Israel Medical Association Journal

Background: Whereas procoagulation abnormalities in acute stress are well established, little is known about the mechanism of hypercoagulation in chronic stress, such as post-traumatic stress disorder (PTSD). This is crucial, given the fact that chronic coagulation disturbances have been associated with increased morbidity and premature mortality due to thromboembolism and cardiovascular disorders, complications recently described in PTSD patients.

Objectives: To explore the mechanisms of hypercoagulation in chronic PTSD.

Methods: Thirty patients diagnosed with chronic PTSD were enrolled and compared with a control group matched for age, gender and ethnicity. Hypercoagulation state was evaluated by levels of fibrinogen, D-dimer, prothrombin fragment F 1+2, von Willebrand factor (vWF) antigen, factor VIII activity, activated protein C resistance, ProC Global assay, and tissue factor antigen. Psychiatric evaluation was performed using the Mini-International Neuropsychiatric Interview and Clinician Administered PTSD Scale (CAPS).

Results: vWF antigen levels were significantly higher in patients with chronic PTSD compared with the controls (121.3 ± 42 vs. 99.7 ± 23, respectively, P = 0.034). Higher levels of vWF antigen and factor VIII activity were found in patients with severe chronic PTSD (CAPS > 80), compared to controls and patients with chronic PTSD and less severe symptoms (CAPS ≤ 80). However, no differences were observed in any other studied coagulation parameters between patients and controls.

Conclusions: Increased levels of vWF antigen and factor VIII activity were documented in severe chronic PTSD. These findings suggest that the higher risk of arterial and venous thromboembolic events in PTSD patients could be related to endothelial damage or endothelial activation.
 

Background: A new approach for assessing non-cognitive attributes in medical school candidates was developed and implemented at the Hebrew University Medical School. The non-cognitive tests included a biographical questionnaire, a questionnaire raising theoretical dilemmas and multiple mini-interviews.

Objectives: To evaluate the effects of the change in the admission process on students' demographics and future career choices.

Methods: A questionnaire including questions on students’ background and future residency preferences was administered to first-year students accepted to medical school by the new admission system. Results were compared with previous information collected from students admitted through the old admission process.

Results: Students accepted by the new process were significantly older (22.49 vs. 21.54, P < 0.001), and more had attended other academic studies before medical school, considered other professions besides medicine, and majored in humanities combined with sciences in high school. Significantly more students from small communities were admitted by the new system.  Differences were found in preferences for future residencies; compared with the old admission process (N=41), students admitted by the new system (N=85) had a more positive attitude towards a career in obstetrics/gynecology (41% vs. 22%, P < 0.001) and hematology/oncology (11.7% vs. 4.8%, P < 0.001), while the popularity of surgery and pediatrics had decreased (34.5% vs. 61%, P < 0.001 and 68.7% vs. 82.5%, P < 0.001 respectively).

Conclusions: Assessment of non-cognitive parameters as part of the admission criteria to medical school was associated with an older and more heterogenic group of students and different preferences for future residency. Whether these preferences in first-year students persist through medical school is a question for further research.
 

Background: Influenza vaccination of community-dwelling elderly is widely recommended. Observational studies have shown a strong association between physicians' personal vaccination status and their reported level of recommendation to patients and possibly their patients' actual vaccination. No published trials have examined whether increasing vaccination rates of primary care staff raises vaccination among their patients. Proof of a positive effect would support the notion that vaccinating health care workers benefits their patients.

Objectives: To examine whether an intervention to increase staff vaccination also increases vaccination of their patients aged 65 and over.

Methods: A trial examining an intervention aiming to raise staff immunization rates was performed in primary care community clinics in the Jerusalem area. The study population comprised the staff of 13 randomly chosen intervention clinics during the season of 2007–2008, with another 14 clinics serving as controls. The intervention resulted in a staff vaccination rate of 52.8% compared to 26.5% in the control clinics (66.1% and 32.2% among physicians). No intervention was directed at the patients. Data on patient vaccination and other patient characteristics were extracted from the health funds’ computerized databases.

