Colorectal Cancer Screening After Sequential Outreach Components in a Demographically Diverse Cohort.

Importance: Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal outreach, are not well known. Objective: To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach. Design, Setting, and Participants: This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test [FIT] kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023. Exposures: Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT. Main Outcomes and Measures: The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test. Results: This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process. Conclusions and Relevance: In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.

Risk of Colorectal Cancer and Colorectal Cancer Mortality Beginning One Year after a Negative Fecal Occult Blood Test, among Screen-Eligible 76- to 85-Year-Olds.

BACKGROUND: Colorectal cancer screening is universally recommended for adults ages 45 to 75 years. Noninvasive fecal occult blood tests are effective screening tests recommended by guidelines. However, empirical evidence to inform older adults' decisions about whether to continue screening is sparse, especially for individuals with prior screening. METHODS: This study used a retrospective cohort of older adults at three Kaiser Permanente integrated healthcare systems (Northern California, Southern California, Washington) and Parkland Health. Beginning 1 year following a negative stool-based screening test, cumulative risks of colorectal cancer incidence, colorectal cancer mortality (accounting for deaths from other causes), and non-colorectal cancer mortality were estimated. RESULTS: Cumulative incidence of colorectal cancer in screen-eligible adults ages 76 to 85 with a negative fecal occult blood test 1 year ago (N = 118,269) was 0.23% [95% confidence interval (CI), 0.20%-0.26%] after 2 years and 1.21% (95% CI, 1.13%-1.30%) after 8 years. Cumulative colorectal cancer mortality was 0.03% (95% CI, 0.02%-0.04%) after 2 years and 0.33% (95% CI, 0.28%-0.39%) after 8 years. Cumulative risk of death from non-colorectal cancer causes was 4.81% (95% CI, 4.68%-4.96%) after 2 years and 28.40% (95% CI, 27.95%-28.85%) after 8 years. CONCLUSIONS: Among 76- to 85-year-olds with a recent negative stool-based test, cumulative colorectal cancer incidence and mortality estimates were low, especially within 2 years; death from other causes was over 100 times more likely than death from colorectal cancer. IMPACT: These findings of low absolute colorectal cancer risk, and comparatively higher risk of death from other causes, can inform decision-making regarding whether and when to continue colorectal cancer screening beyond age 75 among screen-eligible adults.

Risk of Colorectal Cancer and Colorectal Cancer Mortality Beginning Ten Years after a Negative Colonoscopy, among Screen-Eligible Adults 76 to 85 Years Old.

BACKGROUND: Few empirical data are available to inform older adults' decisions about whether to screen or continue screening for colorectal cancer based on their prior history of screening, particularly among individuals with a prior negative exam. METHODS: Using a retrospective cohort of older adults receiving healthcare at three Kaiser Permanente integrated healthcare systems in Northern California (KPNC), Southern California (KPSC), and Washington (KPWA), we estimated the cumulative risk of colorectal cancer incidence and mortality among older adults who had a negative colonoscopy 10 years earlier, accounting for death from other causes. RESULTS: Screen-eligible adults ages 76 to 85 years who had a negative colonoscopy 10 years earlier were found to be at a low risk of colorectal cancer diagnosis, with a cumulative incidence of 0.39% [95% CI, 0.31%-0.48%) at 2 years that increased to 1.29% (95% CI, 1.02%-1.61%) at 8 years. Cumulative mortality from colorectal cancer was 0.04% (95% CI, 0.02%-0.08%) at 2 years and 0.46% (95% CI, 0.30%-0.70%) at 8 years. CONCLUSIONS: These low estimates of cumulative colorectal cancer incidence and mortality occurred in the context of much higher risk of death from other causes. IMPACT: Knowledge of these results could bear on older adults' decision to undergo or not undergo further colorectal cancer screening, including choice of modality, should they decide to continue screening. See related commentary by Lieberman, p. 6.

The effect of using fecal testing after a negative sigmoidoscopy on the risk of death from colorectal cancer.

