Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels.

CONTEXT: Aging in men is associated with reduced testosterone (T) levels and physiological changes leading to frailty, but the benefits of T supplementation are inconclusive. OBJECTIVE: We studied the effects of T supplementation with and without progressive resistance training (PRT) on functional performance, strength, and body composition. DESIGN, SETTING, AND PARTICIPANTS: We recruited 167 generally healthy community-dwelling older men (66 ± 5 years) with low-normal baseline total T levels (200-350 ng/dL). INTERVENTION: Subjects were randomized to placebo or transdermal T gel [2 doses targeting either a lower (400-550 ng/dL) or higher (600-1000 ng/dL) T range] and to either PRT or no exercise for 12 months. MAIN OUTCOME MEASURE: The primary outcome was functional performance, whereas secondary outcomes were strength and body composition. RESULTS: A total of 143 men completed the study. At 12 months, total T was 528 ± 287 ng/dL in subjects receiving any T and 287 ± 65 ng/dL in the placebo group. In the PRT group, function and strength were not different between T- and placebo-treated subjects, despite greater improvements in fat mass (P = .04) and fat-free mass (P = .01) with T. In the non-PRT group, T did not improve function but improved fat mass (P = .005), fat-free mass (P = .03), and upper body strength (P = .03) compared with placebo. There were fewer cardiovascular events in the T-treated groups compared with placebo. CONCLUSIONS: T supplementation was well tolerated and improved body composition but had no effect on functional performance. T supplementation improved upper body strength only in nonexercisers compared with placebo.

Impact of a multidisciplinary intervention on antibiotic use for nursing home-acquired pneumonia.

BACKGROUND: Academic detailing in nursing homes (NHs) has been shown to improve drug use patterns and adherence to guidelines. OBJECTIVE: The purpose of this study was to evaluate the impact of a multidisciplinary intervention that included academic detailing on adherence to national nursing home-acquired pneumonia (NHAP) guidelines related to use of antibiotics. METHODS: This quasi-experimental study evaluated the effects of a 2-year multifaceted and multidisciplinary intervention targeting implementation of national evidence-based guidelines for NHAP. Interventions took place in 8 NHs in Colorado; 8 NHs in Kansas and Missouri served as controls. Interventions included (1) educational sessions for nurses to improve recognition and timely treatment of NHAP symptoms and (2) academic detailing to clinicians by pharmacists regarding diagnostic and prescribing practices. Differences in antibiotic use between groups were compared after 2 intervention years relative to baseline. RESULTS: A total of 549 episodes of NHAP were evaluated in the intervention group and 574 in the control group. Compared with baseline, 1 facility in the intervention group significantly improved in guideline adherence for optimal antibiotic use (P = 0.007), whereas no facilities in the control group improved. The mean adherence score for optimal antibiotic use in intervention NHs increased from 60% to 66%, whereas the control NHs increased from 32% to 39% (P = 0.3). Mean adherence to guidelines recommending antibiotic use within 4 hours of NHAP diagnosis increased from 57% to 75% in intervention NHs but decreased from 38% to 31% in control NHs (P = 0.0003 for difference). There was no difference between intervention and control NHs for guideline adherence regarding optimal duration of antibiotic use. CONCLUSIONS: The ability of this multifaceted study to repeatedly remind nursing staff of the importance of timely antibiotic administration contrasts with its limited academic detailing interaction with clinicians. This difference within the intervention may explain the differential impact of the intervention on antibiotic guideline adherence.

Older adults with multi-morbidity: medication management processes and design implications for personal health applications.

BACKGROUND: Older adults often have multiple chronic problems requiring them to manage complex medication regimens overseen by various clinicians. Personal health applications (PHAs) show promise assisting in medication self-management, but adoption of new computer technologies by this population is challenging. Optimizing the utility of PHAs requires a thorough understanding of older adults' needs, preferences, and practices. OBJECTIVE: The objective of our study was to understand the medication self-management issues faced by older adults and caregivers that can be addressed by an electronic PHA. METHODS: We conducted a qualitative analysis of a series of individual and group semistructured interviews with participants who were identified through purposive sampling. RESULTS: We interviewed 32 adult patients and 2 adult family caregivers. We identified 5 core themes regarding medication self-management challenges: seeking reliable medication information, maintaining autonomy in medication treatment decisions, worrying about taking too many medications, reconciling information discrepancies between allopathic and alternative medical therapies, and tracking and coordinating health information between multiple providers. CONCLUSIONS: This study provides insights into the latent concerns and challenges faced by older adults and caregivers in managing medications. The results suggest that PHAs should have the following features to accommodate the management strategies and information preferences of this population: (1) provide links to authoritative and reliable information on side effects, drug interactions, and other medication-related concerns in a way that is clear, concise, and easy to navigate, (2) facilitate communication between patients and doctors and pharmacists through electronic messaging and health information exchange, and (3) provide patients the ability to selectively disclose medication information to different clinicians.

