Trends in use of hydroxychloroquine during pregnancy in systemic lupus erythematosus patients from 2001 to 2015.

BACKGROUND: Evidence suggests that continuing hydroxychloroquine (HCQ) during pregnancy in women with systemic lupus erythematosus (SLE) improves outcomes. We sought to describe time trends in the continuation, initiation, and duration of HCQ in a large population-based cohort of pregnant SLE women. METHODS: A cohort of pregnant women with SLE enrolled continuously in public (Medicaid, 2001-2010) or private (Optum Clinformatics, 2003-2015) health insurance between three months prior to conception and one month after delivery was identified. We assessed the proportion of women initiating or continuing HCQ and the duration of therapy during each calendar year in the study. RESULTS: A total of 5300 women with SLE were included. Of these, 852 (16.1%) were on HCQ treatment in the three-month period prior to their pregnancy. During pregnancy, the overall proportion of women with SLE taking HCQ increased from 12.4% in 2001 to 37.7% in 2015. Initiation of HCQ therapy during pregnancy increased from 2.7% in 2001 to 7.5% in 2010 ( p = 0.0002) (Medicaid) and from 4.9% in 2003 to 13.6% in 2015 ( p = 0.0001) (Clinformatics). Continuation of HCQ during pregnancy did not change significantly over time in either data set. The average cumulative day-supply of HCQ prescriptions during pregnancy increased from 37 days in 2001 to 77 days in 2010 ( p = 0.05) among HCQ initiators and from 79 days in 2001 to 125 days in 2010 ( p = 0.0009) among HCQ continuers in Medicaid. Among privately insured women, the average cumulative day-supply of HCQ prescriptions among HCQ continuers increased from 84 in 2004 to 163 in 2015 ( p = 0.0006) but did not change significantly among HCQ initiators. CONCLUSION: The proportion of women initiating HCQ during pregnancy and the average cumulative day-supply of HCQ increased from 2001 to 2015. While these findings are encouraging, overall HCQ use during pregnancy remains low.

Patterns of treatment among a cohort of older low-income adults starting new medications for osteoporosis.

UNLABELLED: Among 125,954 new users of osteoporosis (OP) medications, 77 % of subjects stopped OP medications, and 23 % of subjects added or started a new OP medication during follow-up, with the first addition or start of a new OP medication occurring in a mean of 739 days after original OP treatment. INTRODUCTION: We described patterns and predictors of OP medication use, focusing on treatment changes over time. METHODS: We analyzed health and pharmacy insurance claims for a large cohort of low-income Medicare beneficiaries with a drug benefit for the years 1998-2008. Study subjects had documented Medicare claims and no receipt of OP medications (i.e., bisphosphonate, raloxifene, calcitonin, teriparatide, or hormonal therapy) during a baseline of 180 days. Subjects were then required to start an OP medication. Baseline patient and prescriber characteristics were assessed in multivariable Cox regression models to identify correlates of adding or starting a new OP medication. Fractures, bone mineral density testing, and visits with endocrinologists or rheumatologists occurring after baseline were also examined as correlates. RESULTS: We included 125,954 new users of OP medications with a mean age of 78 years, 97 % female, and 92 % white. OP medication prescribers included specialists (i.e., endocrinologists or rheumatologists) (6.2 %), orthopedic surgeons (1.0 %), primary care providers (64.9 %), other physicians (3.7 %), and missing (24.1 %). Seventy-seven percent of subjects stopped OP medications, and 23 % of subjects added or started a new OP medication during follow-up, with the first addition or start of a new OP medication occurring in a mean of 739 days after original OP treatment; 4 % added or started a new OP medication more than once. In fully adjusted models, many baseline variables correlated with starting a second OP medication. Post-baseline fractures [hazard ratio (HR) 1.76, 95 % confidence interval (CI) 1.71-1.82] and bone mineral density testing (HR 2.94, 95 % CI 2.86-3.03) were strong predictors. CONCLUSION: Approximately one quarter of patients starting an OP medication added or started a new OP medication during follow-up. Long-term sequential treatment strategy trials would inform optimal medication treatment for OP.

Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study.

