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December 2008
Click here for article written by Orly Tamir, MHA, MSc, Joshua Shemer, MD, Mordechai Shani, MD, Sharona Vaknin, MSc and Miriam Ines Siebzehner, PhD, MPA, RN. IMAJ 2008: 12: December: 901-905
The Israeli Center for Technology Assessment in Health Care (ICTAHC) was established in 1998 at the Gertner Institute for Epidemiology and Health Policy Research, on foundations set in 1992 by the Medical Technology Assessment Unit. The Center is defined as an independent multidisciplinary research center, whose main aims are to assist in developing processes for the adoption of new technologies, identify and propose health priorities, and serve as an educational center for all stakeholders. Moreover, the Center promotes working relations with overseas counterparts as an essential component for expansion and advancement of the field of health technology assessment. Throughout the years, ICTAHC had contributed significantly to the development of the discipline of health technology assessment in Israel and to actual decision making in the health care system. The Center had outlined the principles, guidelines and overall framework for technology assessment in the country, as well as substantiating the discipline through various research areas, which materialized into a variety of technology-related policy accomplishments. Today, the Center serves as a national focal point in the health care system in Israel, as well as maintaining an active position in the international milieu. It has been a decade since the establishment of ICTAHC. This paper reviews the evolution of the center, describes changes in the HTA[1] field in Israel, identifies areas of focus and main research accomplishments, and illustrates the breadth of potential research scope and projections for the future.





[1] HTA = health technology assessment

November 2008
G. Markel, A. Krivoy, E. Rotman, O. Schein, S. Shrot, T. Brosh-Nissimov, T. Dushnitsky, A. Eisenkraft
The relative accessibility to various chemical agents, including chemical warfare agents and toxic industrial compounds, places a toxicological mass casualty event, including chemical terrorism, among the major threats to homeland security. TMCE[1] represents a medical and logistic challenge with potential hazardous exposure of first-response teams. In addition, TMCE poses substantial psychological and economical impact. We have created a simple response algorithm that provides practical guidelines for participating forces in TMCE. Emphasis is placed on the role of first responders, highlighting the importance of early recognition of the event as a TMCE, informing the command and control centers, and application of appropriate self-protection. The medical identification of the toxidrome is of utmost importance as it may dictate radically different approaches and life-saving modalities. Our proposed emergency management of TMCE values the “Scoop & Run” approach orchestrated by an organized evacuation plan rather than on-site decontamination. Finally, continuous preparedness of health systems – exemplified by periodic CBRN (Chemical, Biological, Radio-Nuclear) medical training of both first responders and hospital staff, mandatory placement of antidotal auto-injectors in all ambulances and CBRN[2] emergency kits in the emergency departments – would considerably improve the emergency medical response to TMCE.

 


[1] TMCE = toxicological mass casualty event

[2] CBRN = chemical, biological, radio-nuclear 
Eran Kozer, MD, Rachel Bar-Hamburger, MD, Noa Y. Rosenfeld, MD, Irena Zdanovitch, MD, Mordechai Bulkowstein, MD and Matitiahu Berkovitch, MD.

Background: Clinicians’ impression of adolescents' alcohol or drug involvement may underestimate substance-related pathology.

Objectives: To describe the characteristics of adolescents presenting to the pediatric emergency department due to substance abuse and to determine whether physicians can reliably identify these patients.

Methods: We conducted a prospective cohort study of all patients aged 12–18 years presenting to a pediatric emergency department between 1 January 2005 and 31 December 2006 for whom a urine drug screen or ethanol blood levels was ordered. According to departmental protocol urine drug screen and ethanol levels are taken for specific indications. Based on the history and clinical findings the pediatrician in the ED[1] assessed on a 5-point likelihood scale the possibility that the patients’ symptoms were related to substance abuse.

