Israel Medical Association Journal

Autoimmune rheumatic diseases (ARD) affect mainly young women during their reproductive years. Fertility is usually not diminished but the time it takes to conceive is usually longer. Factors related to an ARD or to its treatment are responsible for this effect. In addition, contraception counseling is required to prevent negative fetal outcome and exacerbation of disease symptoms. In recent years, advances in therapies, clarification of risk factors for adverse pregnancy outcomes, and a multidisciplinary approach have vastly improved obstetric management, increasing the possibility of successful pregnancy with a high likelihood of favorable outcome.

Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with skin psoriasis and manifests a wide clinical phenotype, with proposed differences between sexes. Current treatments are based on traditional disease-modifying anti-rheumatic drugs (DMARD), and biologic agents and studies have reported different clinical response patterns depending on sex factors. We aimed to identify sex differences in drug retention rate in patients with PsA and performed a systematic research on MEDLINE, EMBASE and Cochrane databases (1979 to June 2015) for studies regarding effectiveness (measured as drug retention rate) in PsA in both traditional DMARDs and biologics. Demographic data as well as retention rates between sexes were extracted. From a total 709 retrieved references, we included 9 articles for the final analysis. Only one study reported data regarding DMARDs, while eight studies reported retention rate for anti-tumor necrosis factor (TNF) biologics, mainly infliximab, adalimumab and etanercept. No differences were reported in retention rates between sexes for methotrexate, while women manifested lower retention rates compared to men with regard to anti-TNF. We highlight the need to include sex differences in the management flow chart of patients with PsA.

Background: Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnical, racial and gender differences.

Objectives: To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.

Methods: We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993–2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.

Conclusions: The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring. 

Objectives: To explore IL-17A-producing CD3+CD4+T cells in peripheral blood of patients with persistent AR and assess the degree of atopy, eosinophil count (Eo count), and bronchial hyper-responsiveness (BHR) to methacholine.

Methods: The study involved 61 patients and 30 controls. The percentage of CD3+CD4+IL-17A+T cells in peripheral blood was measured by flow cytometry, bronchial challenges with Mch were performed, as was skin prick tests with standard inhalant allergens, and Eo count was measured. Atopic status was determined by the number of positive SPT results and wheal mean diameter.

Results: A statistically significant difference in Th17 cell percentage was found in the AR and control groups (2.59 ± 1.32% and 1.24 ± 0.22% respectively, P = 0.001). Forty-one patients (67.2%) were polysensitized to indoor and outdoor allergens, while 20 (32.8%) had positive skin prick tests to indoor allergens. CD4+T cells were significantly higher in the patient group compared to the control group (2.91 ± 1.5% versus 1.91 ± 0.62%, P = 0.005), as was Eo count (4.48 ± 2.13 vs. 2.32 ± 1.83) (P = 0.0001). Forty-one in the AR group (67%) and 7 (23%) in the control group were Mch-positive (P = 0.001). The percentage of IL-17A-producing CD4+T cells was significantly higher in males compared to females (3.15 ± 1.8% versus 2.31 ± 0.9%, P = 0.02)

Conclusions: Polysensitized AR patients exhibited higher IL-17A-producing CD4+T cell levels and eosinophil counts. Male patients displayed a higher frequency of IL-17A-producing T cells. 

Background: There is a striking increase in the number of people with metabolic syndrome (MetS) as a result of the global epidemic of obesity and diabetes. Increasing evidence suggests that uric acid may play a role in MetS.

Objectives: To assess the prevalence of MetS in a large cohort from Israel and its association with hyperuricemia using the latest three definitions of MetS.

Methods: We conducted a retrospective analysis of the database from a screening center in Israel, using the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF) and the Harmonizing definitions of MetS, to assess 12,036 subjects with an age range of 20–80 years.

