Doron Garfinkel

Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy.

BACKGROUND Polypharmacy and inappropriate medication use is a problem in elderly patients, who are more likely to experience adverse effects from multiple treatments and less likely to obtain the same therapeutic benefit as younger populations. The Good Palliative-Geriatric Practice algorithm for drug discontinuation has been shown to be effective in reducing polypharmacy and improving mortality and morbidity in nursing home inpatients. This study reports the feasibility of this approach in community-dwelling older patients. METHODS The Good Palliative-Geriatric Practice algorithm was applied to a cohort of 70 community-dwelling older patients to recommend drug discontinuations. Success rates of discontinuation, morbidity, mortality, and changes in health status were recorded. RESULTS The mean (SD) age of the 70 patients was 82.8 (6.9) years. Forty-three patients (61%) had 3 or more and 26% had 5 or more comorbidities. The mean follow-up was 19 months. Participants used a mean (SD) of 7.7 (3.7) medications. Protocol indicated that discontinuation was recommended for 311 medications in 64 patients (58% of drugs; mean [SD], 4.4 [2.5] drugs per patient overall, 4.9 per patient who had discontinuation). Of the discontinued drug therapies, 2% were restarted because of recurrence of the original indication. Taking nonconsent and failures together, successful discontinuation was achieved in 81%. Ten elderly patients (14%) died after a mean follow-up of 13 months, with the mean age at death of 89 years. No significant adverse events or deaths were attributable to discontinuation, and 88% of patients reported global improvement in health. CONCLUSIONS It is feasible to decrease medication burden in community-dwelling elderly patients. This tool would be suitable for larger randomized controlled trials in different clinical settings.

efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study

Background: Diabetes is a major comorbidity in insomnia patients. The efficacy and safety of prolonged-release melatonin 2 mg in the treatment of glucose, lipid metabolism, and sleep was studied in 36 type 2 diabetic patients with insomnia (11 men, 25 women, age 46–77 years). Methods: In a randomized, double-blind, crossover study, the subjects were treated for 3 weeks (period 1) with prolonged-release melatonin or placebo, followed by a one-week washout period, and then crossed over for another 3 weeks (period 2) of treatment with the other preparation. All tablets were taken 2 hours before bedtime for a period of 3 weeks. In an extension period of 5 months, prolonged-release melatonin was given nightly to all patients in an open-label design. Sleep was objectively monitored in a subgroup of 22 patients using wrist actigraphy. Fasting glucose, fructosamine, insulin, C-peptide, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, and some antioxidants, as well as glycosylated hemoglobin (HbA1c) levels were measured at baseline and at the end of the study. All concomitant medications were continued throughout the study. Results: No significant changes in serum glucose, fructosamine, insulin, C-peptide, antioxidant levels or blood chemistry were observed after 3 weeks of prolonged-release melatonin treatment. Sleep efficiency, wake time after sleep onset, and number of awakenings improved significantly with prolonged-release melatonin as compared with placebo. Following 5 months of prolonged-release melatonin treatment, mean HbA1c (±standard deviation) was significantly lower than at baseline (9.13% ± 1.55% versus 8.47% ± 1.67%, respectively, P = 0.005). Conclusion: Short-term use of prolonged-release melatonin improves sleep maintenance in type 2 diabetic patients with insomnia without affecting glucose and lipid metabolism. Long-term prolonged-release melatonin administration has a beneficial effect on HbA1c, suggesting improved glycemic control.

Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

Background Prolonged-release melatonin (PRM) 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation. Objective To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment. Methods Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary), adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]). Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM. Results Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as “good” or “very good” was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production. Conclusion Results support the efficacy and safety of PRM in primary insomnia patients aged 20–80 throughout 6–12 months of continuous therapy. PRM discontinuation even after 12 months was not associated with adverse events, withdrawal symptoms, or suppression of endogenous melatonin production.

Polymyalgia Rheumatica and Temporal Arteritis in a Married Couple

A husband suffering from temporal arteritis and his wife afflicted with polymyalgia rheumatica are reported. The possibility of the existence of an environmental factor rather than a genetic etiology is discussed.

Life-Threatening Theophylline Intoxication in a Hypothyroid Patient

In a hypothyroid patient who suffered also from chronic obstructive lung disease and mild congestive heart failure, treatment with 1 g/day theophylline administered orally, was followed by a life-threatening theophylline intoxication manifested by repeated epileptic fits and ventricular fibrillation, successfully reverted to sinus rhythm. The plasma theophylline was 34.7 micrograms/ml when the life-threatening arrhythmia occurred. Pharmacokinetic studies conducted during the hypothyroid state revealed a markedly prolonged theophylline plasma half-life of 29.5 h. 2 months later, after reestablishment of an euthyroid state, theophylline plasma half-life was shortened to normal, i.e. 5.7 h and the theophylline plasma level was 13.5 micrograms/ml, while the daily intake was 1 g. We conclude that hypothyroidism may predispose to theophylline intoxication, probably because of the decreased activity of the hepatic microsomal drug-metabolizing enzymes, responsible for the degradation of theophylline.

Roentgenologically Invisible Mucormycosis Pneumonia

A markedly neutropenic patient with aplastic anemia who developed fever unresponsive to massive antibiotic treatment succumbed to mucormycosis pneumonia which could not be demonstrated by repeated che

Severe Herpes Simplex Infection in Diffuse Histiocytic Lymphoma Treated with Adenine Arabinoside

After 10 days of treatment with intravenous adenine arabinoside, complete healing of a severe labial herpes simplex infection was achieved in a patient with disseminated histiocytic lymphoma.

Inappropriate Anti-Diuretic Hormone (ADH) Secretion in a Patient with Extensive Fibrothorax

A 68 year-old woman, treated 30 years ago by collapse therapy for tuberculosis of the lung, presently developed the syndrome of inappropriate antidiuretic hormone scretion. The investigation revealed only an extensive right fibrothorax. The possible relation between the latter and her present illness is discussed.