Physical Forces Modulate Oxidative Status and Stress Defense Meditated Metabolic Adaptation of Yeast Colonies: Spaceflight and Microgravity Simulations.

Baker's yeast (Saccharomyces cerevisiae) has broad genetic homology to human cells. Although typically grown as 1-2mm diameter colonies under certain conditions yeast can form very large (10 + mm in diameter) or 'giant' colonies on agar. Giant yeast colonies have been used to study diverse biomedical processes such as cell survival, aging, and the response to cancer pharmacogenomics. Such colonies evolve dynamically into complex stratified structures that respond differentially to environmental cues. Ammonia production, gravity driven ammonia convection, and shear defense responses are key differentiation signals for cell death and reactive oxygen system pathways in these colonies. The response to these signals can be modulated by experimental interventions such as agar composition, gene deletion and application of pharmaceuticals. In this study we used physical factors including colony rotation and microgravity to modify ammonia convection and shear stress as environmental cues and observed differences in the responses of both ammonia dependent and stress response dependent pathways We found that the effects of random positioning are distinct from rotation. Furthermore, both true and simulated microgravity exacerbated both cellular redox responses and apoptosis. These changes were largely shear-response dependent but each model had a unique response signature as measured by shear stress genes and the promoter set which regulates them These physical techniques permitted a graded manipulation of both convection and ammonia signaling and are primed to substantially contribute to our understanding of the mechanisms of drug action, cell aging, and colony differentiation.

Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic.

BACKGROUND: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. METHODS: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method-the tree-based scan statistic (TreeScan). RESULTS: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. CONCLUSIONS: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds.

Effects of microgravity on the virulence of Listeria monocytogenes, Enterococcus faecalis, Candida albicans, and methicillin-resistant Staphylococcus aureus.

To evaluate effects of microgravity on virulence, we studied the ability of four common clinical pathogens--Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and Candida albicans--to kill wild type Caenorhabditis elegans (C. elegans) nematodes at the larval and adult stages. Simultaneous studies were performed utilizing spaceflight, clinorotation in a 2-D clinorotation device, and static ground controls. The feeding rate of worms for killed E. coli was unaffected by spaceflight or clinorotation. Nematodes, microbes, and growth media were separated until exposed to true or modeled microgravity, then mixed and grown for 48 h. Experiments were terminated by paraformaldehyde fixation, and optical density measurements were used to assay residual microorganisms. Spaceflight was associated with reduced virulence for Listeria, Enterococcus, MRSA, and Candida for both larval and adult C. elegans. These are the first data acquired with a direct in vivo assay system in space to demonstrate virulence. Clinorotation reproduced the effects of spaceflight in some, but not all, virulence assays: Candida and Enterococcus were less virulent for larval worms but not adult worms, whereas virulence of MRSA and Listeria were unaffected by clinorotation in tests with both adult and larval worms. We conclude that four common clinical microorganisms are all less virulent in space.

Geographic variation in cardiovascular procedure use among Medicare fee-for-service vs Medicare Advantage beneficiaries.

IMPORTANCE: Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures. OBJECTIVE: To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states. MAIN OUTCOMES AND MEASURES: Rates of coronary angiography, PCI, and CABG surgery. RESULTS: We evaluated a total of 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates. CONCLUSIONS AND RELEVANCE: Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.

Drug safety data mining with a tree-based scan statistic.

PURPOSE: In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. METHODS: We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. RESULTS: Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. CONCLUSION: The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs.

Neighborhood socioeconomic status and use of colonoscopy in an insured population--a retrospective cohort study.

