High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors.

OBJECTIVE: To compare the incidence of cardiovascular (CV) events in persons with rheumatoid arthritis (RA) with that in people from the general population, adjusting for traditional CV risk factors. METHODS: Two hundred thirty-six consecutive patients with RA were assessed for the 1-year occurrence of 1) CV-related hospitalizations, including myocardial infarction, stroke or other arterial occlusive events, or arterial revascularization procedures, or 2) CV deaths. Both outcomes were ascertained by medical records or death certificates. For comparison, we used CV events that occurred during an 8-year period among participants in an epidemiologic study of atherosclerosis and CV disease who were ages 25-65 years at study entry. We calculated the age- and sex-stratified incidence rate ratio (IRR) of CV events between the 2 cohorts and used Poisson regression to adjust for age, sex, smoking status, diabetes mellitus, hypercholesterolemia, systolic blood pressure, and body mass index. RESULTS: Of the 236 RA patients, 234 were observed for 252 patient-years, during which 15 CV events occurred. Of these, 7 incident events occurred during the 204 patient-years contributed by patients ages 25-65 years, for an incidence of 3.43 per 100 patient-years. In the comparison cohort, 4,635 community-dwelling persons were followed up for 33,881 person-years, during which 200 new events occurred, for an incidence of 0.59 per 100 person-years. The age- and sex-adjusted IRR of incident CV events associated with RA was 3.96 (95% confidence interval [95% CI] 1.86-8.43). After adjusting for CV risk factors using Poisson regression, the IRR decreased slightly, to 3.17 (95% CI 1.33-6.36). CONCLUSION: The increased incidence of CV events in RA patients is independent of traditional CV risk factors. This suggests that additional mechanisms are responsible for CV disease in RA. Physicians who provide care to individuals with RA should be aware of their increased risk of CV events and implement appropriate diagnostic and therapeutic measures.     

Health-related quality of life predicts future health care utilization and mortality in veterans with self-reported physician-diagnosed arthritis: the veterans arthritis quality of life study

OBJECTIVE: To investigate whether health-related quality of life (HRQOL) measures predict health care utilization and mortality in a cohort of veterans with self-reported physician-diagnosed arthritis. METHODS: A cohort of veterans from the Upper Midwest Veterans Integrated Service Network (VISN) was mailed a self-administered questionnaire that was composed of the SF-36V (modified from SF-36 for use in veterans) and questions regarding demographics, current smoking status, limitation of activities of daily living (ADLs), and preexisting physician-diagnosed medical conditions, including arthritis. Within subjects reporting physician-diagnosed arthritis, we analyzed the associations between the SF-36V component summary scales (physical and mental component summary, PCS and MCS, respectively) and the occurrence of any hospitalization, number of hospitalizations, number of outpatient visits, and mortality, for the year after survey administration, using multivariable regression analyses. RESULTS: Of 34,440 survey responders who answered a question regarding arthritis, 18,464 (58%) subjects reported physician-diagnosed arthritis. Arthritic patients in the lowest tertile of PCS scores had significantly higher odds of any hospitalization (Odds ratio (OR) 1.49, 95% confidence interval (CI) [1.25-1.76]) and mortality (OR 1.69, 95% CI [1.18-2.42]), and a significantly higher number of hospitalizations/year (Rate ratio (RR) 1.09, 95% CI [1.05-1.13]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). Arthritic patients in the lowest tertile of MCS scores had significantly higher odds of any hospitalization (OR 1.20, 95% CI [1.02-1.41]), mortality (OR 2.14, 95% CI [1.56-2.94]), and a significantly higher number of hospitalizations/year (RR 1.05, 95% CI [1.02-1.09]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). CONCLUSIONS: HRQOL, as assessed by the SF-36V, predicts future inpatient and outpatient health care utilization and mortality in veterans with self-report of physician-diagnosed arthritis.     