A multifaceted intervention to implement guidelines did not affect hospitalization rates for nursing home-acquired pneumonia.

OBJECTIVE: Determine whether a comprehensive approach to implementing national consensus guidelines for nursing home-acquired pneumonia (NHAP) affected hospitalization rates. DESIGN: Quasi-experimental, mixed-methods, multifaceted, unblinded intervention trial. SETTING: Sixteen nursing homes (NHs) from 1 corporation: 8 in metropolitan Denver, CO; 8 in Kansas and Missouri during 3 influenza seasons, October to April 2004 to 2007. PARTICIPANTS: Residents with 2 or more signs and symptoms of systemic lower respiratory tract infection (LRTI); NH staff and physicians were eligible. INTERVENTION: Multifaceted, including academic detailing to clinicians, within-facility nurse change agent, financial incentives, and nursing education. MEASUREMENTS: Subjects' NH medical records were reviewed for resident characteristics, disease severity, and care processes. Bivariate analysis compared hospitalization rates for subjects with stable and unstable vital signs between intervention and control NHs and time periods. Qualitative interviews were analyzed using content coding. RESULTS: Hospitalization rates for stable residents in both NH groups remained low throughout the study. Few critically ill subjects in the intervention NHs were hospitalized in either the baseline or intervention period. In control NHs, 8.7% of subjects with unstable vital signs were hospitalized during the baseline and 33% in intervention year 2, but the difference was not statistically significant (P = .10). Interviews with nursing staff and leadership confirmed there were significant pressures for, and enablers of, avoiding hospitalization for treatment of acute infections. CONCLUSIONS: Secular pressures to avoid hospitalization and the challenges of reaching NH physicians via academic detailing are likely responsible for the lack of intervention effect on hospitalization rates for critically ill NH residents.

Impact of NHAP guideline implementation intervention on staff and resident vaccination rates.

OBJECTIVES: Determine whether a comprehensive approach to implementing national consensus guidelines for nursing home acquired pneumonia (NHAP), including influenza and pneumococcal vaccination, improves resident subject and staff vaccination rates. METHODS: Quasi-experimental, mixed-methods multifaceted intervention trial conducted at 16 nursing homes (NHs) from 1 corporation (8 in metropolitan Denver, Colorado; 8 in Kansas and Missouri) during 3 influenza seasons, October to April 2004 to 2007. Residents with 2 or more signs and symptoms of systemic lower respiratory tract infection (LRTI) and NH staff and physicians were eligible. Subjects' NH records were reviewed for vaccination. Each director of nursing (DON) completed a questionnaire assessing staffing and the number of direct care staff vaccinated against influenza. DONs and study liaison nurses were interviewed after the intervention. Bivariate analysis compared vaccination outcomes and covariates between intervention and control homes, and risk-adjusted models were fit. Qualitative interview transcripts were analyzed using content coding. RESULTS: No statistically significant relationship between the intervention and improved resident vaccination rates was found, so other factors associated with improved rates were explored. Estimated direct patient care staff vaccination rates were better during the baseline and improved more in the intervention NHs. Qualitative results suggested that facility-specific factors and national policy changes impacted vaccination rates. CONCLUSIONS: External factors influence staff and resident vaccination rates, diluting the potential impact of a comprehensive program to improve care for NHAP on vaccination.

Inappropriate prescribing in the hospitalized elderly patient: defining the problem, evaluation tools, and possible solutions.

Potentially inappropriate medication (PIM) prescribing in older adults is quite prevalent and is associated with an increased risk for adverse drug events, morbidity, and utilization of health care resources. In the acute care setting, PIM prescribing can be even more problematic due to multiple physicians and specialists who may be prescribing for a single patient as well as difficulty with medication reconciliation at transitions and limitations imposed by hospital formularies. This article highlights critical issues surrounding PIM prescribing in the acute care setting such as risk factors, screening tools, and potential strategies to minimize this significant public health problem.