BACKGROUND: Low-socioeconomic status (SES) is associated with a higher colorectal cancer (CRC) incidence and mortality. Screening with colonoscopy, the most commonly used test in the US, has been shown to reduce the risk of death from CRC. This study examined if, among insured persons receiving care in integrated healthcare delivery systems, differences exist in colonoscopy use according to neighborhood SES. METHODS: We assembled a retrospective cohort of 100,566 men and women, 50-74 years old, who had been enrolled in one of three US health plans for ≥1 year on January 1, 2000. Subjects were followed until the date of first colonoscopy, date of disenrollment from the health plan, or December 31, 2007, whichever occurred first. We obtained data on colonoscopy use from administrative records. We defined screening colonoscopy as an examination that was not preceded by gastrointestinal conditions in the prior 6-month period. Neighborhood SES was measured using the percentage of households in each subject's census-tract with an income below 1999 federal poverty levels based on 2000 US census data. Analyses, adjusted for demographics and comorbidity index, were performed using Weibull regression models. RESULTS: The average age of the cohort was 60 years and 52.7% were female. During 449,738 person-years of follow-up, fewer subjects in the lowest SES quartile (Q1) compared to the highest quartile (Q4) had any colonoscopy (26.7% vs. 37.1%) or a screening colonoscopy (7.6% vs. 13.3%). In regression analyses, compared to Q4, subjects in Q1 were 16% (adjusted HR = 0.84, 95% CI: 0.80-0.88) less likely to undergo any colonoscopy and 30%(adjusted HR = 0.70, CI: 0.65-0.75) less likely to undergo a screening colonoscopy. CONCLUSION: People in lower-SES neighborhoods are less likely to undergo a colonoscopy, even among insured subjects receiving care in integrated healthcare systems. Removing health insurance barriers alone is unlikely to eliminate disparities in colonoscopy use.

The effectiveness of screening and brief intervention on reducing driving while intoxicated citations.

The purpose of this study was to use retrospective data, including citations for driving while intoxicated (DWI), to assess the long-term effectiveness of a program consisting of Screening and Brief Intervention (SBI) for at-risk alcohol users and its impact on traffic safety. A second objective was to study ethnic differences in response to SBI. During the time period of 1998-1999, LCF Research, together with the Lovelace Health System, participated in the Cutting Back SBI study for at-risk drinkers. A total of 426 subjects exhibiting at-risk drinking behaviors from the New Mexico cohort were examined for the study, including 211 subjects who received a brief counseling intervention and 215 in the no intervention control group. This study examined DWI citations for all 426 subjects during the 5 years following the Cutting Back study. The brief interventions were shown to have had a significant impact on reducing DWI citations for at-risk drinkers, with the added benefit lasting for the 5-year duration of the study. The SBI was found to be most effective at reducing DWI citations for Hispanic at-risk drinkers. Evidence is presented to show that screening to identify at-risk drinkers followed by a brief intervention has a statistically significant lasting impact on improving traffic safety.

Colorectal cancer screening use among insured primary care patients.

OBJECTIVE: To compare colorectal cancer (CRC) screening use, including changes over time and demographic characteristics associated with screening receipt, between 2 insured primary care populations. STUDY DESIGN: Clinical and administrative records from 2 large health systems, one in New Mexico and the other in Michigan, were used to determine use of CRC screening tests between 2004 and 2008 among patients aged 51 to 74 years. METHODS: Generalized estimating equations were used to evaluate trends in CRC screening use over time and the association of demographic and other factors with screening receipt. RESULTS: Rates of CRC screening use ranged from 48.1% at the New Mexico site to 68.7% at the Michigan site, with colonoscopy being the most frequently used modality. Fecal occult blood test was used inconsistently by substantial proportions of patients who did not meet the definition of screening users. Screening use was positively and significantly associated with older age, male sex, and more periodic health examinations and other types of primary care visits; at the Michigan site, it was also associated with African American race, married status, and higher annual estimated household income. CONCLUSIONS: Among insured primary care patients, CRC screening use falls short. Further research is needed to determine what factors are barriers to routine fecal occult blood test or colonoscopy use among insured patients who have access to and regularly use primary care and how those barriers can be eliminated.

Synergistic effect of statins and postmenopausal hormone therapy in the prevention of skeletal fractures in elderly women.

