Israel Medical Association Journal

Physicians have a great interest in discussions of life and its origin, including life's persistence through successive cycles of self-replication under extreme climatic and man-made trials and tribulations. We review here the fundamental processes that, contrary to human intuition, life may be seen heuristically as an ab initio, fundamental process at the interface between the complementary forces of gravitation and quantum mechanics. Analogies can predict applications of quantum mechanics to human physiology in addition to that already being applied, in particular to aspects of brain activity and pathology. This potential will also extend eventually to, for example, autoimmunity, genetic selection and aging. We present these thoughts in perspective against a background of changes in some physical fundamentals of science, from the earlier times of the natural philosophers of medicine to the technological medical gurus of today. Despite the enormous advances in medical science, including integration of technological changes that have led to the newer clinical applications of magnetic resonance imaging and PET scans and of computerized drug design, there is an intellectual vacuum as to how the physics of matter became translated to the biology of life. The essence and future of medicine continue to lie in cautious, systematic and ethically bound practice and scientific research based on fundamental physical laws accepted as true until proven false.
 

Background: Maternal exposure to alcohol during pregnancy can lead to a wide range of clinical manifestations in their offspring, termed fetal alcohol spectrum disorder (FASD). In Israel, relatively few cases of FASD have been diagnosed and the prevalence has not been systematically evaluated.

Objectives: To determine the number of children with FASD or at risk for FASD in a select population of high risk patients seen at a clinic evaluating foster and adopted children.

Methods: Israeli children under 2 years old who were candidates for domestic adoption or in foster care were prospectively evaluated for clinical manifestations of FASD, and information was obtained regarding parental use of alcohol or other illicit drugs.

Results: Of the 100 patients prospectively evaluated, 8 had mothers with a known history of alcohol consumption during pregnancy. Two of the children had fetal alcohol syndrome (FAS) without known maternal exposure to alcohol and two had partial FAS. Eleven other children were at risk for development of one of the diagnostic categories of FASD.

Conclusions: In a population of pre-adoption and foster children, 15% either had manifestations of FASD or were at risk for developing FASD. Although this is a select high risk population, the data from this study strongly suggest a greater prevalence of FASD than previously assumed. Under-diagnosis of FASD is detrimental to affected children who could benefit from interventions designed to meet the needs of FASD victims.
 

Background: Comorbid depression may play an important role in non-compliance with medical treatment among patients with chronic illnesses. Glaucoma is a potentially blinding chronic disease requiring life-long commitment to medical therapy. Patient's failure to adhere to anti-glaucoma treatment may lead to disease progression and visual loss.

Objectives: To assess the prevalence of depressive symptoms in glaucoma patients and the association between these symptoms and non-compliance with anti-glaucoma therapy.

Methods: This was a cross-sectional observational study. Compliance with pharmacotherapy was assessed with the Morisky Medication Adherence questionnaire (eight items). Screening for depression was performed by means of the CES-D scale (Center for Epidemiologic Studies Depression scale). The association between depression and compliance rates was analyzed.

Results: The study group comprised 76 glaucoma patients; 19.7% of the subjects were classified as "non-compliant" (Morisky cutoff < 10) and 21.1% suffered from depression (CES-D cutoff ≥ 16). We found a similar level of non-compliance when comparing depressed with non-depressed glaucoma patients. However, a significant correlation was observed between the level of depression and the level of non-compliance (P = 0.04).

Conclusions: Our study revealed a similar rate of depression in glaucoma patients and the general Israeli population. The presence of depression was not associated with the presence of non-compliance, yet the level of depression was associated with the level of non-compliance.

Background: Sudden death in athletes can occur during sport activities and is presumably related to ventricular arrhythmias. There are no guidelines concerning athletes who develop ventricular arrhythmias during an exercise test. It is unclear whether they should be allowed to continue with their competitive activity or not.

Objectives: To investigate the long-term follow-up of athletes with ventricular arrhythmias during an exercise test.

Methods: From a database of 56,462 athletes we identified 192 athletes, less than 35 years old, who had ventricular arrhythmias during an exercise test. Ninety athletes had ≥ 3 ventricular premature beats (group A) and 102 athletes had ventricular couplets or non-sustained ventricular tachycardia during an exercise test (group B). A control group of 92 athletes without ventricular arrhythmias was randomly selected from the database (group C).