OBJECTIVE: To determine whether outpatient exposure to calcium-channel blockers (CCBs) at the time of delivery is associated with an increased risk for postpartum haemorrhage (PPH). DESIGN: Cohort study. SETTING: United States of America. POPULATION OR SAMPLE: Medicaid beneficiaries. METHODS: We identified a cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or labetalol for pre-existing or gestational hypertension whose days of supply overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity score matching and stratification were used to address potential confounding. MAIN OUTCOME MEASURES: The occurrence of PPH during the delivery hospitalisation. RESULTS: There were 27 patients exposed to CCBs (2.2%) and 232 patients exposed to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for confounders, there was no meaningful association between CCB exposure and PPH in the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained across multiple sensitivity analyses. CONCLUSIONS: The outpatient use of CCBs in late pregnancy for the treatment of hypertension does not increase the risk of PPH.

The relation between bisphosphonate use and non-union of fractures of the humerus in older adults.

SUMMARY: While nitrogen-containing bisphosphonates have been shown to reduce fracture risk in postmenopausal women and men, their safety in the period after a fracture is unclear. In fully adjusted multivariable regression models, bisphosphonate use in the post-fracture period was associated with an increased probability of non-union [odds ratio (OR) 2.37, 95% confidence interval (CI) 1.13-4.96]. Clinicians might consider waiting for several months before introduction of a bisphosphonate after a fracture. INTRODUCTION: While nitrogen-containing bisphosphonates have been shown to reduce fracture risk in postmenopausal women and men, their safety in the period after a fracture is unclear. We examined the risk of non-union associated with post-fracture bisphosphonate use among a group of older adults who had experienced a humerus fracture. METHODS: We conducted a nested case-control study among subjects who had experienced a humerus fracture. From this cohort, cases of non-union were defined as those with an orthopedic procedure related to non-union 91-365 days after the initial humerus fracture. Bisphosphonate exposure was assessed during the 365 days prior to the non-union among cases or the matched date for controls. Multivariable logistic regression models were examined to calculate the OR and 95% CI for the association of post-fracture bisphosphonate use with non-union. RESULTS: From the cohort of 19,731 patients with humerus fractures, 81 (0.4%) experienced a non-union. Among the 81 cases, 13 (16.0%) were exposed to bisphosphonates post-fracture, while 69 of the 810 controls (8.5%) were exposed in the post-fracture interval. In fully adjusted multivariable regression models, bisphosphonate use in the post-fracture period was associated with an increased odds of non-union (OR 2.37, 95% CI 1.13-4.96). Albeit limited by small sample sizes, the increased risk associated with bisphosphonate use persisted in the subgroup of patients without a history of osteoporosis or prior fractures (OR 1.91, 95% CI 0.75-4.83). CONCLUSIONS: In this study of older adults, non-union after a humerus fracture was rare. Bisphosphonate use after the fracture was associated with an approximate doubling of the risk of non-union.

Glucocorticoids and the risk for initiation of hypoglycemic therapy.

PURPOSE: To quantify risk for the occurrence of hyperglycemia requiring initiation of hypoglycemic therapy in patients treated with oral glucocorticoids. PATIENTS AND METHODS: A case-control study of enrollees in the New Jersey Medicaid program 35 years of age or older. The 11,855 case patients had newly initiated treatment with a hypoglycemic agent (oral or insulin) between 1981 and 1990. The 11,855 controls represented a random sample of other Medicaid enrollees. RESULTS: In patients using oral glucocorticoids, the estimated relative risk for development of hyperglycemia requiring treatment was 2.23 (95% confidence interval, 1.92 to 2.59) as compared with nonusers. Risk increased with increasing average daily steroid dose, in hydrocortisone-equivalent milligrams; the odds ratio was 1.77 for 1 to 39 mg/d, 3.02 for 40 to 79 mg/d, 5.82 for 80 to 119 mg/d, and 10.34 for 120 mg/d or more. The estimated effects persisted after adjustment for a variety of potentially confounding demographic, health service utilization, and medication use variables. CONCLUSION: The findings of this population-based study quantify the risk of developing hyperglycemia requiring hypoglycemic therapy after oral glucocorticoid use. The magnitude of risk increases substantially with increasing glucocorticoid dose. These findings demonstrate the utility of large-scale health claims databases in defining the risk of important adverse drug effects.

Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture.

OBJECTIVE: While benzodiazepine treatment is known to increase the risk of hip fracture in older populations, controversy persists over which characteristics of benzodiazepine use (e.g., elimination half-life, dosage, duration of use) are most associated with such risks. METHOD: The authors reviewed the health care utilization data of 1,222 hip fracture patients and 4,888 comparison patients frequency matched on the basis of age and gender (all were at least 65 years old). Patients were enrolled in Medicare as well as in the New Jersey Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs. Benzodiazepine use, as well as other covariates, were assessed before the index date (which was either the date of hospital admission for hip fracture surgical repair or, for the comparison subjects, a randomly assigned, frequency-matched date). RESULTS: All benzodiazepine doses > or =3 mg/day in diazepam equivalents significantly increased the adjusted risk of hip fracture by 50%. Significantly increased adjusted risks of hip fracture were seen during the initial 2 weeks of use (60% increase) and after more than 1 month of continuous use (80% increase) but not for 2-4 weeks of continuous use. Use of benzodiazepines other than long-acting agents significantly increased the risk of hip fracture by 50%. CONCLUSIONS: Even at modest doses, including some low doses currently advocated in prescribing guidelines for older patients, treatment with benzodiazepines appears to increase the risk of hip fracture. Patients appear to be particularly vulnerable immediately after initiating therapy and after more than 1 month of continuous use. Benzodiazepines with shorter half-lives appear to be no safer than longer half-life agents. Clinicians should be aware of these risks and weigh them against potential benefits when prescribing for elderly patients.

Neuroleptic drug exposure and treatment of parkinsonism in the elderly: a case-control study.

PURPOSE: Despite the widespread use of neuroleptic medications for the elderly, little is known about the frequency of treatment for drug-induced parkinsonian syndromes in this age group, particularly with L-dopa-type drugs, which are more appropriate for the treatment of true idiopathic Parkinson's disease. PATIENTS AND METHODS: We identified 3,512 patients aged 65 to 99 enrolled in a large state Medicaid program who were newly prescribed a drug to treat parkinsonian symptoms. Controls were comparable program enrollees of similar age who had not been prescribed an antiparkinsonian drug. In a case-control study, we evaluated the use of neuroleptic drugs in the 90 days before initiation of antiparkinsonian therapy. RESULTS: Patients taking neuroleptics were 5.4 times more likely to begin antiparkinsonian medication than were nonusers (95% confidence interval [CI] 4.8 to 6.1). They also had a greater than two-fold increase in risk of beginning therapy with a dopaminergic drug specific for idiopathic Parkinson's disease, not generally indicated for treatment of drug-induced parkinsonism (adjusted odds ratio 2.2, 95% CI 1.9 to 2.7). Clear dose-response relationships were demonstrated, as were differences among neuroleptics. Among all patients started on dopaminergic drugs in this population, 37% of such therapy was attributable to prior neuroleptic use. Continuation of the neuroleptic persisted in 71% of patients so treated. CONCLUSION: Neuroleptic use is a common cause of extrapyramidal dysfunction in the elderly, and the side effect is frequently treated by adding an anticholinergic or dopaminergic drug to the regimen. The use of anticholinergic drugs presents risks of additional drug side effects; the use of dopaminergic drugs, generally not appropriate for drug-induced parkinsonian syndrome, suggests that extrapyramidal neuroleptic side effects may often be mistaken for idiopathic Parkinson's disease in older patients.

Thiazide diuretics and the initiation of anti-gout therapy.

