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Biomedical subjects

Alexander M Walker

Publications and source records attributed to Alexander M Walker.

At least 19 recordsLinked to original sources
PubMed2007

Bupropion in pregnancy and the prevalence of congenital malformations.

PURPOSE: Reports from the GlaxoSmithKline Bupropion Pregnancy Registry suggested an increase in cardiovascular defects following exposure to bupropion during pregnancy. We conducted a study of congenital malformations among infants born to women exposed to bupropion during their first trimester. METHODS: The study used data from UnitedHealthcare between January 1995 and September 2004. We calculated the prevalence of all congenital malformations and cardiovascular malformations associated with bupropion exposure in the estimated first trimester (1213 infants), compared with (1) other antidepressant exposure in the first trimester (4743 infants) and (2) bupropion exposure outside the first trimester (1049 infants). Malformation cases were confirmed through medical record abstraction. We calculated adjusted odds ratios (AORs) using the GEE form of logistic regression. RESULTS: For all congenital malformations, the prevalence associated with bupropion first trimester was 23.1 per 1000 infants. The AORs were 0.95 (95%CI 0.62-1.45) and 1.00 (95%CI 0.57-1.73) in comparison to other antidepressants (prevalence 23.2 per 1000) and bupropion outside the first trimester (prevalence 21.9 per 1000), respectively. For cardiovascular malformations, the prevalence associated with bupropion first trimester was 10.7 per 1000 infants. The AORs were 0.97 (95%CI 0.52-1.80) and 1.07 (95%CI 0.48-2.40) in comparison to other antidepressants (prevalence 10.8 per 1000) and bupropion outside the first trimester (prevalence 9.5 per 1000), respectively. CONCLUSIONS: Results do not support a hypothesis of a teratogenic effect of first trimester bupropion exposure. The prevalence of malformations associated with bupropion exposure in the first trimester was not increased relative to the comparison groups.

Adolescent↗
PubMed2007

Asthma drug use and the development of Churg-Strauss syndrome (CSS).

PURPOSE: Case reports suggest that leukotriene modifier use may be associated with the onset of Churg-Strauss syndrome (CSS). Using pooled data from two nested case-control studies, we examined the association between asthma drug use and the development of CSS. METHODS: The study was performed in three US managed care organizations and a US national health plan with chart access and complete electronic pharmacy data, with a covered population of 13.9 million. There were 47 cases of possible or definite CSS and 4700 asthma drug user controls identified between January 1, 1995 and December 31, 2002. We examined exposure to asthma drugs in cases and controls, including leukotriene modifiers (6 cases and 202 controls), in the two to 6 months prior to the onset of adjudicated CSS. RESULTS: While the crude association between use of leukotriene modifiers and CSS was strong (odds ratio (OR) 4.00, 95% confidence interval (CI): 1.49-10.60), in a multivariable analysis controlling for use of oral corticosteroids, inhaled corticosteroids, and number of categories of asthma drugs dispensed, there was no significant association (OR 1.32, 95% CI: 0.44-3.96). Use of inhaled and oral corticosteroids, evaluated as markers of asthma severity, were associated with CSS (OR 3.07, 95% CI: 1.34-7.03 and OR 5.36, 95% CI: 2.51-11.45, respectively). CONCLUSIONS: No association was found between CSS and leukotriene modifiers after controlling for asthma drug use However, it is not possible to rule out modest associations with asthma treatments given CSS is so rare and so highly correlated with asthma severity, suggesting further investigation is warranted.

Adolescent↗
PubMed2006

Anemia as a predictor of cardiovascular events in patients with elevated serum creatinine.