Challenges of treatment adherence in older patients with Parkinson's disease.

Patient adherence to a medication regimen is critical to treatment outcome, quality of life and future healthcare costs. For elderly patients with Parkinson's disease, obstacles to adherence can be particularly complex. Beyond age-related and economic factors, elderly patients with Parkinson's disease often require complicated dosing or titration schedules and have multiple co-morbidities that necessitate administration of therapies from multiple drug classes. In addition, neuropsychiatric disturbances and cognitive impairment, which are often part of the disease process, can affect adherence, as can variable responses to anti-parkinsonian agents as the disease progresses. Several recent studies in patients with Parkinson's disease point to the need for establishing good adherence patterns early and maintaining these throughout the course of treatment. To achieve optimal adherence in elderly patients with Parkinson's disease, a combination of pharmacological and non-pharmacological approaches appears to be the best strategy for success. Examples include a strong provider-patient relationship, educational intervention by phone or face-to-face contact, simplified dosing and administration schedules, management and understanding of medication adverse events, and the use of adherence aids such as pill boxes and hour-by-hour organizational charts. Research into new avenues that include improved drug monitoring, pharmacogenetics and neuroprotective regimens may give rise to better adherence in elderly patients with Parkinson's disease in the future.

Elucidating the mechanism of action and potential interactions of MAO-B inhibitors.

A critical enzyme in neurotransmitter metabolism is monoamine oxidase (MAO). MAO occurs in two isoforms, MAO-A and MAO-B. MAO inhibitors are classified as selective for a particular subtype of MAO or nonselective and can be reversible or irreversible. Nonselective MAO inhibitors originally were studied as antidepressants. Newer MAO-B selective irreversible inhibitors are indicated for use in treatment of Parkinson's disease. MAO-B inhibitors offer modest antiparkinsonian effects, as they do not inhibit brain MAO-A effectively at the dose used in treating Parkinson's disease. In this article, the mechanism of action of MAO-B inhibitors, their potential neuroprotective effects, interactions such as the cheese reaction, and serotonin syndrome are discussed.

Vitamin D intervention by pharmacists in geriatric outpatients.

OBJECTIVES: To develop a pharmacist-provided educational intervention that instructs participants to consume 1,200 IU vitamin D daily and to evaluate its effect on serum 25-hydroxyvitamin D (vitamin D) concentrations and self-reported daily vitamin D intake in geriatric outpatients with insufficient vitamin D. DESIGN: Randomized controlled trial. SETTING: University-affiliated geriatric clinic, December 2005 to May 2006. PATIENTS: 80 participants aged 65 to 89 years. INTERVENTION: Participants with insufficient vitamin D (12-31 ng/mL) were randomized to receive either the educational intervention (n = 23) or no intervention (n = 22). MAIN OUTCOME MEASURES: Difference in change from baseline to 12 weeks in vitamin D concentrations and self-reported daily vitamin D intake between groups. RESULTS: At 12 weeks, vitamin D concentrations in the educational intervention group (n = 22) increased from a mean (+/- SD) of 23.5 +/- 5.0 to 30.4 +/- 6.3 ng/mL. Vitamin D concentrations in the nonintervention group (n = 21) increased from 22.8 +/- 5.4 to 26.9 +/- 6.2 ng/mL. The difference between the groups at 12 weeks did not reach statistical significance (P = 0.07). However, 12 participants (55%) in the educational intervention group achieved sufficient vitamin D concentrations compared with only 5 participants (24%) in the nonintervention group (P = 0.04). Self-reported daily vitamin D intake increased by a mean of 647 IU/day in the educational intervention group and 67 IU/day in the nonintervention group. The difference in self-reported intake between groups at 12 weeks, controlling for baseline, was significant (P < 0.0001). Serum parathyroid hormone concentrations decreased significantly among those in the intervention group (P = 0.04). CONCLUSION: A pharmacist-developed and -administered vitamin D educational intervention increased the proportion of participants achieving sufficient vitamin D concentrations, increased the self-reported daily vitamin D intake, and lowered serum parathyroid hormone concentrations. However, it did not significantly increase the overall mean serum vitamin D concentration, compared with the control group. A daily recommendation of more than 1,200 IU vitamin D daily is likely necessary to ensure that all geriatric outpatients with insufficient vitamin D concentrations achieve the target of at least 32 ng/mL.