Results: The percentage of patients vaccinated during the intervention season was 57.8% in both intervention and control groups, reflecting an increase of 14.4% compared to the previous season in the intervention clinics and of 13.4% in the control clinics. Logistic regression demonstrated a statistically significant association between intervention and patient vaccination with an odds ratio of 1.10 (95% confidence interval 1.03–1.18). However, analysis adjusting for clustering did not show a significant association.

Conclusions: Increasing influenza vaccination of the medical staff did not substantially increase patient vaccination. These results do not show any patient benefit from staff vaccination in primary care.
 

Background: Some specialists and policy makers advocate progression of the mental health reform in Israel by transferring beds from psychiatric to general hospitals.

Objectives: To compare the demographic, diagnostic and psychopathological profiles of psychiatric inpatients hospitalized in psychiatric and general hospitals, as well as their patterns of drug abuse and to estimate the preparedness of general hospitals for the possible expansion of their psychiatric services.

Methods: Between 2002 and 2006 a total of 250 patients were consecutively admitted to the Jerusalem Mental Health Center-Kfar Shaul Hospital and 220 to the psychiatric department of Sheba Medical Center, a general hospital in central Israel; the patients’ ages ranged from 18 to 65. The two groups were compared for demographic features, psychiatric diagnoses and severity of psychopathology (utilizing PANSS, HAD-21, YMRS rating scales). Drug abuse was diagnosed by urine analyses and self-report.

Results: The patients in the psychiatric hospital were significantly younger, predominantly male, and more dependent on social security payments. In the general hospital, diagnoses of affective and anxiety disorders prevailed, while in the psychiatric hospital schizophrenic and other psychotic patients constituted the majority. The patients in the general hospital were decidedly more depressed; in the psychiatric hospital, notably higher rates of manic symptoms as well as positive, negative and general schizophrenic symptoms were reported. For the most abused substances (opiates, cannabis and methamphetamines) the rates in the psychiatric hospital were significantly higher.

Conclusions: The differences between the two groups of inpatients were very pronounced, and therefore, the transferring of psychiatric beds to general hospitals could not be done without serious and profound organizational, educational and financial changes in the psychiatric services of general hospitals. Since each of the two inpatient systems has particular specializations and experience with the different subgroups of patients, they could coexist for a long time.
 

Background: Diarrhea is a leading cause of child mortality worldwide. Rotavirus is one of the most common causes of severe diarrhea and dehydration in children.

Objectives: To compare the demographic, clinical and laboratory characteristics of patients with rotavirus gastroenteritis to those with other causes of gastroenteritis.

Methods: The medical records of children aged 0–18 years hospitalized with acute gastroenteritis in our facility between 1 January 2004 and 31 March 2006 were retrieved. Patients with rotavirus gastroenteritis were compared with patients who were rotavirus negative.

Results: The study group comprised 533 patients; 202 tested positive for rotavirus and 331 tested negative. Compared to patients with rotavirus-negative gastroenteritis, patients with rotavirus-positive gastroenteritis had a higher incidence of vomiting (185/202 vs. 212/331, 92% vs.  64%, P < 0.001), lethargy (67 vs. 51, 33% vs. 15%, P < 0.001), and dehydration (81 vs. 78 vs. 40% vs. 24%, P < 0.001). The need for intravenous rehydration therapy and the duration of hospitalization were higher in patients with rotavirus gastroenteritis.

Conclusions: Vomiting and dehydration are more common in hospitalized children with rotavirus gastroenteritis than in children with gastroenteritis due to other causes.
 

Background: Increased cardiovascular morbidity has become a leading cause of mortality in rheumatoid arthritis (RA). Tumor necrosis factor-alpha (TNFα) inhibitors may influence flow-mediated vasodilation (FMD) of the brachial artery, common carotid intima-media thickness (ccIMT) and arterial stiffness indicated by pulse-wave velocity (PWV) in RA.

Objectives: To assess the effects of adalimumab treatment on FMD[1], ccIMT[2] and PWV[3] in early RA[4].

Methods: Eight RA patients with a disease duration ≤ 1 year received 40 mg adalimumab subcutaneously every 2 weeks. Ultrasound was used to assess brachial FMD and ccIMT. PWV was determined by arteriograph. These parameters were correlated with C-reacive protein, vonWillebrand factor (vWF), immunoglobulin M (IgM)-rheumatoid factor (RF), anti-CCP levels and 28-joint Disease Activity Score (DAS28).

