined MVPA may provide more consistent risk estimates for incident diabetes than self-reported MVPA.

Importance: An increasing prevalence of adult attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment has been reported in clinical settings and administrative data in the United States. However, there are limited data on recent trends of adult ADHD diagnosis among racial/ethnic subgroups., Objective: To examine trends, including associated demographic characteristics, psychiatric diagnoses, and negative outcomes, in the prevalence and incidence of adult ADHD diagnosis among 7 racial/ethnic groups during a 10-year period., Design, Setting, and Participants: This cohort study investigated trends in the diagnosis of ADHD in adults who identified as African American or black, Native American, Pacific Islander, Latino or Hispanic, non-Hispanic white, Asian American, or other using the Kaiser Permanente Northern California health plan medical records. A total of 5 282 877 adult patients and 867 453 children aged 5 to 11 years who received care at Kaiser Permanente Northern California from January 1, 2007, to December 31, 2016, were included. Data analysis was performed from January 2017 through September 2019., Exposures: Period of ADHD diagnosis., Main Outcomes and Measures: Prevalence and incidence of licensed mental health clinician-diagnosed ADHD in adults and prevalence of licensed mental health clinician-diagnosed ADHD in children aged 5 to 11 years., Results: Of 5 282 877 adult patients (1 155 790 [21.9%] aged 25-34 years; 2 667 562 [50.5%] women; 2 204 493 [41.7%] white individuals), 59 371 (1.12%) received diagnoses of ADHD. Prevalence increased from 0.43% in 2007 to 0.96% in 2016. Among 867 453 children aged 5 to 11 years (424 449 [48.9%] girls; 260 236 [30.0%] white individuals), prevalence increased from 2.96% in 2007 to 3.74% in 2016. During the study period, annual adult ADHD prevalence increased for every race/ethnicity, but white individuals consistently had the highest prevalence rates (white individuals: 0.67%-1.42%; black individuals: 0.22%-0.69%; Native American individuals: 0.56%-1.14%; Pacific Islander individuals: 0.11%-0.39%; Hispanic or Latino individuals: 0.25%-0.65%; Asian American individuals: 0.11%-0.35%; individuals from other races/ethnicities: 0.29%-0.71%). Incidence of ADHD diagnosis per 10 000 person-years increased from 9.43 in 2007 to 13.49 in 2016. Younger age (eg, >65 years vs 18-24 years: odds ratio [OR], 0.094; 95% CI, 0.088-0.101; P < .001), male sex (women: OR, 0.943; 95% CI, 0.928-0.959; P < .001), white race (eg, Asian patients vs white patients: OR, 0.248; 95% CI, 0.240-0.257; P < .001), being divorced (OR, 1.131; 95% CI, 1.093-1.171; P < .001), being employed (eg, retired vs employed persons: OR, 0.278; 95% CI, 0.267-0.290; P < .001), and having a higher median education level (OR, 2.156; 95% CI, 2.062-2.256; P < .001) were positively associated with odds of ADHD diagnosis. Having an eating disorder (OR, 5.192; 95% CI, 4.926-5.473; P < .001), depressive disorder (OR, 4.118; 95% CI, 4.030-4.207; P < .001), bipolar disorder (OR, 4.722; 95% CI, 4.556-4.894; P < .001), or anxiety disorder (OR, 2.438; 95% CI, 2.385-2.491; P < .001) was associated with higher odds of receiving an ADHD diagnosis. Adults with ADHD had significantly higher odds of frequent health care utilization (OR, 1.303; 95% CI, 1.272-1.334; P < .001) and sexually transmitted infections (OR, 1.289; 95% CI 1.251-1.329; P < .001) compared with adults with no ADHD diagnosis., Conclusions and Relevance: This study confirmed the reported increases in rates of ADHD diagnosis among adults, showing substantially lower rates of detection among minority racial/ethnic subgroups in the United States. Higher odds of negative outcomes reflect the economic and personal consequences that substantiate the need to improve assessment and treatment of ADHD in adults.