While physiologic and epidemiologic evidence link diuretic therapy with hyperuricemia, no previous study has quantified the risk for initiation of treatment specific for hyperuricemia or gout among elderly patients taking thiazide diuretics. We performed a retrospective cohort study of 9249 enrollees aged 65 or older in the New Jersey Medicaid program who were newly started on an antihypertensive medication from November 1981 through February 1989 and who had no prior use of anti-gout therapy (allopurinol, colchicine, or a uricosutic) during the preceding one-year period. We used Cox proportional hazards analysis to determine the risk for the initiation of anti-gout therapy in patients using various antihypertensive treatment regimens relative to no antihypertensive exposure. Patient follow-up extended for up to two years. Antihypertensive exposure was characterized over the entire period of follow-up according to the following categories: thiazide diuretic therapy alone; non-thiazide antihypertensive therapy; thiazide diuretic therapy in combination with any non-thiazide antihypertensive agent(s); and no antihypertensive use. Antihypertensive exposure was entered into the model as a time-varying covariate. Estimates of risk were adjusted for age, sex, race, nursing home residence, number of prescriptions filled, intensity of physician use, hospitalization history, and year of antihypertensive treatment initiation. The adjusted relative risk for the initiation of anti-gout therapy was 1.00 (95% CI, 0.65-1.53) for non-thiazide antihypertensive therapy alone, 1.99 (95%, CI, 1.21-3.26) for thiazide diuretic therapy, and 2.29 (95% CI, 1.55-3.37) for thiazide diuretic therapy in combination with any non-thiazide agent(s). Risk for anti-gout therapy was significantly increased for thiazide doses of > or = 25 mg/day (in hydrochlorothiazide equivalents); no significant increase in risk was seen for lower doses. We conclude that use of thiazide diuretics in doses of 25 mg/day or higher is associated with a significantly increased risk for initiation of anti-gout therapy. Such treatment may reflect the occurrence of clinical sequelae of diuretic-induced hyperuricemia or the inappropriate treatment of asymptomatic hyperuricemia.

Antipsychotic prescribing patterns and the treatment of extrapyramidal symptoms in older people.

OBJECTIVES: We have previously identified antipsychotic use as a risk factor for the use of both dopaminergic and anticholinergic antiparkinsonian drugs in older people. This study examines whether and how such antipsychotic regimens were adjusted before the addition of an antiparkinsonian drug. DESIGN: Retrospective comparison study PARTICIPANTS: There were 1307 antipsychotic users begun on anticholinergic antiparkinsonian drugs and 345 antipsychotic users begun on dopaminergic drugs; 1864 antipsychotic users not prescribed antiparkinsonian drugs served as comparison subjects. Data were drawn from health care claims of patients aged 65-99 in the New Jersey Medicaid Program from 1981 to 1990. MEASUREMENTS: We determined if antipsychotic regimens were discontinued, reduced in dosage, or modified to reduce extrapyramidal toxicity before the institution of antiparkinsonian therapy. RESULTS: Thirty-five percent of the patients begun on dopaminergic drugs had their antipsychotic medication discontinued before beginning antiparkinsonian therapy; the antipsychotic was discontinued in only 12% of patients who started anticholinergic medications (P < .001). Among the smaller subset of patients with sufficient duration of antipsychotic exposure to examine changes in dose, 54% of patients begun on dopaminergic agents had their antipsychotic regimen reduced or discontinued before antiparkinsonian therapy, whereas 33% of patients begun on anticholinergic agents had one of these regimen changes (P < .001). Controlling for potential clinical and demographic confounders using multivariate logistic regression did not substantively alter these results. CONCLUSIONS: These data indicate that physicians frequently fail to discontinue or modify an antipsychotic regimen before adding a new drug to treat probable drug-induced extrapyramidal symptoms. Such prescribing patterns preceding use of dopaminergic antiparkinsonian drugs suggest that addition of such drugs may represent an inappropriate attempt to treat presumed idiopathic Parkinson's disease in many cases.

Definition of race and ethnicity in older people in Medicare and Medicaid.