Results: All athletes, except one who died from a dilated cardiomyopathy, were alive during a follow-up period of 70 ± 25 months. An abnormal echocardiogram was obtained in seven athletes from group A (10%), four from group B (5%), and one from group C (3%) (not significant). An abnormal echocardiogram was more likely to be present in competitive athletes (P = 0.001) and in female athletes (P = 0.01).

Conclusions: Our results showed that ventricular arrhythmias during exercise are more commonly associated with cardiovascular abnormalities in young competitive athletes and in female athletes. When present, they necessitate a thorough investigation and follow-up.
 

Background: The compliance of hospital staff with guidelines for the active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) in Israel has not been determined.

Objectives: To evaluate the compliance of hospital staff with guidelines for the active surveillance of MRSA and assess its impact on the incidence of nosocomial MRSA bacteremia.

Methods: We assessed compliance with MRSA surveillance guidelines by assessing adherence to the screening protocol and reviewing medical and nursing charts of patients colonized with MRSA, and observed hand hygiene opportunities among health care workers and colonized patients. Rates of nosocomial MRSA bacteremia and of adherence with hand hygiene among overall hospital staff were obtained from archived data for the period 2001–2010.

Results: Only 32.4% of eligible patients were screened for MRSA carriage on admission, and 69.9% of MRSA carriers did not receive any eradication treatment. The mean rate of adherence to glove use among nurses and doctors was 69% and 31% respectively (P < 0.01) and to hand hygiene 59% and 41% respectively (P < 0.01). The hospital overall rate of adherence to hand hygiene increased from 42.3% in 2005 to 68.1% in 2010. Rates of nosocomial MRSA bacteremia decreased by 79.2%, from 0.48 (in 2001) to 0.1 (in 2010) per 1000 admissions (P < 0.001).

Conclusions: The compliance of medical and nursing staff with guidelines for active MRSA surveillance was poor. The encouraging increase in adherence to hand hygiene and concomitant decrease in nosocomial MRSA bacteremia is gratifying. The deficiencies in compliance with MRSA infection control policy warrant an adjusted strategy based on the hospital resources.

Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.

Objectives: To describe the clinical, electrophysiologic and pathologic findings in patients with myotonic dystrophy 2.

Methods: We evaluated 10 patients genetically, clinically and electrophysiologically during the years 2007 to 2008.

Results: All patients were of Jewish European ancestry. Among affected individuals, eight patients had symptoms of proximal muscle weakness, two had muscle pain, and two exhibited myotonia. On physical examination six patients had severe weakness of hip flexor muscles. Seven individuals underwent cataract surgery, and cardiac involvement was seen in one case. On the initial electromyographic (EMG) examination five patients demonstrated myotonic discharges; repeated studies showed these discharges in nine cases. Six muscle biopsies showed non-specific pathological changes. Seven patients had an affected first-degree relative with either a diagnosed or an undiagnosed muscular disorder, consistent with an autosomal dominant trait.

Conclusions: DM2 may often present with proximal muscle weakness without myotonia. EMG may initially fail to show myotonic discharges, but these discharges may eventually show in most cases on repeated EMG. Thus, DM2 may be underdiagnosed and should be included in the differential diagnosis of adult patients of Jewish European ancestry presenting with proximal lower limb weakness.
 

Background: Hepatotoxicity due to intravenous amiodarone (HIVAD) is a rare side effect with a distinct pattern of enzyme disturbances compared to liver damage from oral amiodarone. Intravenous amiodarone is administered for acute arrhythmias often causing heart failure. The enzyme abnormalities and clinical setting are very similar to that of ischemic hepatitis, a far more common condition.

Objectives:  To ascertain if acute HIVAD exists as a separate entity or whether reported cases may be explained by ischemic hepatitis.

Methods: In this case-control retrospective study the files of hospitalized patients with markedly elevated aminotransferases were reviewed for the diagnoses of HIVAD or ischemic hepatitis. Medline was searched for published cases of HIVAD. Pooled data of all patients with HIVAD were compared to a control group with ischemic hepatitis.

Results: There were no significant differences in the clinical characteristics, laboratory results or histological findings between HIVAD and ischemic hepatitis patients.

Conclusions: In our opinion, there is currently insufficient data to support the existence of distinct HIVAD, and ischemic hepatitis is a more probable diagnosis in most reported cases. Withdrawing amiodarone because of assumed hepatic damage could deprive patients of a life-saving therapy.
 

Background: Adjuvant/neoadjuvant chemotherapy in breast cancer patients may be associated with amenorrhea and a marked reduction in ovarian reserve.

