Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer.

Importance: Although colonoscopy is frequently performed in the United States, there is limited evidence to support threshold values for physician adenoma detection rate as a quality metric. Objective: To evaluate the association between physician adenoma detection rate values and risks of postcolonoscopy colorectal cancer and related deaths. Design, Setting, and Participants: Retrospective cohort study in 3 large integrated health care systems (Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente Washington) with 43 endoscopy centers, 383 eligible physicians, and 735 396 patients aged 50 to 75 years who received a colonoscopy that did not detect cancer (negative colonoscopy) between January 2011 and June 2017, with patient follow-up through December 2017. Exposures: The adenoma detection rate of each patient's physician based on screening examinations in the calendar year prior to the patient's negative colonoscopy. Adenoma detection rate was defined as a continuous variable in statistical analyses and was also dichotomized as at or above vs below the median for descriptive analyses. Main Outcomes and Measures: The primary outcome (postcolonoscopy colorectal cancer) was tumor registry-verified colorectal adenocarcinoma diagnosed at least 6 months after any negative colonoscopy (all indications). The secondary outcomes included death from postcolonoscopy colorectal cancer. Results: Among 735 396 patients who had 852 624 negative colonoscopies, 440 352 (51.6%) were performed on female patients, median patient age was 61.4 years (IQR, 55.5-67.2 years), median follow-up per patient was 3.25 years (IQR, 1.56-5.01 years), and there were 619 postcolonoscopy colorectal cancers and 36 related deaths during more than 2.4 million person-years of follow-up. The patients of physicians with higher adenoma detection rates had significantly lower risks for postcolonoscopy colorectal cancer (hazard ratio [HR], 0.97 per 1% absolute adenoma detection rate increase [95% CI, 0.96-0.98]) and death from postcolonoscopy colorectal cancer (HR, 0.95 per 1% absolute adenoma detection rate increase [95% CI, 0.92-0.99]) across a broad range of adenoma detection rate values, with no interaction by sex (P value for interaction = .18). Compared with adenoma detection rates below the median of 28.3%, detection rates at or above the median were significantly associated with a lower risk of postcolonoscopy colorectal cancer (1.79 vs 3.10 cases per 10 000 person-years; absolute difference in 7-year risk, -12.2 per 10 000 negative colonoscopies [95% CI, -10.3 to -13.4]; HR, 0.61 [95% CI, 0.52-0.73]) and related deaths (0.05 vs 0.22 cases per 10 000 person-years; absolute difference in 7-year risk, -1.2 per 10 000 negative colonoscopies [95%, CI, -0.80 to -1.69]; HR, 0.26 [95% CI, 0.11-0.65]). Conclusions and Relevance: Within 3 large community-based settings, colonoscopies by physicians with higher adenoma detection rates were significantly associated with lower risks of postcolonoscopy colorectal cancer across a broad range of adenoma detection rate values. These findings may help inform recommended targets for colonoscopy quality measures.

Long-term Risk of Colorectal Cancer and Related Death After Adenoma Removal in a Large, Community-based Population.

BACKGROUND & AIMS: The long-term risks of colorectal cancer (CRC) and CRC-related death following adenoma removal are uncertain. Data are needed to inform evidence-based surveillance guidelines, which vary in follow-up recommendations for some polyp types. Using data from a large, community-based integrated health care setting, we examined the risks of CRC and related death by baseline colonoscopy adenoma findings. METHODS: Participants at 21 medical centers underwent baseline colonoscopies from 2004 through 2010; findings were categorized as no-adenoma, low-risk adenoma, or high-risk adenoma. Participants were followed until the earliest of CRC diagnosis, death, health plan disenrollment, or December 31, 2017. Risks of CRC and related deaths among the high- and low-risk adenoma groups were compared with the no-adenoma group using Cox regression adjusting for confounders. RESULTS: Among 186,046 patients, 64,422 met eligibility criteria (54.3% female; mean age, 61.6 ± 7.1 years; median follow-up time, 8.1 years from the baseline colonoscopy). Compared with the no-adenoma group (45,881 patients), the high-risk adenoma group (7563 patients) had a higher risk of CRC (hazard ratio [HR] 2.61; 95% confidence interval [CI] 1.87-3.63) and related death (HR 3.94; 95% CI 1.90-6.56), whereas the low-risk adenoma group (10,978 patients) did not have a significant increase in risk of CRC (HR 1.29; 95% CI 0.89-1.88) or related death (HR 0.65; 95% CI 0.19-2.18). CONCLUSIONS: With up to 14 years of follow-up, high-risk adenomas were associated with an increased risk of CRC and related death, supporting early colonoscopy surveillance. Low-risk adenomas were not associated with a significantly increased risk of CRC or related deaths. These results can inform current surveillance guidelines for high- and low-risk adenomas.