BACKGROUND: Race and ethnicity are important predictors of health care access and outcomes, but quality of their documentation in the healthcare system is often problematic. OBJECTIVES: To study the agreement between Medicare and Medicaid descriptions of race and ethnicity in older beneficiaries. DESIGN: Quasiexperimental design in a natural practice setting. SETTING: New Jersey. PARTICIPANTS: 153,241 dually enrolled participants in Medicare and Medicaid. MEASUREMENTS: Agreement rates between administrative databases on recipients' race and ethnicity. RESULTS: Agreement between Medicare and Medicaid on the recipients' race and ethnicity was modest (kappa = .58; 95% CI, .57-.58) for men and women alike and across different age groups. Depending on whether Medicare or Medicaid was used as the reference standard, the relative agreement rates for race and ethnic group assignments varied. For example, using Medicare as the reference, the relative agreement rate was 84% for whites, 74% for blacks, 61% for others, 23% for Hispanics, and only 5% for Asians. Using Medicaid as the reference, a different pattern emerged. However, such gradients of agreement rates across racial groups were observed in both programs. Medicare and Medicaid reported different percentages of all race and ethnicity groups, with Medicaid reporting greater proportions of White and Black beneficiaries, and Medicare reporting greater proportions of Hispanic, Asian, and Other groups. CONCLUSIONS: Depiction of race and ethnicity data in large government health insurance programs is approximate at best and often contradictory from one program to another. This can impede efforts to study the relationship between these important characteristics and health care utilization and outcomes.

Zolpidem use and hip fractures in older people.

OBJECTIVES: The widespread use of sedative-hypnotics in older populations makes it imperative to identify hazardous regimens that should be avoided and safer regimens that may be used preferentially by older people. Although benzodiazepines have been shown to increase fall and fracture risk, zolpidem, a nonbenzodiazepine hypnotic, has been advocated as a safer alternative. DESIGN: Case-control study of hip fracture cases and controls in 1994. SETTING: All subjects were age 65 and older and enrolled in Medicare, and in Medicaid or the Pharmaceutical Assistance to the Aged and Disabled program of New Jersey. PARTICIPANTS: Cases (n=1,222) were patients who underwent surgical repair of a hip fracture. They were frequency-matched to four controls (n=4,888) based on age and gender. MEASUREMENTS: Use of sedative-hypnotics and other medications was assessed in the 180 days before the index event. We assessed other covariates, including demographic, clinical, and healthcare utilization variables in the prior 180 days. RESULTS: Zolpidem use was associated with a significant increased risk of hip fracture (adjusted odds ratio (AOR) 1.95; 95% confidence interval (CI)=1.09-3.51). Other psychotropic medication classes with significantly increased risks included benzodiazepines (AOR 1.46; 95% CI=1.21-1.76), antipsychotic medications (AOR 1.61; 95% CI=1.29-2.01), and antidepressants (AOR 1.46; 95% CI=1.22-1.75). In subanalyses, preferential use of zolpidem by subjects at greater risk of hip fracture did not appear to explain the apparent risk of hip fracture with zolpidem use. CONCLUSION: Use of zolpidem by older people was associated with nearly twice the risk of hip fracture, even after controlling for possible demographic and clinical confounders. Rather than being a safer alternative, zolpidem may be associated with risks that are as great as those seen with conventional benzodiazepines in older patients.

Drugs that inhibit gastric acid secretion may alter the course of inflammatory bowel disease.

BACKGROUND: Recent data suggest that acid suppressive medications may alter factors central to the pathophysiology of inflammatory bowel diseases (IBD), whether through shifts in the intestinal microbiome due to acid suppression or effects on immune function. AIM: To assess the relationship between the use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2Ra) and incidence of 'flares' (hospitalisation/surgery and change in medication). METHODS: We conducted a new user cohort study including individuals diagnosed with IBD in British Columbia using linked healthcare utilisation databases (available from July 1996 through April 2006). Propensity-score matched incidence rates during a 6-month follow-up period and rate ratios (RR) and 95% CI were calculated. RESULTS: Among 16 151 IBD patients, 1307 Crohn's disease (CD) and 996 ulcerative colitis (UC) patients experienced a new use of PPIs, whereas 741 CD and 738 UC used H2Ra. All IBD subgroups were matched separately to an equal number of unexposed IBD patients. H2Ra use in CD doubled the risk of hospitalisation/surgery (RR = 1.94; 95%CI 1.24-3.10) and numerically less so in UC patients (RR = 1.11) with widely overlapping CIs (0.61-2.03). Proton pump inhibitors use was associated with medication change in UC (RR = 1.39; 95%CI 1.20-1.62), but without meaningfully, increased risk of hospitalisation/surgery for UC or CD patients. Extending follow-up showed persistence, but attenuation, of all effects. CONCLUSIONS: Initiation of PPIs or H2Ra may be associated with short-term changes in the course of IBD. Although confounding by indication was adjusted using propensity score matching, residual confounding may persist and findings need to be interpreted cautiously.

