Israel Medical Association Journal

Background: The European Quality of Life 5-Dimensions questionnaire is one of the most commonly used measures of health-related quality of life.

Objectives: To present the feasibility, reliability, and validity of the Hebrew version of the EQ-5D[1].

Methods: We conducted face-to-face interviews with a representative sample (n=1666) of the Israeli Jewish population. The data collected included demographic and medical information, and self-valuation of health using the EQ-5D descriptive system, Visual Analogue Scale and Time Trade-Off. Construct validity was assessed by assuming that older individuals, those with a greater burden of diseases, and those reporting experience with their own severe illness would have lower EQ-5D indexes, VAS[2] and TTO[3] values. Test-retest reliability was assessed in a small sample (n=50) that was reevaluated after a 3 week interval.

Results: Test-retest reliability of the EQ-5D and VAS was very high (r ≥ 0.85). Reliability of the TTO was moderate (r = 0.48). There were significant differences in the EQ-5D index, profiles, VAS and TTO between healthy and sick respondents and younger and older respondents, indicating good validity of the instrument.

Conclusions: The Hebrew translation of the EQ-5D is a practical, reliable and valid instrument for assessing the health-related quality of life of the general Israeli Jewish population.

Background: The prognostic significance of biologic markers in women with ductal carcinoma in situ is not fully understood. HER2/neu is a marker of prognostic significance that is routinely assessed in invasive cancer but its correlation with clinical outcome in DCIS[1] is still obscure.

Objectives: To evaluate the significance of HER-2/neu expression as a prognostic marker in DCIS.

Methods: Clinical and pathologic data from 84 patients treated for DCIS were analyzed. HER-2/neu expression was determined by immunohistochemical staining. Histopathologic parameters (nuclear grade, histologic subtype, necrosis, calcifications, margins) were reviewed by an experienced pathologist. Local recurrence and/or metastatic spread were used as endpoints to determine the prognostic significance of HER-2/neu expression.

Results: With a median follow-up of 94.8 months, nine recurrences were reported. Neither univariate nor multivariate analysis showed a significant correlation between HER-2/neu expression and disease recurrence or the time to disease recurrence. Although HER-2/neu expression demonstrated a significant association with high nuclear grade (P < 0.0001) and comedo subtype (P < 0.0001), there was no correlation between these histologic features and recurrence rate. The correlation between high nuclear grade and disease recurrence approached statistical significance (P = 0.07).

Conclusions: No significant association was found between HER-2/neu expression in DCIS and disease recurrence. However, HER-2/neu correlated with negative markers such as nuclear grading and comedo necrosis, and its role should therefore be investigated in larger studies.
 

[1] DCIS = ductal carcinoma in situ

Background: Blunt chest trauma can cause severe acute pulmonary dysfunction due to hemo/pneumothorax, rib fractures and lung contusion.

Objectives: To study the long-term effects on lung function tests after patients' recovery from severe chest trauma.

Methods: We investigated the outcome and lung function tests in 13 patients with severe blunt chest trauma and lung contusion.

Results: The study group comprised 9 men and 4 women with an average age of 44.6 ± 13 years (median 45 years). Ten had been injured in motor vehicle accidents and 3 had fallen from a height. In addition to lung contusion most of them had fractures of more than three ribs and hemo/pneumothorax. Ten patients were treated with chest drains. Mean intensive care unit stay was 11 days (median 3) and mechanical ventilation 19 (0–60) days. Ten patients had other concomitant injuries. Mean forced expiratory volume in the first second was 81.2 ± 15.3%, mean forced vital capacity was 85 ± 13%, residual volume was 143 ± 33.4%, total lung capacity was 101 ± 14% and carbon monoxide diffusion capacity 87 ± 24. Post-exercise oxygen saturation was normal in all patients (97 ± 1.5%), and mean oxygen consumption max/kg was 18 ± 4.3 ml/kg/min (60.2 ± 15%). FEV1[1]. was significantly lower among smokers (71.1 ± 12.2 vs. 89.2 ± 13.6%, P = 0.017). There was a non-significant tendency towards lower FEV1 among patients who underwent mechanical ventilation.

Conclusions: Late after severe trauma involving lung contusion, substantial recovery is demonstrated with improved pulmonary function tests. These results encourage maximal intensive care in these patients. Further larger studies are required to investigate different factors affecting prognosis.