Results: Of the 139 patients in the study group 40 (30%) tested positive for ethanol or drugs of abuse. The median age was 16. Compared with patients who tested negative, there were more patients with decreased level of consciousness among patients who tested positive for ethanol or drugs (5% vs. 33% respectively, P < 0.001). The median physician estimate for the likelihood of substance abuse was 5 in patients who tested positive and 2 in patients who tested negative (P < 0.001). The likelihood of a positive drug/ethanol test was not affected by age or gender.
Conclusions: Since the likelihood of substance abuse is higher in patients presenting with a low level of consciousness, physicians may accurately assess the likelihood of substance abuse in these patients





[1] ED = emergency department

Michal Tenenbaum, Shahar Lavi, Nurit Magal, Gabrielle J. Halpern, Inbal Bolocan, Monther Boulos, Michael Kapeliovich, Mordechai Shohat, Haim Hammerman

Background: Long QT syndrome is an inherited cardiac disease, associated with malignant arrhythmias and sudden cardiac death.

Objectives: To map and identify the gene responsible for LQTS[1] in an Israeli family.

Methods: A large family was screened for LQTS after one of them was successfully resuscitated from ventricular fibrillation. The DNA was examined for suspicious loci by whole genome screening and the coding region of the LQT2 gene was sequenced.

Results: Nine family members, 6 males and 3 females, age (median and interquartile range) 26 years (13, 46), who were characterized by a unique T wave pattern were diagnosed as carrying the mutant gene. The LQTS-causing gene was mapped to chromosome 7 with the A614V mutation. All of the affected members in the family were correctly identified by electrocardiogram. Corrected QT duration was inversely associated with age in the affected family members and decreased with age.
Conclusions: Careful inspection of the ECG can correctly identify LQTS in some families. Genetic analysis is needed to confirm the diagnosis and enable the correct therapy in this disease







[1] LQTS = long QT syndrome


September 2008
G. Izbicki, G. Fink, A. Algom, R. Hirsch, L. Blieden, E. Klainman, E. Picard, S. Goldberg and M. R. Kramer

Background: Since surgical repair of tetralogy of Fallot was introduced, follow-up studies have shown that the majority of patients lead actives lives and have no subjective exercise limitation.

Objectives: To examine lung function, cardiopulmonary functional capacity and echo-Doppler assessment of pulmonary pressure in adult patients 20 years after repair of TOF.

Methods: Unselected consecutive patients performed full lung function testing, progressive cardiopulmonary exercise, and echo-Doppler assessments of pulmonary pressure.

Results: Fifty consecutive patients (33 men, 17 women) aged 29 ± 11 years who underwent surgical repair of TOF at age 10.1 ± 10.9 years were enrolled in this study. Patients after TOF showed no restriction (forced expiratory vital capacity 80%, total lung capacity 91%) and had normal oxygen saturation (97%) and 6 minute walking distance (600 meters). Echocardiography showed normal pulmonary pressure and left ventricular ejection function (62%). Cardiopulmonary exercise testing showed mild limitation of exercise capacity with oxygen uptake at maximal effort of 75–78% predicted.

Conclusions: After corrections of TOF the study patients had normal lung function and pulmonary arterial pressure but mild limitation in their exercise capacity.
 

July 2008
I. Gotsman, A. Stabholz, D. Planer, T. Pugatsch, L. Lapidus, Y. Novikov, S. Masrawa, A. Soskolne and C. Lotan

Background: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.

Objectives: To determine the relationship between inflammatory markers and the angiographic severity of CAD[1].

Methods: We measured inflammatory markers in sequential patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1[2] receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.

Results: There was a significant correlation between TNFα[3] and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFα; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P < 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFα (P < 0.05) and combined levels of TNFα and IL-6 (P < 0.05). IL-6 levels were independently predictive of Gensini coronary score (P < 0.05).

Conclusion: TNFa and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.