Results: Adalimumab therapy successfully ameliorated arthritis as it decreased CRP[5] levels (P = 0.04) and DAS28[6] (P < 0.0001). Endothelial function (FMD) improved in comparison to baseline (P < 0.05). ccIMT decreased after 24 weeks, indicating a mean 11.9% significant improvement (P = 0.002). Adalimumab relieved arterial stiffness (PWV) after 24 weeks. Although plasma vWF[7] levels decreased only non-significantly after 12 weeks of treatment, an inverse correlation was found between FMD and vWF (R = -0.643, P = 0.007). FMD also inversely correlated with CRP (R = -0.596, P = 0.015). CRP and vWF also correlated with each other (R = 0.598, P = 0.014). PWV and ccIMT showed a positive correlation (R = 0.735, P = 0.038).

Conclusions: Treatment with adalimumab exerted favorable effects on disease activity and endothelial dysfunction. It also ameliorated carotid atherosclerosis and arterial stiffness in patients with early RA. Early adalimumab therapy may have an important role in the prevention and management of vascular comorbidity in RA.

Background: Uterine sarcoma constitutes a highly malignant group of uterine tumors. It accounts for 2–6% of uterine malignancies and its incidence is 1.7 in 100,000 women. The three most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma and carcinosarcoma. Based on relatively small case series, the literature provides little information on the risk factors, the natural course of the disease and the preferred treatment.

Objectives: To evaluate uterine sarcoma patients treated in a tertiary referral center in Israel over a 20 year period (1980–2005).

Methods: We conducted a retrospective review of the charts of 40 uterine sarcoma patients, including their tumor characteristics, stage at diagnosis, treatment modalities, follow-up and survival.

Results: The patients’ mean age was 53 years (range 32–76); 30% of the patients had carcinosarcoma, 55% had leiomyosarcoma and 15% had ESS[1]. Half of the patients presented with stage I disease, 23% stage II, 10% stage III and 15% stage IV. Thirty-nine patients were treated by surgery. Adjuvant radiotherapy was administered to 39% of the patients, adjuvant chemotherapy to 21% and combined radiotherapy and chemotherapy to 9%. The mean follow-up period was 44 months, at which time disease had recurred in 44% of the patients. The disease stage was correlated with the 5-year survival rate, which was 73.1% for stages I-II and 22.2% for stages III- IV.

Conclusions: In accordance with other larger studies our data show that the only prognostic factor that was significantly correlated with prognosis was the stage of the disease at diagnosis. Despite advances in diagnosis and treatment, survival has not improved over the last 25 years.

Background: The age-standardized incidence rate of invasive cervical cancer in Israeli Jewish women is persistently low. Selected demographic characteristics of Israeli Jewish women with cervical squamous cell carcinoma (SCC) were reported recently. 

Objectives: To assess selected clinical characteristics of Israeli Jewish women with cervical SCC.

Methods: Included were all Israeli Jewish women with SCC diagnosed during the 3-year period 2002­–2004. Data were obtained from the Israel National Cancer Registry and the Central Population Registry. Discharge summaries of the patients were reviewed and clinical data were abstracted.

Results: The study was based on 350 Israeli Jewish women with histologically confirmed cervical SCC diagnosed during the 3-year study period. The median age of the patients was 50.3 years. The most common main complaint was discharge/bleeding (35.7%) and only a small percentage (7.4%) was diagnosed subsequent to an abnormal cytological smear. The rate of patients diagnosed in stage I was 47.7%. The overall absolute 5-year survival and survival in stage I was 70% and 83.8% respectively. The rate of Israeli born patients diagnosed in stage I and their overall absolute 5-year survival was significantly higher than in the other ethnic groups.

Conclusions: Age, the most frequent main complaint, the percent of patients diagnosed in stage I and the 5-year survival (overall and in stage I) are similar to data in other countries. The survival of Israeli born women seems to be better than that of other ethnic groups.
 