STUDY OBJECTIVE: To examine the role of concurrent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use and postmenopausal hormone therapy on osteoporosis-related fractures. DESIGN: Case-control study. Data Source. Large integrated health plan in New Mexico. Patients. Case patients were 1001 women with incident fractures of the hip, wrist, forearm, or spine that occurred between January 1, 2000, and December 31, 2005, and controls were 2607 women without fractures during the same time frame; both groups were selected from the same population of women aged 50 years or older who utilized health plan services during the study time frame. MEASUREMENTS AND MAIN RESULTS: Postmenopausal hormone therapy use was classified as "current" (12 mo before index date) or "never or past." The risk of fractures was ascertained among continuous (> or = 80% medication possession ratio during 12 mo before the index date) and current (3 mo before index date) statin users relative to patients without hyperlipidemia who did not use lipid-lowering drugs. The interaction between statins and hormone therapy was examined in multivariable logistic regression. The association between statin use and fractures was examined separately among current and never or past hormone therapy users after controlling for other risk factors. Nineteen percent of the study participants were current hormone therapy users; 9.5% were current and 4.8% were continuous statin users. No association between continuous statin use and fractures was observed among never or past hormone therapy users (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.53-1.22). In contrast, a strong protective effect (OR 0.19, 95% CI 0.04-0.87) was observed among women who concurrently used statins and hormone therapy for 1 year, independent of age; corticosteroid, bisphosphonate, thiazide diuretic, calcitonin, methotrexate, or antiepileptic drug use; chronic kidney disease; and Charlson comorbidity index. CONCLUSION: Concurrent statin use and hormone therapy may have a synergistic protective effect on skeletal fractures beyond the additive effect of each individual therapy.

Early adverse drug event signal detection within population-based health networks using sequential methods: key methodologic considerations.

PURPOSE: Active surveillance of population-based health networks may improve the timeliness of detection of adverse events (AEs). Our objective was to expand our previous signal detection work by investigating the effect on signal detection of alternative study specifications. METHODS: We compared the signal detection performance under various study specifications using historical data from nine health plans involved in the HMO Research Network's Center for Education and Research on Therapeutics (CERT). Five drug-event pairs representing generally accepted associations with an AE and two pairs representing "negative controls" were analyzed. Alternative study specifications related to the definition of incident users and incident AEs were assessed and compared to our previous findings. RESULTS: Relaxing the incident AE exclusion criteria by (1) including members with prior outpatient diagnoses of interest and (2) halving (to 90 days) the time window specified to define incident exposure and diagnoses increased the number of members under surveillance and as a consequence increased the number of exposed days and diagnoses by about 10-20%. The alternative specifications tend to result in earlier signal detection by 10-16 months, a likely consequence of more exposures and events entering the analysis. CONCLUSIONS: This paper provides additional preliminary information related to conducting prospective safety monitoring using health plan data and sequential analytic methods. Our findings support continued investigation of using health plan data and sequential analytic methods as a potentially important contribution to active drug safety surveillance.

Early detection of adverse drug events within population-based health networks: application of sequential testing methods.

PURPOSE: Active surveillance of population-based health networks may improve the timeliness of detection of adverse drug events (ADEs). Active monitoring requires sequential analysis methods. Our objectives were to (1) evaluate the utility of automated healthcare claims data for near real-time drug adverse event surveillance and (2) identify key methodological issues related to the use of healthcare claims data for real-time drug safety surveillance. METHODS: We assessed the ability to detect ADEs using historical data from nine health plans involved in the HMO Research Network's Center for Education and Research on Therapeutics (CERT). Analyses were performed using a maximized sequential probability ratio test (maxSPRT). Five drug-event pairs representing known associations with an ADE and two pairs representing 'negative controls' were analyzed. RESULTS: Statistically significant (p < 0.05) signals of excess risk were found in four of the five drug-event pairs representing known associations; no signals were found for the negative controls. Signals were detected between 13 and 39 months after the start of surveillance. There was substantial variation in the number of exposed and expected events at signal detection. CONCLUSIONS: Prospective, periodic evaluation of routinely collected data can provide population-based estimates of medication-related adverse event rates to support routine, timely post-marketing surveillance for selected ADEs.

Academic detailing to improve laboratory testing among outpatient medication users.

PURPOSE: To determine whether group academic detailing with performance feedback increases recommended laboratory monitoring among outpatients dispensed medications. METHODS: Thirty-eight primary care practices in 3 states were randomized to group academic detailing with physician-level performance feedback (intervention) or a control group. Adjusted differences in creatinine and potassium testing between intervention and control group patients with a new or continuing dispensing for angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), diuretics, or digoxin were evaluated using generalized estimating equation approaches. RESULTS: Monitoring among patients with an initial ACE/ARB and diuretic dispensing significantly improved with the intervention [odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.08-1.38; and OR = 1.25, 95% CI: 1.08-1.44, respectively). The intervention also significantly improved monitoring among patients with a continuing dispensing for an ACE/ARB (OR = 1.39, 95% CI: 1.11-1.74) or a diuretic (OR = 1.28, 95% CI: 1.02-1.60). Adjusted differences in testing rates between study arms were modest (ranging from 2.5% to 4.9%). No significant differences in monitoring by study arm were detected among patients dispensed digoxin. CONCLUSIONS: The impact of a group academic detailing program with feedback on recommended laboratory monitoring among medication users was modest. Yet, given the numbers of outpatients dispensed medications for which laboratory monitoring is recommended, group academic detailing may offer 1 method by which outpatient medication safety can be significantly improved.

