Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges.

UNLABELLED: Bisphosphonate-related osteonecrosis of the jaw (BONJ) is an adverse effect of bisphosphonate use with a poorly described epidemiology in osteoporosis patients. We examined the literature and two new cohorts for BONJ. The literature suggests an incidence rate of 0.028 % to 4.3 %. Our cohort studies found an incidence of 0.02 % (95 % CI 0.004 %-0.11 %). INTRODUCTION: We examined the epidemiology of BONJ associated with osteoporosis dosing of bisphosphonates. METHODS: First, we systematically searched the literature about osteoporosis BONJ. Identified studies were abstracted by two authors. Second, we attempted to estimate the relative risk of BONJ among bisphosphonate users with osteoporosis. Two different large insurance databases, one from 2005-2007 and another from 2007-2010, combined with medical record review, were searched. The older dataset did not include the International Classification of Diagnoses (ICD) diagnosis code for osteonecrosis of the jaw (ONJ; ICD 733.45). Incidence rates and relative risks were estimated using Cox regression. RESULTS: The literature review produced nine studies of varying quality. The incidence rates for BONJ among osteoporosis patients varied from 0.028 % to 4.3 %. Two prior studies estimated the relative risk of ONJ related to bisphosphonates and found odds ratios of 7.2 and 9.2. Our attempts to estimate the incidence rate of BONJ encompassed 41,957 in the dataset from 2005-2007 and 466,645 in a separate dataset from 2007-2010. From the older dataset, we found 51 potential cases of BONJ using a broad definition of possible ONJ. One case was confirmed by a dentist for a prevalence of 0.02 % (95 % CI 0.004 %-0.11 %) among bisphosphonate users. From the newer dataset, we found 13 possible cases, but none could be confirmed. Most subjects with the ONJ diagnosis code appeared to have had an osteoporosis-related fracture and not ONJ. CONCLUSIONS: The literature suggests a broad range of possible values for the prevalence of BONJ; our estimate fell within the range from prior literature.

A blinded randomized controlled trial of motivational interviewing to improve adherence with osteoporosis medications: design of the OPTIMA trial.

UNLABELLED: We have designed an innovative randomized controlled trial for improving adherence with osteoporosis medications. Recruitment and randomization have been successful. Also, the counseling intervention has been well accepted by subjects randomized to this treatment arm. INTRODUCTION: While many effective treatments exist for osteoporosis, most people do not adhere to such treatments long term. No proven interventions exist to improve osteoporosis medication adherence. We report here on the design and initial enrollment in an innovative randomized controlled trial aimed at improving adherence to osteoporosis treatments. METHODS: The trial represents a collaboration between academic researchers and a state-run pharmacy benefits program for low-income older adults. Beneficiaries beginning treatment with a medication for osteoporosis are targeted for recruitment. We randomize consenting individuals to receive 12 months of mailed education (control arm) or an intervention consisting of one-on-one telephone-based counseling and the mailed education. Motivational interviewing forms the basis for the counseling program which is delivered by seven trained and supervised health counselors over ten telephone calls. The counseling sessions include scripted dialog and open-ended questions about medication adherence and its barriers, as well as structured questions. The primary end point of the trial is medication adherence measured over the 12-month intervention period. Secondary end points include fractures, nursing home admissions, health care resource utilization, and mortality. RESULTS: During the first 7 months of recruitment, we have screened 3,638 potentially eligible subjects. After an initial mailing, 1,115 (30.6%) opted out of telephone recruitment and 1,019 (28.0%) could not be successfully contacted. Of the remaining, 879 (24.2%) consented to participate and were randomized. Women comprise over 90% of all groups; mean ages range from 77 to 80 years old, and the majority in all groups was white. The distribution of osteoporosis medications was comparable across groups and the median number of different prescription drugs used in the prior year was eight to ten. CONCLUSIONS: We have developed a novel intervention for improving osteoporosis medication adherence. The intervention is currently being tested in a large-scale randomized controlled trial. If successful, the intervention may represent a useful model for improving adherence to other chronic treatments.

Interventions to improve adherence and persistence with osteoporosis medications: a systematic literature review.

