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March 2012
B. Zafrir and O. Amir

Beta blockers are a fundamental treatment in chronic heart failure (HF), yet concern and disagreement regarding their role in the treatment of decompensated HF and during hospitalization are common in clinical practice. This review summarizes the literature on various aspects of beta blocker treatment during acute and chronic decompensated HF. In recent years evidence has accumulated concerning the efficacy and tolerability of beta blockers in decompensated HF. Clinical analyses show that withdrawal of chronic beta blockade should be avoided when possible during hospitalization and that beta blocker therapy be initiated as soon as hemodynamic stability and a euvolemic state are achieved. This strategy may increase adherence to beta blockers after discharge and lower rehospitalization and mortality rates. We also discuss the various positive inotrope regimens (phosphodiesterase inhibitors, levosimendan, dobutamine) and their interactions with beta blockers in decompensated HF.

January 2012
Pedro Ojeda, MD, MPH, Isabel Ojeda, MD, Gema Rubio, MD and Fernando Pineda, PhD.

Background: In the last decade the use of different types of oral immunotherapy for food-allergic patients has increased with generally satisfactory outcomes. Cow’s milk and hen’s egg, a common element in the daily diet, have received the main interest. Most of these immunotherapy regimens are performed in the hospital, causing inconvenience for both children and their parents.

Objectives: To assess the efficacy and safety of a home-based oral immunotherapy regimen with raw pasteurized egg.

Methods: The study group comprised children aged 6 years and older with allergy to hen’s egg proteins, proven by positive skin prick-tests (SPT) and/or specific immunoglobulin E (sIgE) and positive open oral food challenge (OOFC) with boiled or raw egg. Patients who met the inclusion criteria and signed the informed consent form underwent egg immunotherapy according to an established schedule.

Results: The treatment was given to 31 of the 36 recruited patients: 80.6% of the intention to treat population achieved complete tolerance to the maximum dose equivalent to one raw hen’s egg, 3.2% achieved incomplete tolerance, and 16.2% did not achieve an acceptable tolerance dose. Most of the latter patients had a positive baseline OOFC with low doses of boiled egg. The average number of reactions per treated patient was 5.8, most of them grades 1 and 2 there were no grade 4 reactions.

Conclusions: This home-based oral immunotherapy protocol proved to effectively induce tolerance to hen’s egg in most of the egg-allergic children and its safety profile was acceptable.

Silvia Sanchez-Garcia, MD, Pablo Rodriguez del Rio, MD, Carmelo Escudero, MD, Cristina Garcia-Fernandez, MD, Antonio Ramirez, MD and M.D. Ibanez, MD, PhD

Background: In the last two decades milk oral immunotherapy has gained interest as an effective treatment option for milk-allergic patients.

Objectives: To report on the efficacy of a milk oral immunotherapy.

Methods: Children with immunoglobulin E-mediated cow’s milk allergy were included in the protocol. The treatment consisted of an induction phase in which milk doses were increased weekly in the hospital, while the tolerated dose was continued daily at home. The goal was to achieve a minimum milk intake of 200 ml a day. During the maintenance phase, patients ingested at least 200 ml of milk in a single dose every day.

Results: The protocol was applied to 105 milk-allergic children diagnosed by specific IgE to milk and controlled oral food challenge. The mean duration of the induction phase was 19 weeks. Of the 105 subjects, 86 (81.9%) successfully complied with the protocol and 19 (19.1%) failed. Causes of failure were moderate/severe reactions in 12 patients (12.44%) and personal reasons in 7 (6.66%). A total of 182 adverse reactions occurred during the induction phase, most of them mild. Baseline specific IgE to milk and casein were significantly lower (P < 0.05) in the successfully treated group compared to the group in which the treatment failed.

Conclusions: Milk oral immunotherapy is a safe and effective treatment for milk-allergic children, although adverse reactions may occur. Baseline milk and casein-specific IgE may be useful to predict a good response to milk oral immunotherapy.