Colorectal Cancer Screening in People With and Without HIV in an Integrated Health Care Setting.

BACKGROUND: As people with HIV (PWH) live longer, age-appropriate colorectal cancer (CRC) screening is increasingly important. Limited data exist on CRC screening and outcomes comparing PWH and persons without HIV. SETTING: Large integrated health care system. METHODS: This study included PWH and demographically matched persons without HIV who were aged 50-75 years during 2005-2016 and had no previous CRC screening. We evaluated time to first CRC screening (fecal test, sigmoidoscopy, or colonoscopy). We also assessed detection of adenoma and CRC with sigmoidoscopy or colonoscopy by HIV status, accounting for CRC risk factors including sex, age, race/ethnicity, number of outpatient visits, smoking, body mass index, type-2 diabetes, and inflammatory bowel disease. Among PWH, we evaluated whether CD4 count (<200/200-499/≥500 cells/µL) was associated with adenoma and CRC. RESULTS: Among 3177 PWH and 29,219 persons without HIV, PWH were more likely to be screened (85.6% vs. 79.1% within 5 years, P < 0.001). Among those with sigmoidoscopy or colonoscopy, adenoma was detected in 161 (19.6%) PWH and 1498 (22.6%) persons without HIV, and CRC was detected in 4 (0.5%) PWH and 69 (1.0%) persons without HIV. In adjusted analyses, we found no difference in prevalence of either adenoma or CRC by HIV status (adjusted prevalence ratio = 0.97, 95% confidence interval: 0.83 to 1.12). Lower CD4 count did not increase likelihood of adenoma or CRC. CONCLUSIONS: Within an integrated health care system with an organized CRC screening program, we found no disparities in CRC screening uptake or outcomes among people with and without HIV, and CD4 count did not influence CRC risk among PWH.

Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings.

Importance: Guidelines recommend a 10-year rescreening interval after a colonoscopy with normal findings (negative colonoscopy results), but evidence supporting this recommendation is limited. Objective: To examine the long-term risks of colorectal cancer and colorectal cancer deaths after a negative colonoscopy result, in comparison with individuals unscreened, in a large, community-based setting. Design, Setting, and Participants: A retrospective cohort study was conducted in an integrated health care delivery organization serving more than 4 million members across Northern California. A total of 1 251 318 average-risk screening-eligible patients (age 50-75 years) between January 1, 1998, and December 31, 2015, were included. The study was concluded on December 31, 2016. Exposures: Screening was examined as a time-varying exposure; all participants contributed person-time unscreened until they were either screened or censored. If the screening received was a negative colonoscopy result, the participants contributed person-time in the negative colonoscopy results group until they were censored. Main Outcomes and Measures: Using Cox proportional hazards regression models, the hazard ratios (HRs) for colorectal cancer and related deaths were calculated according to time since negative colonoscopy result (or since cohort entry for those unscreened). Hazard ratios were adjusted for age, sex, race/ethnicity, Charlson comorbidity score, and body mass index. Results: Of the 1 251 318 patients, 613 692 were men (49.0%); mean age was 55.6 (7.0) years. Compared with the unscreened participants, those with a negative colonoscopy result had a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, and although reductions in risk were attenuated with increasing years of follow-up, there was a 46% lower risk of colorectal cancer (hazard ratio, 0.54; 95% CI, 0.31-0.94) and 88% lower risk of related deaths (hazard ratio, 0.12; 95% CI, 0.02-0.82) at the current guideline-recommended 10-year rescreening interval. Conclusions and Relevance: A negative colonoscopy result in average-risk patients was associated with a lower risk of colorectal cancer and related deaths for more than 12 years after examination, compared with unscreened patients. Our study findings may be able to inform guidelines for rescreening after a negative colonoscopy result and future studies to evaluate the costs and benefits of earlier vs later rescreening intervals.