SUMMARY: Adherence and persistence with osteoporosis medications are poor. We conducted a systematic literature review of interventions to improve adherence and persistence with osteoporosis medications. Seven studies met eligibility requirements and were included in the review. Few interventions were efficacious, and no clear trends regarding successful intervention techniques were identified. However, periodic follow-up interaction between patients and health professionals appeared to be beneficial. INTRODUCTION: Adherence and persistence with pharmacologic therapy for osteoporosis are suboptimal. Our goal was to examine the design and efficacy of published interventions to improve adherence and persistence. METHODS: We searched medical literature databases for English-language papers published between January 1990 and July 2008. We selected papers that described interventions and provided results for control and intervention subjects. We assessed the design and methods of each study, including randomization, blinding, and reporting of drop-outs. We summarized the results and calculated effect sizes for each trial. RESULTS: Seven studies met eligibility requirements and were included in the review. Five of the seven studies provided adherence data. Of those five studies, three showed a statistically significant (p < or = 0.05) improvement in adherence by the intervention group, with effect sizes from 0.17 to 0.58. Five of the seven studies provided persistence data. Of those five, one reported statistically significant improvement in persistence by the intervention group, with an effect size of 0.36. CONCLUSIONS: Few interventions were efficacious, and no clear trends regarding successful intervention techniques were identified in this small sample of studies. However, periodic follow-up interaction between patients and health professionals appeared to be beneficial.

Uric acid lowering therapy: prescribing patterns in a large cohort of older adults.

BACKGROUND: Uric acid lowering therapy (UALT) is considered a chronic treatment for gout. Relatively little is known about adherence to UALT. METHODS: We assessed adherence with UALT over a 1-year study period among 9823 older adults enrolled in a pharmacy benefit program. Two adherence measures were calculated, the percentage of days covered (PDC) and the time until an extended break (at least 60 days) in treatment. A PDC <80% was considered poor adherence and its predictors were examined in multivariable logistic models. RESULTS: The mean (SD) PDC was 54% (36%) with 64% of patients considered poorly compliant over the study period. A total of 56% had experienced an extended break in UALT. Predictors of poor adherence included younger age (odds ratio (OR) 1.50, 95% CI 1.33-1.69 for ages 65-74 compared with 85 and above) and African-American race (OR 1.86, 95% CI 1.52-2.27 compared with Caucasian race). Most patients (93%) received their initial UALT prescription from a non-specialist and this also predicted poor adherence (OR 1.15, 95% CI 0.96-1.38 compared with rheumatologists or nephrologists). CONCLUSION: Adherence with UALT is poor. While uric acid levels were not measured in this study, poor adherence with UALT is likely to reduce attainment of goal uric acid levels.

Use of risk stratification to identify patients with unstable angina likeliest to benefit from an invasive versus conservative management strategy.

OBJECTIVES: This study was designed to determine whether patient characteristics collected at presentation can identify which patients benefit from immediate coronary angiography and revascularization. BACKGROUND: Risk stratification may offer a method for identifying which patients with unstable angina or non-Q-wave myocardial infarction (NQMI) are likeliest to benefit from invasive management strategies. METHODS: The analysis was based on data from a randomized controlled trial that enrolled 1,473 patients presenting with unstable angina or NQMI who were randomly assigned to an early invasive or early conservative (medical) management strategy. We constructed a risk-stratification score for each patient based on adjusted odds ratios for clinical variables likely to predict adverse outcomes. We stratified all trial subjects by their risk scores and studied the rates of death or myocardial infarction (MI) of the early invasive management strategy in each stratum. RESULTS: The final multivariate model included older age, ST segment depression on presentation, history of complicated angina before presentation, and elevation in baseline creatine kinase-MB fraction. Although patients with a higher risk score had an increased rate of death or MI within 42 days and 365 days (p < 0.001) in both management strategies, early invasive management for patients in the high and very high risk categories was associated with a lower rate of death or MI within 42 days compared with conservative management. No such benefit was seen in patients in the larger group of patients in the very low, low or moderate risk categories (p = 0.03 for the interaction between risk category and management assignment). CONCLUSIONS: Risk stratification may be an effective method for identifying those patients with unstable angina or NQMI most likely to benefit from early invasive management. Selective use of early invasive management can have a substantial impact in reducing morbidity and mortality in higher risk patients, but may not be warranted in lower risk patients.