______

[1] IgE = immunoglobulin E

Giuseppe Crisafulli, PhD, Lucia Caminiti, MD and Giovanni B. Pajno, MD
Intan H. Ismail, MD, MMed and Mimi L.K. Tang, MB, BS, PhD

Food allergies have increased significantly over recent decades, and are the most common cause of admissions for anaphylaxis in childhood, particularly in children under 5 years of age. Current management of food allergy is limited to strict food allergen avoidance together with education on the recognition and emergency management of allergic reactions, and in some cases provision of self-injectable adrenalin. Although this supportive management approach is generally effective, it is burdensome for patients and families, and in turn leads to reduced quality of life. Patients with food allergy would benefit greatly from a definitive treatment that could achieve long-term tolerance. Recent studies demonstrate that oral immunotherapy (OIT) can induce desensitization and modulate allergen-specific immune responses. However, it remains uncertain whether long-term tolerance can be achieved with current OIT regimens. Increased allergen dose, duration of OIT and/or inclusion of an immune modifying adjuvant may enhance the tolerogenic potential of OIT. Allergic reactions during OIT are common, although severe reactions are infrequent. Oral immunotherapy holds promise as a novel approach to the definitive treatment of food allergy.

December 2011
G.A. Weiss, Y. Goldich, E. Bartov and Z. Burgansky-Eliash

Background: Comorbid depression may play an important role in non-compliance with medical treatment among patients with chronic illnesses. Glaucoma is a potentially blinding chronic disease requiring life-long commitment to medical therapy. Patient's failure to adhere to anti-glaucoma treatment may lead to disease progression and visual loss.

Objectives: To assess the prevalence of depressive symptoms in glaucoma patients and the association between these symptoms and non-compliance with anti-glaucoma therapy.

Methods: This was a cross-sectional observational study. Compliance with pharmacotherapy was assessed with the Morisky Medication Adherence questionnaire (eight items). Screening for depression was performed by means of the CES-D scale (Center for Epidemiologic Studies Depression scale). The association between depression and compliance rates was analyzed.

Results: The study group comprised 76 glaucoma patients; 19.7% of the subjects were classified as "non-compliant" (Morisky cutoff < 10) and 21.1% suffered from depression (CES-D cutoff ≥ 16). We found a similar level of non-compliance when comparing depressed with non-depressed glaucoma patients. However, a significant correlation was observed between the level of depression and the level of non-compliance (P = 0.04).

Conclusions: Our study revealed a similar rate of depression in glaucoma patients and the general Israeli population. The presence of depression was not associated with the presence of non-compliance, yet the level of depression was associated with the level of non-compliance.

November 2011
G. Vashitz, J. Meyer, Y. Parmet, Y. Henkin, R. Peleg, N. Liebermann and H. Gilutz

Background: There is a wide treatment gap between evidence-based guidelines and their implementation in primary care.

Objective: To evaluate the extent to which physicians "literally" follow guidelines for secondary prevention of dyslipidemia and the extent to which they practice "substitute" therapeutic measures.

Methods: We performed a post hoc analysis of data collected in a prospective cluster randomized trial. The participants were 130 primary care physicians treating 7745 patients requiring secondary prevention of dyslipidemia. The outcome measure was physician "literal" adherence or "substitute" adherence. We used logistic regressions to evaluate the effect of various clinical situations on “literal” and “substitute” adherence.

Results: "Literal" adherence was modest for ordering a lipoprotein profile (35.1%) and for pharmacotherapy initiations (26.0%), but rather poor for drug up-titrations (16.1%) and for referrals for specialist consultation (3.8%). In contrast, many physicians opted for "substitute" adherence for up-titrations (75.9%) and referrals for consultation (78.7%). Physicians tended to follow the guidelines “literally” in simple clinical situations (such as the need for lipid screening) but to use "substitute" measures in more complex cases (when dose up-titration or metabolic consultation was required). Most substitute actions were less intense than the actions recommended by the guidelines.