Antidepressants and fracture risk in older adults: a comparative safety analysis.

We examined variations in fracture rates among patients initiated on antidepressant drug treatment as identified from Medicare data in two US states and assessed whether the observed variation could be explained by affinity for serotonin transport receptors. We used Cox proportional hazards models to compare fracture rates of the hip, humerus, pelvis, wrist, and a composite of these, among propensity score-matched cohorts of users of secondary amine tricyclics, tertiary amine tricyclics, selective serotonin reuptake inhibitors (SSRIs), and atypical antidepressants. As compared with secondary amine tricyclics, SSRIs showed the highest association with composite fracture rate (hazard ratio 1.30; 95% confidence interval (CI) 1.12-1.52), followed by atypical antidepressants (hazard ratio 1.12; 95% CI 0.96-1.31) and tertiary amine tricyclics (hazard ratio 1.01; 95% CI 0.87-1.18). The results were robust to sensitivity analyses. Although SSRI use was associated with the highest rate of fractures, variation in fracture risk across specific antidepressant medications did not depend on affinity for serotonin transport receptors.

Concurrent use of antiulcerative agents.

Many physicians prescribe more than one antiulcerative agent (AUA) simultaneously to the same patient, although there is little evidence to support this practice. The purposes of this study were to (a) determine patient factors associated with the concurrent use of these agents and (b) estimate the excess costs generated by the prescription of multiple rather than a single agent. We conducted a case-control study of concurrent AUA users among New Jersey Medicaid enrollees age 65 years and older. To evaluate the excess cost generated by the ongoing prescription of an additional AUA, we measured the additional drug expenditures associated with each regimen of concurrent use. Nearly 1 in 15 AUA users (6.6%) met our conservative definition of concurrent AUA use. In a multiple logistic regression model, previous gastrointestinal procedure, use of a nonsteroidal anti-inflammatory drugs, nursing home residency, and recent hospitalization for more than 20 days were all predictors of concurrent use of more than one AUA. No association was found with age, sex, or number of pharmacies used. The upper bound estimate of the cost generated by the concurrent prescription of a second AUA was $210 (range: $2-$942) over the 180-day study period, with a lower bound of $151 (range: $1-$449). Annually, such excess cost would range from $301 to $420 per patient. This would account for between $457 million and $637 million per year for the nation's elderly if these patterns are generalizable. Despite the lack of evidence of therapeutic benefit from multiple concurrent AUA use in most patients, this practice is fairly common. Besides introducing the risk of additional costs and side effects in the absence of additional efficacy, the costs of such duplicative prescribing are substantial.

Increased incidence of levodopa therapy following metoclopramide use.

OBJECTIVE: To determine whether there is an increase in use of antiparkinsonian therapy in older persons taking metoclopramide hydrochloride. DESIGN: Case-control study. SETTING: New jersey Medicaid program. PATIENTS: Medicaid enrollees aged 65 years and older. Cases were patients newly prescribed a levodopa-containing medication (n = 1253); a secondary case group were patients newly prescribed an anticholinergic antiparkinsonian drug (n = 2377). The control group consisted of 16435 Medicaid enrollees older than 65 years who were not users of any antiparkinsonian therapy. MAIN OUTCOME MEASURES: We used logistic regression to determine the odds ratio (OR) for the initiation of antiparkinsonian therapy in patients using metoclopramide relative to nonusers, after adjusting for age, sex, race, nursing home residence, exposure to antipsychotic medication, and days hospitalized. RESULTS: Metoclopramide users were three times more likely to begin use of a levodopa-containing medication compared with nonusers (OR = 3.09; 95% confidence interval [Cl], 2.25 to 4.26). Risk increased with increasing daily metoclopramide dose: the OR was 1.19 (95% Cl, 0.50 to 2.81) for more than 0 to 10 mg per day, 3.33 (95% Cl, 1.98 to 5.58) for more than 10 to 20 mg per day, and 5.25 (95% Cl, 1.16 to 8.50) for more than 20mg per day. The effect persisted after adjustment for demographic, health service utilization, and medication use variables. The OR for initiation of anticholinergic antiparkinsonian drugs was also elevated in metoclopramide users. CONCLUSION: Metoclopramide use confers an increased risk for the initiation of treatment generally reserved for the management of idiopathic Parkinson's disease in patients with drug-induced parkinsonian symptoms, which should be ruled out before starting dopaminergic therapy for this condition.

HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.

CONTEXT: Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known. OBJECTIVE: To determine whether the use of statins is associated with reduced hip fracture risk. DESIGN: Case-control study. SETTING AND PATIENTS: A total of 6110 New Jersey residents aged 65 years or older and enrolled in Medicare and either Medicaid or the Pharmacy Assistance for the Aged and Disabled program. Case patients (n=1222) underwent surgical repair of a hip fracture in 1994. Control patients (n=4888) were identified at a ratio of 4:1 and frequency-matched to case patients for age and sex. MAIN OUTCOME MEASURE: Adjusted odds ratio (OR) of hip fracture by statin use in the 180 days and 3 years prior to the index date (the earliest date of admission for surgery), adjusted for demographic and clinical characteristics and health care utilization. RESULTS: Use of statins in either the prior 180 days (adjusted OR, 0.50; 95% confidence interval [CI], 0.33-0.76) or prior 3 years (adjusted OR, 0.57; 95% CI, 0.40-0.82) was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psychoactive medications, estrogen and thiazide use, ischemic heart disease, cancer, and diabetes mellitus. No significant relationship was observed between use of nonstatin lipid-lowering agents and hip fracture risk. Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no evidence of such relationships with nonstatin lipid-lowering agents. After adjusting for extent of statin use in the prior 3 years, current use (on the index date) was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% CI, 0.10-0.81). The relationship between statin use and hip fracture risk persisted after controlling for variables such as the number of medications, the Charlson comorbidity index score, and hospitalization or nursing home stay in the last 180 days, as well as after excluding patients who were in a nursing home prior to their index date or who died in the year after their index date. Use of nonstatin lipid-lowering agents was not observed to be associated with reduction in hip fracture risk in any of these alternative models or analyses. CONCLUSIONS: These findings support an association between statin use by elderly patients and reduction in the risk of hip fracture. Controlled trials are needed to exclude the possibility of unmeasured confounders. JAMA. 2000;283:3211-3216

Nonoccupational risk factors for carpal tunnel syndrome.

OBJECTIVE: To examine the relation between selected nonoccupational risk factors and surgery for carpal tunnel syndrome. DESIGN: Case-control study using an administrative database. PARTICIPANTS: Enrollees of New Jersey Medicare or Medicaid programs during 1989 to 1991. MEASUREMENTS: The outcome of interest was open or endoscopic carpal tunnel release. We examined the relation between carpal tunnel release and diabetes mellitus, thyroid disease, inflammatory arthritis, hemodialysis, pregnancy, use of corticosteroids, and hormone replacement therapy. MAIN RESULTS: In multivariate models, inflammatory arthritis was strongly associated with carpal tunnel release (odds ratio [OR] 2.9; 95% confidence interval [CI] 2.2, 3.8). However, corticosteroid use also appeared to be associated with a greater likelihood of undergoing carpal tunnel release, even in the absence of inflammatory arthritis (OR 1.6; 95% CI 1.2, 2.1). Diabetes had a weak but significant association with carpal tunnel release (OR 1.4; 95% CI 1.2, 1.8), as did hypothyroidism (OR 1.7; 95% CI 1.1, 2.8), although patients with hyperthyroidism did not have any change in risk. Women who underwent carpal tunnel release were almost twice as likely to be users of estrogen replacement therapy as controls (OR 1.8; 95% CI 1.0, 3.2). CONCLUSIONS: Although inflammatory arthritis is the most important nonoccupational risk factor for carpal tunnel release, these data substantiate the increase in risk associated with diabetes and untreated hypothyroidism. Further investigation in detailed clinical studies will be necessary to confirm whether changes in corticosteroid use and hormone replacement therapy offer additional means of risk reduction for this common condition.

Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD)

BACKGROUND: Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication. OBJECTIVE: To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy. METHOD: We analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. RESULTS: Patients randomly assigned to enalapril had a 33% greater likelihood of decreased renal function than controls (P =.003). By multivariate analysis, in both the placebo and enalapril groups older age, diuretic therapy, and diabetes were associated with decreased renal function, whereas beta-blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91-0. 96). CONCLUSIONS: Enalapril use caused a 33% increase in the risk of decreased renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy.

Adherence to guidelines for oral anticoagulation after venous thrombosis and pulmonary embolism.

OBJECTIVE: Guidelines for oral anticoagulation after deep venous thrombosis (DVT) or pulmonary embolism (PE) have recommended that patients be anticoagulated for at least 3 months after hospital discharge. We sought to determine whether this recommendation was being followed and what patient characteristics predict a shorter than recommended duration of therapy. DESIGN: Retrospective cohort study using linked health care claims data. SETTING: Routine clinical practice. PATIENTS: Five hundred seventy-three members of New Jersey's Medicaid or Pharmacy Assistance for the Aged and Disabled programs aged 65 years and older who were hospitalized for DVT or PE between January 1, 1991 and June 30, 1994. RESULTS: Of the 573 patients, 129 (23%) filled prescriptions covering less than 90 days of oral anticoagulant therapy. In multivariate models, African-American race was associated with an increased risk of a shorter than recommended duration of therapy (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.14 to 3.08), but age and gender were not. Patients who used anticoagulants in the year prior to admission were less likely to have a short duration of therapy (OR, 0.30; 95% CI, 0.12 to 0.78), than were patients with PE (OR, 0.58; 95% CI, 0.38 to 0.88). CONCLUSIONS: Nearly a quarter of those anticoagulated following DVT or PE received therapy for less than the recommended length of time after hospital discharge, with African Americans more likely to have a shorter than recommended course of treatment. Further research is needed to evaluate the causes of shorter than recommended duration of therapy and racial disparities in anticoagulant use.

Antihypertensive drug therapy and the initiation of treatment for diabetes mellitus.

OBJECTIVE: To quantify the risk for the occurrence of hyperglycemia requiring initiation of therapy among patients taking various antihypertensive regimens. DESIGN: Case-control study. SETTING: New Jersey Medicaid program. PATIENTS: The study included New Jersey Medicaid enrollees 35 years of age or older. The 11,855 case patients were newly started on a hypoglycemic agent (oral agent or insulin) between 1981 and 1990. The 11,855 controls were selected randomly from among other Medicaid enrollees. MEASUREMENTS AND MAIN RESULTS: The frequency of initiation of hypoglycemic therapy was increased for users of virtually all antihypertensive agents relative to nonusers after adjustment for age, gender, race, nursing home residency, number of days hospitalized, total number of prescriptions, and selected medication exposures. The estimated relative risk for initiation of hypoglycemic therapy was 1.40 for patients receiving thiazide diuretics (95% CI, 1.26 to 1.58) and ranged from 1.56 to 1.77 for patients receiving other antihypertensive medications, depending on the medication category. A higher risk was associated with multiple-agent regimens, whether they excluded a thiazide diuretic (odds ratio, 1.76; CI, 1.49 to 2.07) or included one (odds ratio, 1.93; CI, 1.75 to 2.13). When the analysis was restricted to users of antihypertensive agents (n = 8005), the risk associated with other single-agent antihypertensive regimens was not significantly different from that associated with thiazide diuretics. However, patients receiving multiple-agent regimens continued to be at increased risk for hyperglycemia requiring hypoglycemic therapy relative to those who used thiazide diuretic therapy alone. CONCLUSION: The association between antihypertensive therapy and the initiation of treatment for diabetes mellitus is more closely related to the intensity of therapy than to the individual agent used. Our data do not support the hypothesis that thiazide diuretics are more strongly associated with the initiation of hypoglycemic therapy than are other antihypertensive agents.