OBJECTIVE: To examine whether receiving a fecal occult blood test after a negative sigmoidoscopy reduced mortality from colorectal cancer. METHODS: We used a nested case-control design with incidence-density matching in historical cohorts of 1,877,740 50-90-year-old persons during 2006-2012, in an integrated health-system setting. We selected 1758 average risk patients who died from colorectal cancer and 3503 matched colorectal cancer-free persons. Colorectal cancer-specific death was ascertained from cancer and mortality registries. Screening histories were determined from electronic and chart-audit clinical data in the 5- to 10-year period prior to the reference date. We evaluated receipt of subsequent fecal occult blood test within five years of the reference date among patients with negative sigmoidoscopy two to six years before the reference date. RESULTS: Of the 5261 patients, 831 patients (204 colorectal cancer deaths/627 controls) had either negative sigmoidoscopy only (n = 592) or negative sigmoidoscopy with subsequent screening fecal occult blood test (n = 239). Fifty-six (27.5%) of the 204 patients dying of colorectal cancer and 183 (29.2%) of the 627 colorectal cancer-free patients received fecal occult blood test following a negative sigmoidoscopy. Conditional regressions found no significant association between fecal occult blood test receipt and colorectal cancer death risk, overall (adjusted odds ratio = 0.93, confidence interval: 0.65-1.33), or for right (odds ratio = 1.02, confidence interval: 0.65-1.60) or left-colon/rectum (odds ratio = 0.77, confidence interval: 0.39-1.52) cancers. Similar results were obtained in sensitivity analyses with alternative exposure ascertainment windows or timing of fecal occult blood test. CONCLUSIONS: Our results suggest that receipt of at least one fecal occult blood test during the several years after a negative sigmoidoscopy did not substantially reduce mortality from colorectal cancer.

Maternal Gestational Weight Gain in Relation to Antidepressant Continuation in Pregnancy.

OBJECTIVE: Both excessive and inadequate gestational weight gain (GWG) are associated with adverse health outcomes for the woman and her child. Antidepressant use in pregnancy could affect GWG, based on evidence in nonpregnant women that some antidepressants may cause weight gain and others weight loss. Previous studies of antidepressant use and GWG were small with limited ability to account for confounding, including by maternal mental health status and severity. We assessed the association of antidepressant continuation in pregnancy with GWG among women using antidepressants before pregnancy. STUDY DESIGN: Our retrospective cohort study included singleton livebirths from 2001 to 2014 within Kaiser Permanente Washington, an integrated health care system. Data were obtained from electronic health records and linked Washington State birth records. Among women with ≥1 antidepressant fill within 6 months before pregnancy, women who filled an antidepressant during pregnancy were considered "continuers;" women without a fill were "discontinuers." We calculated mean differences in GWG and relative risks (RR) of inadequate and excessive weight gain based on Institute of Medicine guidelines. Using inverse probability of treatment weighting with generalized estimating equations, we addressed differences in maternal characteristics, including mental health conditions. RESULTS: Among the 2,887 births, 1,689 (59%) were to women who continued antidepressants in pregnancy and 1,198 (42%) were to discontinuers. After accounting for confounding, continuers had similar weight gain to those who discontinued (mean difference: 1.3 lbs, 95% confidence interval [CI]: -0.1 to 2.8 lbs) and similar risks of inadequate and excessive GWG (RR: 0.95, 95% CI: 0.80-1.14 and RR: 1.06, 95% CI: 0.98-1.14, respectively). Findings were comparable for specific antidepressants and trimesters of exposure. CONCLUSION: We did not find evidence that continuation of antidepressants in pregnancy led to differences in GWG. KEY POINTS: · Antidepressant use is associated with weight change in nonpregnant populations.. · Prior evidence on whether antidepressant use in pregnancy affects gestational weight gain is sparse.. · We accounted for confounding by characteristics such as mental health conditions and their severity.. · We found no association between pregnancy antidepressant continuation and gestational weight gain..

Antidepressant continuation in pregnancy and risk of gestational diabetes.

