Adverse events associated with testosterone administration.

BACKGROUND: Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. METHODS: Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. RESULTS: A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. CONCLUSIONS: In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy. (ClinicalTrials.gov number, NCT00240981.)

The association between height and prostate cancer grade in the Early Stage Prostate Cancer Cohort Study.

OBJECTIVE: We examined the relationship between height and prostate cancer grade. METHODS: The Early Stage Prostate Cancer Cohort Study is an observational cohort of 1,037 men diagnosed with early-stage prostate cancer, T(0-3)N(x)M(0). High-grade prostate cancer was defined as a biopsy Gleason score ≥ 7 (4 + 3). Logistic regression models were created to calculate odds ratios (OR) and 95% confidence intervals (CI) for the cross-sectional relationship between height and prostate cancer grade in the overall cohort and subpopulations. RESULTS: We identified 939 participants with a biopsy Gleason score. High-grade prostate cancer was diagnosed in 138 participants. Overall, participants in the highest quartile of height were more than twice as likely to have a Gleason score ≥ 7 (4 + 3) than participants in the lowest quartile of height, OR 2.14 (95% CI 1.11, 4.14), after multivariate adjustment. Participants in the highest quartile of height were more likely to be diagnosed with high-grade prostate cancer than participants in the lowest quartile of height among participants who were black, OR 8.00 (95% CI 1.99, 32.18), and participants who had diabetes mellitus, OR 5.09 (95% CI 1.30, 19.98). CONCLUSIONS: Height is associated with increased risk of high-grade prostate cancer overall and perhaps among certain subpopulations.

Serum anion gap, bicarbonate and biomarkers of inflammation in healthy individuals in a national survey.

BACKGROUND: In vitro data suggest that lower extracellular pH activates the immune system. We conducted a population-based study of the relation between serum acid-base status and inflammation. METHODS: We examined the serum anion gap and serum levels of bicarbonate and inflammatory biomarkers in 4525 healthy adults who participated in the National Health and Nutrition Examination Survey during 1999-2006. We excluded participants who had chronic disease, recent infection and an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2. RESULTS: The mean values of serum anion gap, bicarbonate level, leukocyte count and C-reactive protein level were all within normal limits. After adjustment for age, sex, ethnic background, body mass index, serum albumin level and other factors, we found that a higher anion gap and lower bicarbonate level were associated with a higher leukocyte count and higher C-reactive protein level. Compared with participants in the lowest quartile of anion gap, those in the highest quartile had a leukocyte count that was 1.0x10(9)/L higher and a C-reactive protein level that was 10.9 nmol/L higher (p<0.01). Compared with participants in the highest quartile of bicarbonate level, those in the lowest quartile had a leukocyte count that was 0.7x10(9)/L higher and a C-reactive protein level that was 4.0 nmol/L higher (p

The relationship between total plasma carotenoids and risk factors for chronic disease among middle-aged and older men.

Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk factors for chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene, beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and a-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors, the OR for levels of total plasma carotenoids greater than or equal to the median (> or=1.301 micromol/l) was statistically significant for current smoking (OR 0.21; 95% CI 0.06, 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06, 4.99), daily alcohol ingestion (OR 2.46; 95% CI 1.29, 4.67), each 100 mg/l increase in total cholesterol (OR 0.73; 95% CI 0.58, 0.91), LDL-cholesterol (OR 1.48; 95% CI 1.17, 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26, 1.99), each 100 mg/ml increase in intercellular adhesion molecule-1 (OR 0.70; 95% CI 0.53, 0.93) and each 10 micromol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12, 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoids; however, levels of biomarkers such as plasma lipids and alpha-tocopherol may be strongly related.

Trends in prostate-specific antigen testing from 1995 through 2004.

BACKGROUND: The utility of the prostate-specific antigen (PSA) test to screen for prostate cancer has been widely debated for several years. Whether PSA testing rates have changed during this period of controversy is not well known. METHODS: We examined the National Ambulatory Medical Care Survey (1995-2004) of visits to primary care providers by healthy men aged 35 years or older. We examined visits by calendar year and compared the years 2000 through 2004 with the years 1995 through 1999. We also examined visits by men in the overall population and in particular subgroups. RESULTS: Primary care physicians ordered PSA tests in 4.7% of all visits in 1995 and in 7.0% of all visits in 2004 (P = .03). In multivariate analysis, the odds of a primary care physician ordering a PSA test during any clinic visit increased 8% (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.04-1.12; P < .001) per year from 1995 through 2004. The increase was more pronounced among men making visits for general medical examinations (11.2% in 1995 vs 32.3% in 2004; P = .003). Comparing the period 2000-2004 with the period 1995-1999, the odds of PSA testing increased in nearly all subgroups but most dramatically in black men (OR, 2.3; 95% CI, 1.4-3.8; P = .002) and in men 35 through 49 years of age (OR, 1.8; 95% CI, 1.3-2.6; P = .001). CONCLUSION: In a nationally representative sample, we found that despite the lack of clear evidence of benefit, PSA testing for prostate cancer screening has increased dramatically, especially among black men and younger men.