Patients with anemia and patients with chronic kidney disease have elevated risks for cardiovascular disease. Available studies have been too small to provide details about the relationship or to provide for extensive covariate control. In a large insurance database with linked laboratory values, records of women with serum creatinine >1.2 mg/dl and men with serum creatinine >1.4 mg/dl, identified from July 2000 through June 2003, were sought, and the insurance claims searches for hospitalizations that were associated with myocardial infarction, coronary revascularization, unstable angina, stroke, or congestive heart failure. New onset of dialysis also was sought. Multivariate Poisson regression was used to estimate rate ratios for these events at various hemoglobin (Hb) levels, with adjustment for patient characteristics and previous event history. Among 88,657 patients with high serum creatinine, the risk for hospitalization with myocardial infarction was two to five times higher in anemic (Hb <12 g/dl) patients than in people with Hb from 12.0 to 12.9 g/dl. A similar but less dramatic pattern of higher incidence of coronary revascularization was observed with lower Hb levels. Risks for hospitalization with congestive heart failure declined regularly with increasing Hb levels from a doubling of risk at Hb <10 g/dl to a 61% decrease at 15 g/dl, both relative to 12.0 to 12.9 g/dl. The risk for progression to dialysis was only slightly elevated (7 to 34%) in anemic patients. Anemia raises the risk for cardiovascular disease in patients with elevated serum creatinine.

Age Distribution↗
PubMed2006

Algorithms to identify colonic ischemia, complications of constipation and irritable bowel syndrome in medical claims data: development and validation.

PURPOSE: A challenge in the use of insurance claims databases for epidemiologic research is accurate identification and verification of medical conditions. This report describes the development and validation of claims-based algorithms to identify colonic ischemia, hospitalized complications of constipation, and irritable bowel syndrome (IBS). METHODS: From the research claims databases of a large healthcare company, we selected at random 120 potential cases of IBS and 59 potential cases each of colonic ischemia and hospitalized complications of constipation. We sought the written medical records and were able to abstract 107, 57, and 51 records, respectively. We established a 'true' case status for each subject by applying standard clinical criteria to the available chart data. Comparing the insurance claims histories to the assigned case status, we iteratively developed, tested, and refined claims-based algorithms that would capture the diagnoses obtained from the medical records. We set goals of high specificity for colonic ischemia and hospitalized complications of constipation, and high sensitivity for IBS. RESULTS: The resulting algorithms substantially improved on the accuracy achievable from a naïve acceptance of the diagnostic codes attached to insurance claims. The specificities for colonic ischemia and serious complications of constipation were 87.2 and 92.7%, respectively, and the sensitivity for IBS was 98.9%. CONCLUSIONS: U.S. commercial insurance claims data appear to be usable for the study of colonic ischemia, IBS, and serious complications of constipation.

Algorithms↗
PubMed2006

Cardiovascular risk of selective cyclooxygenase-2 inhibitors and other non-aspirin non-steroidal anti-inflammatory medications.

PURPOSE: The purpose of this study was to estimate rates of acute coronary syndrome (ACS), and sudden cardiac death in relation to use of rofecoxib, celecoxib, naproxen, diclofenac, and ibuprofen. METHODS: We conducted a retrospective cohort study among 424,584 health plan enrollees ages 40-64 who used non-aspirin non-steroidal anti-inflammatory drugs (NANSAIDs) by prescription from 1999 to 2001. We used automated medical and pharmacy claims data to compute person-time exposed to study drugs, and to identify hospitalizations for ACS. The primary endpoint was ACS, inclusive of myocardial infarction (MI), unstable angina, and sudden cardiac death as identified through claims data and confirmed through hospital medical records, or through the National Death Index. RESULTS: Compared with ibuprofen or diclofenac use, the relative risk (RR) of ACS during periods of current rofecoxib use was 1.35 (95%CI 1.09-1.68). For current use of celecoxib, the RR was 1.03 (95%CI 0.83-1.27). Risks in the first 30 days of rofecoxib and celecoxib use were modestly elevated. Rofecoxib use at the 25 mg/day (modal) dose was associated with an elevated risk of ACS (RR 1.54, 95%CI 1.15-2.04), while use at 26-50 mg/day (>modal) was not (RR 0.81, 95%CI 0.41-1.60). There were no increased risks with modal or greater than modal doses of celecoxib or naproxen compared with all doses of ibuprofen or diclofenac combined. CONCLUSIONS: The incidence of ACS was 1.35 times greater during rofecoxib use than use of ibuprofen or diclofenac. No statistically significant elevation in risk was observed with celecoxib use. Naproxen use was not associated with risk of ACS.

