Unlabeled uses of botulinum toxins: a review, part 1.

PURPOSE: Efficacy and safety data regarding the unlabeled uses of botulinum toxins are reviewed, and the pharmacology, adverse effects, and characteristics of commercially available botulinum toxins are discussed. SUMMARY: More than 300 articles have been published on the use of botulinum toxins, particularly botulinum toxin type A, to treat conditions characterized by excessive smooth or skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium botulinum and cause temporary local paralysis of the injected muscle by inhibiting acetylcholine release at the neuromuscular junction. While botulinum toxins have Food and Drug Administration-approved labeling to treat a limited number of spasticity disorders, including cervical dystonia and blepharospasm, the toxins have more than 50 reported therapeutic uses. Among these uses, the most rigorously studied indications include achalasia, essential tremors, palmar hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity. The main adverse effects of the toxins are pain and erythema at the injection site, although unintended paralysis of muscles adjacent to the site of toxin injection may also occur. CONCLUSION: Clinical studies support the use of botulinum toxins for certain conditions, although more studies are needed to establish the role of the drug relative to conventional therapies and to determine patient predictors of response. Although botulinum toxins are generally well tolerated, a patient-specific risk-benefit assessment should precede any decision to use them for unlabeled indications.

Unlabeled uses of botulinum toxins: a review, part 2.

PURPOSE: Efficacy and safety data regarding the unlabeled uses of botulinum toxins are reviewed, and the pharmacology, adverse effects, and characteristics of commercially available botulinum toxins are discussed. SUMMARY: More than 300 articles have been published on the use of botulinum toxins, particularly botulinum toxin type A, to treat conditions characterized by excessive smooth or skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium botulinum and cause temporary local paralysis of the injected muscle by inhibiting acetylcholine release at the neuromuscular junction. While botulinum toxins have Food and Drug Administration-approved labeling to treat a limited number of spasticity disorders, including cervical dystonia and blepharospasm, the toxins have more than 50 reported therapeutic uses. Among these uses, the most rigorously studied indications include achalasia, essential tremors, palmar hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity. The main adverse effects of the toxins are pain and erythema at the injection site, although unintended paralysis of muscles adjacent to the site of toxin injection may also occur. CONCLUSION: Clinical studies support the use of botulinum toxins for certain conditions, although more studies are needed to establish the role of the drug relative to conventional therapies and to determine patient predictors of response. Although botulinum toxins are generally well tolerated, a patient-specific risk-benefit assessment should precede any decision to use them for unlabeled indications.

Assessment of factors influencing blood pressure control in a managed care population.

We attempted to determine the percentage of patients meeting Health Plan Employer Data Information Set (HEDIS) criteria for blood pressure control (< or = 140/90 mm Hg), to identify factors contributing to differences in blood pressure control among those who met HEDIS criteria and those who did not, and to assess compliance with blood pressure management recommendations established by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) for diabetes mellitus and myocardial infarction. In this retrospective analysis, we randomly selected 502 patient records from three primary care clinics in southeast Michigan. All patients were commercial members of one health maintenance organization, 74% of whom met HEDIS criteria for blood pressure control. These patients took fewer blood pressure drugs throughout the year (p=0.023) and had lower antihypertensive drug costs than those who did not achieve HEDIS blood pressure goals (p=0.016). According to JNC-VI criteria, 46% of diabetic patients were at their blood pressure goal of below 130/85 mm Hg and 71.6% were managed with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Eighty-five percent of patients were taking beta-blockers after myocardial infarction. The percentage of patients achieving target blood pressure exceeded the national average and was associated with few antihypertensive drugs and low drug cost. Effective and appropriate management of blood pressure in people with diabetes remains a challenge.

Detection of medication nonadherence through review of pharmacy claims data.

