Israel Medical Association Journal

Background: Glioblastoma multiforme (GBM) is an ultimately fatal disease that affects patients of all ages. Elderly patients (65 years and older) constitute a special subgroup of patients characterized by a worse prognosis and frequent comorbidities.

Objectives: To assess the efficacy of different treatment modalities in terms of survival in elderly patients with GBM¹.

Methods: Using retrospective analysis, we extracted, anonymized and analyzed the files of 74 deceased patients (aged 65 or older) treated for GBM in a single institution.

Results: Mean survival time was 8.97 months and median survival time 7.68 months. Patients who underwent tumor resection had a mean survival of 11.83 months, as compared to patients who underwent no surgical intervention or only biopsy and had a mean survival of 5.22 months (P < 0.0001). Patients who underwent full radiation treatment had a mean survival of 11.31 months, compared to patients who received only partial radiotherapy or none at all and had a mean survival of 4.09 months (P < 0.0001). Patients who underwent chemotherapy had a mean survival 12.4 months, compared to patients who did not receive any chemotherapy and had a mean survival of 5.89 months (P < 0.001).

Conclusions: Age alone should not be a factor in the decision on which treatment should be given. Treatment should be individualized to match the patient’s overall condition and his or wishes, while taking into consideration the better overall prognosis expected with aggressive treatment.
 

Background: Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Q pyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change, imposed by this mutation on pyrin structure, may help to understand the role of this mutation

Objectives: To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein.

Methods: The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined.

Results: The E148Q mutation caused deviation from the wild-type pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%.

Conclusions: A quantum-chemistry based model suggests that the structural effect of the E148Q mutation is indeed low, but not zero. 
 

Background: A survey conducted among Israel Defense Force primary care physicians in 2001 revealed that they consider patients' needs more than they do organizational needs and that the education PCPs[1] currently receive is inadequate. In 2003 the medical corps initiated a multi-format continuous medical education program aimed at improving skills in primary care medicine.

Objectives: To measure and analyze the effect of the tailored-made CME[2] program on PCPs’ self-perception 3 years after its implementation and correlate it to clinical performance.

Methods: In 2006 a questionnaire was delivered to a representative sample of PCPs in the IDF[3]. The questionnaire included items on demographic and professional background, statements on self-perception issues, and ranking of roles. We compared the follow-up survey (2006) to the results of the original study (2001) and correlated the survey results with clinical performance as measured through objective indicators.

Results: In the 2006 follow-up survey PCPs scored higher on questions dealing with their perception of themselves as case managers (3.8 compared to 4.0 on the 2001 survey on a 5 point scale, P = 0.046), perceived quality of care and education (3.5 vs. 3.8, P = 0.06), and on questions dealing with organizational commitment (3.5 vs. 3.8, P=0.01). PCPs received higher scores on clinical indicators in the later study (odds ratio 2.05, P < 0.001).

Conclusions: PCPs in the IDF perceive themselves more as case managers as compared to the 2001 survey. A tailor-made CME program may have contributed to the improvement in skills and quality of care.

Background: The American Academy of Pediatrics recently published recommendations for the red reflex assessment in the newborn period to detect and treat ocular disorders as early as possible, and to prevent lifelong visual impairment and even save lives. The test is technically simple to perform, non-invasive, requires minimal equipment and can detect a variety of ocular pathologies including cataracts and retinal abnormalities. No specific national guidelines exist on this issue.

Objectives: To document the implementation of red reflex examination in routine neonatal care and present the findings.

Methods: Our clinical experience following implementation of the red reflex test into the newborn physical examination in a single center was reviewed. In addition, an electronic mail questionnaire was sent to all neonatology departments in Israel regarding the performance of the red reflex test.

Results: During 2007–2008, five infants were identified with congenital cataracts at days 2–6 of life prior to discharge from hospital. Surgery was performed in one infant at age 2 months and all infants underwent a thorough follow-up. The incidence of congenital cataract in our center was 1:2300. Less than half the neonatology departments have endorsed the AAP[1] recommendation and perform the red reflex test routinely.

Conclusions: Abnormal red reflex test after delivery enables a rapid ophthalmologic diagnosis, intervention and close follow-up. We recommend that red reflex screening be performed as part of the newborn physical examination if abnormal, an urgent ophthalmologic referral should be made. 

[1] AAP = American Academy of Pediatrics

Background: Bisphosphonates are effective in the prevention and treatment of osteoporosis, yet their use is suboptimal.

Objectives: To measure bisphosphonate compliance among first-time users and identify factors associated with compliance.

Methods: We conducted a prospective follow-up of all women aged 45+ in the second largest health management organization in Israel who were prescribed bisphosphonates for the first time. The 4448 women were classified by drug dosage. Persistence and adherence measures of compliance were calculated for each woman over a 1 year period.

