Israel Medical Association Journal

Background: Treatment guidelines for well-differentiated papillary thyroid carcinoma (PTC) are based on retrospective studies and vary among different professional thyroid associations.

Objectives: To evaluate physician adherence to guidelines, overall and by specialty.

Methods: Questionnaires on the approach to low risk PTC were distributed among 51 surgeons and endocrinologists treating patients with PTC in tertiary medical centers.

Results: A wide range of answers was recorded among physicians regarding the danger posed by low risk PTC to the patient’s life, urgency with which treatment should be administered, type of treatment, and risks associated with this treatment. There was a significant between-group difference in treatment preference: endocrinologists chose total thyroidectomy with radioactive iodine, while surgeons favored hemithyroidectomy alone.

Conclusions: There is a wide difference in treatment recommendations between treating physicians and different specialties with regard to low risk PTC. The wide variation within and between specialties may be explained by biases. 

Background: The detection and correction of refractive errors is one of the priorities of the World Health Organization Initiative Vision 2020.

Objectives: To determine the factors related to a child having an ocular abnormality (poor vision, refractive error or other abnormality) among schoolchildren in northern Israel.

Methods: A cross-sectional population-based study was conducted among 2113 students aged 6-7 and 13-14 years old in 70 schools in northern Israel. Medical examination included vision history, clinical eye examination and vision testing. If a parent’s informed consent was available, eye drops (cycloplegia) were delivered for fundus and retinoscopy testing. An ophthalmologist was asked to determine the need for the child’s referral for further diagnostic procedures, treatment and/or follow-up. Multivariate analysis was limited to 1708 children, using data pertaining to the ophthalmologist’s decision regarding referral, as well as vision and retinoscopy results.

Results: Vision and/or ocular abnormality was prevalent in 21.5% (95% confidence interval 17.4–26.6%), predominantly among 13-14 year olds and Jewish children. Abnormal clinical findings were found in 5.7% of the students. Retinoscopy showed a higher prevalence of hypermetropia among 6-7 year olds and a higher prevalence of myopia and astigmatism among the 13-14 year olds. The multivariate analysis suggests an independent effect of retinoscopy abnormality (odds ratio = 3.85), vision abnormality (OR [1]= 2.42), Jewish ethnicity (OR = 1.62) and 13-14 year old age group (OR = 1.26) on the ophthalmologist’s referral decision.

Conclusions: Vision and/or ocular abnormality is an important health problem among schoolchildren in northern Israel. The independent effect of ethnicity and age on the ophthalmologist’s referral decision should be further explored.

Background: The prevalence of thyroid dysfunction in early pregnancy in Israel is not known.

Objectives: To assess the rate of abnormal thyroid-stimulating hormone (TSH) tests in low risk pregnant women attending a community clinic in Israel.

Methods: We conducted a retrospective analysis of the charts of low risk pregnant women (n=303) who had undergone a TSH screening during the first trimester of pregnancy at Clalit Health Services Women's Health Centers in Ashkelon and Tel Aviv. The TSH normal range during first trimester was considered to be 0.1–2.5 mIU/L.

Results: The TSH levels ranged from 0.04 to 13.3 mIU/L (median 1.73 mIU/L, mean 1.88 mIU/L). The rate of abnormal TSH was 25.6%, with low TSH 2.3% and high TSH 23.4%. The prevalence of abnormal TSH was not influenced by gravidity (primigravidas versus multigravidas) or place of residence (Ashkelon or Tel Aviv).

Conclusions: In view of the high prevalence of abnormal TSH (25.6%) in pregnant women in Israel during the first trimester, a universal country-wide screening should be considered.

Background: The prevalence of ADHD is controversial, with many feeling that this disorder is over- or under-diagnosed.

Objectives: To study the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its association with socio-demographic characteristics, comorbid mental disorders, medical services, and methylphenidate use in the Israeli adolescent population.

Methods: The Israel Survey of Mental Health among Adolescents was conducted in a representative national sample of 14–17 year olds and their mothers. The Development and Well-Being Assessment was administered to identify DSM-IV diagnoses of ADHD and comorbid mental and learning disorders, and the results were verified by senior child psychiatrists. Respondents were also asked about their use of medical services and psychotropic drug intake in the past 12 months.