Acute Disease↗
PubMed2006

Achilles tendon rupture and its association with fluoroquinolone antibiotics and other potential risk factors in a managed care population.

BACKGROUND: Case reports and observational studies have implicated fluoroquinolone antibiotic exposure as a risk factor for Achilles tendon rupture (ATR), an uncommon condition for which there are few formal studies. We sought to quantify the strength of association between exposure to fluoroquinolone antibiotics and the occurrence of ATR, accounting for other risk factors. METHODS: This was a case-control study nested within a health insurer cohort. Cases of ATR were identified and confirmed using patterns of health insurance claims that were validated through sampled medical record review. Information on risk factors, including fluoroquinolone exposure, came from health insurance claims. RESULTS: There were 947 cases of ATR and 18 940 controls. A dispensing of a fluoroquinolone antibiotic in the past 6 months was more common among ATR cases than controls, although not significantly so (odds ratio (OR) = 1.2; 95% confidence interval (CI) = 0.9-1.7), and exposure to a higher cumulative fluoroquinolone dose was more strongly associated (OR = 1.5, 95%CI = 1.0-2.3). Other risk factors for ATR were trauma (OR = 17.2, 95%CI = 14.0-20.2), male sex (OR = 3.0, 95%CI = 2.6-3.5), injected corticosteroid administration (OR = 2.2, 95%CI = 1.6-2.9), obesity (OR = 2.0, 95%CI = 1.2-3.1), rheumatoid arthritis (OR = 1.9, 95%CI = 1.0-3.7), skin or soft tissue infections (OR = 1.5, 95%CI = 0.9-2.3), oral corticosteroids (OR = 1.4, 95%CI = 1.0-1.8), and non-fluoroquinolone antibiotics (OR = 1.2, 95%CI = 1.1-1.5). CONCLUSIONS: The elevation in ATR risk associated with fluoroquinolones was similar in magnitude to that associated with oral corticosteroids or non-fluoroquinolone antibiotics. Trauma and male sex were more strongly associated with ATR, as were obesity and injected corticosteroids.

Achilles Tendon↗
PubMed2006

Rosuvastatin safety: a comprehensive, international pharmacoepidemiology programme.

Results from clinical trials and clinical practice have shown statins to be generally well tolerated with a low frequency of clinically relevant side effects. Nevertheless, there are rare occasions when adverse events (AEs), sometimes serious, may occur. Rosuvastatin is the newest statin to be approved in the USA and many other countries. As part of the continued assessment of the benefit-risk profile of rosuvastatin, AstraZeneca has developed a progressive, comprehensive pharmacoepidemiology programme to complement safety data obtained from randomised clinical trials and spontaneous reporting systems, which have demonstrated that rosuvastatin has a safety profile in line with comparator statins. This programme comprises nine studies conducted in recognised centres of excellence assessing over 50,000 patients treated with rosuvastatin. It consists of three components: patient characteristics studies (four studies), safety evaluation studies (four studies); and review of data generated from the Prescription-Event Monitoring (PEM) study, designed and run by an independent third party. Patient characteristics studies are designed to describe the characteristics and drug utilisation patterns of new users of rosuvastatin compared with new users of other statins in automated databases. Safety evaluation studies will examine the rates of specific AEs in different cohorts of statin users and determine risk factors for these events using data recorded prospectively in automated databases with case adjudication via medical record review. The independent PEM study will monitor any significant events recorded by general practitioners since starting rosuvastatin treatment. This article is an overview of the rationale and methodology of the rosuvastatin pharmacoepidemiology programme.

Canada↗
PubMed2006

The comparative safety of rosuvastatin: a retrospective matched cohort study in over 48,000 initiators of statin therapy.