Background: Clinicians’ impression of adolescents' alcohol or drug involvement may underestimate substance-related pathology.

Objectives: To describe the characteristics of adolescents presenting to the pediatric emergency department due to substance abuse and to determine whether physicians can reliably identify these patients.

Methods: We conducted a prospective cohort study of all patients aged 12–18 years presenting to a pediatric emergency department between 1 January 2005 and 31 December 2006 for whom a urine drug screen or ethanol blood levels was ordered. According to departmental protocol urine drug screen and ethanol levels are taken for specific indications. Based on the history and clinical findings the pediatrician in the ED[1] assessed on a 5-point likelihood scale the possibility that the patients’ symptoms were related to substance abuse.

Results: Of the 139 patients in the study group 40 (30%) tested positive for ethanol or drugs of abuse. The median age was 16. Compared with patients who tested negative, there were more patients with decreased level of consciousness among patients who tested positive for ethanol or drugs (5% vs. 33% respectively, P < 0.001). The median physician estimate for the likelihood of substance abuse was 5 in patients who tested positive and 2 in patients who tested negative (P < 0.001). The likelihood of a positive drug/ethanol test was not affected by age or gender.
Conclusions: Since the likelihood of substance abuse is higher in patients presenting with a low level of consciousness, physicians may accurately assess the likelihood of substance abuse in these patients

Background: Long QT syndrome is an inherited cardiac disease, associated with malignant arrhythmias and sudden cardiac death.

Objectives: To map and identify the gene responsible for LQTS[1] in an Israeli family.

Methods: A large family was screened for LQTS after one of them was successfully resuscitated from ventricular fibrillation. The DNA was examined for suspicious loci by whole genome screening and the coding region of the LQT2 gene was sequenced.

Results: Nine family members, 6 males and 3 females, age (median and interquartile range) 26 years (13, 46), who were characterized by a unique T wave pattern were diagnosed as carrying the mutant gene. The LQTS-causing gene was mapped to chromosome 7 with the A614V mutation. All of the affected members in the family were correctly identified by electrocardiogram. Corrected QT duration was inversely associated with age in the affected family members and decreased with age.
Conclusions: Careful inspection of the ECG can correctly identify LQTS in some families. Genetic analysis is needed to confirm the diagnosis and enable the correct therapy in this disease

Background: Since surgical repair of tetralogy of Fallot was introduced, follow-up studies have shown that the majority of patients lead actives lives and have no subjective exercise limitation.

Objectives: To examine lung function, cardiopulmonary functional capacity and echo-Doppler assessment of pulmonary pressure in adult patients 20 years after repair of TOF.

Methods: Unselected consecutive patients performed full lung function testing, progressive cardiopulmonary exercise, and echo-Doppler assessments of pulmonary pressure.

Results: Fifty consecutive patients (33 men, 17 women) aged 29 ± 11 years who underwent surgical repair of TOF at age 10.1 ± 10.9 years were enrolled in this study. Patients after TOF showed no restriction (forced expiratory vital capacity 80%, total lung capacity 91%) and had normal oxygen saturation (97%) and 6 minute walking distance (600 meters). Echocardiography showed normal pulmonary pressure and left ventricular ejection function (62%). Cardiopulmonary exercise testing showed mild limitation of exercise capacity with oxygen uptake at maximal effort of 75–78% predicted.

Conclusions: After corrections of TOF the study patients had normal lung function and pulmonary arterial pressure but mild limitation in their exercise capacity.
 

Background: Women frequently suffer perineal trauma while giving birth. Interventions to increase the possibility for an intact perineum are needed.

Objectives: To evaluate the effectiveness of antenatal perineal massage in increasing the likelihood of delivering with an intact perineum.

Methods: This single blinded prospective controlled trial included 234 nulliparous women with a singleton fetus. Women allocated to the study group were instructed to practice a 10 minute perineal massage daily from the 34th week of gestation until delivery. Primary outcome measures included the episiotomy rate; first, second, third and fourth-degree perineal tear rates; and intact perineum. Secondary outcomes were related to specific tear locations and the amount of suture material required for repair.