Background: Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied., Objective: To compare the performance of age-restricted and universal LS screening using reflex mismatch repair (MMR) immunohistochemistry (IHC) of CRC tumors., Design: Retrospective cohort study., Setting: A large, diverse, community-based health care system., Participants: 3891 persons with newly diagnosed CRC who had LS screening between 2011 and 2016., Measurements: Diagnostic yield of different LS screening strategies., Results: Sixty-three LS cases (diagnostic yield, 1.62%) were identified by universal screening, with only 5 (7.9%) detected after age 70 years and 1 (1.6%) detected after age 80 years. When all patients with CRC who had universal screening were used as the denominator, 58 LS cases (diagnostic yield, 1.49% [95% CI, 1.13% to 1.92%]) were identified in patients with CRC diagnosed at or before age 70 years, 60 LS cases (diagnostic yield, 1.54% [CI, 1.18% to 1.98%]) were identified in those with CRC diagnosed at or before age 75 years, and 62 LS cases (diagnostic yield, 1.59% [CI, 1.22% to 2.04%]) were identified in those with CRC diagnosed at or before age 80 years. Using 75 years as the upper age limit for screening missed 3 of 63 (4.8%) LS cases but resulted in 1053 (27.1%) fewer cases requiring tumor MMR IHC. Using 80 years as the upper age limit missed 1 of 63 (1.6%) LS cases and resulted in 668 (17.2%) fewer cases requiring tumor MMR IHC., Limitation: Persons who were eligible for but did not complete germline analysis were excluded from calculations of performance characteristics., Conclusion: The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed., Primary Funding Source: Kaiser Permanente Northern California Division of Research.

Background: The relation between the menopause transition (MT) and changes in body composition or weight remains uncertain. We hypothesized that, independent of chronological aging, the MT would have a detrimental influence on body composition., Methods: Participants were from the longitudinal Study of Women's Health Across the Nation (SWAN) cohort. We assessed body composition by dual energy x-ray absorptiometry. Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of outcomes as a function of time before or after the final menstrual period (FMP). Covariates were age at FMP, race, study site, and hormone therapy., Results: Fat and lean mass increased prior to the MT. At the start of the MT, rate of fat gain doubled, and lean mass declined; gains and losses continued until 2 years after the FMP. After that, the trajectories of fat and lean mass decelerated to zero slope. Weight climbed linearly during premenopause without acceleration at the MT. Its trajectory became flat after the MT., Conclusion: Accelerated gains in fat mass and losses of lean mass are MT-related phenomena. The rate of increase in the sum of fat mass and lean mass does not differ between premenopause and the MT; thus, there is no discernable change in rate of weight gain at the start of the MT., Funding: NIH, Department of Health and Human Services (DHHS), through the National Institute on Aging, National Institute of Nursing Research, and NIH Office of Research on Women's Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495).