Results: Mean bisphosphonate persistence over a year was 216 days, with a mean medication possession ratio of 66%. Women whose medication was changed, whether from weekly to daily or daily to weekly, always had better persistence rates than those who consistently took the original dose. Persistence rates were as follows: 264 days for women who switched back and forth between daily and weekly doses, 229 days for those who switched from daily to weekly, 222 days for those who took the dosage weekly only, 191 days for those who switched to daily dosage, and 167 days for those who took the dosage daily only (P < 0.001). Switchers were also more likely to have adequate adherence rates (MPR[1] ≥ 80%): 81.3%, 76.6%, 67.5%, 61.3% and 52.2% respectively (P < 0.001). More than 20% of women stopped taking their medication within the first month. Women with higher supplemental insurance (offering significant discounts for weekly dose medications) had better persistence rates: 221 vs. 208 days (P = 0.03). Younger women and women on national pension insurance had the lowest persistence rates: 204 and 209 days respectively.

Conclusions: While weekly bisphosphonate takers had better compliance rates, persistence and adherence rates were inadequate for all groups. Changing medication to meet the needs of the patient, discounting weekly medications, and providing follow-up within the first months of prescription may promote compliance. 

Background: The Pittsburgh Sleep Quality Index is a standardized self-administered questionnaire for the assessment of subjective sleep quality. It has been translated into several languages and is widely used in clinical research studies.

Objectives: To assess the reliability and validity of the Pittsburgh Sleep Quality Index Hebrew translation in a sleep clinic sample and in comparison with the Technion Mini Sleep Questionnaire.

Methods: The PSQI[1] was translated into Hebrew based on standard guidelines. The final Hebrew version (PSQI-H) was administered to 450 patients from two sleep clinics and to 61 healthy adults from the community as a non-clinical control sample. The MSQ[2] was administered to 130 patients in one sleep clinic.

Results: For the PSQI-H[3], Cronbach's-alpha scores for sleep clinic and non-clinical samples were 0.70 and 0.52 respectively and 0.72 combined. Clinical sample scores were significantly higher than the non-clinical group, indicating lower sleep quality for the former. Significant correlations were found between the MSQ subscores and PSQI-H component scores for common underlying constructs.

Conclusions: The PSQI-H differentiated between clinical and non-clinical samples and showed adequate reliability and good validity. It may be used as a standardized tool for the assessment of subjective sleep quality in clinical research studies conducted in the Hebrew-speaking population.

Background: Oral lichen planus is a cell-mediated immune condition of unknown etiology. A possible association of OLP[1] with hepatitis C virus infection has been documented in specific populations. However, no such possible association has been studied in Israel.

Objectives: To assess the prevalence of HCV[2] antibodies among patients with OLP in Israel.

Methods: The prevalence of HCV seropositivity was studied in OLP patients (n=62) and compared with that of a control group (n=65) and with the prevalence among healthy volunteer blood donors (n=225,452) as representatives of the general population.

Results: The prevalence of HCV, as detected by the presence of anti-HCV antibodies screened by enzyme-linked immunosorbent assay, and confirmed by recombinant immunoblot assay, was 4.8%, 1.5% and 0.1%, respectively. HCV seropositivity in the OLP patients was significantly higher than in the healthy blood donors (P < 0.001).

Conclusions: A possible association between OLP and HCV is suggested. Therefore, screening OLP patients for antibodies to HCV is recommended.

Background: During the last decade new surgical techniques for mitral valve repair were developed. We have been using those techniques in order to widen the spectrum of patients eligible for MV[1] repair.

Objectives: To assess the operative and mid-term results a wide variety of surgical techniques.

Methods: From January 2004 through December 2006, 213 patients underwent MV repair in our institution. Valve pathology was degenerative in 123 patients (58%), ischemic in 37 (17%), showed annular dilatation in 25 (12%), endocarditis in 16 (8%), was rheumatic in 13 (6%), and due to other causes in 14 (7%). Preoperative New York Heart Association score was 2.35 ± 0.85 and ejection fraction 53 ± 12%. Isolated MV repair was performed in 90 patients (42%) and 158 concomitant procedures were done in 123 patients (58%). A wide variety of surgical techniques was used in order to increase the number of repairs compared to valve replacement.

Results: There were 7 in-hospital deaths (3.3%). NYHA[2] class improved from 2.19 ± 0.85 to 1.4 ± 0.6, and freedom from reoperation was 100%. Echocardiography follow-up of patients with degenerative MV revealed that 93% of the patients (115/123) were free of mitral regurgitation greater than 2+ grade. In patients operated by a minimal invasive approach there were no conversions to sternotomy, no late deaths, none required reoperation, and 96% were free of MR[3] greater than 2+ grade. The use of multiple surgical techniques enabled the repair of more than 80% of pure MR cases.