Objectives: To assess the use of letrozole with follicle-stimulating hormone (FSH) in gonadotropin-releasing hormone (GnRH) analogue protocols, based on reported attempts to avoid the estradiol (E2) increase during controlled ovarian hyperstimulation for embryo cryopreservation in breast cancer patients using a combination of low dose FSH and aromatase inhibitor (letrozole) in a GnRH-antagonist protocol.

Methods: Twenty-four breast cancer patients were treated with recombinant FSH (150–450 U/day) and letrozole (5 mg/day) in a long GnRH-agonist (n=7) or GnRH-antagonist (n=17) protocol. After oocyte retrieval, insemination and/or intracytoplasmic sperm injection was performed. The embryos were frozen.

Results: The average interval from surgery to oocyte retrieval was 40 days. Average duration of treatment was 9.6 days and mean peak E2 level 1342 ± 1091 pmol/L, yielding 16.0 ± 16.3 oocytes (range 0–82). Mean fertilization rate was 69.5 ± 20.4% and mean number of embryos cryopreserved 10.3 ± 9.3. More oocytes were retrieved with the long GnRH protocol, but the difference was not statistically significant (24.8 ± 24.6 vs. 12.0 ± 8.8 pmol/L, P = 0.07).

Conclusions: As previously reported, ovarian stimulation with letrozole and FSH, in both the long GnRH-agonist and GnRH-antagonist protocols, is apparently effective in breast cancer patients and spares them exposure to high E2 levels.
 

Background: Intraarticular injections for the local treatment of osteoarthritis are widely used in the office or hospital setting. Septic arthritis is a potential catastrophic complication of intraarticular injection, as bacterial arthritis of any cause is associated with up to 15% mortality and residual impairment of joint function in up to 50% of survivors. There is lack of evidence regarding the precautions that should be taken to avoid such a complication, as well as how often it is encountered.

Objectives: To report our experience with the clinical presentation, diagnosis and treatment of knee septic arthritis following intraarticular injections. 

Methods: We followed six patients who were admitted to the hospital and underwent surgery for the treatment of pyogenic arthritis following injection to the knee joint in outpatient clinics.

Results: All but one patient were over 70 years old with comorbidities. Three patients were injected with steroid preparations and three with hyaluronic acid several days before admission. In all six patients the infection was treated surgically and three of them had undergone more than one operation during their hospitalization. Four of the six patients were treated by means of an open arthrotomy and synovectomy, and the other two were treated successfully with arthroscopic lavage and synovectomy. One patient underwent an above-knee amputation due to septic shock and died after several days.

Conclusions: Despite the rarity of this complication, surgeons must be aware of the possibility of pyogenic arthritis when administering injections, especially in elderly patients with serious underlying medical conditions.

Suicide is universal within the range of human behaviors and is not necessarily related to psychiatric morbidity, though it is considerably more prevalent among psychiatric patients. Considering the limitations of medical knowledge, psychiatrists cope with an unfounded and almost mythical perception of their ability to predict and prevent suicide. We set out to compose a position paper for the Israel Psychiatric Association (IPA) that clarifies expectations from psychiatrists when treating suicidal patients, focusing on risk assessment and boundaries of responsibility, in the era of defensive medicine. The final draft of the position paper was by consensus. The IPA Position Paper established the first standard of care concerning expectations from psychiatrists in Israel with regard to knowledge-based assessment of suicide risk, elucidation of the therapist's responsibility to the suicidal psychotic patient (defined by law) compared to patients with preserved reality testing, capacity for choice, and responsibility for their actions. Therapists will be judged for professional performance rather than outcomes and wisdom of hindsight. This paper may provide support for psychiatrists who, with clinical professionalism rather than extenuating considerations of defensive medicine, strive to save the lives of suicidal patients.
 

Background: There is a wide treatment gap between evidence-based guidelines and their implementation in primary care.

Objective: To evaluate the extent to which physicians "literally" follow guidelines for secondary prevention of dyslipidemia and the extent to which they practice "substitute" therapeutic measures.

Methods: We performed a post hoc analysis of data collected in a prospective cluster randomized trial. The participants were 130 primary care physicians treating 7745 patients requiring secondary prevention of dyslipidemia. The outcome measure was physician "literal" adherence or "substitute" adherence. We used logistic regressions to evaluate the effect of various clinical situations on “literal” and “substitute” adherence.