The neglected medical history and therapeutic choices for abdominal pain. A nationwide study of 799 physicians and nurses.

A random national sample of 501 physicians and 298 nurse practitioners was presented a case vignette describing a patient with epigastric pain and endoscopy showing diffuse gastritis. Respondents were encouraged to request further information and then were asked for recommendations. History available if requested included substantial use of aspirin, coffee, cigarettes, and alcohol, and severe psychosocial stress. More than one third of the physicians chose to initiate therapy without seeking a relevant history. Nearly half of all physicians indicated that a prescription would be the single most effective therapy; 65% recommended a histamine antagonist. By contrast, only 19% of nurse practitioners opted to treat without taking further history; the nurse sample asked an average of 2.6 questions vs 1.6 for physicians; only 20% of the nurses recommended a prescription medication. These findings raise concerns about the adequacy of basic history taking in this setting and the underuse of nonpharmacologic approaches in favor of excessive reliance on prescription drugs, even when not indicated by clinical circumstances.

Anticholinergic drug use and bowel function in nursing home patients.

BACKGROUND: We sought to measure the relationship between the use of anticholinergic drugs and bowel dysfunction in nursing home patients. METHODS: The study population consisted of 800 residents (average age, 84.7 years; range, 65 to 105 years) from 12 intermediate-care facilities in Massachusetts. Patient characteristics and actual medication use were documented during a 1-month observation period. Neuropsychological and functional testing was performed on all residents receiving psychoactive medications. Constipation was assessed by measuring the frequency of laxative use. RESULTS: Laxatives were used daily by 74% of residents; 45% received more than one laxative a day. After adjusting for potential confounding by logistic regression modeling, we found that daily laxative use was significantly more common in residents taking highly anticholinergic antidepressants such as amitriptyline (odds ratio, 3.12), diphenhydramine (odds ratio, 2.18), highly anticholinergic neuroleptics such as thioridazine (odds ratio, 2.01), and in the very old (odds ratio, > or = 85 years = 2.23). Gender, decreased functional status, impaired cognitive function, and the use of benzodiazepines or antiparkinsonian agents were not associated with increased use of laxatives. CONCLUSIONS: A strong association exists in institutionalized elderly between the use of specific anticholinergic medications and constipation, as reflected in the increased use of laxatives. This effect was not seen with nonanticholinergic sedatives, nor was it explained by the patients' cognitive or functional status. These drugs may be responsible for substantial iatrogenic effects on bowel function in elderly patients.

Cardiovascular responses to phlebotomy and sitting in middle-aged and elderly subjects.

BACKGROUND: Responding appropriately to hypotensive challenges is an important determinant of health and functional independence in elderly individuals. Cardiovascular responses to phlebotomy and postural change were evaluated using a large database developed in a study designed to establish the safety of blood donation by older individuals. METHODS: The groups studied included 464 subjects aged 65 years and younger (range, 52 to 65 years) and 532 subjects more than 65 years old (range, 66 to 78 years old). Blood pressure and pulse rate measurements were followed by the withdrawal of 500 mL of blood. These measurements were repeated, first in the supine and then in the sitting position. RESULTS: Nearly all individuals studied remained hemodynamically stable after these two challenges. Age was not an independent predictor of blood pressure change after either phlebotomy or postural change. Large decreases in diastolic blood pressure were equally rare in both age groups. However, more older subjects (15.2%) exhibited a decline of 20 mm Hg or more in systolic blood pressure following phlebotomy, compared with the middle-aged group (6.9%). These age-related differences did not persist after controlling for the higher initial systolic blood pressures observed in the older subjects. Postphlebotomy postural change to the sitting position had little additional effect. CONCLUSIONS: These results indicate that the ability to respond to hypovolemia and postural change remains relatively intact in healthy elderly individuals. The higher prevalence of a significant drop in systolic blood pressure after phlebotomy, orthostasis, and possibly other homeostatic challenges in older subjects is probably due to the presence of higher basal blood pressure readings, including hypertension. In spite of these differences, blood donation is appropriate and should be encouraged in healthy elderly individuals in this age group.