Laboratory evaluation of potassium and creatinine among ambulatory patients prescribed spironolactone: are we monitoring for hyperkalemia?

BACKGROUND: Serum potassium and creatinine evaluation is recommended in patients prescribed spironolactone, yet the proportion of ambulatory patients chronically dispensed spironolactone receiving evaluation is not well understood. OBJECTIVE: To estimate the rate of potassium and creatinine evaluation and identify factors associated with conducting these tests among ambulatory patients dispensed spironolactone. METHODS: A retrospective cohort study was designed to evaluate patients at 10 health maintenance organizations with ongoing spironolactone dispensing for one year (N = 2257). Potassium and creatinine evaluation were determined from administrative data. Associations between patient characteristics and laboratory testing were assessed, using logistic regression modeling. RESULTS: Serum creatinine and potassium were evaluated in 72.3% of patients during a 13 month period. The likelihood of potassium and creatinine monitoring was greater among patients who were older (OR 1.28; 95% CI 1.17 to 1.41 per decade of life); male (OR 1.25; 95% CI 1.01 to 1.54); had diabetes (OR 1.63; 95% CI 1.31 to 2.03); received concomitant therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (OR 2.23; 95% CI 1.74 to 2.87), potassium supplements (OR 1.96; 95% CI 1.51 to 2.54), or digoxin (OR 2.10 95% CI 1.48 to 2.98); or had more outpatient visits (OR 1.31; 95% CI 1.19 to 1.44). Among patients with heart failure (n = 790), factors associated with the incidence of laboratory testing were diabetes (OR 1.64, 95% CI 1.14 to 2.34), outpatient visits (OR 1.20; 95% CI 1.02 to 1.41), and digoxin therapy (OR 2.26; 95% CI 1.38 to 3.69). CONCLUSIONS: Three-fourths of ambulatory patients dispensed spironolactone receive recommended laboratory evaluation, with monitoring more likely to be completed in patients prescribed concomitant therapy with drugs that increase hyperkalemia risk, older patients, and those with diabetes.

Laboratory monitoring of potassium and creatinine in ambulatory patients receiving angiotensin converting enzyme inhibitors and angiotensin receptor blockers.

PURPOSE: Serum potassium and creatinine monitoring is recommended for patients prescribed angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). Much has been written about hyperkalemia associated with these drugs; little is known about laboratory monitoring patterns. The purpose of this retrospective cohort study was to assess creatinine and potassium monitoring and characteristics associated with monitoring among patients dispensed ACEi or ARB. METHODS: This study was conducted in 10 United States health maintenance organizations. Study patients (n = 52 906) were aged 18 or older with dispensings of ACEi or ARB for at least 1 year. Serum potassium and creatinine monitoring were assessed from administrative data and medical records. RESULTS: More than two-thirds (68.4%) of patients received laboratory monitoring. Likelihood of monitoring increased with age (adjusted odds ratio [OR] 2.10; 95% confidence interval [95%CI] 1.93, 2.28 [individuals >or= 80 compared to <50 years]), >9 outpatient visits (OR 1.46; 95%CI 1.39, 1.54), hospitalization (OR 1.15; 95%CI 1.06, 1.25), concomitant medications (potassium [OR 2.01; 95%CI 1.84, 2.20], diuretics [OR 1.54; 95%CI 1.47, 1.61], digoxin [OR 1.15; 95%CI 1.01, 1.30]), and comorbidities (diabetes [OR 1.68; 95%CI 1.61, 1.75], heart failure [OR 1.73; 95%CI 1.57, 1.90], chronic kidney disease [OR 2.95; 95%CI 2.48. 3.51]). CONCLUSIONS: Nearly one-third of patients dispensed ACEi or ARB did not undergo laboratory monitoring at least yearly. Though patients at increased risk of hyperkalemia were more likely to be monitored, many remained unmonitored.