Conclusions: MV repair provides good perioperative and mid-term results, and supports the preference for MV repair over replacement, when feasible. Multiple valve repair techniques tailored to different pathologies increases the feasibility of mitral repair.

Background: Cardiovascular disease is now well established as a multifactorial disease. In a given individual, the level of cardiovascular risk is due to the interaction between genetic and environmental components. The BIP cohort comprised 3000 patients with cardiovascular disease who were tested for the benefits of bezafibrate treatment. This cohort has the data for the lipid profile of each individual, fibrinogen, Insulin, as well as clinical, demographic and lifestyle parameters

Objectives: To genotype up to 64 variable sites in 36 genes in the BIP cohort. The genes tested in this assay are involved in pathways implicated in the development and progression of atherosclerotic plaques, lipid and homocystein metabolism, blood pressure regulation, thrombosis, rennin-angiotensin system, platelet aggregation, and leukocyte adhesion.

Methods:  DNA was extracted from 1000 Israeli patients from the BIP cohort. A multilocus assay, developed by the Roche Molecular System, was used for genotyping. Allele frequencies for some of the markers were compared to the published frequencies in a healthy population (the French Stanislas cohort, n=1480).

Results: Among the 26 comparable alleles checked in the two cohorts, 16 allele frequencies were significantly different from the healthy French population: ApoE (E3, E2, E4), ApoB (71ile), ApoC (3482T, 455C, 1100T, 3175G, 3206G), CETP (405val), ACE (Del), AGT (235thr), ELAM (128arg); p<0001 and LPL (93G, 291Ser, 447ter); p < 005.

Conclusions: Although a comparable healthy Israeli population study is needed for more precise interpretation of these results, frequency differences in these polymorphic alleles, associated with lipid metabolism, renin-angiotensin system and leukocyte adhesion mechanism, between CVD patients and healthy individuals nevertheless implicate these candidate genes as predisposing for CVD.lic safety.
 

Objective: To assess the effect of establishing a new dedicated acute stroke unit within a department of neurology on indicators of process of care and outcome of acute stroke in a routine clinical setting in Israel.

Methods: Stroke patients admitted to the Sheba Medical Center during the period March 2001 to June 2002 were included in a prospective study according to selection criteria. Data on demographics, risk factors, co-morbidities and stroke severity were collected. Indicators of process of care and outcome were assessed at hospital discharge and 30 days follow-up. Comparison between outcome variables by hospitalization ward was conducted using logistic regression analysis adjusting for confounders.

Results: Of 616 acute stroke patients (mean age 70 years, 61% men, 84% ischemic stroke), 353 (57%) were admitted to general wards and 263 (43%) to the stroke unit. Diagnostic procedures were performed more often, and infection rate was lower in the setting of the stroke unit. Poor outcome (modified Rankin scale ≥3 or death) was present less often in patients managed in the stroke unit both at hospital discharge (adjusted odds ratio 0.5, 95% confidence interval 0.3–0.8) and at 30 day follow-up (adjusted OR[1] 0.6, 95%CI[2] 0.3–0.9). A Functional Independence Measure score ≤90 or death at 30 day follow-up was less frequent among patients managed in the stroke unit than in general wards (adjusted OR 0.5, 95%CI 0.2–0.8).

Conclusions: Improved outcomes and higher adherence to guidelines were observed in patients treated in a stroke unit within a department of neurology. The results suggest that patients with acute stroke should have access to treatment in a dedicated stroke unit.

Objective: To analyze the clinical features of cutaneous mastocytosis in a large series of children.

Methods: We conducted a file review of all children clinically diagnosed with cutaneous mastocytosis in our department over the last 20 years. We evaluated gender, age at onset, character and distribution of the lesions, associated symptoms, and course of the disease.

Results: Altogether, 180 patients with cutaneous mastocytosis were identified. The male to female ratio was 1.5:1. About one-third of patients had a mastocytoma, which was present at birth in over 40% and appeared during the first year of life in most of the remainder. Urticaria pigmentosa was noted in 65% of the patients, presenting at birth in 20% and during the first year in most of the remainder. The majority of lesions was distributed over the trunk and limbs. Different kinds of associated symptoms were noted. Prognosis, in general, was good. Only 11% of the cases, all urticaria pigmentosa, were familial.

Conclusions: Most cases of pediatric mastocytosis are sporadic and appear during the first 2 years of life, especially on the trunk. Urticaria pigmentosa is the most frequent variant. The prognosis of pediatric mastocytosis, in general, is good.