PURPOSE: The purpose of this study was to compare incidence rates of hospitalization associated with rhabdomyolysis, myopathy, renal, or hepatic dysfunction, and of in-hospital death, between initiators of rosuvastatin and other statins. METHODS: This was a matched cohort study of statin initiators from the administrative database of a large health insurer in the US, during the first 6 months of rosuvastatin availability with up to 18 months of follow-up. All outcome events were verified by medical record review. Incidence rates, risk ratios, and associated 95% confidence intervals were estimated. RESULTS: From an initial pool of 12,217, 11,249 eligible rosuvastatin initiators were matched to 37,282 initiators of other statins. The incidence rate (IR) per 1000 person-years for rhabdomyolysis was 0.10 [0.00, 0.55] for rosuvastatin initiators (n = 1) and 0.06 [0.01, 0.22] for other statin initiators (n = 2), for a hazard ratio (HR) of 1.98 [0.18, 21.90]. The IR for myopathy was 0.20 [0.02, 0.71] for rosuvastatin initiators (n = 2) and 0.00 [0.00, 0.09] for other statin initiators (n = 0). The IR for renal dysfunction was 1.18 [0.61, 2.06] for rosuvastatin initiators (n = 12) and 1.26 [0.91, 1.71] for other statin initiators (n = 42), for a HR of 0.90 [0.47, 1.73]. The IR for hepatic dysfunction was 0.20 (0.02, 0.71) for rosuvastatin initiators (n = 2) and 0.24 (0.10, 0.47) for other statin initiators (n = 8), for a HR of 0.87 (0.18, 4.14). CONCLUSIONS: This study found no difference between rosuvastatin and the other statins in the incidence of hospitalizations associated with renal or hepatic events, or death. The absolute incidence rates of rhabdomyolysis and myopathy were reassuringly low among all statin initiators but remain too small for firm conclusions to be drawn on any difference between the statins.

Adolescent↗
PubMed2006

Temporal trends and drug exposures in pulmonary hypertension: an American experience.

BACKGROUND: Reports have linked anorexigen intake to an increased risk of pulmonary arterial hypertension (PAH). With the rise in anorexigen use in the latter half of the last decade, we established a surveillance network within the United States to monitor temporal trends in the number of reported cases of PAH. We also studied whether use of anorexigens and other drugs differed among patients with pulmonary hypertension of different etiologies. METHODS: Newly diagnosed subjects (N = 1335) at 13 tertiary pulmonary hypertension centers were enrolled between January 1998 and June 2001. Patient-reported medication use was obtained by a telephone interview. Patients were classified as to the type of pulmonary hypertension. Poisson regression models were fitted to monthly case counts, and logistic regression methods were used to assess the association between type of pulmonary hypertension and medication use. RESULTS: The average monthly number of reported cases of PAH and other categories of pulmonary hypertension did not change over the study period. Fenfluramine or dexfenfluramine use during the 5 years before the time of the interview was preferentially associated with PAH. Fenfluramine/dexfenfluramine use was particularly common in cases referred but found not to have pulmonary hypertension. CONCLUSIONS: No epidemic of anorexigen-related PAH was evident during the study period. As persons who had taken fenfluramine or dexfenfluramine were particularly likely to be referred for evaluation of pulmonary hypertension, it is unlikely that the failure to detect an anorexigen-induced rise in primary pulmonary hypertension was because of underascertainment. The association between fenfluramine derivatives and PAH is consistent with the risk elevations previously reported.

Adolescent↗
PubMed2006

Drug copayment and adherence in chronic heart failure: effect on cost and outcomes.