Prevalent herpes simplex virus type 2 infection is associated with altered vaginal flora and an increased susceptibility to multiple sexually transmitted infections

BACKGROUND: Prevalent herpes simplex virus type 2 (HSV-2) infection increases human immunodeficiency virus acquisition. We hypothesized that HSV-2 infection might also predispose individuals to acquire other common sexually transmitted infections (STIs). Methods: We studied the association between prevalent HSV-2 infection and STI incidence in a prospective, randomized trial of periodic STI therapy among Kenyan female sex workers. Participants were screened monthly for infection with Neisseria gonorrhoeae and Chlamydia trachomatis, and at least every 6 months for bacterial vaginosis (BV) and infection with Treponema pallidum, Trichomonas vaginalis, and/or HSV-2. RESULTS: Increased prevalence of HSV-2 infection and increased prevalence of BV were each associated with the other; the direction of causality could not be determined. After stratifying for sexual risk-taking, BV status, and antibiotic use, prevalent HSV-2 infection remained associated with an increased incidence of infection with N. gonorrhoeae (incidence rate ratio [IRR], 4.3 [95% confidence interval {CI}, 1.5-12.2]), T. vaginalis (IRR, 2.3 [95% CI, 1.3-4.2]), and syphilis (IRR, 4.7 [95% CI, 1.1-19.9]). BV was associated with increased rates of infection with C. trachomatis (IRR, 2.1 [95% CI, 1.1-3.8]) and T. vaginalis (IRR, 8.0 [95% CI, 3.2-19.8]). CONCLUSION; Increased prevalences of HSV-2 infection and BV were associated with each other and also associated with enhanced susceptibility to an overlapping spectrum of other STIs. Demonstration of causality will require clinical trials that suppress HSV-2 infection, BV, or both.     

Progression of HIV infection and mortality by hepatitis C infection in patients with haemophilia over 20 years.

Hepatitis C virus (HCV) infection is an important cause of mortality in human immune deficiency virus (HIV)-positive haemophiliacs. This study describes progression to AIDS, death from HCV end-stage liver disease (ESLD) and all-cause mortality over 20 years. All HIV-positive haemophiliacs in La Paz University Hospital were included in this cohort. HIV seroconversion was estimated using mathematical techniques for interval-censored data from 1979 to 1985. Poisson regression was used to estimate rates of AIDS, death from ESLD and all causes in different periods: before 1988, 1988-89, 1990-91, 1992-93, 1994-95, 1996-97 and 1998-2001 using competing risk models. Among 383 cohort members, global AIDS incidence was 9.7 per 100 person-years, peaking in 1992-93 and dropping by 87% in 1998-2001 compared with before 1988 [incidence rate ratio (IRR) 0.13; 95% CI: 0.03-0.53]. Overall mortality was 7.5 per 100 person-years, was highest from 1992 to 1997, and fell by 66% in 1998-2001 compared with before 1988 (IRR 0.34; 95% CI: 0.14-0.81). Eighteen (5%) persons died of ESLD which represented 19% of deaths before 1988, 4% during 1988-89, 1990-91 and 1992-93, 2% in 1994-95, 10% in 1996-97 and 33% in 1998-2001. Overall death rate from ESLD was 0.5 cases per 100 person-years with no statistically significant trend observed over time. Important reductions in HIV disease progression to AIDS and death have been observed from 1998 to 2001, and can be attributed to highly active antiretroviral therapy. Although no increase in the rate of HCV-related deaths can be demonstrated, HCV accounts for an increasing proportion of deaths in the recent years.     

Male circumcision and herpes simplex virus type 2 infection in female partners: a randomized trial in Rakai, Uganda

Male circumcision reduces acquisition of herpes simplex virus type 2 (HSV-2) in men. We assessed whether male circumcision reduces HSV-2 infection among female partners. HSV-2-negative, human immunodeficiency virus-negative female partners of 368 males who were and 372 males who were not randomized to receive male circumcision were enrolled. The incidence of HSV-2 infection among females over a period of 2 years was 6.09 cases per 100 person-years in the intervention arm and 6.32 cases per 100 person-years in the control arm (incidence rate ratio [IRR], 0.96 [95% confidence interval {CI}, .62-1.49]; P = .87). Among female partners of HSV-2-positive males, the incidence of HSV-2 infection was 9.55 cases per 100 person-years in the intervention arm and 11.17 cases per 100 person-years in the control arm (IRR, 0.85 [95% CI, .44-1.67]; P = .62). Contrary to findings in males, male circumcision did not affect HSV-2 acquisition among female partners.     

