Barry J Gales

Relationship Between the Administration of Selected Medications and Falls in Hospitalized Elderly Patients

Objective: To examine the relationship between administration of selected medications and falls experienced by hospitalized elderly patients. Benzodiazepines and other medications previously associated with falls in elderly patients residing in the community and nursing homes were the primary focus. Design: Retrospective case control. Setting: Private, not-for-profit, 575-bed acute care hospital. Participants: A total of 100 patients who had fallen and 100 control patients, aged at least 70 years, admitted during the same 17-month time period. Main Outcome Measures: We examined the relationship between falls and patient demographics, underlying disease states, number of concurrent disease states, and length of hospitalization. Possible associations between the administration of narcotics, benzodiazepines, antidepressants, antipsychotics, other sedating agents, antihypertensives, diuretics, nitrates, and digoxin 48 hours prior to the fall or reference day were explored. The relationships between benzodiazepine half-life, dosage, administration frequency, cumulative dose, and falls were also examined. Results: Demographically the groups were similar except that patients who had fallen were hospitalized significantly longer (mean 18.8 vs 12.2 d; p < 0.00001) than control patients. Benzodiazepines were received by more (40% vs 20%, odds ratio = 2.67) patients who had fallen than control patients. The use of long (>24 h) half-life benzodiazepines was similar in patients who had fallen (48%) and control patients (45%). Long half-life benzodiazepines were commonly administered (65%) to patients who had fallen in doses greater than that recommended for the elderly. Benzodiazepine use, expressed as milligrams of diazepam equivalents received during the 48-hour study, was higher in patients who had fallen than in control patients (15.00 ± 17.80 vs 9.73 ± 6.58 mg), but this was not statistically significant (p = 0.1030). Congestive heart failure (37% vs 24%), digoxin therapy (35% vs 22%), or administration of 3 or more psychoactive agents (17% vs 4%) were all more common in patients who had fallen than in control patients. Conclusions: Falls experienced by the elderly patients in our acute care institution were associated with the presence of congestive heart failure along with digoxin therapy, benzodiazepine use, or the use of at least 3 psychoactive agents.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for the Prevention of Migraines

Objective: To evaluate the literature examining the efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for migraine prophylaxis. Data Sources: MEDLINE (1966–October 2009) and International Pharmaceutical Abstracts were searched using the terms migraine, headache, renina-ngiotensin system, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, aldosterone antagonist, and the individual agents in these classes. Study Selection and Data Extraction: English-language human clinical trials, case reports, and systematic reviews were evaluated for efficacy and safety data. The references of reviewed articles were examined to identify additional sources. Data Synthesis: Preventative trials evaluating ACE inhibitors consist of a case series, 2 open-label trials, and a placebo-controlled trial. Lisinopril reduced headache hours 20%, headache days 17%, and migraine days 21% versus placebo In the controlled trial (p < 0.06). Clinically significant (>50%) reductions in migraine measures were more common (52–66%) in open-label ACE inhibitor trials than in the controlled (32–36%) trial. Preventive trials evaluating ARBs consist of a meta-analysis, an open-label trial, and 2 placebo-controlled trials. Candesartan reduced headache hours 31%, headache days 26%, and migraine days 28% versus placebo in the first controlled trial (p ≤ 0.001). Telmisartan did not reduce any prespecified primary or secondary outcome measures in the second controlled trial. Clinically significant reductions (>50%) in migraine measures were more common (54–88%) in open-label ARB trials than in the controlled (26–38%) trials. A prescription database review found that ACE inhibitor or ARB therapy halved the use of abortive migraine agents compared to diuretic therapy. Conclusions: ACE inhibitors and ARBs have migraine prophylaxis activity similar to that of some currently utilized agents. Low-dose lisinopril or candesartan may be reasonable second- or third-line agents, particularly in patients with other indications for ACE inhibitor or ARB therapy. Further controlled clinical trials are needed to delineate the role of these agents in migraine prevention.