Background and Aims: Sessile serrated adenomas (SSAs) are precursors of 15% to 30% of colorectal cancers but are frequently underdiagnosed. We sought to measure the SSA detection rate (SDR) and predictors of SSA detection after educational training for community gastroenterologists and pathologists., Methods: Colonoscopy and pathology data (2010-2014) from 3 medical centers at Kaiser Permanente Northern California were accessed electronically. Gastroenterologists and pathologists attended a training session on SSA diagnosis in 2012. Mean SDRs and patient-level predictors of SSA detection post-training (2013-2014) were investigated., Results: Mean SDRs increased from .6% in 2010-2012 to 3.7% in 2013-2014. The increase in the detection of proximal SSAs was accompanied by a decrease in the detection of proximal hyperplastic polyps (HPs). Among 34,161 colonoscopies performed in 2013 to 2014, SDRs for screening, fecal immunochemical test positivity, surveillance, and diagnostic indication were 4.2%, 4.5%, 4.9%, and 3.0%, respectively. SSA detection was lower among Asians (adjusted odds ratio [aOR], .46; 95% confidence interval [CI], .31-.69) and Hispanics (aOR, .59; 95% CI, .36-.95) compared with non-Hispanic whites and higher among patients with synchronous conventional adenoma (aOR, 1.46; 95% CI, 1.15-1.86), HP (aOR, 1.74; 95% CI, 1.30-2.34), and current smokers (aOR, 1.78; 95% CI, 1.17-2.72). SDRs varied widely among experienced gastroenterologists, even after training (1.1%-8.1%). There was a moderately strong correlation between adenoma detection rate (ADR) and SDR for any SSA (r = .64, P = .0003) and for right-sided SSAs (r = .71, P < .0001)., Conclusions: Educational training significantly increased the detection of SSA, but a wide variation in SDR remained across gastroenterologists. SSA detection was inversely associated with Asian and Hispanic race/ethnicity and positively associated with the presence of conventional adenoma, HP, and current smoking. There was a moderately strong correlation between ADR and SDR., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic utility of 5 established variables (functional capacity, Duke treadmill score, chronotropic response to exercise, heart rate recovery, and premature ventricular contractions) together after routine exercise treadmill testing (ETT) has not been determined., Methods: We assessed the combined prognostic ability of 5 established variables for the primary outcome (myocardial infarction [MI], coronary revascularization [CR] or all-cause mortality) and the secondary outcome of unnecessary downstream testing (defined as receipt of further noninvasive imaging without CR, MI, or death) compared with standard methods. Using a retrospective study design, 1857 consecutive patients were enrolled in the year 2014 and followed until December 31, 2015. Optimal discrimination and global fit statistics were assessed from logistic regression models. Classification and regression tree (CART) methodology was used for the final model., Results: The mean [SD] age was 56.0 [12.5]years; median comorbidities (2, IQR 2) with 26% having an equivocal report. Compared to other models, a model with age, sex, and the 5 established variables showed an improvement in discrimination for the primary [c-statistic 0.85 versus (0.69-0.79)] and secondary [c-statistic 0.73 versus (0.65-0.71)] outcomes with substantial improvement in global fit. The final, optimal, 10-fold cross-validated CART model had a c-statistic of 0.78., Conclusions: The utility of the 5-established variables, based on the current study, resides in its ability to decrease unnecessary downstream testing and improve cardiovascular event prognostication. This is accomplished by removing the subjective interpretation of currently used ETT variables that can lead to an equivocal report., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Gastric intestinal metaplasia and dysplasia are precursor lesions for adenocarcinoma. The risks of progression to malignancy from these lesions are not well characterized, particularly in the US populations., Methods: We identified 4,331 Kaiser Permanente Northern California members who were diagnosed with gastric intestinal metaplasia or dysplasia between 1997 and 2006 and followed them through December 2013. The incident rates of gastric adenocarcinoma, relative risks in comparison with the Kaiser Permanente general population, and predictors of progression to malignancy were investigated., Results: Among 4,146 individuals with gastric intestinal metaplasia and 141 with low-grade dysplasia with 24,440 person-years follow-up, 17 and 6 cases of gastric adenocarcinoma were diagnosed, respectively, after 1 year from the index endoscopy. The incidence rate of gastric adenocarcinoma was 0.72/1,000 person-years in patients with intestinal metaplasia, with a relative risk of 2.56 (95% confidence interval (CI) 1.49-4.10) compared with the Kaiser Permanente member population, and 7.7/1,000 person-years for low-grade dysplasia, with a relative risk of 25.6 (95% CI, 9.4-55.7). The median time for gastric intestinal metaplasia to progress to adenocarcinoma was 6.1 years, and for low-grade dysplasia, 2.6 years. Hispanic race/ethnicity and history of dysplasia were associated with significantly higher risk of progression to gastric adenocarcinoma., Conclusions: Gastric intestinal metaplasia and dysplasia are significant predictors for gastric adenocarcinoma. The low risk for malignancy associated with intestinal metaplasia does not support routine endoscopic surveillance. However, surveillance should be considered in patients at higher risks, including those with suspicious endoscopic features, presence of dysplasia, and Hispanic race/ethnicity.