STUDY OBJECTIVE: To measure the association among prescription copayment, drug adherence, and subsequent health outcomes among patients with chronic heart failure (CHF). DESIGN: Retrospective cohort study. DATA SOURCE: Database of a large, national health insurance plan. PATIENTS: Patients with CHF receiving commercial and Medicare supplemental benefits. MEASUREMENTS AND MAIN RESULTS: We estimated adherence to therapy with beta-blockers or angiotensin-converting enzyme (ACE) inhibitors in 2002 by using the medication possession ratio, an estimate of the proportion of days a patient was exposed to a drug while taking a drug regimen. For 2003, we measured the annualized total cost of health care and identified hospitalizations with a diagnostic code for CHF. We used a two-stage regression approach to model the association among copayment, adherence, and patient outcomes. For patients taking ACE inhibitors, a $10 increase in copayment was associated with a 2.6% decrease in the medication possession ratio (95% confidence interval [CI] 2.0-3.1%). This change in adherence was associated with a predicted 0.8% decrease in medical costs (95% CI -4.2-2.5%) but a predicted 6.1% increase in the risk of hospitalization for CHF (95% CI 0.5-12.0%). Among patients taking beta-blockers, a $10 increase in copayment was associated with a 1.8% decrease in the medication possession ratio (95% CI 1.4-2.2%). This change in adherence was associated with a predicted 2.8% decrease in medical costs (95% CI -5.9-0.1%) and a predicted 8.7% increase in the risk of hospitalization for CHF (95% CI 3.8-13.8%). CONCLUSION: Among patients with CHF, higher drug copayments were associated with poorer adherence. The change was relatively small and did not affect predicted total health care costs, but it was sufficient to increase the predicted risk of hospitalization for CHF.

Adrenergic beta-Antagonists↗
PubMed2005

Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect.

Observational studies often provide the only available information about treatment effects. Control of confounding, however, remains challenging. The authors compared five methods for evaluating the effect of tissue plasminogen activator on death among 6,269 ischemic stroke patients registered in a German stroke registry: multivariable logistic regression, propensity score-matched analysis, regression adjustment with the propensity score, and two propensity score-based weighted methods-one estimating the treatment effect in the entire study population (inverse-probability-of-treatment weights), another in the treated population (standardized-mortality-ratio weights). Between 2000 and 2001, 212 patients received tissue plasminogen activator. The crude odds ratio between tissue plasminogen activator and death was 3.35 (95% confidence interval: 2.28, 4.91). The adjusted odds ratio depended strongly on the adjustment method, ranging from 1.11 (95% confidence interval: 0.67, 1.84) for the standardized-mortality-ratio weighted to 10.77 (95% confidence interval: 2.47, 47.04) for the inverse-probability-of-treatment-weighted analysis. For treated patients with a low propensity score, risks of dying were high. Exclusion of patients with a propensity score of <5% yielded comparable odds ratios of approximately 1 for all methods. High levels of nonuniform treatment effect render summary estimates very sensitive to the weighting system explicit or implicit in an adjustment technique. Researchers need to be clear about the population for which an overall treatment estimate is most suitable.

Aged↗
PubMed2005

Determinants of the differences in LDL-cholesterol after initiation of statin treatment.

BACKGROUND: Randomized clinical trials may not accurately predict drug benefit in clinical practice because the patients and conditions of therapy almost always differ between those settings. OBJECTIVE: To determine whether differences in low-density lipoprotein cholesterol (LDL-C) time curves between clinical trial results and usual care experience after initiation of statin therapy could be explained fully in terms of observable characteristics of patients and practice in usual care. METHODS: We compared LDL-C measurements for 3 years after initiation of statin treatment in individuals enrolled in a health maintenance organization (HMO), with enrollees in the active treatment arm of the CARE (Cholesterol and Recurrent Events) trial. Analysis of the determinants of variation in LDL-C in the HMO cohort was used to adjust the crude results to the distribution of patient and treatment characteristics in the trial. RESULTS: The mean percent decrease in LDL-C was lower in the HMO cohort (n = 1245) than in the clinical trial at the end of each 6-month period, with the difference diminishing over time. Adjustment of the HMO time curve to the baseline characteristics of the clinical trial cohort did not significantly change the mean estimates at any time point. Assuming optimal adherence in the HMO cohort raised the curve over time, with 95% confidence intervals including the means observed in CARE after 18 months. Fixing treatment to pravastatin 40 mg/day, as in CARE, brought the estimates in the HMO cohort very close to those of the clinical trial, with 95% confidence intervals including the means observed in CARE at all time points. CONCLUSIONS: Treatment selection, dosing, and adherence under usual care were the primary reasons for which improvements in LDL-C in practice fell short of expectations that are based on clinical trial findings for statin therapy. Beginning with a low dose of statins and titrating to a satisfactory response can delay effective treatment by 18 months or more. Poor adherence accounts for a further substantial shortfall from maximal effect. Differences between trial populations and the general population of statin users with respect to age, gender, and baseline LDL-C have no measurable impact on discrepancies between predicted and observed LDL-C improvement in usual practice.

