Israel Medical Association Journal

The prevalence of obesity worldwide has risen sharply during the last four decades. The etiology of obesity is complex and includes a host of genetic influences in addition to the overconsumption of energy coupled with a sedentary lifestyle. Obesity is known to cause or exacerbate many co-morbid conditions such as diabetes, hypertension, dyslipidemia, coronary heart disease, stroke, certain cancers, arthritis and obstructive sleep apnea. Modest weight losses of 5–10% of actual weight are related to significant improvements in co-morbid conditions, but unfortunately the rate of recidivism with short-term therapy for obesity is high. The recent recognition of obesity as a chronic disease that should be treated with long-term programs and possibly with polypharmacy, and the alarming increase in its prevalence, have prompted extensive research and the development of new pharmacotherapy.

Background: Until recently trimethoprim-sulfamethoxazole was the drug recommended in the Leumit Health Fund for the empiric treatment of uncomplicated urinary tract infection in women. However, due to increased uropathogen resistance to this drug, the fund has designated nitrofurantoin as its new drug of choice.

Objectives: To evaluate the potential economic impact of implementing this new pharmaco-policy.

Methods: Using data derived from the electronic patient records of the Leumit Health Fund we identified all non-recurrent cases of women aged 18–49 with a diagnosis of acute cystitis or UTI[1] without risk factors for complicated UTI and empirically treated with antibiotics throughout 2003. The final sample comprised 5,489 physician-patient encounters. The proportion of cases treated with each individual drug was calculated, and the excess expenditure due to non-adherence to the new guideline from the perspective of the health fund was evaluated using 5 days of therapy with nitrofurantoin as the reference treatment.

Results: Ofloxacin was the most frequently prescribed drug (30.24%), followed by TMP-SMX[2] (22.43%), cephalexin (15.08%), and nitrofurantoin (12.59%). The observed net aggregate drug expenditure was 2.3 times greater than expected had all cases been treated with nitrofurantoin according to the guideline duration of 5 days. The cost of treatment in 53% of the cases exceeded the expected cost of the guideline therapy.

Conclusions: Successful implementation of the new drug policy will likely improve quality of care and reduce costs to the health fund.

Behavioral genetics is the identification of behavioral traits that are genetically determined, the identification of the genes that are involved, and the discovery of modes of intervention to alter the expected course of the disease. Unlike the classical Mendelian traits, many specific aspects of behavior are, in part, determined by several genes. The corresponding abnormalities of behavior or deficiencies are therefore polygenic. New genetic techniques are leading to the discovery of these genes, and the techniques and knowledge developed in the Human Genome Project make it possible to screen the genome of any individual for the presence of known polymorphisms. This raises great hopes for diagnosis and the individualization of therapy. However, the genetic prediction of unacceptable behavior can further lead to social and occupational discrimination and enforced therapy. This raises serious concerns about how this information will be collected and who will have access to it.

Background: Acarbose has become an important adjuvant therapy for diabetic patients. Many of these patients are also treated with digoxin for congestive heart failure or chronic atrial fibrillation

Objective: To evaluate a possible drug interaction between acarbose and digoxin.

Methods: An open-label, analyst-blind, randomized, crossover, two-period study was conducted in 11 healthy subjects. In period I, each subject received one single oral dose of 0.75 mg digoxin. In period ll, they were given acarbose tablets., 60 mg-3 times a day for 12 days. On day 8, one hour after acarbose administration, a single oral dose of 0.75 mg digoxin was administered. The study periods were separated by a 3 week washout interval: Serum. digoxin levels., over. time, in the two periods were compared by standard techniques;

Results: There were no differences in the pharmacokinetic parameters of digoxin in the two periods, apart from a significant increase in the mean maximum serum concentration (Cmax) when digoxin was given with acarbose (5.97 compared to 4.67 g/L, P = 0.02). Simulated steady-state peak levels of digoxin (Cmax,ss) achieved with a daily dose of 0.25 mg digoxin, in the presence.and absence of acarbose, were 2.89 and 2.40 g/L respectively (P =0.05); Simulated steady-state trough (Cmin,ss) and average (Cave,ss) concentrations were similar and within the therapeutic window.

Conclusion: There was no significant pharmacokinetic interaction between digoxin and acarbose at current therapeutic doses in the healthy volunteers. This interaction should be further studied with higher doses of acarbose and at steady-state conditions.
 

Background: Lithium has been a part of the psychiatric pharmacopoeia for more than half a century. Its efficacy is marred by a narrow therapeutic index and significant toxicity.

Objectives: To increase physicians’ awareness of the various manifestations of lithium intoxication.

Methods: We reviewed the clinical data of cases of lithium poisoning occurring in a municipal hospital during a 10 year period.

Results: Eight patient records were located. The mortality rate was 12.5%. All patients were women and the mean age was 66.4 years. The most common symptoms were neurological. One illustrative case is described in detail with lithium serum levels showing the usual two-phase decline.

Conclusions: Lithium poisoning can present in many forms. Increased physician awareness and the early use of effective treatment, mainly hemodialysis, will prevent mortality and protracted morbidity associated with this condition.
 

Background: The prevalence of attention deficit-hyperactivity disorder and its pharmacologic treatment have increased dramatically in the past decade in the United States and Britain. We examined the use of methylphenidate hydrochloride for the treatment of ADHD in children in northern Israel.

Methods: We evaluated all prescriptions for methylphenidate filled in 1999 for children aged 5–18 years residing in northern Israel who were insured by Clalit Health Services, a health maintenance organization that covers approximately 70% of the population.

Results: Methylphenidate was prescribed to 1.45% of the children in northern Israel in 1999, an increase of 20% in the overall prevalence of methylphenidate use since 1992. Eighty-two percent were boys. The rate of prescription varied widely by type of settlement, from 0.2% in Arab cities and towns to 5.7% in kibbutzim. Primary care physicians wrote 78% of all the prescriptions.

Conclusions: The increase in methylphenidate use was much smaller in northern Israel than in most other developed regions and countries. More efforts at diagnosis and treatment of attention deficit disorders may need to be directed at Arab populations and those with inadequate medical services.

Background: Familial Mediterranean fever is a genetic disease in which some characteristic gene mutation have been found.

Objective: To analyze the phenotype-genotype correlations in North African Jews and Armedians with FMF.

Methods: We studied MEFV gene mutations and phenotype-genotype correlations in North African Jews and Armedians with Familial Mediterranean Fever living in France.

Results: M694V mutation was the most common mutation in Jews and in Armenians. Patients with M6801 homozygosity or M6801/M694V compound heterozygosity had a phenotype as severe as patients with M694V homozygosity.

Conclusions: This study characterizes the phenotype-genotype in specific ethnic groups of patients with FMF.