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עמוד בית
Tue, 03.12.24

August 2014


Focus
Elon Glassberg MD MHA, Roy Nadler MD, Ari M. Lipsky MD PhD, Avi Shina MD, David Dagan MD MHA and Yitshak Kreiss MD MHA MPA
Perspective
Reuben Baumal MD, Jochanan Benbassat MD and Julie A.D. Van
"Clinician-scientists" is an all-inclusive term for board-certified specialists who engage in patient care and laboratory-based (biomedical) research, patient-based (clinical) research, or population-based (epidemiological) research. In recent years, the number of medical graduates who choose to combine patient care and research has declined, generating concerns about the future of medical research. This paper reviews: a) the various current categories of clinician-scientists, b) the reasons proposed for the declining number of medical graduates who opt for a career as clinician-scientists, c) the various interventions aimed at reversing this trend, and d) the projections for the future role of clinician-scientists. Efforts to encourage students to combine patient care and research include providing financial and institutional support, and reducing the duration of the training of clinician-scientists. However, recent advances in clinical and biomedical knowledge have increased the difficulties in maintaining the dual role of care-providers and scientists. It was therefore suggested that rather than expecting clinician-scientists to compete with full-time clinicians in providing patient care, and with full-time investigators in performing research, clinician-scientists will increasingly assume the role of leading/coordinating interdisciplinary teams. Such teams would focus either on patient-based research or on the clinical, biomedical and epidemiological aspects of specific clinical disorders, such as hypertension and diabetes.
Original Articles
Noa Berar Yanay MD MHA, Lubov Scherbakov MD, David Sachs MD, Nana Peleg MD, Yakov Slovodkin MD and Regina Gershkovich MD

Background: Late nephrology referral, before initiation of dialysis treatment, is associated with adverse outcome.

Objectives: To investigate the implications of late nephrology referral on mortality among dialysis patients in Israel.

Methods: We retrospectively analyzed 200 incident dialysis patients. Patients were defined as late referrals if they started dialysis less than 3 months after their first nephrology consultation. Survival rates and risk factors for mortality were analyzed

Results: The early referral (ER) group comprised 118 patients (59%) and the late referral (LR) group 82 patients (41%). The mortality rate was 44.5% (53 patients) in the ER and 68% (n=56) in the LR group. The 4 year survival rate was 41.1% in the ER and 18.7% in the LR group (P < 0.0001). The mortality rate increased with late nephrology referral (HR 1.873, 95%CI 1.133–3.094), with age (HR 1.043 for each year, 95%CI 1.018–1.068), with diabetes (HR 2.399, CI 1.369-4.202), and with serum albumin level (HR 0.359 for an increase of each 1 g/dl, 95%CI 0.242–0.533). The median survival time was higher for the ER group in women, in patients younger than 70, and in diabetic patients. A trend for longer survival time was found in non-diabetic patients. Survival time was not increased in early referred patients older than 70 and in male patients.

Conclusions: Late nephrology referral is associated with an overall higher mortality rate in dialysis patients. The survival advantage of early referral may have a different significance in specific subgroups. The timing of nephrology referral should be considered as a modifiable risk factor for mortality in patients with end-stage renal disease. 

Ronit Nesher MD, on behalf of the Israel Glaucoma Screening Group*

* 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. 

Menachem Rottem MD, Ramit Segal MD, Shmuel Kivity MD, Laliv Shamshines MD, Yael Graif MD, Meir Shalit MD, Aharon Kessel MD, Josef Panasoff MD, Shai Cohen MD, Elias Toubi MD and Nancy Agmon-Levin MD

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. 

Daniel Elbirt MD*, Ilan Asher MD*, Keren Mahlab-Guri MD, Shira Bezalel-Rosenberg MD, Victor Edelstein MD and Zev Sthoeger MD

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.

Matti Eskelinen MD PhD, Tuomas Selander MSc, Pertti Lipponen MD PhD and Petri Juvonen MD PhD

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.

Moshe D. Fejgin MD, Tal Y. Shvit MD, Yael Gershtansky MSc and Tal Biron-Shental MD

Background: Removal of retained placental tissue postpartum and retained products of conception (RPOC) abortion is done by uterine curettage or hysteroscopy. Trauma to the endometrium from surgical procedures, primarily curettage, can cause intrauterine adhesions (Asherman's syndrome) and subsequent infertility. The incidence of malpractice claims relating to intrauterine adhesions is rising, justifying reevaluation of the optimal way of handling these complications. 

Objectives: To review malpractice claims regarding intrauterine adhesions, and to explore the clinical approach that might reduce those claims or improve their medical and legal outcomes.

Methods: We examined 42 Asherman's syndrome claims handled by MCI, the largest professional liability insurer in Israel. The clinical chart of each case was reviewed and analyzed by the event preceding the adhesion formations, timing and mode of diagnosis, and outcome. We also assessed whether the adverse outcome was caused by substandard care and it it could have been avoided by different clinical practice. The legal outcome was also evaluated.

Results: Forty-seven percent of the cases occurred following vaginal delivery, 19% followed cesarean section, 28% were RPOC following a first-trimester pregnancy termination, and 2% followed a second-trimester pregnancy termination.

Conclusions: It is apparent that due to a lack of an accepted management protocol for cases of RPOC, it is difficult to legally defend those cases when the complication of Asherman syndrome develops. 

Imaging
Avi Rubinov MD, Eitan Z. Blumenthal MD and Itzchak Beiran MD
Meetings
Maria João Oliveira MD, Tiago Borges MD and Carlos Dias MD, Ph D
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