Rates and Predictors of Vaccinations Among Inflammatory Bowel Disease Patients Receiving Anti-Tumor Necrosis Factor Agents.

BACKGROUND: As an important quality measure, the rates of recommended immunizations among immunocompromised inflammatory bowel disease (IBD) patients in community practice have not been well studied. AIMS: This study sought to investigate the rates and predictors of recommended immunizations and screening tests among IBD patients receiving anti-tumor necrosis factor (TNF) therapy in a large integrated healthcare organization. METHODS: We conducted a retrospective cohort study of 1401 IBD patients on anti-TNF therapy between 2010 and 2013 within the Kaiser Permanente Northern California healthcare system. The rates of vaccinations and screening tests were quantified, and the associated predictors were investigated. RESULTS: Vaccination rates for influenza and pneumococcus were 43.5 and 24.1%, respectively. The majority of patients (73.7%) received hepatitis B screening and/or vaccine. Patients receiving infliximab had higher rates of pneumococcal vaccine (P = 0.002), hepatitis B screening (P < 0.001), and tuberculin skin test (P < 0.001) compared with patients receiving adalimumab. Older patient age (≥50 years) was associated with higher likelihood of having HBsAg test (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0, P = 0.002), influenza vaccine (OR 2.6 [2.1-3.4], P < 0.001), and pneumococcal vaccine (OR 4.0 [3.0-5.3], P < 0.001). In contrast, older providers (≥50 years) were associated with significantly lower likelihood of their patients' having hepatitis A and B screening tests, and pneumococcal vaccination. CONCLUSIONS: The rates of immunizations for IBD patients receiving anti-TNF treatment were lower than recommended. Structured reminders for vaccinations and education for both patients and providers (older physicians in particular) may prove beneficial in improving immunization rates among immunocompromised IBD patients.

Minilaparotomy Versus Laparoscopic Myomectomy After Cessation of Power Morcellation: Rate of Wound Complications.

STUDY OBJECTIVE: After the US Food and Drug Administration statement warning against electronic morcellation devices, gynecologic surgeons are performing laparoscopic and robotic myomectomies with minilaparotomy incisions for tissue morcellation and removal. No data exist that focus on the superficial wound complications as a result of these larger incisions. The objective of this study is to compare the rate of wound complications for myomectomy via minilaparotomy versus laparoscopic or robotic myomectomy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Kaiser Permanente Northern California, a large integrated healthcare delivery system. PATIENTS: Women > 18 years of age who underwent a myomectomy from either complete laparoscopic or robotic approach (LR) were compared with minilaparotomy myomectomy (MM), comprising complete minilaparotomy (ML) and laparoscopic or robotic assisted by a minilaparotomy for morcellation purposes only (LRM) from January 2011 through December 2014. INTERVENTION: Myomectomy via LR, complete ML, and LRM. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for outcomes of interest, including superficial wound complications and surgical and demographic data. After exclusion criteria were met, 405 cases were included in the study; 270 cases were classified as MM, which included ML (n = 224), or LRM (n = 46). One hundred thirty-five cases were classified as LR. Parametric and nonparametric analyses were used to compare the 2 groups. There was no significant difference between the groups insofar as patient morbidity, including the primary outcome of wound complications and other postoperative complications; emergency visits; or readmissions. There were 2 (1.5%) wound complications in the LR group and 7 (2.6%) in the MM group (p = .72). Similarly, there were no significant differences in the subcategories of wound complications, including cellulitis, seroma, hematoma, skin separation, wound infection, or postprocedure wound complication. The distribution of estimated blood loss was significantly different between LR and MM groups with an interquartile range of 50 to 150 mL in the LR group versus 50 to 300 mL in the MM group (p < .01). The MM group experienced a shorter procedure time with a median procedure time of 125 minutes compared with 169.5 minutes in LR surgeries (p < .01). The LR group demonstrated a significantly shorter median length of hospital stay (LR 5.0 hours vs MM 23 hours; p < .01). CONCLUSION: Compared with MM, LR is associated with a shorter length of hospital stay and longer operating time but no reduction in wound complication or other patient morbidity.