Background: Complete heart block (CHB) is a common complication of cardiac surgery, which may resolve spontaneously. The optimal number of days to wait for resolution of CHB prior to proceeding with a permanent pacemaker (PPM) and the long-term utility of PPMs placed in this setting remain uncertain., Methods and Results: This was a retrospective cohort study, which included members of Kaiser Permanente Northern California who had cardiac surgery, a PPM placed within 30 days after surgery, and one year of follow-up time. Chart review was performed to determine the frequency of ventricular pacing at each PPM interrogation visit up to one year after surgery. A PPM was categorized as underutilized at the time of an interrogation if none of the following were present: underlying rhythm <40 bpm, persistent CHB, or >1% ventricular pacing. The study included 247 patients with a mean time from cardiac surgery to PPM of 6.5 days. In 33 cases (13%), underutilized status was confirmed. The time from surgery to PPM implant was significantly higher in the underutilized group (8.1 ± 4.2 days vs. 6.2 ± 4.2 days, p = 0.003)., Conclusions: The majority of PPMs placed early after cardiac surgery are not underutilized. In this retrospective, observational study, longer delay from surgery to PPM implantation was not associated with a greater likelihood that the PPM would be utilized long term. A prospective study is required to determine optimal timing of PPM implantation in this setting., (© 2016 Wiley Periodicals, Inc.)

Introduction: Racial and ethnic differences in gastric cancer are not well understood. This study sought to compare the clinicopathological features and survival of noncardia gastric adenocarcinoma (NCGA) patients with different racial/ethnic backgrounds in Kaiser Permanente Northern California (KPNC), a large integrated health care system., Methods: This was a retrospective cohort study of 1,366 patients with newly diagnosed NCGA between 2000 and 2010. The subjects were categorized into four racial/ethnic groups: non-Hispanic Whites, Blacks, Asians, and Hispanics. Clinicopathological information and survival data were obtained from the KPNC electronic databases and compared among the four racial/ethnic groups., Results: The incidence of NCGA declined in Blacks and Whites, but remained stable in Asians and Hispanics. Whites had a lower incidence of NCGA compared with non-Whites. Asians and Hispanics were diagnosed at a younger age compared with Whites (mean age at diagnosis: 66, 63, and 72 years, respectively; P < 0.0001). Diffuse/mixed histological type (Lauren classification) was more prevalent in Asians and Hispanics than in Whites and Blacks (46 and 45 vs. 36 and 29 %, respectively, P = 0.001). History of Helicobacter pylori testing was associated with better survival. Asians had the highest survival rates at 1, 2, and 5 years, while Whites had the lowest (P < 0.0001)., Conclusions: Significant racial/ethnic differences exist in patients with noncardia gastric cancer. Asians and Hispanics were younger at diagnosis and had more diffuse/mixed histological type. Asians had the highest survival, while Whites had the lowest. Such differences may be related to biological, environmental, and treatment-related factors.

Purpose: Gastric cancer often occurs in the elderly but is uncommon in young individuals. Whether young patients have different clinical behaviors and outcomes from those of older patients remain unclear., Materials and Methods: We identified 1,366 cases of newly diagnosed noncardia gastric adenocarcinoma from the Kaiser Permanente Northern California Cancer Registry between 2000 and 2010. We then compared the clinicopathological features and survival among the different age groups., Results: The male : female ratio differed significantly between the younger and older patient groups (0.84 in age <50 years vs. 1.52>60 years, P<0.01). More younger patients were Hispanic (54% patients <40 years vs. 19% patients ≥70 years, P<0.0001), while more older patients were Caucasian (49% patients ≥70 years vs. 15% patients <40 years; P<0.0001). The diffuse/mixed histological type was more prevalent in younger patients (70% patients <40 years vs. 27% patients ≥70 years; P<0.0001), whereas the intestinal type was more frequent in older patients (71% in patients ≥70 years vs. 30% in patients <40 years; P<0.0001). Poorly differentiated adenocarcinoma was more common in the younger patients (80% in patients <40 years vs. 60% in patients ≥70 years; P=0.016). Survival rates at 1, 2, and 5 years gradually declined with increasing age (overall P=0.0002)., Conclusions: Young patients with gastric cancer had more aggressive disease but higher overall survival rates than older patients. Younger Hispanic patients and older Caucasian patients were more likely to be diagnosed with gastric cancer. These differences may be due to biological predisposition and/or environmental exposure.