Risk of colorectal cancer in women with a prior diagnosis of gynecologic malignancy

GOALS AND BACKGROUND: Earlier studies regarding the risk of colorectal cancer (CRC) in women with a prior diagnosis of gynecologic malignancies have revealed conflicting results. We sought to further clarify this association. METHODS: A retrospective cohort study was performed using the General Practice Research Database of the United Kingdom. Patients with a prior diagnosis of ovarian, uterine, or cervical cancers were compared with control patients without a prior gynecologic malignancy. The primary outcome was a diagnosis of CRC. Poisson regression analysis was used to assess the effects of potential confounders. RESULTS: The study included 1995 ovarian, 1348 uterine, and 1101 cervical cancer patients and 7980, 5392, and 4404 matched control patients, respectively. The adjusted incidence rate ratio (IRR) of CRC among ovarian cancer patients was 2.90 [95% confidence intervals (CI) 1.45-5.82]. Five of 10 cases of CRC in ovarian cancer patients were diagnosed within 6 months of the cancer diagnosis with an adjusted IRR of 8.0 (95% CI 1.9-33.6). Excluding the initial 6 months of follow-up after the diagnosis of ovarian cancer, the adjusted IRR was 1.6 (95% CI 0.76-5.03). The adjusted IRR of CRC in patients with a prior diagnosis of uterine and cervical cancer was 0.79 (95% CI 0.24-2.61) and 1.50 (95% CI 0.43-5.21), respectively. CONCLUSIONS: Women with a prior diagnosis of ovarian cancer are at an increased risk of CRC. The risk of CRC was not increased among patients with a prior history of uterine and cervical cancer.     

Factors associated with the development of opportunistic infections in HIV-1-infected adults with high CD4+ cell counts: a EuroSIDA study

BACKGROUND: Limited data exist on factors predicting the development of opportunistic infections (OIs) at higher-than-expected CD4(+) cell counts in human immunodeficiency virus (HIV) type 1-infected adults. METHODS: Multivariate Poisson regression models were used to determine factors related to the development of groups of OIs above their respective traditional upper CD4(+) cell count thresholds: group 1 (>or=100 cells/ microL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (>or=200 cells/ microL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (>or=300 cells/ microL), pulmonary and extrapulmonary tuberculosis. RESULTS: In groups 1, 2, and 3, 71 of 9,219, 125 of 7,934, and 36 of 7,838 patients, respectively, developed >or=1 intragroup OI. The strongest predictor of an OI in groups 1 and 2 was current CD4(+) cell count (for group 1, incidence rate ratio [IRR] per 50% lower CD4(+) cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4(+) cell count predicted risk in group 3. Use of antiretroviral treatment was associated with a lower incidence of OIs in all groups, likely by reducing HIV-1 RNA levels (IRR per 1-log(10) copies/mL higher HIV-1 RNA levels for group 1, 1.50 [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89 [95% CI, 1.40-2.54]). CONCLUSION: Although the absolute incidence is low, the current CD4(+) cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4(+) cell counts.     

Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials

BACKGROUND: We performed a meta-analysis of randomized controlled trials to assess ongoing concerns about the safety profile of combination angiotensin II receptor blockers (ARBs) plus angiotensin-converting enzyme (ACE) inhibitors in symptomatic left ventricular dysfunction. METHODS: MEDLINE (January 1966-December 2006) and Web sites for the National Institute of Health Clinical Trials and the Food and Drug Administration were searched for eligible RCTs that included 500 or more subjects, had a follow-up of 3 months or longer, and reported adverse effects. We used a random effects model to calculate the relative risk (RR) and 95% confidence interval (CI) for the following outcome measures: medication discontinuations because of adverse effects, worsening renal function (an increase in serum creatinine level of > 0.5 mg/dL [to convert to micromoles per liter, multiply by 88.4]), hyperkalemia (serum potassium level > 5.5 mEq/L [to convert to millimoles per liter, multiply by 1]), and symptomatic hypotension. RESULTS: Four studies (N = 17 337; mean follow-up, 25 months [range, 11-41 months]) were selected. Combination ARB plus ACE inhibitor vs control treatment that included ACE inhibitors was associated with significant increases in medication discontinuations because of adverse effects in patients with chronic heart failure (RR, 1.38 [95% CI, 1.22-1.55]) or in patients with acute myocardial infarction with symptomatic left ventricular dysfunction (RR, 1.17 [95% CI, 1.03-1.34]), and for both conditions there were significant increases in worsening renal function (RR, 2.17 [95% CI, 1.59-2.97] and RR, 1.61 [95% CI, 1.31-1.98], respectively), hyperkalemia (RR, 4.87 [95% CI, 2.39-9.94] and RR, 1.33 [95% CI, 0.90-1.98], respectively; the latter was not significant), and symptomatic hypotension (RR, 1.50 [95% CI, 1.09-2.07], and RR, 1.48 [95% CI, 1.33-3.18], respectively). CONCLUSION: Combination ARB plus ACE inhibitor therapy in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects.     

Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy

OBJECTIVE: To assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of < 500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART). RESULTS: HCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a > or = 50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a > or = 50 cells/microL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation. CONCLUSIONS: HCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatus.     

Effect of home-based water chlorination and safe storage on diarrhea among persons with human immunodeficiency virus in Uganda

Diarrhea is frequent among persons infected with human immunodeficiency virus (HIV) but few interventions are available for people in Africa. We conducted a randomized controlled trial of a home-based, safe water intervention on the incidence and severity of diarrhea among persons with HIV living in rural Uganda. Between April 2001 and November 2002, households of 509 persons with HIV and 1,521 HIV-negative household members received a closed-mouth plastic container, a dilute chlorine solution, and hygiene education (safe water system [SWS]) or simply hygiene education alone. After five months, HIV-positive participants received daily cotrimoxazole prophylaxis (160 mg of trimethoprim and 800 mg of sulfamethoxazole) and were followed for an additional 1.5 years. Persons with HIV using SWS had 25% fewer diarrhea episodes (adjusted incidence rate ratio [IRR] = 0.75, 95% confidence interval [CI] = 0.59-0.94, P = 0.015), 33% fewer days with diarrhea (IRR = 0.67, 95% CI = 0.48-0.94, P = 0.021), and less visible blood or mucus in stools (28% versus 39%; P < 0.0001). The SWS was equally effective with or without cotrimoxazole prophylaxis (P = 0.73 for interaction), and together they reduced diarrhea episodes by 67% (IRR = 0.33, 95% CI = 0.24-0.46, P < 0.0001), days with diarrhea by 54% (IRR = 0.46, 95% CI = 0.32-0.66, P < 0.0001), and days of work or school lost due to diarrhea by 47% (IRR = 0.53, 95% CI = 0.34-0.83, P < 0.0056). A home-based safe water system reduced diarrhea frequency and severity among persons with HIV living in Africa and large scale implementation should be considered.     

Associations of diabetes,prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: A prospective UK Biobank study

Aim

To investigate the associations of diabetes, prediabetes and diabetes duration with chronic obstructive pulmonary disease (COPD) risk and survival in the UK Biobank.

Materials and Methods

We conducted a prospective analysis among 452 680 participants without COPD at baseline using UK Biobank data. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox regression models. The dose–response relationship was explored using restricted cubic splines. A separate survival analysis was conducted for 12 595 patients with incident COPD.

Results

Over a median follow-up of 12.3 years, 12 595 cases of COPD were documented. Compared with the reference group, those with prediabetes and diabetes were associated with an 18% (HR 1.18 [95% CI: 1.13-1.24]) and 35% (HR 1.35 [95% CI: 1.24-1.47]) higher risk of COPD, respectively. Diabetes duration was associated with COPD risk, with multivariable HRs (95% CIs) of 1.23 (1.05-1.44), 1.20 (1.04-1.39) and 1.18 (1.01-1.37) for diabetes duration of 7 years or longer, 3 to less than 7 years, and 1 to less than 3 years versus less than 1 year, respectively. Dose–response analysis revealed a non-linear relationship between diabetes duration and COPD risk. Regarding COPD survival, COPD patients with prediabetes and diabetes had a 9% (HR 1.09 [95% CI: 1.00-1.19]) and 21% (HR 1.21 [95% CI: 1.05-1.41]) higher risk of overall death, respectively. Compared with the cases with a diabetes duration of less than 1 year, those with a diabetes duration of 7 years or longer were associated with a 46% higher risk of overall death (HR 1.46 [95% CI: 1.11-1.92]).