Conclusions: Physicians often do not blindly follow guidelines, but rather evaluate their adequacy for a particular patient and adjust the treatment according to their assessment. We suggest that clinical management be evaluated in a broader sense than strict guideline adherence, which may underestimate physicians' efforts.
 

D. Rosengarten, M.R. Kramer, G. Amir, L. Fuks and N. Berkman

Pulmonary epithelioid hemangioendothelioma (PEH), previously known as "intravascular bronchoalveolar tumor," is a rare vascular malignancy with an unpredictable prognosis. Treatment can vary from observation in asymptomatic patients to surgery in patients with resectable disease or chemotherapy in patients with disseminated disease. This report describes the clinical, radiological and pathological features of three cases of PEH and a review of the current literature.
 

July 2011
G. Pines, Y. Klein, E. Melzer, E. Idelevich, V. Buyeviz, S. Machlenkin and H. Kashtan

Background: Surgery is considered the mainstay of treatment for esophageal carcinoma. Transhiatal esophagectomy with cervical esophagogastric anastomosis is considered relatively safe with an oncological outcome comparable to that using the transthoracic approach.

Objectives: To review the results of the first 100 transhiatal esophagectomies performed in a single Israeli center.

Methods: The records of all patients who had undergone transhiatal esophagectomy during the period 2003–2009 were reviewed. The study group comprised the first 100 patients. All patients who had undergone colon or small bowel transposition were excluded. Indications for surgery included esophageal cancer, caustic injury and achalasia.

Results: The median follow-up period was 19.5 months. The anastomotic leakage rate was 15% and all were managed successfully with local wound care. The benign stricture rate was 10% and all were managed successfully with endoscopic balloon dilation. Anastomotic leakage was found to be a risk factor for stricture formation. Overall survival was 54%. Response to neoadjuvant therapy was associated with a favorable prognosis.

Conclusions: Transhiatal esophagectomy is a relatively safe approach with adequate oncological results, as long as it is performed in a high volume center.
 

June 2011
O. Chechik, R. inbar, B. Danino, R. Lador, R. Greenberg and S. Avital

Background: The effect of anti-platelet drugs on surgical blood loss and perioperative complications has not been studied in depth and the management of surgical patients taking anti-platelet medications is controversial.

Objective: To assess the effect of anti-platelet therapy on perioperative blood loss in patients undergoing appendectomy either laparoscopically or via open surgery.

Methods: We reviewed the files of all patients > 40 years old who underwent open or laparoscopic appendectomies from 2007 to 2010. Excluded were patients with short hospitalization and no follow-up of hemoglobin level, patients on warfarin treatment and patients who underwent additional procedures. Estimation of blood loss was based on decrease in hemoglobin level from admission to discharge. Risk factors for blood loss, such as anti-platelet therapy, age, gender, surgical approach, surgical time, surgical findings and complications, were analyzed.

Results: The final cohort included 179 patients (mean age 61 ± 14 years, range 40–93) of whom 65 were males. The mean perioperative hemoglobin decrease was 1.59 ± 1.07 mg/dl (range 0–5 mg/dl). Thirty-nine patients received anti-platelet therapy prior to surgery and 140 did not. No significant differences in decrease of hemoglobin level were found between patients receiving anti-platelet therapy and those who were not (1.73 ± 1.21 vs. 1.55 ± 1.02 mg/dl, P = 0.3). In addition, no difference was found between patients on anti-platelet therapy operated laparoscopically and those operated in an open fashion (1.59 ± 1.18 vs. 2.04 ± 1.28 mg/dl, P = 0.29). Five patients required blood transfusions, two of whom were on anti-platelet therapy. Blood loss was significantly greater in patients with a perforated appendicitis and in those with an operative time of more than one hour.