Results: Episiotomy rates, overall spontaneous tears and intact perineum rates were similar in the study and control groups. Women in the massage group had slightly lower rates of first-degree tears (73.3% νs. 78.9%, P = 0.39) and slightly higher rates of second-degree tears (26.7% νs. 19.3%, P = 0.39), although both of these outcomes did not reach statistical significance. The rates of anterior perineal tears were significantly higher in the massage group (9.5% vs. 3%, P = 0.05), whereas internal lateral tears rates were slightly lower but without statistical significance (11.5% νs.13.1%, P = 0.44).

Conclusions: The practice of antenatal perineal massage showed neither a protective nor a detrimental significant effect on the occurrence of perineal trauma.
 

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.

Chronic disease management has been a rapidly growing entity in the 21st century as a strategy for managing chronic illnesses in large populations. However, experience has shown that disease management programs have not been able to demonstrate their financial value. The objectives of disease management programs are to create quality benchmarks, such as principles and guidelines, and to establish a uniform set of metrics and a standardized methodology for evaluating them. In order to illuminate the essence of disease management and its components, as well as the complexity and the problematic nature of performing economic calculations of their profitability and value, we collected data from several reports that dealt with the economic intervention of disease management programs. The disease management economic evaluation is composed of a series of steps, including the following major categories: Data/information technology, information generation, assessment/recommendations, actionable customer plans, and program assessment/reassessment. We demonstrate the elements necessary for economic analysis. Disease management is one of the most innovative tools in the managed care environment and is still in the process of being defined. Therefore, objectives should include the creation of quality benchmarks, such as principles and guidelines, and the establishment of a uniform set of metrics and a standardized methodology for evaluating them.

Background: Diseases causing increased pulmonary pressure will subsequently cause a dilation of the pulmonary arteries and right heart chambers.

Objectives: To assess the capability of computed tomography angiography and high resolution CT to diagnose and estimate the severity of pulmonary arterial hypertension as compared with standard means of right heart catheterization, echocardiography and pulmonary function tests.

Methods: The study included 38 patients with PHT[1] who underwent CT angiography and HRCT[2] as part of their routine evaluation. Diagnose included: primary PHT (n=20), Eisenmenger syndrome (n=6), scleroderma (n=3), thromboembolic disease (n=3), and others (n=6). Mean pulmonary artery pressure was 58 mmHg (range 39–92 mmHg) by catheterization and peak systolic pressure 79 mmHg (range 40–135) by echocardiography. Findings for the diameters of the main pulmonary artery and its main branches, the ascending aorta, the right atria and ventricle as well as the position of the interventricular septum were compared with 22 chest CT scans as compared to patients with no known clinical history of pulmonary hypertension, performed for other reasons (trauma, oncology follow-up) during the study period. Correlations were also calculated with recent right heart catheterization, echocardiography and pulmonary function tests of the study group.

Results: Mean main pulmonary artery diameter in the study group was 3.55 ± 0.66 cm, pulmonary artery/ascending aorta ratio 1.2 ± 0.29, right pulmonary artery 2.63 ± 0.49 cm, left pulmonary artery 2.57 ± 0.5 cm. All diameters were significantly different from the control group (P < 0.0001). Main and right pulmonary artery diameters correlated to the pressure measurement by echocardiography (P = 0.001). Bronchial collaterals were found in 11 patients (30%). The position of the interventricular septum correlated well with the echocardiography study.

Conclusions: The size of the main pulmonary artery on CT angiography has a good predictive value regarding the severity of PHT.

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: The measurement of maternal serum human chorionic gonadotropin as a predictor of fetuses with Down syndrome has been in use since 1987.

Objectives: To determine the correlation between extremely high levels of hCG[1] at mid-gestation and maternal and fetal complications.

Methods: The study group consisted of 75 pregnant women with isolated high levels of hCG (> 4 MOM) at mid-gestation, and the control group comprised 75 randomly selected women with normal hCG levels (as well as normal alpha-fetoprotein and unconjugated estriol levels). The data collected included demographic details, fetal anomalies, chromosomal aberrations, pregnancy complications, and results of neonatal tests.

Results: There was a significant increase in the frequency of fetal anomalies (detected by ultrasound), low birth weight and neonatal complications in the study group. We also found an increased rate of fetal/neonatal loss proportional to the increasing levels of hCG (up to 30% in levels exceeding 7 MOM).

Conclusion: Our study demonstrated an increased frequency of obstetric complications that was closely associated with raised hCG levels. The study also raises questions about the accuracy of the Down syndrome probability equation in the presence of extremely high levels of hCG where data on the frequency of Down syndrome is severely limited.