Conclusions

Our findings indicate that diabetes, prediabetes and a longer diabetes duration are associated with a higher risk of and worse survival for COPD. Future studies are warranted to determine the optimal way of diabetes control that might reduce COPD risk.     

Clinical Outcomes with β-Blockers for Myocardial Infarction: A Meta-analysis of Randomized Trials

BackgroundDebate exists about the efficacy of β-blockers in myocardial infarction and their required duration of usage in contemporary practice.MethodsWe conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating β-blockers in myocardial infarction enrolling at least 100 patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion-era (> 50% undergoing reperfusion or receiving aspirin/statin) or pre-reperfusion-era trials.ResultsSixty trials with 102,003 patients satisfied the inclusion criteria. In the acute myocardial infarction trials, a significant interaction (P_interaction = .02) was noted such that β-blockers reduced mortality in the pre-reperfusion (incident rate ratio [IRR] 0.86; 95% confidence interval [CI], 0.79-0.94) but not in the reperfusion era (IRR 0.98; 95% CI, 0.92-1.05). In the pre-reperfusion era, β-blockers reduced cardiovascular mortality (IRR 0.87; 95% CI, 0.78-0.98), myocardial infarction (IRR 0.78; 95% CI, 0.62-0.97), and angina (IRR 0.88; 95% CI, 0.82-0.95), with no difference for other outcomes. In the reperfusion era, β-blockers reduced myocardial infarction (IRR 0.72; 95% CI, 0.62-0.83) (number needed to treat to benefit [NNTB] = 209) and angina (IRR 0.80; 95% CI, 0.65-0.98) (NNTB = 26) at the expense of increase in heart failure (IRR 1.10; 95% CI, 1.05-1.16) (number needed to treat to harm [NNTH] = 79), cardiogenic shock (IRR 1.29; 95% CI, 1.18-1.41) (NNTH = 90), and drug discontinuation (IRR 1.64; 95% CI, 1.55-1.73), with no benefit for other outcomes. Benefits for recurrent myocardial infarction and angina in the reperfusion era appeared to be short term (30 days).ConclusionsIn contemporary practice of treatment of myocardial infarction, β-blockers have no mortality benefit but reduce recurrent myocardial infarction and angina (short-term) at the expense of increase in heart failure, cardiogenic shock, and drug discontinuation. The guideline authors should reconsider the strength of recommendations for β-blockers post myocardial infarction.     

Calcium and phosphate concentrations and future development of type 2 diabetes: the Insulin Resistance Atherosclerosis Study

Aims/hypothesis

Low phosphate and high calcium concentrations have been linked to altered glucose tolerance and reduced insulin sensitivity in non-diabetic individuals. The aim of this study was to examine the relationships of calcium and phosphate levels and the calcium–phosphate product with the development of type 2 diabetes.

Methods

Participants were 863 African-Americans, Hispanics and non-Hispanic whites in the Insulin Resistance Atherosclerosis Study who were free of diabetes at baseline. The mean follow-up period was 5.2 years. The insulin sensitivity index (S_I) and acute insulin response (AIR) were directly measured using the frequently sampled IVGTT.

Results

Calcium concentration (OR per 1 SD unit increase, 1.26 [95% CI 1.04, 1.53]) and calcium–phosphate product (OR 1.29 [95% CI 1.04, 1.59]) were associated with incident diabetes after adjustment for demographic variables, family history of diabetes, and 2 h glucose. The relationship between phosphate concentration and progression to diabetes was close to statistical significance (OR 1.21 [95% CI 0.98, 1.49]). Calcium concentration (OR 1.37 [95% CI 1.09, 1.72]) and calcium–phosphate product (OR 1.39 [95% CI 1.09, 1.77]) remained associated with incident diabetes after additional adjustment for BMI, plasma glucose, S_I, AIR, C-reactive protein, estimated GFR, diuretic drugs and total calcium intake.

Conclusions/interpretation

Elevated serum calcium and calcium–phosphate product are associated with increased risk of developing type 2 diabetes independently of measured glucose, insulin secretion and insulin resistance. Future studies need to analyse the role of calcium–phosphate homeostasis in the pathophysiology of diabetes.     