PURPOSE: Previous studies observed modestly higher risk of gestational diabetes (GDM) associated with antidepressant use in pregnancy, potentially due to confounding by indication. We assessed the association of antidepressant continuation in pregnancy with GDM, as well as blood glucose levels, after accounting for confounding. METHODS: We conducted a retrospective cohort study of singleton live births from 2001 to 2014 to women enrolled in Kaiser Permanente Washington, an integrated health care delivery system, utilizing electronic health data and linked Washington State birth records. We required that women have ≥1 antidepressant prescription fills ≤6 months before pregnancy. Women with an antidepressant fill during pregnancy were categorized as "continuers" (n = 1634); those without a fill were "discontinuers" (n = 1211). We calculated relative risks (RRs) for GDM and mean differences in screening blood glucose levels using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including mental health conditions and indicators of mental health severity. RESULTS: Compared with discontinuers, antidepressant continuers had comparable risk of GDM (RR: 1.10; 95% confidence interval [CI], 0.84-1.44) and blood glucose levels (mean difference: 2.3 mg/dL; 95% CI, -1.5 to 6.1 mg/dL). We observed generally similar results for specific antidepressants, with the potential exceptions of risk of GDM associated with sertraline (RR: 1.30; 95% CI, 0.90-1.88) and venlafaxine (RR: 1.52; 95% CI, 0.87-2.68), but neither association was statistically significant. CONCLUSIONS: Our study suggests that overall, women who continue antidepressants in pregnancy are not at increased risk for GDM or higher blood glucose, although further study may be warranted for sertraline and venlafaxine.

Proton pump inhibitor use and the risk of fractures among an older adult cohort.

PURPOSE: The purpose of the study is to determine if the use of a proton pump inhibitor (PPI) is associated with an increased fracture risk, as some prior studies have suggested. METHODS: This retrospective cohort study included data on 4438 participants aged 65 and older who had no fracture in the year prior to baseline and had ≥5 years of enrollment history in Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, WA, during 1994 to 2014. Time-varying cumulative exposure to PPIs was determined from automated pharmacy data by summing standard daily doses (SDDs) across fills, and patients were categorized as no use (reference group, ≤30 SDD), light use (31-540 SDD), moderate use (541-1080 SDD), and heavy use (≥1081 SDD). Incident fractures were assessed using International Classification of Diseases, Ninth Revision codes from electronic medical records. Potential confounders, chosen a priori, were assessed at baseline and at each 2-year follow-up visit. Fracture risk was analyzed using a Cox proportional hazards model. RESULTS: Over a mean follow-up of 6.1 years, 802 (18.1%) participants experienced a fracture. No overall association was found between PPI use and fracture risk. Adjusted hazard ratios comparing users to the referent category were 1.08 (95% CI 0.83-1.40) for light users, 1.31 (95% CI 0.86-1.95) for moderate users, and 0.95 (95% CI 0.68-1.34) for heavy users. Among patients with SSD > 30, no appreciable increase in fracture risk was present in persons with recent versus distant use (adjusted hazard ratio of 1.14 [95% CI 0.91-1.42]). CONCLUSIONS: No association was observed between PPI use and fracture risk among older adults.

Ten-year incidence of colorectal cancer following a negative screening sigmoidoscopy: an update from the Colorectal Cancer Prevention (CoCaP) programme.

OBJECTIVE: To examine the rates of colorectal cancer (CRC) following a negative screening sigmoidoscopy. DESIGN: Cohort study. SETTING: An integrated healthcare delivery organisation in California, USA. PARTICIPANTS: 72,483 men and women aged 50 years and above who had a negative screening sigmoidoscopy between 1994 and 1996. Those at elevated risk of CRC due to inflammatory bowel disease, prior polyps or CRC, or a strong family history of CRC were excluded. MAIN OUTCOME MEASURES: Incidence rates of distal and proximal CRC. Standardised Incidence Ratios were used to compare annual incidence rates of distal and proximal CRC in the cohort to expected rates based on Surveillance, Epidemiology, and End Results data. Additionally, rate ratios (RR) and rate differences (RD) comparing the incidence rate of distal CRC in years 6+ postscreening with that in years 1-5 were calculated. RESULTS: Incidence rates of distal CRC were lower than those in the San Francisco Bay area population at large during each of the first 10 years postsigmoidoscopy screening. However, the incidence of distal CRC rose steadily, from 3 per 100,000 in the first year of follow-up to 40 per 100,000 in the 10th year. During the second half of follow-up, the rate of distal CRC was twice as high as in the first half (RR 2 .08, 95% CI 1.38 to 3.16; RD 14 per 100,000 person-years, 95% CI 6 to 22). CONCLUSIONS: Though still below population levels, the incidence of CRC during years 6-10 following a negative sigmoiodoscopy is appreciably higher than during the first 5 years.