Pyridostigmine in the Treatment of Orthostatic Intolerance

Objective: To review the efficacy of pyridostigmine bromide for the treatment of orthostatic intolerance. Data Sources: MEDLINE and International Pharmaceutical Abstracts were searched (1966–December 2006) using the terms pyridostigmine, acetylcholinesterase inhibitor, orthostatic intolerance, orthostatic hypotension, neurogenic orthostatic hypotension, postural tachycardia syndrome, tachycardia, and orthostatic tachycardia. Study Selection and Data Extraction: Pertinent English-language human clinical trials, case reports, and background material were evaluated for safety and efficacy data. The references of reviewed articles were reviewed and used to identify additional sources. Data Synthesis: Pyridostigmine bromide has been associated with improved baroreceptor sensitivity and presents a novel approach to treatment of orthostatic intolerance. Four single-dose trials and a follow-up survey encompassing a total of 106 patients were identified. One open-label and one placebo-controlled single-dose trial in patients with neurogenic orthostatic hypotension (NOH) found statistically significant improvement in standing diastolic blood pressures (DBP). Absolute improvements in standing DBP were 3.7 and 6.4 mm Hg in the open-label and controlled trials, respectively. Long-term data consist of a single survey of patients receiving open-label pyridostigmine bromide. Twenty-nine percent of patients who initiated maintenance pyridostigmine bromide discontinued therapy. Concomitant NOH medications were taken by 75% of patients, and 85% of patients reported receiving benefit from pyridostigmine bromide. When evaluated for postural tachycardia syndrome, pyridostigmine bromide significantly reduced standing heart rate (10%). Pyridostigmine bromide significantly reduced symptom scores when compared with baseline but not placebo. The majority of patients included in these trials did not have supine hypertension. Conclusions: Single doses of pyridostigmine bromide produced modest but statistically significant improvements in hemodynamic measurements. At this time, long-term data are insufficient to support recommending the routine use of pyridostigmine bromide for treatment of orthostatic intolerance.

Phosphodiesterase-5 Inhibitors for Lower Urinary Tract Symptoms in Men

Objective: To review the efficacy of phosphodiesterase-5 (PDE-5) inhibitors for the treatment of lower urinary tract symptoms in men. Data Sources: MEDLINE and International Pharmaceutical Abstracts were searched (1970–August 2007) using the terms phosphodiesterase inhibitor, sildenafil, vardenafil, tadalafil, tower urinary tract symptoms, and benign prostatic hypertrophy. Study Selection and Data Extraction: English-language clinical trials, case reports, and background material were evaluated for safety and efficacy data. References of reviewed articles were examined and used to identify additional sources. Data Synthesis: Erectile dysfunction (ED) and lower urinary tract symptoms have numerous shared risk factors and are common in aging men. PDE-5 inhibitors may relax urinary tract smooth muscle tissue, which has led to interest in their utility for lower urinary tract symptoms. Six 12 week clinical trials were identified. Three uncontrolled trials (N = 158) examined the effects of on-demand sildenafil ED dosing on lower urinary tract symptoms. The 2 largest trials found that, the greater the ED response, the larger the reduction in lower urinary tract symptoms. A single prospective placebo-controlled trial (N = 369) studied sildenafil 100 mg daily in men with ED and lower urinary tract symptoms. Lower urinary tract symptoms improved significantly in the sildenafil group; patents with the worst lower urinary tract symptoms experienced the greatest benefits. An open-label trial (N = 62) compared daily sildenafil 25 mg, alfuzosin 10 mg, or sildenafil 25 mg plus alfuzosin 10 mg on ED and tower urinary tract symptoms. Combination therapy resulted in greater improvements in ED and lower urinary tract symptoms and urinary flow than did either drug alone. The effects of daily tadalafil 20 mg were studied in 281 men with lower urinary tract symptoms independent of ED. Tadalafil produced statistically significant but clinically modest improvements in tower urinary tract symptoms when compared with placebo. Conclusions: PDE-5 inhibitors consistently produced modest reductions in lower urinary tract symptoms. Further studies are needed to fully elucidate the efficacy, cost effectiveness, safety, and appropriate place in therapy of PDE-5 inhibitors. At this time, data are insufficient to routinely recommend chronic use of PDE-5 Inhibitors for tower urinary tract symptoms in men.

Severe Thrombocytopenia Associated with Alatrofloxacin

OBJECTIVE: To report the development of severe thrombocytopenia during alatrofloxacin therapy. CASE SUMMARY: A 54-year-old Native American woman was admitted for pneumonia after completing a 10-day course of loracarbef 200 mg po bid. On admission, the woman was hypoxic (PO2 56 mm Hg) and had a platelet count of 408 times 103/mm3. Alatrofloxacin 300 mg iv piggyback qd was initiated in the emergency department. The patients condition gradually improved during the next three days. While preparing for discharge on hospital day 4, the patient developed epistaxis that lasted approximately three hours. Laboratory testing revealed a platelet count of 7 times 103/mm3; stable red blood cell count, hemoglobin, and hematocrit values; and a normal white blood cell count. Alatrofloxacin therapy was discontinued and azithromycin was initiated on hospital day 4. Methylprednisolone 125 mg iv piggyback every 12 hours was initiated on hospital day 5. The platelet count fell to 2 times103/mm3 on hospital day 5 and then began to rise, reaching 60 times 103/mm3 when the patient was discharged on hospital day 8. DISCUSSION: Numerous infectious, disease-related, environmental, and pharmacologic factors may cause thrombocytopenia. Drug-induced thrombocytopenia usually develops during the first two weeks of therapy and resolves within one week of drug discontinuation. Thrombocytopenia occurred in <1% of more than 7000 patients receiving alatrofloxacin or trovafloxacin during clinical trials. CONCLUSIONS: The time course of this patients development of and recovery from thrombocytopenia suggests that it was induced by alatrofloxacin. Clinicians should monitor patients receiving alatrofloxacin or trovafloxacin for signs and symptoms of bleeding and thrombocytopenia.