Comparison of Acute Respiratory Events Between Asthma–COPD Overlap Syndrome and COPD Patients: A Population-Based Cohort Study

Epidemiologic studies investigating the differences in respiratory outcomes between asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) and chronic obstructive pulmonary disease (COPD) in an Asian population are lacking.We conducted a population-based cohort study to compare the incidence of acute respiratory events between ACOS and COPD cohorts in Taiwan. This study investigated the incidence of acute respiratory events, namely, pneumonia, acute exacerbation, acute respiratory failure, and cardiopulmonary arrest, in 8571 patients with physician-diagnosed ACOS between 2000 and 2007 from the Longitudinal Health Insurance Database. The comparison cohort comprised 17,088 COPD patients, frequency-matched according to age, sex, and the index-year. The duration of follow-up was measured for each patient from the index date to 5 years thereafter. We used univariable and multivariable Poisson regression models to analyze the risk of acute respiratory events by including the variables of sex, age, and comorbidity.The overall prevalence of ACOS was approximately 17.4% in patients with COPD. The prevalence of ACOS increased with age. During the 5-year follow-up, a greater incidence of acute respiratory events was observed in the ACOS cohort than in the COPD cohort (11.5 and 4.62, per 100 person-years, respectively) with an adjusted incidence rate ratio (IRR) of 1.72 (95% confidence interval [CI] = 1.63–1.81). Compared with the COPD cohort, the ACOS patients had a 1.13-fold adjusted IRR of pneumonia (95% CI = 1.07–1.20) and a 2.58-fold adjusted IRR of acute exacerbation (95% CI = 2.43–2.74). Clinicians should be aware of frequent exacerbation of ACOS and prescribe appropriate treatment.     

Cholecystectomy and the risk of colorectal cancer

OBJECTIVES: Cholecystectomy has been implicated as a possible risk factor for colorectal cancer. However, the clinical evidence and the underlying mechanism for this association are still inconclusive. We conducted a population-based study to further clarify this association. METHODS: We conducted a retrospective cohort study among all patients aged 40 yr or older in the General Practice Research Database from the United Kingdom. We excluded patients with <1 yr of colorectal cancer-free database follow-up as well as those patients who developed colorectal cancer within 1 yr after their cholecystectomies. Crude and adjusted incidence rate ratios (IRRs) were determined using Poisson regression. RESULTS: The incidence rate of colorectal cancer among cholecystectomy patients (n = 55,960) was 119 (95% CI: 106-133) per 100,000 person-years, compared to 86 (95% CI: 83-90) per 100,000 person-years among patients without a cholecystectomy (n = 574,668). Among the covariates examined, only sex and age were significant confounders and were included in the adjusted analyses. The adjusted IRR of colorectal cancer associated with cholecystectomy was 1.32 (95% CI: 1.16-1.48, p < 0.001). The positive association was present for colon cancer (adjusted IRR 1.51, 95% CI: 1.30-1.74, p < 0.001), but not for rectal cancer (adjusted IRR 1.00, 95% CI: 0.85-1.17, p= 0.99). The pattern of association was similar in men versus women. A similar association with colon cancer was observed for cholelithiasis. CONCLUSIONS: Cholecystectomy is associated with a modestly increased risk of colon cancer but not for rectal cancer. Lithogenic bile could be the underlying mechanism.     

Ethnic differences in hypertension incidence among middle-aged and older adults: the multi-ethnic study of atherosclerosis

The prevalence of hypertension is higher among blacks than whites. However, inconsistent findings have been reported on the incidence of hypertension among middle-aged and older blacks and whites, and limited data are available on the incidence of hypertension among Hispanics and Asians in the United States. Therefore, this study investigated the age-specific incidence of hypertension by ethnicity for 3146 participants from the Multi-Ethnic Study of Atherosclerosis. Participants, age 45 to 84 years at baseline, were followed for a median of 4.8 years for incident hypertension, defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or the initiation of antihypertensive medications. The crude incidence rate of hypertension, per 1000 person-years, was 56.8 for whites, 84.9 for blacks, 65.7 for Hispanics, and 52.2 for Chinese. After adjustment for age, sex, and study site, the incidence rate ratio (IRR) for hypertension was increased for blacks age 45 to 54 (IRR: 2.05 [95%CI: 1.47 to 2.85]), 55 to 64 (IRR: 1.63 [95% CI: 1.20 to 2.23]), and 65 to 74 years (IRR: 1.67 [95% CI: 1.21 to 2.30]) compared with whites but not for those 75 to 84 years of age (IRR: 0.97 [95% CI: 0.56 to 1.66]). Additional adjustment for health characteristics attenuated these associations. Hispanic participants also had a higher incidence of hypertension compared with whites; however, hypertension incidence did not differ for Chinese and white participants. In summary, hypertension incidence was higher for blacks compared with whites between 45 and 74 years of age but not after age 75 years. Public health prevention programs tailored to middle-aged and older adults are needed to eliminate ethnic disparities in incident hypertension.     