Restless legs syndrome induced by escitalopram: case report and review of the literature.

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by distressing sensations deep inside the limbs, typically occurring at bedtime or rest. These paresthesias involve an irresistible urge to move the limb, which provides temporary relief but at the expense of sleep and quality of life. The pathophysiology of RLS has been related to dopaminergic pathway dysfunction, thereby aligning it closely with depression from both pathophysiologic and treatment perspectives. Certain antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), may induce or exacerbate RLS. We describe the case of a 34-year-old woman with no history of RLS who came to the emergency department with acute decompensated heart failure. After 7 days of hospitalization, she was waitlisted to receive a heart transplant. Her mood became depressed, and she requested a psychiatric consultation; escitalopram 10 mg at bedtime was started. Within 2 days of starting therapy, she developed very severe (determined by a score based on an RLS symptom rating scale) RLS symptoms, warranting the discontinuation of escitalopram. Within 2 days of stopping therapy, her RLS symptoms improved considerably (rated as mild). One week later, the patient was rechallenged with a lower dose of escitalopram, and her very severe RLS symptoms reappeared. Within 2 days of stopping escitalopram, her RLS symptoms again improved, with complete resolution 1 week later. Using the Naranjo adverse drug reaction probability scale, which assesses the probability of a drug causing an adverse event, the patient's score was 9, indicating a definite adverse drug reaction. Although published case reports have linked fluoxetine, sertraline, citalopram, paroxetine, and mirtazapine to RLS, this is the first report, to our knowledge, of escitalopram as a cause of RLS. Based on this case and additional data published with other SSRIs and SNRIs, we believe that escitalopram should be added to the list of agents that can induce RLS.

Prevalence of vitamin D insufficiency in elderly ambulatory outpatients in Denver, Colorado.

BACKGROUND: Vitamin D insufficiency is common in the elderly. However, previous studies have utilized 25-hydroxvvitamin D (25[OH]D) concentrations as low as <16 ng/mL for defining vitamin D insufficiency. Moreover, most of the studies have been conducted in European patients, in certain geographic areas of the United States, or in institutionalized elderly. OBJECTIVE: The goal of this study was to characterize vitamin D concentrations in ambulatory elderly living in metropolitan Denver, Colorado, utilizing 25(OH)D concentrations <32 ng/mL as the definition for vitamin D insufficiency. METHODS: Ambulatory older adults (aged 65-89 years) with clinic visits during December 2005 and January 2006 were enrolled. Serum concentrations of 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, creatinine, and albumin were measured; height and weight were also measured. Data regarding dietary and over-the-counter vitamin D intake were collected, as well as information on body mass index, history of osteoporosis, osteoporosis treatment, and history of falls and fractures. RESULTS: Eighty patients (mean [SD] age, 77.8 [5.3] years; age range, 66-89 years) completed the study; there were no dropouts. The majority of patients were white (88%) and female (68%). Fifty-nine (74%) were found to have vitamin D insufficiency. Mean total and over-the-counter vitamin D intake was significantly higher in sufficient (P < 0.01) and insufficient (P < 0.05) patients compared with deficient patients, but dietary intake did not differ significantly between groups. The majority of patients who were vitamin D insufficient consumed more than the recommended 400 to 600 IU/d of vitamin D. Obese patients were found to have significantly lower 25(OH)D concentrations (P < 0.001) and higher PTH concentrations (P = 0.04) than nonobese patients. CONCLUSIONS: Vitamin D insufficiency is prevalent in ambulatory, and especially obese, elderly living in Denver, Colorado, despite vitamin D intake consistent with national recommendations. Dietary intake of vitamin D appeared to be unreliable to prevent insufficiency. Based on our results, along with other published data, we feel that national recommendations for vitamin D intake in the elderly should be increased to at least 800 to 1000 IU/d of over-the-counter supplemental cholecalciferol.

A multifaceted intervention to implement guidelines improved treatment of nursing home-acquired pneumonia in a state veterans home.