Background: Multiple sclerosis (MS) is a common demyelinating disorder of the central nervous system (CNS) and although it is a well-established autoimmune disease its ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity.

Objectives: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease.

Methods: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls.

Results: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P ≤ 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05)

Conclusions: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.
 

Background: The fish-eating habits of Israelis who present with impacted fish bones in the aerodigestive tract are unknown.

Objectives: To retrospectively investigate the relation between an impacted fish bone in the aerodigestive tract, the species of fish, and the place of occurrence in an Israeli population.

Methods: The current prospective observational study included all patients with aerodigestive impacted fish bones who were treated in our emergency department from 1 September 2008 to 30 September 2009. The data retrieved from their medical records included age, gender, place of event (at home or elsewhere), species of fish, and method of removing the bone.

Results: A total of 108 patients aged 1.5–87 years (median 48 years), 52.8% female, met the study criteria. Most (87%) of the events occurred at home, and 50.9% occurred during the weekend (Friday- Saturday). The bones were from low-priced fish (e.g., carp, hake) in 62% of the cases, high-priced fish (e.g., salmon, red snapper) in 30.5%, and of unknown species in 10.2%. The proportion of cases in which the fish bone belonged to a high-priced fish eaten out of the home was significantly higher than the cases in which a low-priced fish was eaten at home (64.3% vs. 22.3%, P = 0.04). One hundred bones were removed during direct oral inspection and 8 bones were removed under general anesthesia by endoscopy.

Conclusions: Most fish bone impactions in the aerodigestive tract in central Israel involve low-priced fish and take place at home over the weekend.
 

Background: Infertility is one of the most prevalent health disorders in young adults.

Objectives: To study the distribution of causes of infertility in couples referred to primary infertility clinics in Israel.

Methods: Data for a 9 year period were derived from two clinics of major women's hospitals run by the country's largest health insurance funds. All patients were treated by one physician. Laparoscopy was not performed to rule out endometriosis.

Results: Of the 2515 couples identified, 1991 (79.2%) had a definitive diagnosis following complete workup (including hysterosalpingography). Mean age was 29.6 ± 6.0 years; mean duration of infertility was 1.7 ± 1.8 years. Primary infertility accounted for 65% of cases. Causes of infertility were male factor (45%), oligo-ovulation disorders (37%), and tubal damage (18%). Infertility factors were identified in the woman alone in 30.6% of cases and the man alone in 29.2%. Two combined infertility factors were found in 18% of patients, and three combined factors in 0.5%. The rate of unexplained infertility (which probably includes non-tubal endometriosis) was 20.7%.

Conclusions: As male factor accounts for almost half of all cases of infertility in couples, sperm analysis is mandatory before any treatment.
 

Background: Traditionally, medication dosage was based on clinical and demographic parameters, but drug metabolism was recently recognized as an important factor for proper dosing and prediction of side effects. Metabolic considerations are crucial when administering drugs with a narrow therapeutic index, such as those of the thioguanides family (azathioprine and 6-MP). These can cause life-threatening myelosuppression due to low activity of a critical metabolic enzyme, thiopurine S-methyl transferase. A number of single nucleotide substitutions encoding variant enzymes account for most enzyme deficiencies.

Objectives: To determine the frequency of individuals from different Israeli ethnic groups who may be at risk for drug toxicity from drugs of the thioguanide family due to enzymatic variants.

Methods: DNA analysis was performed using polymerase chain reaction methods. We tested TPMT[1] allelic variants TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G) in five subpopulations in Israel: mixed-origin Israeli Jews, Arabs, Druze, Jews of Kurdish extraction, and Ethiopian Jews.

Results: The Druze (P = 0.0002) and Ethiopian Jewish (P = 0.015) subpopulations had a significantly unique distribution of allelic variants compared to the rest of the Israeli population. The Druze subpopulation showed a high number of TPMT variants with decreased activity, and a homozygote for TPMT*3A/ *3A was detected.  Ethiopian Jews were found to carry mainly the TPMT*3C variant, also observed in other studies of African populations.

Conclusions: It is advisable that Druze patients be tested for the TPMT enzyme before starting treatment with 6-MP or azathioprine. Such testing may also be considered for other Israeli ethnic subgroups.