Results: Three percent of the adolescents met the DSM-IV criteria for ADHD. ADHD was significantly associated with gender (higher prevalence in boys than girls), ethnicity (higher prevalence in Jews than Arabs/Druze), referral to a medical professional, and maternal help-seeking for the emotional or behavioral problems of the adolescent. Medication was prescribed to 2.9% of adolescents: 34.6% with a diagnosis of ADHD had not been prescribed methylphenidate in the past year, and 34.6% of the medicated subjects did not have a diagnosis of ADHD. None of the Arab/Druze adolescents was receiving stimulants compared to 3.7% of the Jewish adolescents.

Conclusions: Despite advances in public awareness of mental disorders in youth, a substantial proportion of older Israeli adolescents, especially from minority groups, are under-diagnosed or untreated. At the same time, many, especially from the Jewish majority, are over-diagnosed and potentially over-treated. Ethnic disparities in rates of mental health care highlight the urgent need to identify and overcome barriers to the recognition and treatment of these conditions.

The major autoantigens in the inflamed synovium in rheumatoid arthritis (RA) are citrullinated peptides. Citrullinated peptides are employed in diagnostic kits for detection of anti-citrullinated protein antibodies (ACPA), a serological marker with high specificity and sensitivity in the diagnosis of RA, and have been included in the new ACR/EULAR classification criteria for RA. ACPA-positive RA patients suffer from an erosive and more aggressive disease compared to ACPA-negative patients. In view of the mounting indications that ACPA plays a seminal role in the pathogenesis of RA, it might be valuable to pursue a specific treatment aiming ACPA as a target. We found that citrullinated peptides, which contain a unique amino acid, citrulline, alter the protein structure within the connective tissue, leading to tolerance breakdown and triggering the autoimmune response in RA. However, with different doses and routes of administration, citrullinated peptides can promote immune tolerance rather than induction of disease. 

* Israel Glaucoma Screening Group 2009-2010 (in alphabetical order):

Applebaum E, Arodi A, Avidar A, Barkana Y, Beiran I, Bracha Z, Burgansky Z, Cotlear D, Dafna O, Drori L, ElNaddaf H, Epstein E, Garzozi H, Gawi H, Geffen N, Glovinsky Y, Hadayer A, Jubran R, Kalev-Landoy M, Kaniezer B, Kratz A, Kurtz S, Matanes M, Mazover A, Mazzawi N, Naveh L, Nesher R, Neuman H, Pedut T, Pikel Y, Rachmiel R, Rath E, Robinson A, Segev E, Shemesh G, Shoham N, Silverston B, Tam G, Tessler Z, Tiosano B, Vidan A, Vishinevski I, Zalish M, Zarfati D, Zorani Y.

Background: Early detection of glaucoma enables early initiation of treatment. Screening populations at risk is likely to help achieve this goal.

Objectives: To increase public awareness regarding early detection of glaucoma, and estimate the prevalence of increased intraocular pressure (IOP) and optic disk cupping in the screened population.

Methods: A public awareness campaign was carried out in Israel during the 2009 and 2010 World Glaucoma Week, culminating each year in a one-day, free-of-charge screening of individuals in 13 outreach public locations. Screening was performed by 45 ophthalmologists and included a brief medical history, slit-lamp exam with measurement of intraocular pressure (IOP), and evaluation of cup/disk ratio.

Results: A total of 2560 individuals were screened; the mean age was 59 ± 13 years. IOP ≥ 21 mmHg was found in 4.8%, and 12.3% had cupping ≥ 0.5. IOP ≥ 21 mmHg together with cupping ≥ 0.5 were present in 1.4% and this rate increased with age: 3.7% of cases in the age group ≥ 70 years compared to 1% and 0.6% in the age groups 50–69 and < 50 years, respectively (P < 0.001). Likewise, the prevalence of cupping ≥ 0.7 and of IOP ≥ 24 mmHg increased significantly with age. The prevalence of IOP ≥ 21 mmHg increased in cases with a family history of glaucoma in first-degree relatives (10.5% compared to 3.9%, P < 0.001). The prevalence of IOP ≥ 21 mmHg was also increased in diabetic patients (8.3% vs. 4.3% in non-diabetics, P = 0.002). Further ophthalmologic evaluation was recommended to 13% of the screened individuals.

Conclusions: Outreach screening for glaucoma is a valuable tool for detecting glaucoma, pre-perimetric glaucoma, or ocular hypertension in a meaningful number of previously undiagnosed cases. Yet, cost-effectiveness issues should also be considered. The yield of such screening increases with age and seems to be most advantageous in cases with diabetes or a family history of glaucoma. 

Background: Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monoclonal antibody, was recently shown to be effective in treating resistant CSU.

Objectives: To investigated the treatment of CSU with omalizumab in Israel.