OBJECTIVES: To assess the feasibility of a multifaceted strategy to translate evidence-based guidelines for treating nursing home-acquired pneumonia (NHAP) into practice using a small intervention trial. DESIGN: Pre-posttest with untreated control group. SETTING: Two Colorado State Veterans Homes (SVHs) during two influenza seasons. PARTICIPANTS: Eighty-six residents with two or more signs of lower respiratory tract infection. INTERVENTION: Multifaceted, including a formative phase to modify the intervention, institutional-level change emphasizing immunization, and availability of appropriate antibiotics; interactive educational sessions for nurses; and academic detailing. MEASUREMENTS: Subjects' SVH medical records were reviewed for guideline compliance retrospectively for the influenza season before the intervention and prospectively during the intervention. Bivariate comparisons-of-care processes between the intervention and control facility before and after the intervention were made using the Fischer exact test. RESULTS: At the intervention facility, compliance with five of the guidelines improved: influenza vaccination, timely physician response to illness onset, x-ray for patients not being hospitalized, use of appropriate antibiotics, and timely antibiotic initiation for unstable patients. Chest x-ray and appropriate and timely antibiotics were significantly better at the intervention than at the control facility during the intervention year but not during the control year. CONCLUSION: Multifaceted, evidence-based, NHAP guideline implementation improved care processes in a SVH. Guideline implementation should be studied in a national sample of nursing homes to determine whether it improves quality of life and functional outcomes of this debilitating illness for long-term care residents.

The risk of adverse drug events and hospital-related morbidity and mortality among older adults with potentially inappropriate medication use.

BACKGROUND: Inappropriate medication prescribing is a significant problem among older adults that may contribute to increased morbidity and mortality as well as increased costs of care. The development of specific lists of medications that are considered potentially inappropriate for older adults, such as the Beers criteria (BC), make it relatively easy to study prescribing practices in large numbers of patients. OBJECTIVE: The goal of this study was to determine how frequently adverse drug events (ADEs) in the acute care setting are related to BC medications and to determine if BC medication prescribing is significantly associated with the occurrence of ADEs and other negative outcomes in older hospitalized adults. METHODS: This was a retrospective review of patients aged > or =75 years admitted to 2 adult internal medicine services over 18 months (March 2000-August 2001). Data regarding general demographic and clinical information were collected; this information included place of residence before admission and at discharge; medications at admission, during the hospital stay, and at discharge; ADEs; length of stay; and in-hospital mortality Patient medical records were used to determine the occurrence of ADEs. RESULTS: : A total of 389 patients (68.9% female; mean age, approximately 79 years) were included. Of these 389 eligible patients, 107 (27.5%) were prescribed a total of 116 BC medications, and 124 (31.9%) experienced a total of 131 ADEs. Only 9.2% (12/131) of the ADEs were attributed to medications listed among the BC. After controlling for covariates, prescription of a BC medication was not significantly associated with experiencing an ADE (adjusted odds ratio [OR], 1.51; 95% CI, 0.98-2.35; P = 0.064), length of stay (adjusted OR, 1.03; 95% CI, 0.64-1.63; P = 0.91), discharge to higher levels of care (adjusted OR, 1.39; 95% CI, 0.82-2.34; P = 0.22), or in-hospital mortality (adjusted OR, 1.49; 95% CI, 0.77-2.92; P = 0.24). CONCLUSIONS: Interventions targeted specifically at BC medications would have seemingly done little to change the risk of ADEs in this population. Interventions that are more comprehensive than the BC are necessary to reduce the risk of ADEs and the associated morbidity and mortality in acute care of the elderly.

Hydrochlorothiazide-induced angioedema in a patient allergic to sulfonamide antibiotics: evidence from a case report and a review of the literature.

BACKGROUND: Hypersensitivity reactions in patients receiving sulfonamide antibiotics have been frequently documented in the literature, but cross-reactivity with sulfonamide non-antibiotics rarely has been reported. CASE SUMMARY: An 82-year-old woman with a history of hypersensitivity reactions to sulfamethoxazole-trimethoprim resulting in angioedema and rash presented to the emergency department (ED) with angioedema and severe dysphagia, shortness of breath, and rash after receiving valsartan and hydrochlorothiazide (HCTZ) for 4 months. Valsartan was identified as the most likely cause of the symptoms and was discontinued; however, the patient continued to have weekly episodes of angioedema and eventually returned to the ED. HCTZ was discontinued at the second ED visit, and the angioedema disappeared. However, it reappeared after reinitiation of HCTZ, and the patient returned to the ED again; this time with more severe symptoms. After the third ED visit and second hospitalization, HCTZ was permanently discontinued, and the angioedema has not returned. HCTZ was the definite cause of angioedema in this patient based on a score of 9 on the 10-point Naranjo adverse drug reaction probability scale. CONCLUSIONS: Although the probability of true cross-reactivity is not known, clinicians should be aware that an allergic-like reaction to sulfonamide-containing non-antibiotics may occur in patients with known allergies to sulfonamide-containing antibiotics. These patients should be monitored closely when receiving these drugs. Further evaluation is needed to determine whether angioedema should be added to the list of adverse events associated with HCTZ.