Results: "Literal" adherence was modest for ordering a lipoprotein profile (35.1%) and for pharmacotherapy initiations (26.0%), but rather poor for drug up-titrations (16.1%) and for referrals for specialist consultation (3.8%). In contrast, many physicians opted for "substitute" adherence for up-titrations (75.9%) and referrals for consultation (78.7%). Physicians tended to follow the guidelines “literally” in simple clinical situations (such as the need for lipid screening) but to use "substitute" measures in more complex cases (when dose up-titration or metabolic consultation was required). Most substitute actions were less intense than the actions recommended by the guidelines.

Conclusions: Physicians often do not blindly follow guidelines, but rather evaluate their adequacy for a particular patient and adjust the treatment according to their assessment. We suggest that clinical management be evaluated in a broader sense than strict guideline adherence, which may underestimate physicians' efforts.
 

Background: The "obesity paradox" is defined as an inverse association of good health, survival and obesity. Usually in healthy persons the more obese you are the more metabolic complications you have; however, thin patients with chronic obstructive pulmonary disease (COPD) have more cardiovascular complications and a higher mortality rate.

Objectives: To explore whether atherosclerosis and peripheral artery disease (PAD) contribute to the higher morbidity and mortality of patients with COPD.

Methods: This prospective study included 87 patients with chronic COPD who were treated in the pulmonary outpatient clinic; all signed a consent form before enrollment. We documented their lung function (FEV1%), body mass index (BMI) and ankle brachial index (ABI). The primary endpoints were to find an association between atherosclerosis and BMI in patients with COPD, and between atherosclerosis and severity of lung disease.

Results: Average ABI[1] was 1.01 ± 0.20, BMI[2] was 29.33 ± 7.48 kg/m2, and the abdominal circumference was 107.34 ± 18.87 cm. A positive correlation was found between BMI and ABI (P = 0.001) and between abdominal circumference and ABI (P = 0.000). Patients with peripheral artery disease were older (73.6 ± 11.5 vs. 68.1 ± 11.6 years old, P = 0.04), were thinner (average BMI 25.5 ± 6.2 vs. 31.06 ± 7.3, P = 0.001), and had a lower abdominal circumference (97.7 ± 18.3 vs. 111.7 ± 17.5 cm, P = 0.001). No such difference was observed for years of smoking. Male PAD patients with COPD had a lower BMI (25.2 ± 5.6 vs. 29.9 ± 7.4, P = 0.016), and their abdominal circumference was smaller (96.1 ± 18.0 vs. 110.2 ± 16.5 cm, P = 0.004). Female PAD patients with COPD had a lower BMI (26.3 ± 8.2 vs. 33.1 ± 7.0, P = 0.045), but their abdominal circumference was not different from females without PAD (102.0 ± 19.7 vs. 114.0 ± 19.4 cm, P = 0.162). Patients with PAD had a worse lung disease (FEV1% 34 ± 8% vs. 45 ± 16%, P = 0.01). During the 1 year of follow-up five patients died: two PAD patients due to acute myocardial infarction and three non-PAD patients died from pulmonary insufficiency (two patients) and pulmonary emboli (one patient).

Discussion: We found that COPD patients with PAD were older and thinner and had a lower abdominal circumference and a more progressive lung disease. Extensive atherosclerosis in patients with COPD may partly explain the “obesity paradox” observed in patients with COPD.

Background: Little is known of the risk factor disparities in first stroke among Jewish and Arab patients undergoing rehabilitation in Israel.

Objectives: To investigate the age, gender and risk factor disparities in first stroke among Jewish (immigrant and non-immigrant) and Arab patients undergoing rehabilitation and to compare the prevalence and odds ratio of stroke risk factors in these patients.

Methods: The database of the Department of Neurological Rehabilitation C at Loewenstein Rehabilitation Center was used to investigate first ischemic and hemorrhagic stroke patients admitted for hospital rehabilitation over a 15 year period, January 1993 to December 2008. Particular attention was paid to age, gender and risk factor disparities.

Results: The 2000 patients with first stroke who were included in the study were grouped as Jewish (immigrant and non-immigrant) and Arab (237 Arabs, 370 non-immigrant Jews and 1393 immigrant Jews). A high percentage of Arab patients were found to have hypertension and diabetes mellitus, while a high percentage of Jewish immigrants had stenosis of the internal carotid artery.

Conclusions: The study demonstrated some differences in the effect of risk factors between the groups. It may be important to address such differences when developing stroke preventative strategies in this population of Jewish and Arab stroke survivors in Israel.