[1] CAD = coronary artery disease



[2] IL = interleukin



[3] TNFa = tumor necrosis factor-alpha


E. Mei-dan, A. Walfisch, I. Raz, A. Levy and M. Hallak

Background: Women frequently suffer perineal trauma while giving birth. Interventions to increase the possibility for an intact perineum are needed.

Objectives: To evaluate the effectiveness of antenatal perineal massage in increasing the likelihood of delivering with an intact perineum.

Methods: This single blinded prospective controlled trial included 234 nulliparous women with a singleton fetus. Women allocated to the study group were instructed to practice a 10 minute perineal massage daily from the 34th week of gestation until delivery. Primary outcome measures included the episiotomy rate; first, second, third and fourth-degree perineal tear rates; and intact perineum. Secondary outcomes were related to specific tear locations and the amount of suture material required for repair.

Results: Episiotomy rates, overall spontaneous tears and intact perineum rates were similar in the study and control groups. Women in the massage group had slightly lower rates of first-degree tears (73.3% νs. 78.9%, P = 0.39) and slightly higher rates of second-degree tears (26.7% νs. 19.3%, P = 0.39), although both of these outcomes did not reach statistical significance. The rates of anterior perineal tears were significantly higher in the massage group (9.5% vs. 3%, P = 0.05), whereas internal lateral tears rates were slightly lower but without statistical significance (11.5% νs.13.1%, P = 0.44).

Conclusions: The practice of antenatal perineal massage showed neither a protective nor a detrimental significant effect on the occurrence of perineal trauma.
 

A. Malkiel, P. Mor, H. Aloni, E. Gdansky and S. Grisaru-Granovsky

Background: Intrapartum risk is based mainly on obstetric history, which is lacking in primiparous women.

Objectives: To ascertain whether the traditional known risk of primiparity is an independent variable for both maternal and neonatal outcome.

Methods: All women admitted to labor during March-April 2002 were canvassed for eligibility for participation in the study based on an obstetric risk scoring system developed and validated for our population. During the study period, 1473 women presented for delivery. Of these, 298 women (20%) were eligible according to the exclusion criteria as "low risk" parturients: 135 (45%) were primiparous and 163 (55%) were multiparous (2–5 births).

Results: After correction for significant confounding factors, primiparity was revealed as an independent significant risk factor for instrumental delivery (odds ratio 15.5, 95%confidence interval 1.88–125) and for early postpartum hemorrhage (OR[1] 5.6, 95%CI[2] 1.9–16.6).

Conclusions:
This study highlights early postpartum hemorrhage as a significant risk for primiparous women, independent of mode of delivery, and also confirms previous reports of maternal complications requiring transfer from birth centers/home deliveries to tertiary centers.






[1] OR = odds ratio

[2] CI = confidence interval


A. Mager, N. Koren-Morag, M. Shohat, A. Dadashev, R. Kornowski, A. Battler and D. Hasdai

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.






[1] CAD = coronary artery disease

[2] CI = confidence interval

[3] OR = odds ratio


June 2008
A. Shemer, H. Trau, B. Davidovici, B. Amichai and M.H. Grunwald

Background: Fungal infection of the nail affects millions of people worldwide and has an estimated prevalence of more than 10% of the general population.

Objectives To determinate the prevalence of fungal infection in toenails, in order to decide the treatment policy in onychomycosis.   

Methods: We evaluated 331 patients with suspected clinical toenail onychomycosis affecting at least two toenails. Mycological examination of the affected nails was performed, both the KOH test and fungal culture were used. 

Results: Of 331 patients with psoriasis, 78.2% of the patients had at least three infected nails. The first toenail was the most affected. Trichophyton rubrum was by far the most common dermatophyte cultured from all samples.

Conclusions: Most of the patients had at least three affected toenails. Topical treatment is not effective or practical, and systemic treatment should therefore be considered.
 