Tumor necrosis factor-alpha and involuntary weight loss in elderly, community-dwelling adults.

STUDY OBJECTIVE: To evaluate the association between involuntary weight loss and serum concentrations of tumor necrosis factor (TNF)-alpha in elderly, community-dwelling adults. DESIGN: Cross-sectional, single-time point investigation. SETTING: Two primary care ambulatory clinics. SUBJECTS: Ambulatory adults aged 70 years or older with involuntary weight loss of 2.27 kg (5 lbs) or more, or with stable weight (+/-0.91 kg [2 lbs]) for the 3 months before enrollment. MEASUREMENTS AND MAIN RESULTS: Ten subjects with weight loss (mean+/-SD-4.9+/-2.6 kg) and 25 subjects with stable weight (+0.06+/-0.55 kg) were enrolled. The latter group was recruited to serve as a comparison group to the weight-loss group. Subjects donated a venous blood sample and were administered the Mini Nutritional Assessment at a single clinic visit. Serum concentrations of TNF-alpha were measured by using enzyme-linked immunosorbent assay. The TNF-alpha concentrations were significantly higher in subjects with weight loss (mean+/-SD 19.3+/-24.9 pg/ml) than in subjects with stable weight (mean+/-SD 1.1+/-2.0 pg/ml, p<0.01). No relationship was found between the TNF-alpha concentration and the degree of weight loss expressed as a percentage of total body weight. CONCLUSION: Older adults with involuntary weight loss had increased circulating concentrations of TNF-alpha. Whether TNF-alpha plays a causal role in involuntary weight loss among older adults is unclear; however, this finding is consistent with those in other disease states associated with cachexia. Further research is necessary to clarify this relationship and to determine if pharmacotherapeutic interventions targeted at TNF-alpha can prevent or reverse involuntary weight loss and its associated morbidity and mortality.

Update on the role of anticholinergic drug therapy in the management of overactive bladder.

OBJECTIVE: To review the published literature and describe the pathophysiology and management of overactive bladder (OAB), with emphasis on the comparative efficacy and adverse event profiles of anticholinergic agents approved for the management of OAB symptoms and evaluation of their place in therapy. DATA SOURCES: A MEDLINE search of English language literature that addresses the pathophysiology and management of OAB symptoms. The references in identified articles were evaluated for additional relevant articles. Drug Topics' Red Book was referenced for cost comparisons, and package inserts were used for specific drug and dosing information. STUDY SELECTION: Human studies that presented efficacy and safety data with respect to anticholinergic medications in the treatment of OAB were selected. DATA EXTRACTION: Studies were abstracted to identify key characteristics with respect to efficacy and safety in OAB, in particular anticholinergic side effects, with the greatest weight given to studies that compared two or more anticholinergic medications. DATA SYNTHESIS: Epidemiologic studies have shown that the unpredictable and bothersome symptoms associated with OAB occur in approximately 16% of the worldwide adult population. Conservative management of OAB should include a combination of pharmacologic and nonpharmacologic interventions that have been found to improve outcomes when used in appropriately selected patients. Although long recognized as the most effective pharmacotherapy for OAB, anticholinergic agents have been associated with poor tolerability attributable to anticholinergic adverse events. New medications, formulations, and drug delivery systems have been developed with the goal of achieving effective treatment with improved tolerability. CONCLUSIONS: Among these agents, extended-release and transdermal formulations have improved tolerability while retaining at least comparable efficacy. More research is needed regarding other routes of administration and new drug entities that specifically target the pathologic mechanisms involved in OAB.

A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults.