Efficacy of screening in preventing cervical cancer among older women.

BACKGROUND: Although the effectiveness of cervical cancer screening has been firmly established in reproductive-age women, its usefulness in older women is unclear. We sought to evaluate the efficacy of cervical cancer screening in older women. METHODS: We conducted a case-control study within two integrated health care systems in the northwestern United States. Cases (n = 69) were women aged 55-79 years who were diagnosed with invasive cervical cancer during 1980-1999. Controls (n = 208) were women with an intact uterus and no diagnosis of cervical cancer, but otherwise similar to cases in terms of age and length of enrollment in the health plan. We reviewed medical records to ascertain screening history during the 7 years prior to reference date. RESULTS: Compared to cases, controls were more likely to have received a Pap test. After adjustment for age and current smoking status, screening prior to an estimated 1-year duration of the occult invasive phase of cervical cancer was associated with a substantial reduction in risk [odds ratio (OR) 0.23; 95% CI 0.11-0.44]. Similar results were obtained using different estimates of the duration of the occult invasive phase. Analysis of the relative incidence of invasive cervical cancer in relation to the time following a negative screening test suggested a large reduction during the first year (OR 0.09; 95% CI 0.03-0.24). The incidence remained low for several years thereafter, returning to the incidence among unscreened women after 5-7 years. CONCLUSIONS: Cervical cancer screening by means of cytology is highly efficacious in older women. Our findings also suggest that five-yearly screening is approximately as efficacious as more frequent screening.

Risk of non-Hodgkin lymphoma in relation to tricyclic antidepressant use.

PURPOSE: We investigated the relationship between use of tricyclic antidepressants (TCAs) and risk of non-Hodgkin lymphoma (NHL). Previous studies provided some evidence of an association, but did not assess risk of NHL subtypes. METHODS: Cases and controls were members of Group Health, an integrated healthcare delivery system. Cases were persons diagnosed with NHL between 1980 and 2011 at age 25 years or older; eight control subjects were matched to each case on age, sex, and length of enrollment. Information on previous TCA use was ascertained from automated pharmacy data. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for NHL, overall and for common subtypes, for various patterns of TCA use. RESULTS: We identified 2768 cases and 22,127 matched control subjects. We did not observe an appreciably increased risk of NHL among TCA ever-users compared to non-users (OR, 1.1; 95% CI, 1.0-1.2). Overall risk of NHL was associated to at most a small degree with longer-term use (OR, 1.2; 95% CI, 1.0-1.4; ≥10 prescriptions), high-dose use (OR, 1.1; 95% CI, 0.8-1.5; ≥50 mg), or non-recent use (OR, 1.0; 95% CI, 0.9 = 1.2; >5 years previously). TCA use was not associated with NHL subtypes, except chronic lymphocytic leukemia/small lymphocytic lymphoma (OR, 1.5; 95% CI, 1.1-2.0; longer-term use). CONCLUSIONS: We found little evidence that the use of TCAs increases the risk of NHL overall or for specific common subtypes of NHL.

Angiotensin-converting enzyme inhibitor use and pneumonia risk in community-dwelling older adults: results from a population-based case-control study.