Sensitivity of a Clinical Decision Rule and Early Computed Tomography in Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Application of a clinical decision rule for subarachnoid hemorrhage, in combination with cranial computed tomography (CT) performed within six hours of ictus (early cranial CT), may be able to reasonably exclude a diagnosis of aneurysmal subarachnoid hemorrhage (aSAH). This study's objective was to examine the sensitivity of both early cranial CT and a previously validated clinical decision rule among emergency department (ED) patients with aSAH and a normal mental status. METHODS: Patients were evaluated in the 21 EDs of an integrated health delivery system between January 2007 and June 2013. We identified by chart review a retrospective cohort of patients diagnosed with aSAH in the setting of a normal mental status and performance of early cranial CT. Variables comprising the SAH clinical decision rule (age≥40, presence of neck pain or stiffness, headache onset with exertion, loss of consciousness at headache onset) were abstracted from the chart and assessed for inter-rater reliability. RESULTS: One hundred fifty-five patients with aSAH met study inclusion criteria. The sensitivity of early cranial CT was 95.5% (95% CI [90.9-98.2]). The sensitivity of the SAH clinical decision rule was also 95.5% (95% CI [90.9-98.2]). Since all false negative cases for each diagnostic modality were mutually independent, the combined use of both early cranial CT and the clinical decision rule improved sensitivity to 100% (95% CI [97.6-100.0]). CONCLUSION: Neither early cranial CT nor the SAH clinical decision rule demonstrated ideal sensitivity for aSAH in this retrospective cohort. However, the combination of both strategies might optimize sensitivity for this life-threatening disease.

Thirty-day mortality after ischemic stroke and intracranial hemorrhage in patients with atrial fibrillation on and off anticoagulants.

BACKGROUND AND PURPOSE: Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of such events. We assessed the impact of anticoagulation on 30-day mortality from ischemic stroke versus ICH in a large community-based cohort of patients with atrial fibrillation. METHODS: We followed 13,559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system for a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. The association of warfarin and international normalized ratio at presentation with 30-day mortality was modeled using multivariable logistic regression adjusting for clinical factors. RESULTS: We identified 1025 incident ischemic strokes and 299 ICHs during follow-up. Compared with no antithrombotic therapy, warfarin was associated with reduced Rankin score and lower 30-day mortality from ischemic stroke (adjusted OR, 0.64; 95% CI, 0.45-0.91) but a higher mortality from ICH (OR, 1.62; 95% CI, 0.88-2.98). Therapeutic international normalized ratios (2-3) were associated with an especially low ischemic stroke mortality (OR, 0.38; 95% CI, 0.20-0.70), whereas international normalized ratios>3 increased the odds of dying of ICH by 2.66-fold (95% CI, 1.21-5.86). CONCLUSIONS: Warfarin reduces 30-day mortality from ischemic stroke but increases ICH-related mortality. Both effects on event severity as well as on event rates need to be incorporated into rational decision-making about anticoagulants for atrial fibrillation.

The net clinical benefit of warfarin anticoagulation in atrial fibrillation.