Results: The mean age of the study sample was 46.1 ± 10.2 years and 69.8% were male. The prevalence of MetS was 10.6%, 18.2% and 20.2% in the revised NCEP ATP III, the IDF and the Harmonizing definitions respectively. The prevalence of hyperuricemia in subjects with MetS, for all three MetS definitions, was similar: 20.0%, 19.9% and 19.1% respectively. There was a graded increase in the prevalence of MetS among subjects with increasing levels of uric acid. The increasing trend persisted after stratifying for age and gender and after multivariate analysis (P for trend < 0.001).

Conclusions: This large cohort shows a high prevalence of MetS in Israel, but is still lower than the prevalence in western countries. Hyperuricemia is common in those subjects and might be considered a potential clinical parameter in the definition of MetS.
 

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.
 

The cause for gender differences in the epidemiology, natural history and response to therapy in many diseases is unknown and has seldom been investigated in depth. Sex hormones are blamed for many of these changes, mostly without any scientific evidence. In this review I will describe some of the evidence for gender differences in gastrointestinal diseases. Gender medicine and its application for gastroenterology is a new field and one warranting research.
 

Objectives: To evaluate factors that might influence the decision of pregnant women to choose chorionic villous sampling for prenatal testing.

Methods: The study group comprised 239 women referred for prenatal diagnosis who elected to undergo CVS[1]. The data were analyzed according to indication, ethnic group and religion.

Results: Among women undergoing CVS because of advanced maternal age and because of anxiety, we noted a significantly high proportion of unbalanced families, i.e., with three or more children of the same gender and deviated gender ratio. We found a significant excess of males among the Jewish families and a significant excess of females among the non-Jewish families. Jews were over-represented in the monogenic group while Christian Arabs were over-represented in the maternal age/anxiety group.

Conclusions: The proportion of women who chose CVS for prenatal diagnosis varied according to indication, ethnic group and religion. The data in this study indicate that CVS may have been utilized for balancing families with ≥ 3 or more children of the same sex. Christian Arabs chose CVS more often than the other groups. Jewish women may have utilized CVS for family balancing of both sexes, while non-Jews may have utilized CVS for balancing families with ≥ 3 daughters. 

Objectives: To characterize the academic background of graduates, evaluate their attitudes towards current and alternative medical education programs, and examine subgroups among graduates according to gender, medical school, high school education, etc.

Methods: The survey included graduates from all four Israeli medical schools who graduated between the years 1981 and 2000 in a sample of 1:3. A questionnaire and stamped return envelope were sent to every third graduate; the questionnaire included open and quantitative questions graded on a scale of 1 to 5. The data were processed for the entire graduate population and further analyzed according to subgroups such as medical schools, gender, high school education, etc.

Results: The response rate was 41.3%. The survey provided a demographic profile of graduates over a 20 year period, their previous educational and academic background, additional academic degrees achieved, satisfaction, and suggestions for future medical education programs.

Conclusions: The profile of the medical graduates in Israel is mostly homogenous in terms of demographics, with small differences among the four medical schools. In line with recommendations of the graduates, and as an expression of the changing requirements in the healthcare system and the medical profession, the medical schools should consider alternative medical education programs such as a bachelor’s degree in life sciences followed by MD studies, or education programs that combine medicine with disciplines such as law, engineering, computer science, etc.

Objective: To investigate gender differences in the baseline characteristics, clinical presentation, treatment and prognosis of women with unstable angina.

Method: Data were collected prospectively as part of the Acute Coronary Syndromes Israeli Survey in 2000 at Soroka University Medical Center. In-hospital management and 2 year follow-up were monitored for 226 consecutive patients with unstable angina admitted to our medical center during February and March 2000.