Methods: We conducted a multicenter retrospective analysis of patients with refractory CSU treated with omalizuamb in Israel during 2012–2013. Complete improvement was defined as resolution of symptoms with no need for other medications, or satisfactory when patients’ condition improved but required regular or intermittent doses of antihistamines.

Results: Forty-three patients received omalizumab off-label for refractory CSU. Their mean age was 45 ± 12 years and CSU duration was 4.3 ± 4 years. In this cohort, 98% were unsuccessfully treated with high dose H(1)-antihistamines, 88% with systemic glucocorticoids and 30% with cyclosporine and/or other immune-modulators. Fourteen patients received only one injection of omalizumab, while the other 29 received on average of 4.3 ± 3.2 injections; 30 patients received 150 mg/month and 13 received 300 mg/month. Following omalizumab therapy, disease remitted within weeks in 86% of patients, of whom half achieved complete remission. The latter was associated with usage of high dose omalizumab, 300 mg/month vs. 150 mg/month (P = 0.02) and repeated therapy (i.e., multiple injections vs. a single injection) (P = 0.0005).

Conclusions: Omalizumab is an effective and safe treatment for refractory CSU with rapid onset of action for inducing and maintaining remission. Treating CSU patients mandates an individual approach, because while low dose omalizumab will suffice for some patients others might need higher doses and prolonged therapy. 

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of the innate and adaptive immune systems with the production of autoantibodies by stimulated B lymphocytes. The BLyS protein (B lymphocyte stimulator) is secreted mainly by monocytes and activated T cells and is responsible for the proliferation, maturation and survival of B cells.

Objectivs: To study sera BLyS level and its clinical significance in Israeli lupus patients over time.

Methods: The study population included 41 lupus patients (8 males, 33 females; mean age 35.56 ± 15.35 years) and 50 healthy controls. The patients were followed for 5.02 ± 1.95 years. We tested 221 lupus sera (mean 5.4 samples/patient) and 50 normal sera for BLyS levels by a capture ELISA. Disease activity was determined by the SLEDAI score.

Results: Sera BLyS levels were significantly higher in SLE patients than in controls (3.37 ± 3.73 vs. 0.32 ± 0.96 ng/ml, P < 0.05). BLyS levels were high in at least one sera sample in 80.5% of the patients but were normal in all sera in the control group. There was no correlation between sera BLyS and anti-ds-DNA autoantibody levels. BLyS levels fluctuated over time in sera of lupus patients with no significant correlation to disease activity.

Conclusions: Most of our lupus patients had high sera BLyS levels, suggesting a role for BLyS in the pathogenesis and course of SLE. Our results support the current novel approach of targeting BLyS (neutralization by antibodies or soluble receptors) in the treatment of active lupus patients.

Background: The primary diagnosis of functional dyspepsia (FD) is made on the basis of typical symptoms and by excluding organic gastrointestinal diseases that cause dyspeptic symptoms. However, there is difficulty reaching a diagnosis in FD.

Objectives: To assess the efficiency of the Usefulness Index (UI) test and history-taking in diagnosing FD.

Methods: A study on acute abdominal pain conducted by the World Organizati­on of Gast­roentero­logy Research Committee (OMGE) included 1333 patients presenting with acute abdo­minal pain. The clinical history-taking variables (n=23) for each pa­tient were recorded in detail using a prede­fined structured data collection sheet, and the collected data were compared with the final diagnoses.

Results: The most signifi­cant clinical history-taking variables of FD in univa­riate analysis were risk ratio (RR): location of pain at diagnosis (RR = 5.7), location of initial pain (RR = 6.5), previous similar pain (RR = 4.0), duration of pain (RR = 2.9), previous abdominal surgery (RR = 4.1), previous abdominal diseases (RR = 4.0), and previous indigestion (RR = 3.1). T­he sensi­tivity of the physicians’ initial de­cisi­on in detecting FD was 0.44, speci­fi­city 0.99 and effi­ciency 0.98; UI was 0.19 and RR 195.3. In the stepwise multivariate logistic regression analysis, the independent predictors of FD were the physicians’ initial decision (RR = 266.4), location of initial pain (RR = 3.4), duration of pain (RR = 3.1), previous abdominal surgery (RR = 3.7), previous indigestion (RR = 2.2) and vomiting (RR = 2.0).

Conclusions: The patients with upper abdominal pain initially and a previous history of abdominal surgery and indigestion tended to be at risk for FD. In these patients the UI test could help the clinician differentiate FD from other diagnoses of acute abdominal pain.