BACKGROUND: Guidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage. OBJECTIVE: To quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation. DESIGN: Mixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003. SETTING: An integrated health care delivery system. PATIENTS: 13 559 adults with nonvalvular atrial fibrillation. MEASUREMENTS: Warfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism. RESULTS: Patients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used. LIMITATIONS: Residual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable. CONCLUSION: Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation. PRIMARY FUNDING SOURCE: National Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened.

OBJECTIVE: To screen commonly used prescription drugs for possible carcinogenic effects. METHODS: In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least 2 years between drug dispensing and cancer. Positive associations entailed a relative risk of 1.50, with p ≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment. RESULTS: There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with nonHodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer. CONCLUSIONS: These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide, and nifedipine.

Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients.

PURPOSE: Determine the risk of cancer in statin users. METHODS: Risk of cancer in up to 9.4 years after first recorded receipt of statins was evaluated in subscribers of an integrated health care program in northern California. Statin use and cancer development were ascertained from the program's pharmacy records and cancer registry from August 1994 to December 2003. RESULTS: Most of the 361,859 statin users received lovastatin, simvastatin or both. Results are presented from analyses with 2-year lag and use for over 5 years. Most of the observed associations were likely due to chance or confounding. The few associations that seemed less readily explainable were increased risk of cancers of the thyroid, esophagus and urinary tract and decreased risk of colon cancer in men. Increased risk of lung cancer was the only nominally statistically significant positive association in women and could be partially attributable to their smoking habits. CONCLUSIONS: Overall this study provided no strong evidence of either causation or prevention of cancer by statins.

Coffee, cirrhosis, and transaminase enzymes.

BACKGROUND: A minority of persons at risk develop liver cirrhosis, but knowledge of risk modulators is sparse. Several reports suggest that coffee drinking is associated with lower cirrhosis risk. METHODS: We studied 125,580 multiethnic members of a comprehensive prepaid health care plan without known liver disease who supplied baseline data at voluntary health examinations from 1978 to 1985. Subsequently, through 2001, 330 of them were diagnosed with liver cirrhosis. Review of medical records confirmed the diagnosis of cirrhosis and ascertained probable etiology. The association of coffee drinking with cirrhosis was estimated by Cox proportional hazards models with 7 covariates. We also did a cross-sectional analysis of baseline aspartate aminotransferase and alanine aminotransferase levels, studied by logistic regression. RESULTS: In the cohort study, relative risks of alcoholic cirrhosis (199 subjects) for coffee drinking (vs none) were less than 1 cup per day, 0.7 (95% confidence interval [CI], 0.4-1.1); 1 to 3 cups, 0.6 (95% CI, 0.4-0.8; P<.001); and 4 or more cups, 0.2 (95% CI, 0.1-0.4; P<.001). For 131 subjects with nonalcoholic cirrhosis, relative risks were less than 1 cup, 1.2 (95% CI, 0.6-2.2); 1 to 3 cups, 1.3 (95% CI, 0.8-2.1); and 4 or more cups, 0.7 (95% CI, 0.4-1.3). These relative risks for coffee drinking were consistent in subsets. Tea drinking was unrelated to alcoholic or nonalcoholic cirrhosis. In the cross-sectional analyses, coffee drinking was related to lower prevalence of high aspartate aminotransferase and alanine aminotransferase levels; for example, the odds ratio of 4 or more cups per day (vs none) for a high aspartate aminotransferase level was 0.5 (95% CI, 0.4-0.6; P<.001) and for a high alanine aminotransferase level, 0.6 (95% CI, 0.6-0.7; P<.001), with stronger inverse relations in those who drink large quantities of alcohol. CONCLUSION: These data support the hypothesis that there is an ingredient in coffee that protects against cirrhosis, especially alcoholic cirrhosis.

Early symptoms of ovarian cancer: a case-control study without recall bias.