Overmedication of the low-weight elderly.

This study analyzes age, weight, and drug doses using cimetidine hydrochloride, flurazepam hydrochloride, and digoxin as tracers. Data were obtained for 1797 patients (mean age, 72 years) filling consecutive prescriptions from a national pharmacy service. With all three drugs, patients with lower weight received substantially higher doses with correlations of weight vs dose, based on milligrams per kilogram of body weight, ranging from -0.34 to -0.40. Because body weight declines with increasing age, lower-weight patients are also older and at greatest risk for drug toxicity. Patients weighing 50 kg or less (n = 155) received milligram-per-kilogram doses that were 31% to 46% higher than the group mean and 70% to 88% higher than patients weighing more than 90 kg. For all three study drugs, as patient weight declines, the mean milligram-per-kilogram dose rose sharply. There was no trend seen toward reducing doses for older patients. Low body weight, in addition to advanced age, is a major risk factor for overmedication. Physicians must recognize the need to reduce drug doses for their low-weight elderly patients.

Atrial fibrillation and stroke prevention with warfarin in the long-term care setting.

BACKGROUND: While the benefits of warfarin sodium therapy for stroke prevention in patients with atrial fibrillation (AF) have been extensively documented, generalizing clinical trial results to the majority of elderly persons with AF, especially to those who reside in the long-term care setting, remains challenging. OBJECTIVES: To determine the prevalence of AF in the institutionalized elderly population and the proportion receiving anticoagulation therapy with warfarin: to identify the clinical and functional characteristics of institutionalized elderly persons with AF that are associated with the use of warfarin; and to assess the quality of prescribing and monitoring of warfarin therapy in institutionalized elderly persons with AF. METHODS: This study involved 30 long-term care facilities (total No. of beds, 6437) located in New England, Quebec, and Ontario. The proportion of patients with AF who were receiving treatment with warfarin was determined. The association between clinical and functional characteristics and the use of warfarin was examined with crude and multivariable-adjusted analyses. For study subjects with at least 2 weeks of warfarin therapy during the 12-month period preceding the date of medical record abstraction, we assessed the quality of warfarin prescribing based on all international normalized ratio or prothrombin time ratio values during this period. RESULTS: An electrocardiogram indicating AF was present in the records of 413 of 5500 long-term care residents (7.5%); 32% of such patients were being treated with warfarin. Only a history of stroke was found to be positively associated with the use of warfarin in this setting. Patients with a diagnosis of dementia and those in the oldest age group (> or = 85 years) were less likely to receive warfarin therapy. Warfarin was commonly prescribed to patients with a history of bleeding, substantial comorbidity and functional impairment, a history of falls, or concomitant potentiating drug therapy. Patients were maintained above or below the recommended therapeutic range 60% of the time. CONCLUSIONS: Atrial fibrillation is common in patients residing in long-term care facilities, but its management with warfarin is highly variable. A more systematic approach to decision making regarding the use of warfarin for stroke prevention in these patients is required. Among patients receiving warfarin, the quality of anticoagulation care warrants improvement.

Clinical assessment of extrapyramidal signs in nursing home patients given antipsychotic medication.

