Israel Medical Association Journal

Abstract:

Background: Waterpipe tobacco smoking (WTS) is common in some populations and may add increased risk for tobaccorelated diseases.

Objectives: To assess the rates of WTS and risk practices associated with WTS in three distinct populations in Israel: long-term Jewish residents (LTJR), immigrants from the former Soviet Union (fSU), and Arabs.

Methods: We conducted a cross-sectional survey of 899 randomly selected participants, age 30–65 years, using face-toface interviews with subjects from the three population groups in Israel. Respondents reported WTS, cigarette smoking, alcohol consumption, and socioeconomic characteristics.

Results: Among men, WTS at least once a week was reported by 4.8% of LTJR, 3.2% of fSU immigrants and 20.3% of Arabs. Lower rates were reported among women of all groups. The younger, less educated men and the younger unmarried women had higher odds of WTS. LTJR who smoked cigarettes and drank alcohol had higher odds of WTS [odds ratio (OR) 32.6, confidence interval (CI) 9.36–113.6; OR = 3.57, CI =1.48–8.63, respectively], compared to non-smokers and non-drinkers. fSU immigrants who smoked cigarettes had higher odds of WTS (OR = 3.40, CI = 0.99–11.7) compared to non-smokers. Among Arabs, cigarette smoking and alcohol consumption were not associated with WTS.

Conclusions: Arabs are more likely than other Israeli populations to engage in WTS. This behavior may add to increased inequalities in rates of tobacco-induced diseases between Arabs and Jews in Israel. Including WTS in the policies for smoke-free public places is called for.

Background: QT segment prolongation is a high risk factor for fatal arrhythmias. Several studies have indicated a possible relation between low testosterone levels and QT interval prolongation. 

Objectives: To compare the QT interval length in elderly patients with prostate carcinoma who were on anti-testosterone treatment and those who were not.

Methods: We screened the electrocardiograms (ECGs) of 100 prostate cancer patients divided into two groups: 50 patients on anti-testosterone drug treatment and 50 patients not. QT interval length was measured according to the accepted methods.

Results: The mean QTc 12 leads in the entire group was 0.45 ± 0.04 sec, which is close to the upper limit. Mean QTc was actually longer in the control group and there was no QTc difference between the groups after adjustment for possible confounders. Prolonged QTc 12-lead ECG (48% in treated and 54% in non-treated) and lead L2 QT interval (50% in treated and 56% in non-treated) did not differ significantly between the groups. The analysis of QTc 12-lead ECG indicated no significant effects of anti-testosterone drug treatment. Only the use of furosemide was associated with QT prolongation. 

Conclusions: The results of this preliminary study do not support our initial concern of an alarmingly prolonged QT interval in the anti-testosterone treated group. However, further prospectively designed studies are needed. In the meanwhile we call for a close follow-up of the QT interval length in patients receiving anti-testosterone treatment. 

 

Background: The number of patients awaiting organ transplantation continues to exceed the number of available organs. 

Objectives: To document changes in the demographic characteristics of brain-dead, heart-beating organ donors over the past 10 years which may impact on organ utilization. 

Methods: Data were extracted from the Israel Transplant Registry and the Donor Action database for the 10 year period 2004–2013, inclusive. 

Results: The median age of the donors increased from 44 (range 3–73 years) to 53.5 years (range 1–79 years) (P < 0.001). There was a significant increase in the median age of donors of kidney (33 to 51 years, P < 0.001), liver (41 to 53 years, P < 0.001) and lung (40 to 49.5 years, P < 0.001). The number of donors dying from trauma decreased (34.5% to 20%, P < 0.001), while those with anoxic brain damage increased (14.5% to 25%, P < 0.001). The percent of male donors decreased over the study period, from 63% to 53%. An increase was noted in the mean number of organs transplanted per donor, from 3.29 to 3.82 per donor, due mainly to a significant increase in the utilization of lungs (31.5% to 51.3%, P < 0.001) and livers (76.3% to 82.4%, P < 0.001) while heart utilization decreased significantly since 2006 (40.9% to 17.5%, P < 0.001). 