Monitoring of drugs with a narrow therapeutic range in ambulatory care.

OBJECTIVES: To describe the proportion of patients receiving drugs with a narrow therapeutic range who lacked serum drug concentration monitoring during a 1-year period of therapy and to identify patient characteristics associated with lack of monitoring. STUDY DESIGN: Retrospective cohort. METHODS: Ambulatory patients (n = 17,748) at 10 health maintenance organizations who were receiving ongoing continuous drug therapy with digoxin, carbamazepine, divalproex sodium, lithium carbonate, lithium citrate, phenobarbital sodium, phenytoin, phenytoin sodium, primidone, quinidine gluconate, quinidine sulfate, procainamide hydrochloride, theophylline, theophylline sodium glycinate, tacrolimus, or cyclosporine for at least 12 months between January 1, 1999, and June 30, 2001, were identified. Serum drug concentration monitoring was assessed from administrative data and from medical record data. RESULTS: Fifty percent or more of patients receiving digoxin, theophylline, procainamide, quinidine, or primidone were not monitored, and 25% to 50% of patients receiving divalproex, carbamazepine, phenobarbital, phenytoin, or tacrolimus were not monitored. Younger age was associated with lack of monitoring for patients prescribed digoxin (adjusted odds ratio, 1.86; 95% confidence interval, 1.39-2.48) and theophylline (adjusted odds ratio, 1.58; 95% confidence interval, 1.23-2.04), while older age was associated with lack of monitoring for patients prescribed carbamazepine (adjusted odds ratio, 0.59; 95% confidence interval, 0.44-0.80) and divalproex (adjusted odds ratio, 0.50; 95% confidence interval, 0.38-0.66). Patients with fewer outpatient visits were also less likely to be monitored (P < .001). CONCLUSIONS: A substantial proportion of ambulatory patients receiving drugs with narrow intervals between doses resulting in beneficial and adverse effects did not have serum drug concentration monitoring during 1 year of use. Clinical implications of this finding need to be evaluated.

Frequency of serum creatinine monitoring during allopurinol therapy in ambulatory patients.

BACKGROUND: Allopurinol dosage reduction is recommended in patients with renal dysfunction because drug toxicity risk is increased. Little information is available about serum creatinine (SCr) monitoring in ambulatory patients taking allopurinol. OBJECTIVE: To evaluate SCr monitoring among patients prescribed allopurinol, identify associated factors, and evaluate administrative data in assessing monitoring. METHODS: Information for this retrospective cohort study was drawn from a dataset of 2 020 037 individuals; approximately 200 000 members from each of 10 organizations. Study patients had received at least one year of ongoing allopurinol prescription dispensings. Patient variables analyzed included age, gender, chronic diseases, outpatient visits, hospitalizations, gout diagnosis, and SCr monitoring. A random sample of medical records was reviewed to assess the accuracy of the automated data. Statistical analysis included descriptive and logistic regression techniques. RESULTS: Overall, 1139 (26%) of 4357 patients did not have SCr monitoring. For individuals without recent hospitalization, factors protective against lack of monitoring were increasing age (OR 0.77 per 10 y; 95% CI 0.74 to 0.79), more chronic diseases (OR 0.81; 95% CI 0.78 to 0.83), more outpatient visits (OR 0.87 per 5 visits; 95% CI 0.83 to 0.91), and gout diagnosis (OR 0.74; 95% CI 0.65 to 0.85). The sensitivity and specificity of administrative data compared with medical records for SCr monitoring were 92% and 65%, respectively. CONCLUSIONS: More than one-fourth of patients dispensed allopurinol did not have SCr monitoring during one year of therapy. Lack of monitoring and lack of subsequent possible dosage adjustment put patients at increased risk of allopurinol toxicity.

Liver and thyroid monitoring in ambulatory patients prescribed amiodarone in 10 HMOs.

