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. 

* 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: 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.

Background: The VEGFR/PDGFR inhibitor sunitinib was approved in Israel in 2008 for the treatment of metastatic renal cell carcinoma (mRCC), based on an international trial. However, the efficacy of sunitinib treatment in Israeli mRCC patients has not been previously reported.

Objectives: To report the outcome and associated factors of sunitinib treatment in a large cohort of Israeli mRCC patients.

Methods: We conducted a retrospective study of an unselected cohort of mRCC patients who were treated with sunitinib during the period 2006–2013 in six Israeli hospitals. Univariate and multivariate analyses were performed to determine the association between treatment outcome and clinicopathologic factors.

Results: We identified 145 patients; the median age was 65 years, 63% were male, 80% had a nephrectomy, and 28% had prior systemic treatment. Seventy-nine percent (n=115) had clinical benefit (complete response 5%, n=7; partial response 33%, n= 48; stable disease 41%, n=60); 21% (n=30) were refractory to treatment. Median progression-free survival (PFS) was 12 months and median overall survival 21 months. Factors associated with clinical benefit were sunitinib-induced hypertension: [odds ratio (OR) 3.6, P = 0.042] and sunitinib dose reduction or treatment interruption (OR 2.4, P = 0.049). Factors associated with PFS were female gender [hazard ratio (HR) 2, P = 0.004], pre-sunitinib treatment neutrophil to lymphocyte ratio ≤ 3 (HR 2.19, P = 0.002), and active smoking (HR 0.19, P < 0.0001). Factors associated with overall survival were active smoking (HR 0.25, P < 0.0001) and sunitinib-induced hypertension (HR 0.48, P = 0.005). To minimize toxicity, the dose was reduced or the treatment interrupted in 39% (n=57). 

Conclusions: The efficacy of sunitinib treatment for mRCC among Israeli patients is similar to that of international data.

Objectives: To investigate the association between CAD and H. pylori infection using MPI.

Methods: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD-positive group included patients with ischemia and/or myocardial infarctions (MI) on a stress MPI, coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients’ demographic data, risk factors for CAD, and childhood socioeconomic status were recorded.

Results: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD- positive (odds ratio 1.83, 95% confidence interval 1.06–3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95%CI 1.44–7.84, P = 0.005). No association was noted with CagA positivity.

Conclusions: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors. 

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: A growing number of Eritrean and Sudanese refugees seek medical assistance in the labor and delivery ward of our facility. Providing treatment to this unique population is challenging since communication is limited and pregnancy follow-up is usually absent.

Objectives: To compare the perinatal outcome of refugees and Israeli parturients.

Methods: The medical and financial records of all refugees delivered between May 2010 and April 2011 were reviewed. Perinatal outcome was compared to that of native Israeli controls.

Results: During this period 254 refugees were delivered (2.3% of deliveries). Refugees were significantly younger and leaner. They had significantly more premature deliveries under 37 weeks (23 vs. 10, P = 0.029) and under 34 weeks gestation (9 vs. 2, P = 0.036) with more admissions to the neonatal intensive care unit (15 vs. 5, P = 0.038). Overall cesarean section rate was similar but refugees required significantly more urgent surgeries (97% vs. 53%, P = 0.0001). Refugees had significantly more cases of meconium and episiotomies but fewer cases of epidural analgesia. There were 2 intrauterine fetal deaths among refugees, compared to 13 of 11,239 deliveries during this time period (P = 0.036), as well as 7 pregnancy terminations following sexual assault during their escape. Sixty-eight percent of refugees had medical fees outstanding with a total debt of 2,656,000 shekels (US$ 767,250).

Conclusions: The phenomenon of African refugees giving birth in our center is of unprecedented magnitude and bears significant medical and ethical implications. Refugees proved susceptible to adverse perinatal outcomes compared to their Israeli counterparts. Setting a pregnancy follow-up plan could, in the long run, prevent adverse outcomes and reduce costs involved in treating this population.