BACKGROUND: Ovarian cancer is usually diagnosed after it has spread and is difficult to cure. Previous attempts to identify early symptoms have either lacked a control group or have been based on interviews of cases, with possible recall bias. OBJECTIVE: The purpose of this study was to identify early symptoms of ovarian cancer by reviewing prediagnostic medical records, free of recall bias, and comparing women with and without ovarian cancer. METHODS: In an integrated health care delivery system, symptoms recorded in medical records of 102 women with ovarian cancer during the two years before diagnosis were compared with those of 102 matched control women. RESULTS: More cases than controls complained of several symptoms up to one year before diagnosis. Most of these symptoms were abdominal or gastrointestinal in nature and were more prevalent in the advanced stage cases. Other symptom sites included pelvic, urinary, back, and systemic. Because case-control differences were not large and prevalence is low, positive predictive values were generally quite low. CONCLUSION: Previous reports of early symptoms of ovarian cancer were confirmed in a study with a control group and free of recall bias. It is not clear that these symptoms occurred while the disease was still localized. Because hundreds of women would have to be investigated to detect one case of ovarian cancer, the clinical utility of these symptoms is uncertain. Nevertheless, health care providers should keep ovarian cancer in mind, when women present with symptoms such as abdominal pain and bloating.

Cryptococcosis: the 1981-2000 epidemic.

The annual incidence of cryptococcosis during 1981-2000 was determined in subscribers of a large integrated health care program in Northern California and in those among them who were HIV positive. The incidence of cryptococcosis had been measured in this setting in the previous decade. The 20-year incidence per million person-years was 19.0 in males and 2.6 in females. In males, annual incidence rose sharply but irregularly from 1981 to 1992, then decreased irregularly. In females, trends were less marked, with maximum incidence in 1997. In HIV-positive patients cryptococcosis incidence was highest in 1981-85 and decreased thereafter in men. In women, maximum incidence occurred in 1986-90 and was followed by a decrease. Cryptococcosis was rare in the non-predisposed. Thus, cryptococcosis incidence increased markedly in men early in the AIDS epidemic, and began to decrease in both male and female HIV-positive patients well before highly active antiretroviral therapy became available.

Smoking, coffee, and pancreatitis.

OBJECTIVES: We studied relationships of cigarette smoking and coffee drinking to risk of pancreatitis. METHODS: This was a cohort study among 129,000 prepaid health plan members who supplied data about demographics and habits in 1978-85. Among 439 persons subsequently hospitalized for pancreatitis, probable etiologic associations were cholelithiasis (168/439 = 38%), alcohol (125/439 = 29%), idiopathic (110/430 = 25%), and miscellaneous (36/439 = 8%). Cox proportional hazards models with seven covariates (including alcohol intake) yielded relative risk estimates for smoking and coffee use. RESULTS: Increasing smoking was strongly related to increased risk of alcohol-associated pancreatitis, less related to idiopathic pancreatitis, and unrelated to gallstone-associated pancreatitis. Relative risks (95% confidence intervals, CI) of one pack per day (vs never) smokers for pancreatitis groups were: alcohol = 4.9 (2.2-11.2, p < 0.001), idiopathic = 3.1 (1.4-7.2, p < 0.01), and gallstone = 1.3 (0.6-3.1). The relationship of smoking to alcohol-associated pancreatitis was consistent in sex and race subsets. Drinking coffee, but not tea, was weakly inversely related to risk only of alcohol-associated pancreatitis, with relative risk (95% CI) per cup per day = 0.85 (0.77-0.95; p= 0.003). Male sex, black ethnicity, and lower-educational attainment were other predictors of alcohol-associated pancreatitis. CONCLUSIONS: Cigarette smoking is an independent risk factor for alcohol-associated and idiopathic pancreatitis. Coffee drinking is associated with reduced risk of alcohol-associated pancreatitis. The data are compatible with the hypotheses that smoking may be toxic to the pancreas or may potentiate other pancreatic toxins while some ingredient in coffee may have a modulating effect.