Acetaminophen for Patent Ductus Arteriosus

Objective: To evaluate the literature describing acetaminophen use in treatment of patent ductus arteriosus (PDA). Data Sources: Searches were conducted in MEDLINE with full text (EBSCOhost; 1946 to September 2014) using the search terms acetaminophen, paracetamol, and patent ductus arteriosus. The references of identified articles were reviewed to identify other relevant articles. Study Selection and Data Extraction: Human clinical trials and case reports limited to the English language were reviewed. In all, 12 case reports and 2 randomized, controlled clinical trials explored the use of acetaminophen in treating PDA. Data Synthesis: The case reports described the use of oral or intravenous acetaminophen in patients with contraindications to or who had previously failed nonsteroidal anti-inflammatory drug therapy for PDA. More than 76% of patients achieved successful PDA closure in reported cases. The clinical trials compared the efficacy of oral acetaminophen versus oral ibuprofen in preterm infants. Acetaminophen was noninferior to ibuprofen, with closure rates from 72.5% to 81.2%. The acetaminophen dose used in most case series and trials was 15 mg/kg dose every 6 hours for 3 days. Acetaminophen therapy was well tolerated, with only a few incidents of elevated liver enzymes being reported. Conclusion: Oral acetaminophen is an alternative to PDA therapy in preterm infants when indomethacin/ibuprofen is not effective or is contraindicated, and it may be considered before surgical ligation.

Use of stun guns for venomous bites and stings: a review

During the past 2 decades, articles suggesting that stun guns be utilized to treat venomous bites and stings have appeared in both the lay and medical press. Although never widely considered to be standard therapy for venomous bites and stings, stun guns are still considered to be a treatment option by some medical practitioners and outdoor enthusiasts. A Medline search was performed using these terms: venomous bites, venomous stings, snake bites, spider bites, electrical, stun gun, high voltage electricity, low amperage electricity, direct current, and shock therapy. Articles selected included laboratory-based isolated venom studies, animal studies, and case reports involving humans in which a stun gun or some other source of high voltage, low amperage direct current electric shocks were used to treat actual or simulated venomous bites or stings. We concluded that the use of stun guns or other sources of high voltage, low amperage direct current electric shocks to treat venomous bites and stings is not supported by the literature.

Nebivolol versus other beta blockers in patients with hypertension and erectile dysfunction

Erectile dysfunction (ED) impacts over 100 million men worldwide and occurs at a higher incidence in men with hypertension. Beta blockers are one of several antihypertensive drug classes associated with ED. Nebivolol is a beta blocker with vasodilating properties mediated through endothelial release of nitric oxide which facilitates penile erection. Thus, nebivolol may offer an advantage over other beta blockers in the patient with hypertension and ED. A literature search comparing nebivolol with other beta blockers identified four European studies of limited duration, with the longest study being 28 weeks. Survey scores for erectile function showed significant improvement in erectile function with nebivolol in two of the studies, while the other two studies showed erectile function did not significantly worsen with nebivolol as compared with other beta blocker agents. One study showed improved erectile function scores, possibly due to the presence of a Hawthorne effect. Based on this small sample of studies, nebivolol may be of use in the patient with or at risk of developing ED, when a practitioner specifically wants to use a beta blocker as add-on antihypertensive treatment.

Gabapentin in Alcohol Dependence

Objective: To review the literature related to the use of gabapentin in alcohol dependence following acute alcohol withdrawal. Data Sources: Searches of MEDLINE (1946-January 2015) and Cochrane Database (2005-January 2015) were performed using gabapentin, alcohol, and alcoholism as MeSH terms and keywords. Results were limited to human trials in English-language journals. Study Selection and Data Extraction: Inclusion criteria included randomized controlled trials with a minimum 4 weeks of gabapentin therapy and at least one alcohol dependence related outcome measure (ie, cravings, abstinence, percent days abstinent, or heavy drinking days). Six randomized clinical trials were identified. Data Synthesis: Four trials identified beneficial effects of gabapentin on at least one alcohol-related outcome measure. Two smaller studies, which enrolled patients with minimal withdrawal symptoms, failed to demonstrate beneficial effects on primary outcomes related to heavy drinking or abstinence. Gabapentin at doses up to 1800 mg daily was well tolerated with no serious adverse drug reactions being reported. Conclusions: Clinical trials have shown gabapentin is a well-tolerated adjunctive therapy in the management of alcohol dependence. The strongest efficacy evidence occurred in patients experiencing moderate to severe withdrawal when gabapentin was administered early in or concurrently during acute withdrawal and continued for up to 12 weeks.