Conclusion: Trends in the heart-beating, brain-dead organ donor pool in Israel over the past 10 years reveal significant changes in demographic characteristics which in the future will impact on the number of organs available for transplantation. 

 

Abstract

Background: Findings of studies addressing outcomes of war-related famine in non-Jewish populations in Europe during the Second World War (WWII) confirmed an association between prenatal/early life exposure to hunger and adult obesity, diabetes, hypertension, cardiovascular heart disease and the metabolic syndrome. Fetal programming was suggested as the explanatory mechanism.

Objectives: To study the association between being born during WWII in Europe and physical long-term outcomes in child Holocaust survivors.   

Methods: We conducted a cross-sectional study on all Jewish Clalit Health Services (CHS) North District members born in 1940–1945 in Europe ('exposed', n=653) or in Israel to Europe-born parents ('non-exposed', n=433). Data on socio-demographic variables, medical diagnoses, medication procurement, laboratory tests and health services utilization were derived from the CHS computerized database and compared between the groups.

Results: The exposed were significantly more likely than the non-exposed to present with dyslipidemia (81% vs. 72%, respectively), hypertension (67% vs. 53%), diabetes mellitus (41% vs. 28%), vascular disease (18% vs. 9%) and the metabolic syndrome (17% vs. 9%). The exposed also made lower use of health services but used anti-depressive agents more often compared to the non-exposed. In multivariate analyses, being born during WWII remained an independent risk marker for hypertension (OR = 1.52), diabetes mellitus (OR = 1.60), vascular disease (OR = 1.99) and the metabolic syndrome (OR = 2.14).

Conclusions: The results of this cross-sectional study based on highly validated data identify a high risk group for chronic morbidity. A question regarding potential trans-generational effects that may impact the ‘second generation’ is also raised.

Abstract

Background: A single self-rated health (SRH) assessment is associated with clinical outcome and mortality, but the biological process linking SRH with immune status remains incompletely understood.

Objectives: To examine the association between SRH and inflammation in apparently healthy individuals.

Methods: Our analysis included 13,773 apparently healthy individuals attending the Tel Aviv Sourasky Medical Center for periodic health examinations. Estimated marginal means of the inflammation-sensitive biomarkers [i.e., highly sensitive C-reactive protein (hs-CRP) and fibrinogen] for the different SRH groups were calculated and adjusted for multiple potential confounders including risk factors, health behavior, socioeconomic status, and coexistent depression.

Results: The group with the lowest SRH had a significantly higher atherothrombotic profile and significantly higher concentrations of all inflammation-sensitive biomarkers in both genders. Hs-CRP was found to differ significantly between SRH groups in both genders even after gradual adjustments for all potential confounders. Fibrinogen differs significantly according to SRH in males only, with low absolute value differences.

Conclusions: A valid association exists for apparently healthy individuals of both genders between inflammation-sensitive biomarker levels and SRH categories, especially when comparing levels of hs-CRP. Our findings underscore the importance of assessing SRH and treating it like other markers of poor health.

Abstract

Background: The mass influx of immigrants from tuberculosis-endemic countries into Israel was followed by a considerable increase in the incidence of tuberculosis (TB). All contacts of active TB patients are obliged to be screened by tuberculin skin tests (TST) and, if found positive, prophylactic treatment is considered.

Objectives: To assess the utility of interferon-gamma (IFNγ)-release assay with a prolonged follow-up in preventing unnecessary anti-TB therapy in individuals with suspected false positive results.

Methods: Between 2008 and 2012 the QuantiFERON TB gold-in-tube test (QFT-G) was performed in 278 sequential individuals who were mostly TST-positive and/or were in contact with an active TB patient. In all, whole blood was examined by the IFNγ-release assay. We correlated the TST diameter with the QFT-G assay and followed those patients with a negative assay.

Results: The QFT-G test was positive in only 72 (42%) of all 171 TST-positive individuals. There was no correlation between the diameter of TST and QFT-G positivity. Follow-up over 5 years was available in 128 (62%) of all QFT-G-negative individuals. All remained well and none developed active TB.