Purpose: The objective of this study is to determine whether summary estimates of a self-report physical activity questionnaire that does not specifically assess frequency or duration (the Coronary Artery Risk Development in Young Adults (CARDIA) physical activity history (PAH)) differs from the summary estimates of one that does (CARDIA Supplemental Questionnaire)., Methods: After the year 25 examination (2010-2011), 203 CARDIA black and white men and women (age 50.3 ± 3.6 yr) at the Oakland, CA, site participated in this comparison study. The between-questionnaire association and agreement were determined for continuous and categorical estimates on the basis of 1) quartiles and 2) meeting 2008 physical activity guidelines. Differences in participant characteristics by concordance/discordance status were also examined. Finally, receiver operating characteristic curves were computed to determine the accuracy of the PAH compared with the supplemental questionnaire., Results: Reported physical activity levels were high and varied significantly by race and sex (all P < 0.01). Between-questionnaire estimates were significantly correlated (rho = 0.75 to 0.90, all P < 0.001) and had high agreement (κ = 0.51 to 0.80) across all race/sex groups. A higher proportion of women than men were classified as concordant by quartile of vigorous intensity (P = 0.001), but no other participant characteristics were associated with concordant/discordant quartile ranking. Participants classified as concordant on the basis of physical activity guidelines had lower body mass index than those classified as discordant (both P < 0.05). The area under the curve was 0.95, suggesting that the PAH has high accuracy for classifying individuals as meeting physical activity guidelines., Conclusions: Although it is inconvenient that the PAH is not expressed in more standard units, these findings support the practice of not directly assessing frequency and duration, which are frequent sources of reporting error.

Purpose: Physical activity (PA) diaries reduce the recall error inherent in self-reported PA but are burdensome. The purpose of this study was to compare a cell phone-based diary with a paper diary and examine the reliability and validity of the cell phone diary., Methods: In a pilot study, 25 women and 23 men, age 45-65 yr, completed cell phone and paper PA diaries 4 d·wk(-1) for three consecutive weeks and a user satisfaction survey. In the subsequent validation study, 623 middle-age participants (52.5% women) were asked to complete the cell phone diary and wear an accelerometer for two 7-d periods, approximately 6 months apart. They also completed two PA questionnaires. Fitness, body mass index, and percent body fat were obtained as indirect validation criteria., Results: Estimates of PA from the cell phone and paper diaries were similar (mean within person difference = -43.8 MET·min·d(-1) of total PA, SD = 360, P = 0.49, 7.4 min·d(-1) of moderate-vigorous PA, SD = 66, P = 0.53). Users preferred the cell phone diary over the paper diary (59.6% vs 35.4%). In the subsequent study, intraclass correlations for the cell phone diary ranged from 0.55 for light PA to 0.63 for vigorous PA. Although PA estimates from the cell phone diary were generally significantly higher than those from the accelerometer and the questionnaires, correlations for moderate and vigorous PA were moderate (ρ = 0.25-0.59 with the questionnaires and 0.27-0.35 with the accelerometer). The correlations between the cell phone diary and the indirect validation criteria were generally in the expected direction and of moderate magnitude., Conclusions: A cell phone-based PA diary is equivalent to a paper diary, acceptable to users, and a relatively reliable and valid approach to self-reported PA.

Thorough review by the International Agency for Research on Cancer (IARC) has resulted in classifying many substances, including pharmaceuticals, as probably or possibly carcinogenic to humans, based on experiments on animals or limited data on humans. We evaluated 9 such pharmaceuticals for evidence of carcinogenicity in patients receiving them in a large medical care program with automated pharmacy records and a cancer registry. Nested case-control analyses were performed in a cohort of 6.5 million subscribers with up to 12 years of follow-up, focusing on cancer sites suggested by previous evidence and other sites with odds ratio of at least 1.50, p < 0.01 and some evidence of dose-response. Unmeasured confounding was estimated in sensitivity analyses. We found some supportive evidence for carcinogenicity of griseofulvin, metronidazole and phenytoin and for the known carcinogen, cyclophosphamide, which was added for validation of our data and analyses. Findings for chloramphenicol, iron-dextran complex, phenoxybenzamine and phenobarbital were essentially non-contributory. Confounding by cigarette smoking and prior thyroid disease could account, respectively, for associations of oxazepam with lung cancer and propylthiouracil with thyroid cancer. Although not definitive, these findings should be considered in the evaluations of these pharmaceuticals., ((c) 2009 UICC.)