A. Shemer, B. Kaplan, N. Nathansohn, M.H. Grunwald, B. Amichai and H. Trau

Background: Seborrheic dermatitis is a common chronic disease. Malassezia yeasts have been implicated in the pathogenesis of this disease. Antifungal agents are known to be effective in the treatment of Malassezia yeast infections.

Objectives To evaluate the efficacy of itraconazole in the treatment of mild to severe facial seborrheic dermatitis.

Methods: Sixty patients with moderate to severe seborrheic dermatitis were evaluated in an open non-comparative study. Patients were treated with oral itraconazole, initially 200 mg/day for a week, followed by a maintenance therapy of a single dose of 200 mg every 2 weeks. Four clinical parameters (erythema, scaling, burning, itching) were assessed using a 0–3 score. Mycological evaluation determined the presence of Malassezia spores in the scales using a direct smear.

Results: At the end of the initial treatment significant improvement was reported in three clinical parameters: erythema, scaling, itching. Maintenance therapy led to only slight further improvement. Burning sensation was only mildly improved during the treatment. The quantity of Malassezia spores present in the direct smear decreased throughout the treatment period. No blood test abnormalities were found during the treatment.

Conclusions: In this study initial treatment with itraconazole was beneficial in patients with moderate to severe seborrheic dermatitis.

A.D. Cohen, D. Van-Dijk, L. Naggan and D.A. Vardy

Background: The Beer Sheva Psoriasis Severity Score is a novel instrument for the assessment of psoriasis severity, designed for use in routine clinical conditions.

Objective: To identify the main factors of the BPSS[1].

Methods: The sample used to study the BPSS comprised 70 patients with psoriasis vulgaris treated by climatotherapy at the Dead Sea. Psoriasis severity was assessed using BPSS and PASI (Psoriasis Area and Severity Index). Factor analysis was used to identify the main factors of BPSS. Internal consistency analysis was performed. Correlation matrices were generated to compare BPSS factors.

Results: Factor analysis demonstrated that BPSS included six factors that explained 74.0% of the variance as follows: patient assessment 26.0%; physician assessment 13.2%; palms and soles involvement 11.9%; genitals, nails, and pruritus 9.0%; face involvement 7.3%; and scalp involvement 6.6%. Total scale Cronbach’s alpha was 0.76; alpha for the factors ranged between 0.39 and 0.81.

Conclusion: The major factors of BPSS were identified. BPSS may be used as a comprehensive tool for measuring psoriasis severity.




 

[1] BPSS = Beer Sheva Psoriasis Severity Score

May 2008
S. Padeh, N. Stoffman, Y. Berkun.

Background: The new syndrome, known as PFAPA, of periodic fever characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis and cervical adenopathy  has been described only in pediatric patients. It usually begins before the age of 5 years and in most cases resolves spontaneously before age 10. 

Objectives: To describe a series of adults with PFAPA syndrome.

Methods: This 6 year retrospective descriptive study includes all newly diagnosed incident adult cases aged 18 years and over referred to our center with symptomatology suggestive of PFAPA syndrome. Patients’ medical records were reviewed for past history of the disease, demographic characteristics, symptoms and signs, course of the disease, laboratory findings, and outcome following corticosteroid therapy. The comparison group included our pediatric cohort children (N=320, age 0–18 years) followed for the last 14 years (1994–2008).

Results: Fifteen adult patients were diagnosed with PFAPA syndrome. Episodes of fever occurred at 4.6 ± 1.3 week intervals, beginning at the age of 20.9 ± 7.5.  All patients had monthly attacks at the peak of the disease, with attacks recurring at 4–8 week intervals over the years. Between episodes the patients were apparently healthy, without any accompanying diseases. Attacks were aborted by a single 60 mg dose of oral prednisone in all patients.

Conclusions: This study reports the presence of PFAPA syndrome in adult patients. Although the disease is rare, an increased awareness by both patients and family physicians of this clinical syndrome has resulted in more frequent diagnosis in adult patients.
 

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