BACKGROUND: We sought to quantify the relationship between antipsychotic drug use and clinical evidence of extrapyramidal dysfunction in a large population of elderly nursing home patients. METHODS: Subjects were 251 residents (mean age, 84.1 years; range, 65 to 105 years) who were taking psychoactive drugs in 12 long-term care facilities. Patient characteristics and all medication use (both scheduled and as needed) were measured during a 1-month observation period. We then performed neuropsychological and functional testing on residents who received any psychoactive medications during the study month. The presence of rigidity, bradykinesia, or masklike facies was assessed in each patient by a research assistant who was unaware of diagnoses and medication use. RESULTS: The parkinsonian signs studied were found in 127 (50.6%) of these residents. Using logistic regression modeling to adjust for potential confounding, we found this outcome to be increased more than threefold in patients who took low-potency neuroleptics (odds ratio [OR], 3.49 for > or = 50 mg/d of chlorpromazine-type drugs; 95% confidence interval [CI], 1.28 to 9.57) and more than sixfold for use of 1 mg/d or more of haloperidol (OR, 6.42; 95% CI, 2.16 to 19.04). Age, gender, and use of nonneuroleptic psychoactive drugs were not associated with an increase in parkinsonian signs. CONCLUSIONS: Clinical evidence of extrapyramidal dysfunction is three to six times more common in institutionalized elderly patients given antipsychotic medication than in comparable patients not using such drugs. Its risk is substantially increased even in patients given low-potency chlorpromazine-type drugs, as well as those taking haloperidol. The effect is not explained by age or mental status and is not seen with other psychoactive medications. The expected frequency of parkinsonian symptoms can help to inform the balancing of risks vs therapeutic effect when the use of all drugs in this class is considered.

Noncompliance with congestive heart failure therapy in the elderly.

BACKGROUND: Noncompliance with long-term medication regimens, such as those employed in the treatment of congestive heart failure (CHF), has been found to be approximately 50%. However, no evaluation has been performed on a population-based cohort of elderly patients beginning the use of digoxin and followed up longitudinally for an extended observation period. METHODS: To study patterns of medication compliance, we conducted a retrospective follow-up of 7247 outpatients aged 65 to 99 years newly prescribed digoxin between 1981 and 1991, with the use of the complete prescription claims file of the New Jersey Medicaid program. Noncompliance was measured in terms of the number of days during the 12-month period after an initial digoxin prescription in which no CHF medication was available to the patient. RESULTS: Patients started on a regimen of digoxin were without digoxin or any other common alternative CHF drug for an average of 111 of the 365 days of follow-up. Only 10% of the population filled enough prescriptions to have daily CHF medication available for the entire year of follow-up. Compliance rates were higher in patients over 85 years of age, women, those taking multiple medications, and those with hospital or nursing home stays before the initiation of therapy. CONCLUSIONS: A large proportion of patients who begin digoxin therapy end CHF therapy or consume substantially less medication than expected in the first year of therapy. Such high rates of cessation could represent an important impediment to effective CHF therapy.

Bowel habit in relation to age and gender. Findings from the National Health Interview Survey and clinical implications.

BACKGROUND: Constipation is widely considered to be a common problem among the elderly, as evidenced by the high rate of laxative use in this population. Yet, age-related prevalence studies of constipation generally do not distinguish between actual alteration in bowel movement frequency and subjective self-report of constipation. OBJECTIVE: To determine the relationship between advancing age and bowel habit. METHODS: We employed data collected on 42,375 subjects who participated in the National Health Interview Survey on Digestive Disorders based on interviews with a random nationwide sample of US households. We examined the following characteristics reported by this population according to selected age groupings by decade: constipation, levels of laxative use, and two bowel movements per week or less. RESULTS: Contrary to conventional wisdom, there was no age-related increase in the proportion of subjects reporting infrequent bowel movements. Nonetheless, the prevalence of self-report of constipation increased with advancing age, with a greater proportion of women reporting this symptom than men across all age groups. Laxative use also increased substantially with aging; while women were more likely to use laxatives than men, this effect attenuated with advancing age. A U-shaped relationship was observed between advancing age and bowel habit in men and women; 5.9% of individuals younger than 40 years reported two bowel movements per week or less compared with 3.8% of those aged 60 to 69 years and 6.3% of those aged 80 years or older. This relationship persisted after adjusting for laxative use. CONCLUSION: These findings suggest that a decline in bowel movement frequency is not an invariable concomitant of aging. In elderly patients who report being constipated, it is essential to take a careful physical, psychological, and bowel history rather than to automatically assume the need for laxative use.

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.

Reduction of incorrect antibiotic dosing through a structured educational order form.