Adult↗
PubMed2005

Posttransplant lymphoproliferative disorder among renal transplant patients in relation to the use of mycophenolate mofetil.

BACKGROUND: The introduction of increasingly effective immunosuppressants has raised the question of whether posttransplant lymphoproliferative disorder (PTLD), a complication of immunosuppression, would become more frequent. This study assessed the risk of PTLD in relation to immunosuppression during a period that saw the introduction and eventual market dominance of mycophenolate mofetil (MMF). METHODS: A case-control study was conducted at 23 U.S. transplant centers. All participants received a renal-only transplant on or after July 1, 1995. PTLD cases were reported by centers and confirmed by central review. The United Network for Organ Sharing (UNOS) supplemented case ascertainment and identified controls matched on center, transplant date, and age. Center personnel abstracted risk factor and therapy data for cases and up to four controls per case. Cases and controls were compared, using a matched multivariate analysis, to assess the impact of MMF as one component of triple-therapy adjusted for other drug therapies and known risk factors. RESULTS: Data were collected for 108 PTLD cases and 404 controls. PTLD risk for individuals on triple therapy with MMF was similar to the risk experienced by individuals on triple therapy with no MMF (adjusted odds ratio=1.19; 95% CI 0.55-2.55). There was no dose response relationship between MMF and PTLD risk. CONCLUSIONS: Use of MMF was not associated with an increase in PTLD among patients who received triple immunosuppressive therapy, but an excess in risk as large as 155% or a reduction in risk by as much as 45% cannot be ruled out.

Case-Control Studies↗
PubMed2005

An application of propensity score matching using claims data.

BACKGROUND: Confounding by indication is a common problem in pharmacoepidemiology, where predictors of treatment also have prognostic value for the outcome of interest. The tools available to the epidemiologist that can be used to mitigate the effects of confounding by indication often have limits with respect to the number of variables that can be simultaneously incorporated as components of the confounding. This constraint becomes particularly apparent in the context of a rich data source (such as administrative claims data), applied to the study of an outcome that occurs infrequently. In such settings, there will typically be many more variables available for control as potential confounders than traditional epidemiologic techniques will allow. METHODS: One tool that can indirectly permit control of a large number of variables is the propensity score approach. This paper illustrates the application of the propensity score to a study conducted in an administrative database, and raises critical issues to be addressed in such an analysis. In this example, the effect of statin therapy on the occurrence of myocardial infarction was examined, and numerous potential confounders of this association were adjusted simultaneously using a propensity score to form matched cohorts of statin initiators and non-initiators. RESULTS: The incidence of myocardial infarction observed in the statin treated cohort was lower than the incidence in the untreated cohort, and the magnitude of this effect was consistent with results from randomized placebo controlled clinical trials of statin therapy. CONCLUSIONS: This example illustrates how confounding by indication can be mitigated by the propensity score matching technique. Concerns remain over the generalizability of estimates obtained from such a study, and how to know when propensity scores are removing bias, since apparent balance between compared groups on measured variables could leave variables not included in the propensity score unbalanced and lead to confounded effect estimates.

Cohort Studies↗
PubMed2005

The incidence of abdominal and pelvic surgery among patients with irritable bowel syndrome.

Rates of abdominopelvic surgery, with a particular focus on gallbladder procedures, were measured in patients with irritable bowel syndrome (IBS) (n = 108,936) and compared with those in a general population sample (n = 223,082). The patient sample was selected from persons who were members of a managed care organization during the years 1995-2000. Medical records from a randomly selected subset of IBS patients were reviewed to confirm the diagnosis. Crude and standardized rates and adjusted rate ratios for surgery were calculated. The incidence of abdominopelvic surgery, excluding gallbladder procedures, was 87% higher in patients with IBS than that for the general population. The incidence of gallbladder surgery was threefold higher in IBS patients than the general population. Patients with IBS have an increased risk for abdominopelvic and gallbladder surgery and, thus, an associated risk for experiencing morbidity and mortality associated with these surgical procedures.