Non-high-density lipoprotein cholesterol versus low-density lipoprotein cholesterol as a risk factor for a first nonfatal myocardial infarction.

Low-density lipoprotein (LDL) cholesterol is the primary lipid parameter targeted to prevent myocardial infarction. Alternatively, non-high-density lipoprotein (HDL) cholesterol includes LDL cholesterol and other atherogenic particles but does not require a fasting sample. Non-HDL cholesterol and LDL cholesterol as predictors of first nonfatal myocardial infarction were compared in 303 patients and 297 controls matched for age, gender, and community within the Boston Area Health Study. Patients were white men or women aged <76 years living in the Boston area, without a history of myocardial infarction or angina pectoris, in whom symptoms of confirmed myocardial infarction began during the 24 hours before admission. After multivariate adjustment for coronary risk factors in unmatched analyses, the corresponding odds ratios (ORs) of a first nonfatal myocardial infarction for non-HDL cholesterol in the second, third, and fourth quartiles were 1.83 (95% confidence interval [CI] 1.07 to 3.14), 2.07 (95% CI 1.23 to 3.49), and 2.33 (95% CI 1.39 to 3.90) (p trend <0.01). For LDL cholesterol, the ORs were 1.10 (95% CI 0.67 to 1.81), 0.87 (95% CI 0.52 to 1.46), and 1.45 (95% CI 0.90 to 2.35) (p trend = 0.16). Including HDL cholesterol in the model increased the ORs and strengthened the test for a trend for LDL cholesterol, whereas the ORs were decreased and the test for a trend was weakened for non-HDL cholesterol. In conclusion, given that non-HDL cholesterol accounts for LDL cholesterol plus other atherogenic particles but does not require a fasting sample, this study suggests that non-HDL cholesterol may be at least as useful as LDL cholesterol to initially screen patients for risk of a first nonfatal myocardial infarction.

Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial.

BACKGROUND: In a phase 2 study, dexpramipexole (25-150 mg twice daily) was well tolerated for up to 9 months and showed a significant benefit at the high dose in a combined assessment of function and mortality in patients with amyotrophic lateral sclerosis. We aimed to assess efficacy and safety of dexpramipexole in a phase 3 trial of patients with familial or sporadic disease. METHODS: In our randomised, double-blind, placebo-controlled phase 3 trial (EMPOWER), we enrolled participants aged 18-80 years (with first amyotrophic lateral sclerosis symptom onset 24 months or less before baseline) at 81 academic medical centres in 11 countries. We randomly allocated eligible participants (1:1) with a centralised voice-interactive online system to twice-daily dexpramipexole 150 mg or matched placebo for 12-18 months, stratified by trial site, area of disease onset (bulbar vs other areas), and previous use of riluzole. The primary endpoint was the combined assessment of function and survival (CAFS) score, based on changes in amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) total scores and time to death up to 12 months. We assessed the primary endpoint in all participants who received at least one dose and had at least one post-dose ALSFRS-R measurement or died. We monitored adverse events in all participants. This study is registered with ClinicalTrials.gov, number NCT01281189. FINDINGS: Between March 28, 2011, and Sept 30, 2011, we enrolled 943 participants (474 randomly allocated dexpramipexole, 468 randomly allocated placebo, and one withdrew). Least-square mean CAFS scores at 12 months did not differ between participants in the dexpramipexole group (score 441·76, 95% CI 415·43-468·08) and those in the placebo group (438·84, 412·81-464·88; p=0·86). At 12 months, we noted no differences in mean change from baseline in ALSFRS-R total score (-13·34 in the dexpramipexole group vs -13·42 in the placebo group; p=0·90) or time to death (74 [16%] vs 79 [17%]; hazard ratio 1·03 [0·75-1·43]; p=0·84). 37 (8%) participants in the dexpramipexole group developed neutropenia compared with eight (2%) participants in the placebo group, and incidence of other adverse events was similar between groups. INTERPRETATION: Dexpramipexole was generally well tolerated but did not differ from placebo on any prespecified efficacy endpoint measurement. Our trial can inform the design of future clinical research strategies in amyotrophic lateral sclerosis. FUNDING: Biogen Idec.