Smoking,alcohol consumption,and risk of systemic lupus erythematosus in the Black Women's Health Study

OBJECTIVE: Several case-control studies, mostly of prevalent disease, have suggested that systemic lupus erythematosus (SLE) is positively associated with cigarette smoking and inversely associated with alcohol consumption. We prospectively investigated the associations of smoking and alcohol consumption with incident SLE in the Black Women's Health Study (BWHS). METHODS: In 1995, 64,500 African-American women provided information on demographic characteristics, reproductive and medical histories, smoking, and alcohol consumption. Followup questionnaires in 1997 and 1999 ascertained incident cases of SLE. Cox proportional hazards regression was used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: Sixty-seven women reported a new diagnosis of SLE and use of appropriate medication for that illness. In multivariate analyses, the IRR for current and past smoking were 1.6 (both 95% CI 0.8-3.3). The risk was greater for women who began smoking before age 19 years (IRR 1.9, 95% CI 1.0-3.6). Neither current alcohol consumption (IRR 1.0, 95% CI 0.4-2.4) nor past alcohol consumption (IRR 0.9, 95% CI 0.3-2.7) was associated with SLE. CONCLUSION: Our results suggest an increased risk of SLE among smokers, but no effect of alcohol consumption on risk. The inverse association of alcohol consumption with SLE found in studies of prevalent disease may have resulted from women with SLE giving up drinking.     

Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm

RATIONALE: The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results. OBJECTIVES: To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. METHODS: An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV(1)/FVC ratio >/= 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV(1)/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up. MAIN RESULTS: The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44-5.79). CONCLUSIONS: The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits.     

Risk of malignant disease among 1525 adult male US Veterans with Gaucher disease

BACKGROUND: Some, but not all, reports suggest that patients with Gaucher disease are at increased risk of developing malignancies, particularly hematopoietic tumors. The aim of this study was to assess the pattern of Gaucher disease and subsequent malignancies among male veterans admitted to US Veterans Affairs hospitals. METHODS: Among 832 294 African American and 3 668 983 white male veterans with at least 1 hospital admission in US Veterans Affairs hospitals and up to 27 years of follow-up, we identified a total of 1525 patients with Gaucher disease; 11.7% were African Americans. We used Poisson regression methods for cohort data to estimate relative risks (RRs) and 95% confidence intervals (CIs) after adjusting for attained age and calendar year, race, number of hospital visits, and latency. RESULTS: When patients with Gaucher disease were compared with patients without Gaucher disease, the RR of any cancer was 0.91 (95% CI, 0.76-1.08 [n = 137]). When we stratified our analyses by race, risks were similar for whites (RR, 0.89; 95% CI, 0.74-1.07 [n = 120]) and African Americans (RR, 1.00; 95% CI, 0.61-1.64 [ n = 17]). Patients with Gaucher disease had an elevated risk for non-Hodgkin lymphoma (RR, 2.54; 95% CI, 1.32-4.88 [n = 9]), malignant melanoma (RR, 3.07; 95% CI, 1.28-7.38 [n = 5]), and pancreatic cancer (RR, 2.37; 95% CI, 1.13-4.98 [n = 7]). Among the remaining 19 cases involving defined solid tumors and 7 other hematologic malignancies, we found no statistical association with Gaucher disease. CONCLUSION: We found 2- to 3-fold risks of non-Hodgkin lymphoma, malignant melanoma, and pancreatic cancer in patients with Gaucher disease, but no significant association between Gaucher disease and cancer in general or with other specific malignancies such as multiple myeloma.