Conclusions: Anti-platelet therapy does not pose a risk for increased blood loss following emergent appendectomy performed either laparoscopically or in an open fashion.
 

A. Schlez, I. Litmanovitz, S. Bauer, T. Dolfin, R. Regev and S. Arnon

Background: Music therapy has been recommended as an adjuvant therapy for both preterm infants and mothers during their stay in the neonatal intensive care unit (NICU), and has been shown to have beneficial effects.

Objectives: To study the usefulness of combining live harp music therapy and kangaroo care (KC) on short-term physiological and behavioral parameters of preterm infants and their mothers in the NICU setting.

Methods: Included in this study were stable infants born between 32 and 37 weeks of gestation, with normal hearing .Mother-infant dyads were randomly assigned to KC and live harp music therapy or to KC alone. Using repeated measures, neonatal and maternal heart rate, oxygen saturation and respiratory rate were recorded along with neonatal behavioral state and maternal anxiety state. Maternal age, ethnicity, education, and love of music were documented.

Results: Fifty-two mother-infant dyads were tested. Compared with KC alone, KC and live harp music therapy had a significantly beneficial effect on maternal anxiety score (46.8 ± 10 vs. 27.7 ± 7.1, respectively, P < 0.01). Infants’ physiological responses and behavior did not differ significantly. No correlation was found between mothers’ age, ethnicity, years of education and affinity for music, and anxiety scores (P = 0.2 to 0.5 for all four variables).

Conclusions: KC combined with live harp music therapy is more beneficial in reducing maternal anxiety than KC alone. This combined therapy had no apparent effect on the tested infants’ physiological responses or behavioral state.
 

April 2011
M. Harari, E. Dramsdahl, S. Shany, Y. Baumfeld, A. Ingber, V. Novack and S. Sukenik

Background: Ultraviolet B (UVB) rays are required by the skin for the production of vitamin D. The intensity of UVB at the Dead Sea area is the lowest in the world. Low vitamin D levels are often associated with musculoskeletal symptoms.

Objectives: To assess the effectiveness of climatotherapy at the Dead Sea on the production of vitamin D in Norwegian patients suffering from various rheumatic diseases and to investigate possible associations between increased vitamin D serum levels, musculoskeletal symptoms and disease severity.

Methods: Sixty Norwegian patients who came to the Dead Sea area for 21 days of medical rehabilitation were divided into three groups according to their diagnosis: chronic pain syndromes, i.e., low back pain or fibromyalgia (Group 1, n=33); rheumatoid arthritis (Group 2, n=16); and osteoarthritis (Group 3, n=11). Serum 25-hydroxyvitamin D (25-OH-D) levels were determined at arrival and prior to departure. The treatment protocol included daily sun exposure (climatotherapy), bathing in the Dead Sea and mineral spring water (balneotherapy), mud applications and fitness classes.

Results: 25-OH-D serum levels increased significantly from 71.3 ± 26.6 nM at arrival to 89.3 ± 23.2 nM prior to departure (P < 0.001). Adjusted for the initial levels of pain (assessed by a visual analog scale) and disease severity, a direct correlation was observed between increased 25-OH-D serum levels and pain reduction (P = 0.012) and reduction of disease severity (P = 0.02).

Conclusions: Climatotherapy at the Dead Sea induces significant changes in vitamin D. Increased 25-OH-D serum levels are associated with reduced musculoskeletal pain and disease severity.
 

March 2011
O. Beyar Katz, A. Ben Barak, G. Abrahami, N. Arad, Y. Burstein, R. Dvir, S. Fischer, J. Kapelushnik, H. Kaplinsky, A. Toren, S. Vilk-Revel, M. Weintraub, I. Yaniv, S. Linn, B. Futerman and M. Weyl Ben-Arush

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.






[1] NHL = non-Hodgkin lymphoma



[2] BFM = Berlin-Frankfurt-Munster


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