Statins and prostate cancer diagnosis and grade in a veterans population.

BACKGROUND: Although prostate cancer is commonly diagnosed, few risk factors for high-grade prostate cancer are known and few prevention strategies exist. Statins have been proposed as a possible treatment to prevent prostate cancer. METHODS: Using electronic and administrative files from the Veterans Affairs New England Healthcare System, we identified 55,875 men taking either a statin or antihypertensive medication. We used age- and multivariable-adjusted Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer incidence among patients taking statins (n = 41,078) compared with patients taking antihypertensive medications (n = 14,797). We performed similar analyses for all lipid parameters including total cholesterol examining each lipid parameter as a continuous variable and by quartiles. All statistical tests were two-sided. RESULTS: Compared with men taking an antihypertensive medication, statin users were 31% less likely (HR = 0.69, 95% CI = 0.52 to 0.90) to be diagnosed with prostate cancer. Furthermore, statin users were 14% less likely (HR = 0.86, 95% CI = 0.62 to 1.20) to be diagnosed with low-grade prostate cancer and 60% less likely (HR = 0.40, 95% CI = 0.24 to 0.65) to be diagnosed with high-grade prostate cancer compared with antihypertensive medication users. Increased levels of total cholesterol were also associated with both total (HR = 1.02, 95% CI = 1.00 to 1.05) and high-grade (HR = 1.06, 95% CI = 1.02 to 1.10) prostate cancer incidence but not with low-grade prostate cancer incidence (HR = 1.01, 95% CI = 0.98 to 1.04). CONCLUSIONS: Statin use is associated with statistically significantly reduced risk for total and high-grade prostate cancer, and increased levels of serum cholesterol are associated with higher risk for total and high-grade prostate cancer. These findings indicate that clinical trials of statins for prostate cancer prevention are warranted.

Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation.

CONTEXT: Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation. Trial's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm. The changes in muscle performance and physical function were evaluated in relation to participant's perception of change. METHODS: Men aged 65 years and older, with mobility limitation, total testosterone 100-350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months. Primary outcome was leg-press strength. Secondary outcomes included chest-press strength, stair-climb, 40-m walk, muscle mass, physical activity, self-reported function, and fatigue. Proportions of participants exceeding minimally important difference in study arms were compared. RESULTS: Of 209 randomized participants, 165 had follow-up efficacy measures. Mean (SD) age was 74 (5.4) years and short physical performance battery score 7.7 (1.4). Testosterone arm exhibited greater improvements in leg-press strength, chest-press strength and power, and loaded stair-climb than placebo. Compared with placebo, significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths (43% vs 18%, p = .01) and stair-climbing power (28% vs 10%, p = .03) more than minimally important difference. Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass. Physical activity, walking speed, self-reported function, and fatigue did not change. CONCLUSIONS: Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power. Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population.

Prevalence and characteristics of tinnitus among US adults.

BACKGROUND: Tinnitus is common; however, few risk factors for tinnitus are known. METHODS: We examined cross-sectional relations between several potential risk factors and self-reported tinnitus in 14,178 participants in the 1999-2004 National Health and Nutrition Examination Surveys, a nationally representative database. We calculated the prevalence of any and frequent (at least daily) tinnitus in the overall US population and among subgroups. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for multiple potential confounders. RESULTS: Approximately 50 million US adults reported having any tinnitus, and 16 million US adults reported having frequent tinnitus in the past year. The prevalence of frequent tinnitus increased with increasing age, peaking at 14.3% between 60 and 69 years of age. Non-Hispanic whites had higher odds of frequent tinnitus compared with other racial/ethnic groups. Hypertension and former smoking were associated with an increase in odds of frequent tinnitus. Loud leisure-time, firearm, and occupational noise exposure also were associated with increased odds of frequent tinnitus. Among participants who had an audiogram, frequent tinnitus was associated with low-mid frequency (OR 2.37; 95% CI, 1.76-3.21) and high frequency (OR 3.00; 95% CI, 1.78-5.04) hearing impairment. Among participants who were tested for mental health conditions, frequent tinnitus was associated with generalized anxiety disorder (OR 6.07; 95% CI, 2.33-15.78) but not major depressive disorder (OR 1.58; 95% CI, 0.54-4.62). CONCLUSIONS: The prevalence of frequent tinnitus is highest among older adults, non-Hispanic whites, former smokers, and adults with hypertension, hearing impairment, loud noise exposure, or generalized anxiety disorder. Prospective studies of risk factors for tinnitus are needed.

Comparative effectiveness research and medical informatics.