Results: Women were older (71 ± 12 vs. 66 ± 12, P = 0.006), more diabetic (41.3% vs. 34.5%, not significant) and hypertensive (76.3% vs. 64.6%, P = 0.07). Women presented more often with atypical chest pain (18.8% vs. 7.5%, P = 0.038). Heparin, aspirin and angiotensin-converting enzyme inhibitor were equally delivered, but more beta-blockers were administered to women (88.5% vs. 75.7%, P = 0.02) and more statins to men (48.1% vs. 35.4%, P = 0.07). Angiography rates were similar (17.7% vs. 19.6%). Similar management was documented during the 2 year follow-up. Re-hospitalization rates were similar (53.3% of women and 63.7% of men, NS). Men had a tendency to develop acute myocardial infarction more often (9.6% vs. 2.7%, P = 0.06) and to develop peripheral vascular disease (3.7% vs. 0%, P = 0.09), and they had a non-significant higher rate of coronary artery bypass graft (6.7% vs. 1.3%, P = 0.08). No gender difference was found in angiography (14.7% of women vs. 16.3% of men) or percutaneous intervention (13% vs. 16.7%). At 2 years there was no gender-related difference in mortality (13.3% of women vs. 16.3% of men, NS). Kaplan-Meier analysis for event-free survival after 2 years showed no gender difference in survival. Multi-regression analysis showed that gender was not a prognostic factor for survival.

Conclusions. We found no major difference in the management of men and women with unstable angina. Although men showed a tendency to suffer more major cardiac events, their 2 year prognosis was the same as for women.

Background: Multiple sclerosis is a chronic demyelinating disease of the central nervous system that presents with variable signs and symptoms. This variability in the clinical presentation may result in misdiagnosis, unnecessary referrals and misleading information to the patients.

Objectives: To identify the types of misdiagnoses made on the presentation of MS.

Methods: Fifty consecutive MS patients were questioned on their early symptoms, their mental status, the disease course until the diagnosis was confirmed, and the different diagnoses they received.

Results: The patients had been referred to 2.2 ± 1.3 specialists before seeing a neurologist, and learned about their disease 3.5 years after the onset of symptoms. Twenty-nine patients (58%) were initially given 41 wrong diagnoses. While the majority of women were misdiagnosed mentally, orthopedic work-up was offered to the men. Misdiagnosis of MS occurred most often in patients who presented with non-specific sensory symptoms that did not conform to a specific neurologic syndrome. The patients emphasized the fact that not knowing worsened their anxiety, whereas receiving the diagnosis enabled them to begin coping with their disease.

Conclusions: MS is often overlooked when patients present with non-specific sensory complaints. The difference in type of misdiagnosis between men and women may reflect a gender-dependent bias in the way physicians interpret sensory complaints.

Background: Prior studies have suggested that women are at higher risk for morbidity and mortality during coronary angioplasty, although long-term prognosis is similar after successful procedures.

Objectives: To examine the role of gender in coronary stenting, including immediate procedural success as well as early and late outcomes.

Methods: The study group comprised 560 consecutive patients (119 women and 441 men) who had undergone stenting over a 3 year period.

Results: The indications for coronary stenting were similar among women and men, and stents were successfully deployed at similar rates without complications (92 vs. 90% respectively). Cardiac death or myocardial infarction within 30 days of the procedure was observed in 5% of women and men, whereas none of the women, compared to 1.4% of men, had early revascularization. Bleeding complications occurred in 4% of women and 2% of men. During 10 ± 2.8 months of follow-up, 58% of women and men underwent repeat cardiac catheterization, revealing similar rates of restenosis, 36 vs. 32% respectively. During the study period, 3.3% of women as compared to 0.9% of men had a cardiac death (not significant). Cardiac death or myocardial infarction was observed in 7% of women and 8% of men, and the combined endpoint of death, myocardial infarction or revascularization, was noted in 24% and 26% respectively. Multivariate Cox analyses of the clinical, angiographic and procedural characteristics revealed that multiple stent deployment was the only predictor of major adverse cardiac event among men, whereas none of these characteristics predicted outcome in women.

Conclusion: Coronary stenting is performed with similar success rates among women and men, with similar restenosis rates, as well as early and late major adverse cardiac events.