PURPOSE: To test whether angiotensin-converting enzyme (ACE) inhibitor use is associated with decreased risk of community-acquired pneumonia in older adults. METHODS: We analyzed data from a nested case-control study of community-dwelling, immunocompetent adults aged 65-94 within an integrated healthcare delivery system. Cases of ambulatory and hospitalized pneumonia from 2000 to 2003 were identified from International Classification of Disease, version 9, codes and validated using medical record review. Controls were matched to cases by age, sex, and calendar year. Using health plan pharmacy data, we defined current use as filling ≥2 prescriptions during the 180 days prior to the case's diagnosis date. We calculated standardized doses per day using World Health Organization defined daily doses. Multivariable conditional logistic regression estimated adjusted odds ratios (ORs) for pneumonia in relation to ACE inhibitor use, adjusting for comorbidity, functional and cognitive status, and other covariates from medical record review and pharmacy data. RESULTS: Current use of ACE inhibitors was seen in 23% (242/1039) of cases and 21% (433/2022) of controls. Lisinopril accounted for 95% of prescriptions. The OR for pneumonia comparing current use to no current use was 0.99 (95% confidence interval [CI] 0.83-1.19). The OR for use of more than two standardized daily doses per day was 1.39 (95% CI 0.93-2.06) compared to no current use. CONCLUSIONS: ACE inhibitor use is not associated with reduced pneumonia risk in community-dwelling older adults.

Use of opioids or benzodiazepines and risk of pneumonia in older adults: a population-based case-control study.

OBJECTIVES: To examine whether use of opioids or benzodiazepines is associated with risk of community-acquired pneumonia in older adults. DESIGN: Population-based case-control study. SETTING: An integrated healthcare delivery system. PARTICIPANTS: Community-dwelling, immunocompetent adults aged 65 to 94 from 2000 to 2003. Presumptive pneumonia cases were identified from health plan automated data and validated through medical record review. Two controls were selected for each case with pneumonia, matched on age, sex, and calendar year. MEASUREMENTS: Information about opioid and benzodiazepine use came from computerized pharmacy data. Information on covariates including comorbid illnesses and functional and cognitive status came from medical record review and electronic health data. RESULTS: One thousand thirty-nine validated cases of pneumonia and 2,022 matched controls were identified. One hundred forty-four (13.9%) cases and 161 (8.0%) controls used prescription opioids (adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08-1.76 vs nonuse). Risk was highest for opioids categorized as immunosuppressive based on immunological studies (OR = 1.88, 95% CI = 1.26-1.79 vs nonuse), whereas for nonimmunosuppressive opioids the OR was 1.23 (95% CI = 0.89-1.69). Risk was highest in the first 14 days of use (OR = 3.24, 95% CI = 1.64-6.39 vs nonuse). For long-acting opioids, the OR was 3.43 (95% CI = 1.44-8.21) versus nonuse, whereas for short-acting opioids, it was 1.27 (95% CI = 0.98-1.64). No greater risk was seen for current benzodiazepine use compared to nonuse (OR = 1.08, 95% CI = 0.80-1.47). CONCLUSION: Use of opioids but not benzodiazepines was associated with pneumonia risk. The differences in risk seen for different opioid regimens warrant further study.

A phase II randomized placebo-controlled trial of omega-3 fatty acids for the treatment of acute lung injury.

OBJECTIVES: Administration of eicosapentaenoic acid and docosahexanoic acid, omega-3 fatty acids in fish oil, has been associated with improved patient outcomes in acute lung injury when studied in a commercial enteral formula. However, fish oil has not been tested independently in acute lung injury. We therefore sought to determine whether enteral fish oil alone would reduce pulmonary and systemic inflammation in patients with acute lung injury. DESIGN: Phase II randomized controlled trial. SETTING: Five North American medical centers. PATIENTS: Mechanically ventilated patients with acute lung injury ≥18 yrs of age. INTERVENTIONS: Subjects were randomized to receive enteral fish oil (9.75 g eicosapentaenoic acid and 6.75 g docosahexanoic acid daily) or saline placebo for up to 14 days. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage fluid and blood were collected at baseline (day 0), day 4 ± 1, and day 8 ± 1. The primary end point was bronchoalveolar lavage fluid interleukin-8 levels. Forty-one participants received fish oil and 49 received placebo. Enteral fish oil administration was associated with increased serum eicosapentaenoic acid concentration (p < .0001). However, there was no significant difference in the change in bronchoalveolar lavage fluid interleukin-8 from baseline to day 4 (p = .37) or day 8 (p = .55) between treatment arms. There were no appreciable improvements in other bronchoalveolar lavage fluid or plasma biomarkers in the fish oil group compared with the control group. Similarly, organ failure score, ventilator-free days, intensive care unit-free days, and 60-day mortality did not differ between the groups. CONCLUSIONS: Fish oil did not reduce biomarkers of pulmonary or systemic inflammation in patients with acute lung injury, and the results do not support the conduct of a larger clinical trial in this population with this agent. This experimental approach is feasible for proof-of-concept studies evaluating new treatments for acute lung injury.