As is the case for environmental, ecological, astronomical, and other sciences, medical practice and research finds itself in a tsunami of data. This data deluge, due primarily to the introduction of digitalization in routine medical care and medical research, affords the opportunity for improved patient care and scientific discovery. Medical informatics is the subdiscipline of medicine created to make greater use of information in order to improve healthcare. The 4 areas of medical informatics research (information access, structure, analysis, and interaction) are used as a framework to discuss the overlap in information needs of comparative effectiveness research and potential contributions of medical informatics. Examples of progress from the medical informatics literature and the Veterans Affairs Healthcare System are provided.

Evaluation of a generalizable approach to clinical information retrieval using the automated retrieval console (ARC).

Reducing custom software development effort is an important goal in information retrieval (IR). This study evaluated a generalizable approach involving with no custom software or rules development. The study used documents "consistent with cancer" to evaluate system performance in the domains of colorectal (CRC), prostate (PC), and lung (LC) cancer. Using an end-user-supplied reference set, the automated retrieval console (ARC) iteratively calculated performance of combinations of natural language processing-derived features and supervised classification algorithms. Training and testing involved 10-fold cross-validation for three sets of 500 documents each. Performance metrics included recall, precision, and F-measure. Annotation time for five physicians was also measured. Top performing algorithms had recall, precision, and F-measure values as follows: for CRC, 0.90, 0.92, and 0.89, respectively; for PC, 0.97, 0.95, and 0.94; and for LC, 0.76, 0.80, and 0.75. In all but one case, conditional random fields outperformed maximum entropy-based classifiers. Algorithms had good performance without custom code or rules development, but performance varied by specific application.

Lack of cholesterol awareness among physicians who smoke.

Cigarette use is a known risk factor for the development of coronary artery disease (CAD) as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR) and 95% confidence intervals (CI) of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively), as did the diagnosis of diabetes (2.40 to 7.79%). Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively), however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol at both time points if they were current smokers (1982 OR 1.44, CI 1.4-1.7; 1997 OR 1.71, CI 1.48-1.97), past smokers (1982 OR 1.12, CI 1.05-1.18; 1997 OR 1.13, CI 1.06-1.20), overweight (BMI 25 kg/m2) or sedentary. In addition, physicians who never quit smoking were likely to be unaware of their cholesterol throughout the study (OR 1.42, CI 1.21-1.67). Cholesterol awareness in general and among those with CAD risk factors improved after 14-years of follow-up. However, the likelihood of being unaware was greater among smokers at both time points. Therefore, smokers do not appear to take advantage of other preventive strategies that would minimize their risk of developing CAD.

Primary care visit duration and quality: does good care take longer?

BACKGROUND: It is unclear if increasing pressure on primary care physicians to be more efficient has affected visit duration or quality of care. We sought to describe changes in the duration of adult primary care visits and in the quality of care provided during these visits and to determine whether quality of care is associated with visit duration. METHODS: We conducted a retrospective analysis of visits by adults 18 years or older to a nationally representative sample of office-based primary care physicians in the United States. RESULTS: Between 1997 and 2005, US adult primary care visits to physicians increased from 273 million to 338 million annually, or 10% on a per capita basis. The mean visit duration increased from 18.0 to 20.8 minutes (P < .001 for trend). Visit duration increased by 3.4 minutes for general medical examinations and for the 3 most common primary diagnoses of diabetes mellitus (4.2 minutes, P = .002 for trend), essential hypertension (3.7 minutes, P < .001 for trend), and arthropathies (5.9 minutes, P < .001 for trend). Comparing the early period (1997-2001) with the late period (2002-2005), quality of care improved for 1 of 3 counseling or screening indicators and for 4 of 6 medication indicators. Providing appropriate counseling or screening generally took 2.6 to 4.2 minutes. Providing appropriate medication therapy was not associated with longer visit duration. CONCLUSIONS: Adult primary care visit frequency, quality, and duration increased between 1997 and 2005. Modest relationships were noted between visit duration and quality of care. Providing counseling or screening required additional physician time, but ensuring that patients were taking appropriate medications seemed to be independent of visit duration.

The association between statins and cancer incidence in a veterans population.