Risk of breast cancer in women was assessed for eight pharmaceuticals that produce mammary tumors in experimental animals, using nested case-control analyses in two cohorts with prescription records in a comprehensive medical care program. The two cohorts were: (1) earlier cohort: 78,118 female members who received prescriptions in 1969-1973, of whom 2,467 developed breast cancer, and (2) later cohort: 3,289,408 female members who received prescriptions in 1994-2006 of whom 24,528 developed breast cancer. Longest follow-up was until June 30, 2006. Ten randomly selected concurrent control women were age-matched to almost every case. Relative risks were estimated by conditional logistic regression. Case ascertainment was lagged by 2 years, or unlagged and subdivided by number of prescriptions received. Some analyses were controlled for hormone use and sensitivity analyses were conducted to estimate the effects of uncontrolled confounding. In the later cohort furosemide, and metronidazole showed statistically significant but very small increases in relative risk (ranging from 1.07 to 1.13). Of these, only furosemide showed increased risk in the earlier cohort: 2-year lag relative risk 1.66 (95% confidence interval 1.23-2.24) or as low as 0.97, assuming uncontrolled positive confounding. Griseofulvin showed significant increases in the later cohort: relative risk for three or more prescriptions 1.48 (1.08-2.03) or as low as 1.23 assuming uncontrolled positive confounding and non-significant increases were noted in the earlier cohort. Our findings are limited by their inconsistency across the two cohorts and our inability to directly control for most established breast cancer risk factors. Although inconclusive, our findings suggest a need for more research on furosemide and griseofulvin.

Background: Body mass index (BMI) is directly related to testosterone (total T and free T) and inversely to SHBG cross-sectionally, but little is known about how changes in body fat and androgen markers affect each other over time., Methods: Participants included 969 White and Black women from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, who were ages 18-30 at entry into the study and were pre- or perimenopausal 16 yr later at the time of the CARDIA Women's Study (CWS). Total T and SHBG were assayed from specimens drawn at the CWS examination and stored serum from the yr 2 and 10 CARDIA exams. Free T was calculated based on total T and SHBG. BMI and waist circumference were measured at yr 2, 10, and 16., Results: Despite clinically significant increases in BMI and waist circumference, total T and free T tended to decline, whereas SHBG remained relatively constant. BMI and waist circumference were directly correlated with free T and inversely correlated with SHBG in cross-sectional analyses. In longitudinal, multivariable analyses, an annualized increase in BMI was inversely related to a concurrent annualized decrease in SHBG (beta = -0.79 ng/dl, and se = 0.22 in Blacks; beta = -1.07 ng/dl; and se = 0.31 in Whites). However, early increases in BMI were not related to later decreases in SHBG., Conclusion: Increases in adiposity are closely tied to decreases in SHBG, but changes in BMI and SHBG may occur concurrently rather than sequentially.

Purpose: A recent report linked methylphenidate (MPH) use in children to cytologic abnormalities in plasma lymphocytes, a possible cancer biomarker. The purpose of this study was to investigate the association of MPH use and childhood cancer risk., Methods: Using automated pharmacy databases and the SEER-affiliated cancer registry of the Kaiser Permanente Medical Care Program (KPMCP), we compared cancer rates at 18 sites among 35,400 MPH users who received it before age 20 to rates among KPMCP membership (age, sex, and calendar year standardized). Medical records of MPH exposed cancer cases were reviewed to identify the presence of established risk factors., Results: There were 23 cancers among MPH users, versus 20.4 expected (standardized morbidity ratio, SMR = 1.13, 95% confidence interval (0.72, 1.70)). Given the small number of cancers, site-specific SMR estimates were imprecise. Only one SMR was statistically significant at the p < 0.05 level, which given the number of comparisons is consistent with the absence of a true association at any site. MPH use was associated with increased risk of lymphocytic leukemia (SMR = 2.64 (1.14, 5.20)), based on eight observed cases). The medical records of these exposed cases did not reveal any lymphocytic leukemia risk factors (prior cancer, radiotherapy or chemotherapy, or Down syndrome)., Conclusions: Our results are consistent with no moderate or strong association between MPH use and cancer risk in children, although our ability to examine dose and duration of use or risk at specific sites was limited by small numbers. Further study of MPH use and lymphocytic leukemia risk is needed to determine whether our results are due to chance alone., (Copyright 2007 John Wiley & Sons, Ltd.)