Conclusions: A negative QFT-G test may obviate the need for anti-TB therapy in more than half of those with a positive TST.

Abstract

Background: The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF.

Objectives: To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine.

Methods: We reanalyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants without worsening of the sixth criterion).

Results: In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered responders to rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept.

Conclusions: The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study. 

Abstract

Background: Diabetes mellitus-related lower extremity amputation is a major complication severely affecting patient survival and quality of life.

Objectives: To analyze epidemiological and clinical trends in the incidence and survival of lower extremity amputations among diabetes patients.

Methods: We conducted a retrospective observational cohort study of 565 consecutive diabetes patients who underwent their first non-traumatic lower extremity amputation between January 2002 and December 2009.

Results: Major amputations were performed in 316 (55.9%) patients: 142 above the knee (25.1%) and 174 below (30.8%); 249 (44.1%) had a minor amputation. The incidence rates of amputations decreased from 2.9 to 2.1 per 1000 diabetes patients. Kaplan-Meier survival analysis showed that first year mortality rates were lower among patients with minor amputations (31.7% vs. 39.6%, P = 0.569). First year mortality rates following below-knee amputation were somewhat lower than above-knee amputation (33.1 vs.45.1%, respectively). Cox regression model of survival at 1 year after the procedure found that age (HR 1.06 per year, 95% CI 1.04–1.07, P < 0.001), above-knee amputation (HR 1.36, 95% CI 1.01–1.83, P = 0.045) and ischemic heart disease (HR 1.68, 95% CI 1.26–2.24, P < 0.001) significantly increased one year mortality risk.

Conclusions: In this population-based study the incidence rate of non-traumatic amputations in diabetes patients between January 2002 and December 2009 decreased slightly. However, one year mortality rates after the surgery did not decline and remained high, stressing the need for a multidisciplinary effort to prevent amputations in diabetes patients.

Abstract

Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

 

Abstract

Background: Gaucher disease is the most common lysosomal storage disorder and is caused by a deficiency of the enzyme glucocerebrosidase. Enzyme deficiency leads to the accumulation of undegraded substrates, mainly in cells of the monocyte/macrophage lineage, which is responsible for the clinical manifestations of the disease. To date, no study has attempted to identify the mutation spectrum of the glucocerebrosidase gene (GBA) in Slovak patients

Objectives: To identify mutations in 14 Slovak patients with confirmed glucocerebrosidase deficiency.

Methods: Using molecular genetics methods PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and direct sequencing of coding region GBA we identified the spectrum of mutations in our patients.

Results: Five mutations (N370S, L444P, G377S, D409H and RecNciI) accounted for 75% of the mutant alleles. The remaining 25% were rare and probably individual mutations.

Conclusions: The mutational spectrum in our patients is similar to that observed in other European countries and corresponds to a Caucasian population, with N370S, L444P, RecNciI being the most common mutation. Interestingly, mutation G377S was more frequent in our patients as compared to other published data. The C4W, L96P, H311N, 745delG and 1127_1128delTT mutations are described here for the first time in Gaucher disease, contributing to the panel of published GBA mutations.  

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem involvement due to immune dysregulation. Neuropsychiatric systemic lupus erythematosus (NPSLE) includes neurological syndromes involving the central, peripheral and autonomic nervous system, as well as psychiatric syndromes observed in patients with SLE in which other causes have been excluded. The pathogenesis of NPSLE has been attributed to many different mechanisms. In particular, autoantibody-mediated vasculopathy seems to play a major role in the pathogenesis of the clinical features. Several autoantibody specificities have been reported in the serum and cerebrospinal fluid of NPSLE patients. Recently, we demonstrated an association between serum anti-endothelial antibodies (AECA) and psychosis or depression in SLE patients, strengthening the notion of a possible role of this class of autoantibodies in the pathogenesis of the disease. The study of these autoantibodies could be a useful diagnostic and prognostic tool in patients with NPSLE.