BACKGROUND: Meta-analyses of trials of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors or statins for cardiovascular disease prevention have failed to show any statistically significant benefit of statins for cancer prevention. However, these trials included relatively young participants, who develop few cancers, and their follow-up periods may have been too short to detect an association between statin use and cancer incidence. We investigated this association in a population of veterans. METHODS: We identified patients using antihypertensive medications but no cholesterol-lowering medications (n = 25,594) and patients using statins (n = 37,248) who were enrolled in the Veterans Affairs New England Healthcare System between January 1, 1997, and December 31, 2005. Age- and multivariable-adjusted Cox proportional hazards models were used to calculate the hazard ratio (HR) and its 95% confidence interval (CI) for cancer incidence, excluding nonmelanoma skin cancer, among patients taking statins compared with patients taking antihypertensive medications and among patients grouped by statin dose (as equivalent simvastatin dose). All statistical tests were two-sided. RESULTS: The absolute incidence of total cancers was 9.4% among statin users and 13.2% among nonusers (difference = 3.8%, 95% CI = 3.3% to 4.3%, P(difference) < .001). Statin users had a statistically significant lower risk for total cancer than nonusers after adjustment for age (HR = 0.76, 95% CI = 0.73 to 0.80) and multiple potential confounders (HR = 0.74, 95% CI = 0.70 to 0.78). After multivariable adjustment, a statistically significantly decreased risk of all cancers was also associated with increasing statin use (P(trend) < .001). CONCLUSIONS: Patients using statins may be at lower risk for developing cancer. Additional observational studies and randomized trials of statins for cancer prevention are warranted.

Serum anion gap and blood pressure in the national health and nutrition examination survey.

Increased production of organic acid can result in an elevated serum anion gap and may play a role in the development of hypertension. We studied the cross-sectional associations between anion gap and blood pressure and between serum bicarbonate and blood pressure in the 1999-2000 and 2001-2002 National Health and Nutrition Examination Surveys. We included 5043 adult participants who were not taking antihypertensive medications or diuretics and who denied hypertension, cardiovascular disease, diabetes, and other diseases. Linear regression was used to adjust for age, race, body mass index, creatinine, albumin, and other factors. Sample weights were used to produce weighted regression parameters. In the lowest quintile of anion gap, mean values of sodium, chloride, and bicarbonate were 139 mEq/L, 105 mEq/L, and 25 mEq/L, respectively. In the highest quintile, mean values of sodium, chloride, and bicarbonate were 140 mEq/L, 101 mEq/L, and 22 mEq/L, respectively. Mean blood pressure was 118/72 mm Hg. After multivariable adjustment, participants in the highest quintile of anion gap had systolic blood pressure 3.73 mm Hg higher (95% CI: 1.83 to 5.63 mm Hg; P for trend: <0.01) than participants in the lowest quintile. Participants in the highest quintile of bicarbonate had systolic blood pressure 2.73 mm Hg lower (95% CI: 1.26 to 4.20 mm Hg; P for trend: <0.01) than participants in the lowest quintile. No associations were observed between anion gap or bicarbonate and diastolic blood pressure. The results were unchanged after excluding participants with estimated glomerular filtration rate <60 cc/min per 1.73 m(2). The anion gap is independently associated with higher blood pressure. Further research is needed to elucidate the relation between organic acid and hypertension.

Weight gain and new onset diabetes associated with olanzapine and risperidone.

OBJECTIVE: To assess whether newer antipsychotic medications are associated with weight gain and development of diabetes. DESIGN: Retrospective cohort study. SETTING: Data from a comprehensive electronic medical record serving an urban public hospital and a citywide network of mental health clinics. PATIENTS/PARTICIPANTS: Three thousand one hundred fifteen patients at least 18 years old who were prescribed a single antipsychotic drug for at least 1 year. METHODS: We identified independent predictors of significant weight gain (> or =7%) and new onset of diabetes mellitus in the first year of antipsychotic drug treatment, using logistic regression adjusted for demographic characteristics, obesity, preexisting psychiatric diagnoses, alcohol and drug abuse, number of primary care, psychiatric clinic, and emergency department visits, and pretreatment weight. MEASUREMENTS AND MAIN RESULTS: Twenty-five percent of patients taking older phenothiazines developed significant weight gain in the first year of treatment compared to 40% of the patients taking olanzapine (adjusted odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7 to 4.6; P <.0001) and 37% of patients taking risperidone (adjusted OR, 2.3; 95% CI, 1.5 to 3.4; P <.0001). New diabetes developed in 3% of patients taking older phenothiazines was new onset diabetes compared to 8.0% of patients taking olanzapine (adjusted OR, 1.9; 95% CI, 1.1 to 3.3; P=.03) and 3.5% of patients taking risperidone (adjusted OR, 0.7; 95% CI, 0.4 to 1.4; P=.3). No association was found between significant weight gain and developing diabetes (adjusted OR, 0.7; 95% CI, 0.4 to 1.4; P=.4). CONCLUSIONS: Olanzapine and risperidone use was associated with gaining weight in the first year, but only olanzapine was associated with developing diabetes mellitus.