Antibiotics are often used inappropriately in hospitals. We created a structured antibiotic order form designed to guide physicians toward correct therapeutic decisions without restricting their clinical options. Educational messages and graphic reminders were incorporated into a new form required to order parenteral antibiotics at a teaching hospital. Pharmacokinetic considerations were emphasized. The forms were supplemented with brief literature reviews and appropriate references. Before introduction of the form, pharmacokinetically incorrect orders for clindamycin, cefazolin sodium, and metronidazole hydrochloride accounted for 90%, 60%, and 75% of patient-days of therapy for these drugs, respectively. Immediately after implementation of the form, nonrecommended dosing schedules dropped to under 6% of patient-days for all three antibiotics. Savings from these drugs alone accounted for over $76,000 annually. We conclude that in a period of increasing constraints on hospital budgets and proliferating restrictions on physicians' clinical choices, educational intervention at the time orders are written can provide a cost-effective and noncoercive means of improving some forms of acute-care clinical decision making.

Risk factors for adverse drug events among nursing home residents.

BACKGROUND: In a prospective study of nursing home residents, we found adverse drug events (ADEs) to be common, serious, and often preventable. To direct prevention efforts at high-risk residents, information is needed on resident-level risk factors. METHODS: Case-control study nested within a prospective study of ADEs among residents in 18 nursing homes. For each ADE, we randomly selected a control from the same home. Data were abstracted from medical records on functional status, medical conditions, and medication use. RESULTS: Adverse drug events were identified in 410 nursing home residents. Independent risk factors included being a new resident (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.5-5.2) and taking anti-infective medications (OR, 4.0; CI, 2.5-6.2), antipsychotics (OR, 3.2; CI, 2.1-4.9), or antidepressants (OR, 1.5; CI, 1.1-2.3). The number of regularly scheduled medications was associated with increased risk of ADEs; the OR associated with taking 5 to 6 medications was 2.0 (CI, 1.2-3.2); 7 to 8 medications, 2.8 (CI, 1.7-4.7); and 9 or more, 3.3 (CI, 1.9-5.6). Taking supplements or nutrients was associated with lower risk (OR, 0.42; CI, 0.27-0.63). Preventable ADEs occurred in 226 residents. Independent risk factors included taking opioid medications (OR, 6.6; CI, 2.3-19.3), antipsychotics (OR, 4.0; CI, 2.2-7.3), anti-infectives (OR, 3.0; CI, 1.6-5.8), antiepileptics (OR, 2.2; CI, 1.1-4.5), or antidepressants (OR, 2.0; CI, 1.1-3.5). Scores of 5 or higher on the Charlson Comorbidity Index were associated with increased risk of ADEs (OR, 2.6; CI, 1.1-6.0). The number of regularly scheduled medications was also a risk factor: the OR for 7 to 8 medications was 3.2 (CI, 1.4-6.9) and for 9 or more, 2.9 (CI, 1.3-6.8). Residents taking nutrients or supplements were at lower risk (OR, 0.27; CI, 0.14-0.50). CONCLUSIONS: It is possible to identify nursing home residents at high risk of having an ADE. Particular attention should be directed at new residents, those with multiple medical conditions, those taking multiple medications, and those taking psychoactive medications, opioids, or anti-infective drugs.

Academic detailing to improve use of broad-spectrum antibiotics at an academic medical center.

BACKGROUND: Antibiotic misuse is common and costly and may promote antibiotic resistance. We tested the efficacy of a targeted one-on-one educational program ("academic detailing") designed to improve the appropriateness of broad-spectrum antibiotic use. METHODS: A randomized controlled trial was conducted in a large US teaching hospital. During an 18-week study period, 17 general medical, oncology, and cardiology services either received academic detailing or did not. The intervention was prompted by an order for either levofloxacin or ceftazidime that led to a computer-based review of data for that patient. Orders for the 2 target antibiotics deemed unnecessary by a priori criteria were included in the study. The primary outcome examined was the number of days that unnecessary levofloxacin or ceftazidime was administered in intervention and control groups. RESULTS: Before the trial, intervention and control services had similar prescribing patterns for the target antibiotics; the drugs were used for similar indications throughout the study period. During the intervention, there was a reduction of 37% in days of unnecessary levofloxacin or ceftazidime use per 2-week interval on services randomized to the educational intervention vs control services (P< .001). In multivariable analyses controlling for baseline prescribing and study interval, the rate of unnecessary use of the 2 target antibiotics was reduced by 41% on the intervention services compared with controls (95% confidence interval, 44%-78%; P< .001). Length of stay, intensive care unit transfers, readmission rates, and in-hospital death rates were similar in both groups (P> or =.10 for all). CONCLUSION: Targeted one-on-one education is a practical, effective, and safe method for reducing excessive broad-spectrum antibiotic use.