Use of proton pump inhibitors and H2 blockers and risk of pneumonia in older adults: a population-based case-control study.

PURPOSE: To examine whether use of proton pump inhibitors (PPIs) and H2 blockers is associated with increased pneumonia risk. METHODS: We conducted a population-based, nested case-control study within Group Health, an integrated healthcare delivery system. Among community-dwelling, immunocompetent adults aged 65-94, we identified presumptive cases of ambulatory and hospitalized community-acquired pneumonia in 2000-2003 from ICD-9 codes and validated them by medical record review (N = 1125). Controls were selected, matched to cases on age, sex, and calendar year (N = 2235). Current PPI or H2 blocker use was ascertained from computerized pharmacy records. Comorbid illnesses and other characteristics were ascertained by medical record review. Multivariable conditional logistic regression was used to examine the association between medication use and pneumonia risk. We conducted sensitivity analyses using only administrative and pharmacy data to assess how these results differed from our primary results. RESULTS: The prevalence of PPI or H2 blocker use was 21% (241/1125) for pneumonia cases and 16% (350/2235) for controls (adjusted odds ratio [OR] 1.03, 95% CI 0.86-1.24, compared to nonuse). No increased risk was seen for recent initiation. The prevalence of PPI use was 12% (132/1125) for cases and 7% (160/2235) for controls (adjusted OR 1.13, 95% CI 0.88-1.44). Analyses using only administrative and pharmacy data yielded risk estimates farther from the null (adjusted OR 1.32, 95% CI 1.17-1.49, for current PPI use versus nonuse). CONCLUSIONS: Use of PPIs and H2 blockers is not associated with increased pneumonia risk in older adults. The increased risk observed in some prior studies may reflect confounding.

Complex hyperplasia with and without atypia: clinical outcomes and implications of progestin therapy.

OBJECTIVE: Limited data exist to inform clinicians and patients as to the likelihood of long-term endometrial hyperplasia response to progestin therapy, especially for atypical hyperplasia. We evaluated women with complex and atypical endometrial hyperplasia, comparing those prescribed progestin with those not prescribed progestin. METHODS: This retrospective cohort study was conducted in 1985-2005 among women aged 18-88 years at an integrated health plan in Washington State. Women were ineligible if they achieved an outcome (endometrial carcinoma, hysterectomy, or both) within 8 weeks of hyperplasia diagnosis. Exposure was progestin use for at least 14 days by duration and recency. Outcomes included rate of 1) endometrial carcinoma, 2) hysterectomy, or 3) both. Analyses performed included Kaplan-Meier, incident rate ratios, and Cox proportional hazard ratios. RESULTS: One thousand four hundred forty-three eligible women were identified. One thousand two hundred one had complex (n=164 no progestin) and 242 had atypical (n=62 no progestin) hyperplasia. During follow-up, a median of 5.3 years (range 8 weeks to 20.8 years), 71 women were diagnosed with endometrial carcinoma (35 complex, 36 atypia) and 323 underwent hysterectomy (216 complex, 107 atypia). Among women with complex and atypical hyperplasia, rates of endometrial carcinoma among progestin users were 3.6 and 20.5 per 1,000 woman-years, respectively (compared with women who did not use progestin, 10.8 and 101.4). Among women with complex and atypical hyperplasia, rates of hysterectomy among progestin users were 23.3 and 61.4 per 1,000 woman-years, respectively (compared with women who did not use progestin, 55.1 and 297.3). CONCLUSION: Endometrial carcinoma risk is diminished approximately threefold to fivefold in women diagnosed with complex or atypical endometrial hyperplasia and dispensed progestin; hysterectomy risk is also decreased. LEVEL OF EVIDENCE: II.