The utility of pharmacy claims data in detecting improper medication use, medication changes, and formulary adherence was assessed. Pharmacists provided six months of pharmacy claims data to primary care physicians for patients on the day of their scheduled clinic appointments. Similar data, not supplied to physicians, were generated for a matched population of patients on the day of their scheduled clinic appointments. A blinded pharmacist abstracter reviewed dictated office notes for both control and treatment groups. Medication adherence and medication changes were assessed by the abstracter as well as the difference in total medication costs for each of the groups before and after the pharmacy claims data were supplied. Surveys were distributed to physicians to determine whether pharmaceutical care was improved by the pharmacy claims data. In the treatment group, physicians detected medication nonadherence in 30.5% of their patients, while the abstracter noted nonadherence in 58.1% of patients. Physicians failed to detect any nonadherence in the control group, but the abstractor detected nonadherence in 57.1% of these patients. Changes in medication regimens occurred more often in the treatment group (p < 0.001). The mean percentage of patients switched to formulary agents significantly differed between the treatment and control groups (27.7% versus 0.0%, respectively) (p < 0.001). There were no differences in median drug costs for either group before or after the pharmacy claims data were provided. Provision of pharmacy claims data to physicians helped them detect medication nonadherence, evaluate therapeutic duplication or omissions, increase formulary use, and reduce the time required to obtain an accurate medication history.

The economic impact of irritable bowel syndrome in a managed care setting.

GOALS: To compare the healthcare resource consumption of patients who have irritable bowel syndrome (IBS) with an age-, gender-, and comorbidity-matched cohort of patients without IBS from a managed care perspective. STUDY: Retrospective cohort analysis. Data were obtained electronically through the Henry Ford Health System corporate data warehouse. Patients with IBS were eligible if they had at least one primary diagnosis of irritable colon (ICD-9-CM 564.1). The control cohort was identified from an age, gender, and comorbidity population-matched (5:1) sample. The index date for the IBS and control cohorts was defined as the first initial diagnosis and first clinical encounter in 1998, respectively. The charges per patient by resource use type were collected for the 12 months before and after the index date. RESULTS: A total of 501 patients with IBS and 2505 controls fulfilled the inclusion and exclusion criteria (70% female, 58% between 40 and 65 years). The IBS cohort, before the IBS diagnosis, had significantly higher total charges (p < 0.001), drug charges (p < 0.001), and outpatient charges (p < 0.001) than the control cohort. During the postindex (postdiagnosis period), the patients with IBS had higher total charges (p < 0.006), outpatient charges (p < 0.022), and drug charges (p < 0.001) than the control population. The control cohort had higher procedure charges (p < 0.001) during both periods. CONCLUSIONS: Patients with an IBS diagnosis represent a substantial cost to managed care before and after the diagnosis of IBS. Costs associated with these patients result mainly from non-IBS conditions. Further research is warranted to identify these patients earlier, and to prevent the economic burden associated with them.

Factors affecting medication adherence in hypertensive patients.

BACKGROUND: Adherence to medication is a critical factor in the continued health and well-being of patients with hypertension. Patients' acceptance of medical advice and information may be influenced by their subjective beliefs about their health condition; therefore, it is essential that their beliefs be taken into account when giving health advice or medical treatment. OBJECTIVE: To determine whether a relationship exists between illness attribution, perceived control, and adherence to antihypertensive medications. METHODS: A prospective, cross-sectional survey of hypertensive patients was conducted at the University of Michigan Medical Centers, Hypertension Clinic, Ann Arbor, MI. One hundred two patients with a goal to reduce their blood pressure were included in the study. Written and follow-up telephone survey questions assessing patients' illness attributions, perceived control, and medication adherence were administered. Associations between these variables were analyzed using correlation analyses. RESULTS: The majority of patients (67.7%) were adherent with their hypertensive medications. Patients indicated that modifiable variables were the most common attribution believed to cause hypertension; however, there was no significant relationship to medication adherence. A significant inverse relationship was found between perceived control over hypertension and medication adherence (p < 0.01). CONCLUSIONS: The findings suggest that patients' greater perception of control over trying to reduce blood pressure may result in decreased reliance on medications and subsequent nonadherence to drug therapy. Implications of these findings on pharmacy practice are discussed.