BACKGROUND: Amiodarone can cause liver and thyroid toxicity, but little is known about compliance with laboratory tests to evaluate liver and thyroid function among ambulatory patients who are dispensed amiodarone. OBJECTIVES: The primary objective of this study was to identify the proportion of ambulatory patients who had liver aminotransferase and thyroid function tests during amiodarone therapy. Secondary objectives were to (1) describe factors associated with receipt of laboratory tests and (2) determine the accuracy of administrative data for assessing aminotransferase and thyroid function monitoring. METHODS: This retrospective cohort study was conducted at 10 health maintenance organizations (HMOs) for the dates of service from January 1, 1999, through June 30, 2001. Participants included 1,055 patients dispensed amiodarone for at least 180 days within this date range; these patients were not necessarily new starts on amiodarone. Administrative claims data were analyzed to assess the percentage of patients with completed alanine/aspartate aminotransferase and thyroid function tests. Depending on the HMO site, electronic or paper medical records were reviewed to evaluate the validity of administrative claims data. Logistic regression models were used to explore factors associated with receipt of laboratory tests. RESULTS: Both aminotransferase and thyroid function tests were completed in 53.3% of patients within a 210-day follow-up period that included the 180-day period of amiodarone dispensings plus 30 days. Thyroid function, with or without liver function (aminotransferase tests), was assessed in 61.9% of patients, and aminotransferase tests, with or without thyroid function, were assessed in 68.2% of patients. After adjusting for patient characteristics and site, the factor most strongly associated with having both types of laboratory tests evaluated was concomitant therapy with a statin (adjusted odds ratio (OR) 1.55; 95% confidence interval (CI), 1.05-2.29). Other factors associated with having both types of laboratory tests evaluated included the number of outpatient visits in the 6 months before the period of amiodarone dispensings (adjusted OR 1.06; 95% CI, 1.00- 1.13 for each additional 5 visits) and living in a neighborhood where a higher median percentage of people had a high school or higher education (adjusted OR 1.09; 95% CI, 1.00-1.18 for every 10% increase in educational level at the block level). There was no association between monitoring and patient illness severity as measured by the number of comorbid conditions. On the basis of an evaluation of a randomly selected subset of 104 patient records, the sensitivity and specificity of automated data were 94.2% and 85.7% for aminotransferase tests and 83.3% and 81.1% for thyroid function tests, respectively. CONCLUSIONS: Approximately half of ambulatory patients dispensed amiodarone received both recommended laboratory tests for liver and thyroid function. Improved rates of testing for liver aminotransferase and thyroid function are needed for patients who receive amiodarone.

Management of epilepsy in adults. Diagnosis guidelines.

In this first of two articles on new epilepsy guidelines for primary care physicians, the authors present detailed algorithms for the diagnosis and classification of seizure disorders in adults. They discuss the differentiation between generalized and partial seizures and stress that accurate identification is especially important because the type of seizure determines the appropriate treatment. The second article (page 29) looks at the treatment portion of the new guidelines.

Management of epilepsy in adults. Treatment guidelines.

In this second of two articles on new epilepsy guidelines for primary care physicians, the authors discuss which treatments are the most effective in adults with this disease. They describe the antiepileptic drugs that are currently approved and elucidate the differences between established and newer options. Detailed algorithms cover pharmacotherapy, follow-up, and ongoing maintenance.

Laboratory safety monitoring of chronic medications in ambulatory care settings.

OBJECTIVE: To evaluate laboratory safety monitoring in patients taking selected chronic prescription drugs. DESIGN: Retrospective study using 1999-2001 claims data to calculate rates of missed laboratory tests (potential laboratory monitoring errors). Eleven drugs/drug groups and 64 laboratory tests were evaluated. SETTING: Two staff/network model health maintenance organizations. PATIENTS: Continuously enrolled health plan members age> or =19 years taking > or =1 chronic medications. MEASUREMENTS AND MAIN RESULTS: Among patients taking chronic medications (N=29,823 in 1999, N=32,423 in 2000, and N=36,811 in 2001), 47.1% in 1999, 45.0% in 2000, and 44.0% in 2001 did not receive > or =1 test recommended for safety monitoring. Taking into account that patients were sometimes missing more than 1 test for a given drug and that patients were frequently taking multiple drugs, the rate of all potential laboratory monitoring errors was 849/1,000 patients/year in 1999, 810/1,000 patients/year in 2000, and 797/1,000 patients/year in 2001. Rates of potential laboratory monitoring errors varied considerably across individual drugs and laboratory tests. CONCLUSIONS: Lapses in laboratory monitoring of patients taking selected chronic medications were common. Further research is needed to determine whether, and to what extent, this failure to monitor patients is associated with adverse clinical outcomes.