Adult↗
PubMed2005

Persistence and adherence with topical glaucoma therapy.

PURPOSE: The present study describes the patterns and predictors of treatment persistence and adherence among patients who are diagnosed with glaucoma or as glaucoma suspects (based on claims codes). DESIGN: A retrospective cohort study using health insurance claims data. METHODS: Newly treated individuals with diagnosed glaucoma (n = 3623) and suspect glaucoma (n = 1677) were obtained from healthcare claims data in the Ingenix Research Database. For each of these two diagnostic groups, we calculated the duration of continuous treatment with the initially prescribed medication (persistence) and the prevalence of use of the initial medication at various time points (adherence). Four drug classes were included: beta-blockers, alpha-agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. RESULTS: Nearly one half of the individuals who had filled a glaucoma prescription discontinued all topical ocular hypotensive therapy within six months, and just 37% of these individuals recently had refilled their initial medication at three years after the first dispensing. Prostaglandins were associated with better persistence than any other drug class, which was indicated by hazard ratios for discontinuation of prostaglandins compared with beta-blockers of 0.40 (95% confidence interval, 0.35-0.44) for diagnosed patients and 0.44 (95% confidence interval, 0.37-0.52) for patients with suspect glaucoma. Prostaglandins showed a similar advantage in adherence. Furthermore, patients with diagnosed glaucoma were more likely to adhere to therapy than patients with suspect glaucoma (relative risk = 1.11; 95% confidence interval, 1.05-1.18). CONCLUSION: Persistence and adherence were substantially better with prostaglandins than with other drug classes, and patients with diagnosed open-angle glaucoma were more likely to adhere to treatment than suspected glaucoma.

Administration, Topical↗
PubMed2005

The long-term course of low-density lipoprotein cholesterol after initiation of statin treatment: retrospective database analysis over 3 years in health maintenance organization enrollees.

OBJECTIVES: Our primary objective was to obtain robust estimates of the low-density lipoprotein cholesterol (LDL-C) decrease from baseline over a long period (ie, 3 years) after initiation of statin treatment in a usual-care setting. Our secondary objective was to investigate the predictors of the LDL-C time course. METHODS: We retrospectively analyzed the data for a sample of enrollees in a health maintenance organization (HMO) who started statin treatment between October 1, 1995, and December 31, 1998. Using the HMO's claims database, we examined the LDL-C change from baseline (as measured at the prescribing physicians' discretion) and computed mean estimates every 6 months up to 3 years. We investigated potential predictors of the LDL-C time course (ie, age, sex, baseline LDL-C, previous treatment, prescribing physician's specialty, and most recent treatment) with a mixed model applied to longitudinal data. This model enabled us to impute missing data for all enrollees still being followed, including those who had stopped treatment, and to discuss the robustness of our findings. We applied 2 methods of imputation, assuming either of the following: (1) data were missing at random but could be estimated from the parameters in the mixed model, or (2) LDL-C returned to the baseline value > or =15 days after treatment cessation. RESULTS: We examined data from 3193 individuals. In most cases, the statin used was fluvastatin or pravastatin. The observed mean (95% CI) LDL-C decrease from baseline widened progressively from 23.6% (23.0%-24.3%) at 6 months to 28.0% (27.1%-28.9%) at 18 months and 30.2% (28.7%-31.7%) at 36 months after treatment initiation. These results remained robust after the imputation of missing data, with mean LDL-C reduction consistently >20% at each 6-month time point during the 3 years after treatment initiation. Variations as a function of baseline characteristics were limited (demographics) or explicable by extraneous factors (baseline LDL-C). There were predictable variations as a function of the most recent treatment. CONCLUSIONS: This analysis indicates a long-term reduction in LDL-C among a sample of HMO enrollees who initiated statin treatment in a usual-care setting. The results were robust after imputation of missing data, with mean decrease from baseline consistently >20% over 3 years. However, given the retrospective design of our study and the absence of a control group, we cannot determine how much of the decrease was attributable to treatment.

Aged↗