Statin use and risk of community acquired pneumonia in older people: population based case-control study.

OBJECTIVE: To test the hypothesis that hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of community acquired pneumonia. DESIGN: Population based case-control study. SETTING: Group Health, a large integrated healthcare delivery system. Population Immunocompetent, community dwelling Group Health members aged 65 to 94; two matched controls for each case with pneumonia. Information on comorbid illnesses and functional and cognitive status, potential confounders of the association between statin use and risk of pneumonia, came from medical record review and computerised pharmacy data. MAIN OUTCOME MEASURE: Adjusted estimates of risk of pneumonia in relation to current statin use. RESULTS: 1125 validated cases of pneumonia and 2235 matched controls were identified. Compared with controls, cases were more likely to have chronic lung and heart disease, especially severe disease, and functional or cognitive impairment. Current statin use was present in 16.1% (181/1125) of cases and 14.6% (327/2235) of controls (adjusted odds ratio 1.26, 95% confidence interval 1.01 to 1.56). Among cases admitted to hospital and matched controls, current statin use was present in 17.2% (68/395) of cases and 14.2% (112/788) of controls (adjusted odds ratio 1.61, 1.08 to 2.39, compared with non-use). In people in whom statins were indicated for secondary prevention, the adjusted odds ratio for risk of pneumonia in relation to current statin use was 1.25 (0.94 to 1.67); in those with no such indication, it was 0.81 (0.46 to 1.42). CONCLUSIONS: Statin use was not associated with decreased risk of pneumonia among immunocompetent, community dwelling older people. Findings of previous studies may reflect "healthy user" bias.

Incidence of endometrial hyperplasia.

OBJECTIVE: The objective of the study was to estimate the age-specific incidence of endometrial hyperplasia: simple, complex, and atypical, in order of increasing likelihood of progression to carcinoma. STUDY DESIGN: Women aged 18-90 years with endometrial pathology specimens (1985-2003) at a large integrated health plan were identified using automated data. Incidence rates were obtained by dividing the number of cases by the estimated number of female health plan enrollees who retained a uterus. RESULTS: Endometrial hyperplasia peak incidence was: simple, 142 per 100,000 woman-years, complex, 213 per 100,000 woman-years, both in the early 50s; and atypical, 56 per 100,000 woman-years in the early 60s. Age-adjusted incidence decreased over the study period, especially for atypical hyperplasia. CONCLUSION: Endometrial hyperplasia incidence without and with atypia peaks in the early postmenopausal years and in the early 60s, respectively. Given that some cases of endometrial hyperplasia likely go undiagnosed, the figures provided should be viewed as minimum estimates of the true incidence.

Progestin therapy of complex endometrial hyperplasia with and without atypia.

OBJECTIVE: To assess the likelihood of histologic persistence/progression of complex hyperplasia and atypical hyperplasia among women treated with progestin compared with those not treated, with attention to type, dose, and duration. METHODS: This was a cohort study at an integrated health plan of women, ages 18-85 years, with complex or atypical hyperplasia on independent pathology review with a second endometrial specimen in the 2-6 months after the index diagnosis. Progestin therapy between index diagnosis and follow-up biopsy was determined from the pharmacy database. Medical record abstraction was performed. Relative risks (RRs), adjusted for age and body mass index, were calculated. RESULTS: Among 185 women, average age 55.9 years, follow-up 16.1 weeks, 115 had complex and 70 had atypical hyperplasia. Among women with complex hyperplasia, 28.4% of those treated with progestin and 30.0% of those not treated had persistence/progression (RR 1.20, 95% confidence interval [CI] 0.53-2.72). Among women with atypical hyperplasia, 26.9% of those treated with progestin and 66.7% of those not treated had persistence/progression (RR 0.39, 95% CI 0.21-0.70); there was a suggestion that use of at least a medium dose, or a duration of at least 3 months, was associated with a particularly low probability of persistence/progression. CONCLUSION: Although progestin treatment of women with atypical hyperplasia was associated with a substantial increase in the likelihood of regression of the lesion during the ensuing 2-6 months, persistence/progression was nonetheless present in more than one quarter of treated women. Regression of complex hyperplasia without atypia was common whether progestin had or had not been used.

Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial.

CONTEXT: Stimulant medication can effectively treat 60% to 70% of youth with attention-deficit/hyperactivity disorder (ADHD). Yet many parents seek alternative therapies, and Hypericum perforatum (St John's wort) is 1 of the top 3 botanicals used. OBJECTIVE: To determine the efficacy and safety of H. perforatum for the treatment of ADHD in children. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted between March 2005 and August 2006 at Bastyr University, Kenmore, Washington, among a volunteer sample of 54 children aged 6 to 17 years who met Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for ADHD by structured interview. INTERVENTION: After a placebo run-in phase of 1 week, participants were randomly assigned to receive 300 mg of H. perforatum standardized to 0.3% hypericin (n = 27) or a matched placebo (n = 27) 3 times daily for 8 weeks. Other medications for ADHD were not allowed during the trial. MAIN OUTCOME MEASURES: Performance on the ADHD Rating Scale-IV (range, 0-54) and Clinical Global Impression Improvement Scale (range, 0-7), and adverse events. RESULTS: One patient in the placebo group withdrew because of an adverse event. No significant difference was found in the change in ADHD Rating Scale-IV scores from baseline to week 8 between the treatment and placebo groups: inattentiveness improved 2.6 points (95% confidence interval [CI], -4.6 to -0.6 points) with H. perforatum vs 3.2 points (95% CI, -5.7 to -0.8 points) with placebo (P = .68) and hyperactivity improved 1.8 points (95% CI, -3.7 to 0.1 points) with H. perforatum vs 2.0 points (95% CI, -4.1 to 0.1 points) with placebo (P = .89). There was also no significant difference between the 2 groups in the percentage of participants who met criteria for improvement (score < or = 2) on the Clinical Global Impression Improvement Scale (H. perforatum, 44.4%; 95% CI, 25.5%-64.7% vs placebo, 51.9%; 95% CI, 31.9%-71.3%; P = .59). No difference between groups was found in the number of participants who experienced adverse effects during the study period (H. perforatum, 40.7%; 95% CI, 22.4%-61.2% vs placebo, 44.4%; 95% CI, 25.5%-64.7%; P = .78). CONCLUSION: In this study, use of H. perforatum for treatment of ADHD over the course of 8 weeks did not improve symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00100295.

Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women's Health Initiative.

OBJECTIVE: Experimental and epidemiologic studies suggest that calcium and vitamin D may reduce the risk of developing diabetes. We examined the effect of calcium plus vitamin D supplementation on the incidence of drug-treated diabetes in postmenopausal women. RESEARCH DESIGN AND METHODS: The Women's Health Initiative Calcium/Vitamin D Trial randomly assigned postmenopausal women to receive 1,000 mg elemental calcium plus 400 IU of vitamin D3 daily, or placebo, in a double-blind fashion. Among 33,951 participants without self-reported diabetes at baseline, we ascertained by treatment assignment new diagnoses of diabetes treated with oral hypoglycemic agents or insulin. Effects of the intervention on fasting measurements of glucose, insulin, and insulin resistance were examined among a subset of participants. RESULTS: Over a median follow-up time of 7 years, 2,291 women were newly diagnosed with diabetes. The hazard ratio for incident diabetes associated with calcium/vitamin D treatment was 1.01 (95% CI 0.94-1.10) based on intention to treat. This null result was robust in subgroup analyses, efficacy analyses accounting for nonadherence, and analyses examining change in laboratory measurements. CONCLUSIONS: Calcium plus vitamin D3 supplementation did not reduce the risk of developing diabetes over 7 years of follow-up in this randomized placebo-controlled trial. Higher doses of vitamin D may be required to affect diabetes risk, and/or associations of calcium and vitamin D intake with improved glucose metabolism observed in nonrandomized studies may be the result of confounding or of other components of foods containing these nutrients.