OBJECTIVE: Acid-suppressant drugs are commonly prescribed for elderly patients, a population in which vitamin B(12) deficiency is a common disorder. The purpose of this study was to examine the possible association between use of prescription histamine H-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) and vitamin B(12) deficiency in older adults. STUDY DESIGN AND SETTING: This was a case-control study in a University-based geriatric primary care setting. Among patients aged 65 years or older with documented serum vitamin B(12) studies between 1990 and 1997, 53 vitamin B(12)-deficient cases were compared with 212 controls for past or current use of prescription H2RA/PPI according to information in subjects' medical records. RESULTS: Controlling for age, gender, multivitamin use, and Helicobacter pylori infection, chronic (#10878;12 months) current use of H2RA/PPI was associated with a significantly increased risk of vitamin B(12) deficiency (OR 4.45; 95% CI 1.47-13.34). No association was found between past or short-term current use of H2RA/PPI and vitamin B(12) deficiency. CONCLUSION: These findings support an association between chronic use of H2RA/PPI by older adults and development of vitamin B(12) deficiency. Additional studies are needed to confirm these findings.

Possible heart failure exacerbation associated with rosiglitazone: case report and literature review.

Increasing evidence suggests that neurohumoral manifestations of heart failure may lead to insulin resistance, predisposing patients with heart failure to the development of glucose intolerance or worsening of existing diabetes. Theoretically, insulin-sensitizing thiazolidinediones (TZDs) should be beneficial in this patient population. A 74-year-old man with well-compensated systolic dysfunction and longstanding type 2 diabetes mellitus treated with glyburide began therapy with rosiglitazone 4 mg/day, which was increased to 8 mg/day after 1 month. Two weeks later he was seen with a 5-kg weight gain, shortness of breath, bibasilar rales, +S3 gallop, and increased jugular venous distention. Twelve days later symptoms worsened, with pulmonary edema on chest radiograph, continued weight gain, and +4 pitting edema resistant to oral diuretics. The patient was admitted to the hospital for exacerbation of heart failure. Five days after discharge he was readmitted for similar symptoms, including an 11.8-kg weight gain. He reported adherence to drug therapy and diet. Rosiglitazone was immediately discontinued and 11 days later the man's weight stabilized to 79 kg and remained between 79 and 80 kg 2 and 3 months after discharge. This case demonstrates that TZDs may precipitate weight gain and pulmonary and peripheral edema in patients with stable heart failure. Earlier reports documented similar symptoms in patients without a history of heart failure. Although current recommendations state that TZDs should not be administered to patients with New York Heart Association class III or IV disease, practitioners should be aware that these adverse effects also may occur in patients with milder forms heart failure as well as those without heart failure.

Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor.

OBJECTIVE: To report a case of vitamin B(12) deficiency associated with long-term use (approximately 4 1/2 y) of histamine(2) (H(2))-receptor antagonists and a proton-pump inhibitor (PPI) in a patient with gastroesophageal reflux. CASE SUMMARY: A 78-year-old nonvegetarian white woman with symptomatic gastroesophageal reflux (GER) was started on cimetidine 300 mg 4 times daily in February 1990 and took various other antisecretory medications over the course of the next 4 1/2 years. She had a normal serum vitamin B(12) concentration of 413 pg/mL in August 1992. In June 1994, her serum vitamin B(12) concentration was found to be in the low normal range at 256 pg/mL. Biochemical markers of vitamin B(12)-dependent enzyme activity were measured at that time, and methylmalonic acid (MMA) and homocysteine (HCYS) were elevated at 757 nmol/L and 27.3 micromol/L, respectively. Serum folate was within the normal range at 4.9 ng/mL, and serum creatinine was slightly elevated at 1.4 mg/dL. MMA and HCYS concentrations decreased dramatically with oral replacement of vitamin B(12) 1000 microg/d, which confirmed vitamin B(12) deficiency. Oral replacement also demonstrated that the woman was able to adequately absorb nonprotein-bound vitamin B(12) from the gastrointestinal tract, suggesting that her deficiency was a result of food-cobalamin malabsorption. The accumulation of MMA and HCYS was not a consequence of renal dysfunction, since both metabolites dramatically decreased with vitamin B(12) replacement. DISCUSSION: Malabsorption of dietary protein-bound vitamin B(12) has been demonstrated with the use of H(2)-receptor antagonists and PPIs. One previous case report of vitamin B(12) deficiency resulting from long-term use of omeprazole has been published. The malabsorption of dietary vitamin B(12) is thought to be a result of its impaired release from food protein, which requires gastric acid and pepsin as the initial step in the absorption process. CONCLUSIONS: The use of H(2)-receptor antagonists and/or PPIs may impair the absorption of protein-bound dietary vitamin B(12) and could contribute to the development of vitamin B(12) deficiency with prolonged use. Patients taking these medications for extended periods of time, particularly >4 years, should be monitored for vitamin B(12) status.