Are risk evaluation and mitigation strategies associated with less off-label use of medications? The case of immune thrombocytopenia.

Using data from a large commercial health insurer, we studied prescribing of romiplostim (Nplate) and eltrombopag (Promacta), two drugs for primary immune thrombocytopenia (ITP) for which risk evaluation and mitigation strategies (REMS) with elements to assure safe use were initially imposed and then removed. We identified 103 and 117 new users of romiplostim and eltrombopag, respectively. Use was almost exclusively for FDA-approved indications ("on-label") while the REMS with elements to assure safe use were in place. After these elements were lifted, off-label use of eltrombopag among patients with hepatitis C virus (HCV), a subsequently approved indication, increased. The ratio of incidence rate ratios of off-label/HCV to on-label initiation of eltrombopag between the two time periods was significant (13.41; P < 0.001). Our finding of an association with reduced off-label prescribing suggests that REMS with elements to assure safe use can help promote patient safety but may also prevent promising off-label drug uses.

A randomized trial of an education and support program for HIV-infected individuals.

OBJECTIVES: To assess the effectiveness of an intervention for providing information and support to HIV-positive donors on changes in their sexual behavior, and to assess which donor characteristics are predictive of behavior change. DESIGN: Subjects were randomly assigned to a structured intervention or community referral group. Follow-up assessments were conducted every 6 months. SETTING: New York City, New York, USA. PARTICIPANTS: A cohort of 271 HIV-infected persons who donated blood to the New York Blood Center. INTERVENTION: Donors randomized to the structured intervention program met individually with a nurse for counseling and were offered a six-session support group. The program was designed to provide information, encourage safer sexual behavior and provide support. MAIN OUTCOME MEASURES: Sexual behavior, psychological distress and psychological help seeking, and immune function. RESULTS: In both groups there was a large decrease over time in reports of unsafe sexual activity. However, more than 30% of participants in both groups reported unsafe sexual activity at the 1-year follow-up visit. Donors randomized to the structured intervention program did not report significantly more behavior change at the 1-year follow-up. CONCLUSIONS: Better programs to promote behavior change in seropositive individuals are needed.

Trends in medication choices for hypertension in the elderly. The decline of the thiazides.

We studied the evolution in choice of antihypertensive therapy in the elderly over a seven-year period and defined factors associated with such prescribing. To accomplish this, we performed a retrospective analysis of 8428 enrollees older than 65 years of age in the New Jersey Medicaid and Medicare programs newly begun on antihypertensive therapy between 1982 and 1988. Diuretics were the most common agents prescribed (51%), followed by calcium channel blockers (14%), beta-blockers (13%), central adrenergic antagonists (11%), and angiotensin-converting enzyme inhibitors (5%). However, the use of diuretics declined sharply during the latter part of the time interval studied. Using logistic regression modeling, we determined that the odds of a subject being started on a diuretic compared with any other antihypertensive drug decreased from 1.0 during the referent years 1982 to 1984 to 0.75 in 1985 to 1986 and to 0.41 in 1987 to 1988, after controlling for demographics, comorbidity, and hospital and physician visits (P < .001). The relative odds of diuretic use were significantly increased (P < .05) for the oldest subjects (odds ratio, 1.28 for age 85 and older versus ages 65 to 74 odds), women (odds ratio, 1.15), and blacks (odds ratio, 1.14). Despite the growing evidence during the study interval of the efficacy of diuretics in treating hypertension in the elderly, diuretic use diminished throughout this period in relation to other antihypertensive drugs. Subject characteristics (oldest subjects, women, and blacks) were important determinants of physicians' choice of antihypertensive therapy.