Heresco-Levy U.,Hebrew University of Jerusalem |
Gelfin G.,Hebrew University of Jerusalem |
Bloch B.,Haemek Medical Center |
Bloch B.,Technion - Israel Institute of Technology |
And 5 more authors.
International Journal of Neuropsychopharmacology | Year: 2013
Antagonism of N-methyl-d-aspartate glutamatergic receptors (NMDAR) may represent an effective antidepressant mechanism. d-cycloserine (DCS) is a partial agonist at the NMDAR-associated glycine modulatory site that at high doses acts as a functional NMDAR antagonist. Twenty-six treatment-resistant major depressive disorder patients participated in a double blind, placebo-controlled, 6-wk parallel group trial with a gradually titrated high dose (1000mg/d) of DCS added to their antidepressant medication. DCS treatment was well tolerated, had no psychotomimetic effects and led to improvement in depression symptoms as measured by Hamilton Depression Rating Scale (HAMD; p=0.005) and Beck Depression Inventory (p=0.046). Of the 13 subjects treated with DCS, 54% had a ≥50% HAMD score reduction vs. 15% of the 13 patients randomized to placebo (p=0.039). A significant (p=0.043) treatment× pre-treatment glycine serum levels interaction was registered. These findings indicate that NMDAR glycine site antagonism may be a cost-effective target for development of mechanistically novel antidepressants. Larger-sized DCS trials are warranted. © 2012 CINP.
Mizrahi H.,Haemek Medical Center |
Mizrahi H.,Darent Valley Hospital |
Parker M.C.,Darent Valley Hospital |
Parker M.C.,Fawkham Manor Hospital
Archives of Surgery | Year: 2012
Objective: To establish a literature-based surgical approach to asymptomatic inguinal hernia (IH). Data Sources: PubMed, the Cochrane Library database, Embase, national guidelines (including the National Library of Guidelines Specialist Library), National Institute for Health and Clinical Excellence guidelines, and the National Research Register were searched for prospective randomized trials comparing surgical treatment of patients with asymptomatic IH with conservative treatment. Study Selection: The literature search retrieved 216 article headlines, and these articles were analyzed. Of those studies, a total of 41 articles were found to be relevant and 2 large well-conducted randomized controlled studies that published their results in several articles were reviewed. Data Extraction: The pain and discomfort, general health status, complications, and life-threatening events of patients with asymptomatic IH managed by surgery or watchful waiting were determined. Data Synthesis: No significant difference in pain scores and general health status were found when comparing the patients who were followed up with the patients who had surgery.Asignificant crossover ratio ranging between 23% and 72% from watchful waiting to surgery was found. In patients with watchful waiting, the rates of IH strangulation were 0.27% after 2 years of follow-up and 0.55% after 4 years of follow-up. In patients who underwent elective surgery, the range of operative complications was 0% to 22.3% and the recurrence rate was 2.1%. Conclusion: Both treatment options for asymptomatic IH are safe, but most patients will develop symptoms (mainly pain) over time and will require operation. ©2012 American Medical Association. All rights reserved.
Dodiuk-Gad R.P.,University of Toronto |
Dodiuk-Gad R.P.,Haemek Medical Center |
Laws P.M.,University of Toronto |
Shear N.H.,University of Toronto
Seminars in Cutaneous Medicine and Surgery | Year: 2014
Epidemiological studies of severe drug hypersensitivities are important to understanding the morbidity and mortality of this heterogeneous group of disorders. These insights also allow greater identification of at-risk patient groups. However, epidemiological studies of drug hypersensitivity reactions are challenging due to the variable diagnostic criteria applied and incomplete data sets studied. We review the epidemiology of severe drug hypersensitivity reactions with a particular focus on severe cutaneous adverse reactions (SCARs). SCAR diseases include: Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash eosinophilia and systemic symptoms, serum-sickness-like reaction and acute generalized exanthematous pustulosis. © 2014 Frontline Medical Communications.
Lin G.,Western Galilee Hospital |
Becker A.,Haemek Medical Center |
Lynn M.,University of Miami
Injury | Year: 2012
Objective: Efficient triage may have a major influence on mortality and morbidity as well as financial consequences. A continuous effort to improve this decision making process and update the trauma alert criteria is being made. However, criteria for determining the evacuation priority are not well developed. We performed a prospective study to evaluate which pre-hospital parameters identify major trauma victims with an emphasis on a need for emergent surgical procedures. Methods: A prospective cohort included 601 patients admitted to a level one trauma centre over a three months period. The pre-hospital trauma alert criteria were recorded and set as independent variables. All major surgical procedures were graded in real time as: emergent, urgent, or not urgent. The ISS was calculated after completion of all the diagnostic workup. Patients were classified as major trauma victims if their calculated ISS was 16 or greater, and those needed an urgent intervention or intensive care. The relative risks (RR) for major trauma and a need for an emergent operation were calculated. Results: 243 (40%) patients were classified as having a major trauma. 39 (6.5%) patients required an emergent operative intervention: 24 for an active bleeding, 5 for a pericardial tamponade and 10 for an imminent cerebral herniation. Paramedic judgement and a penetrating injury to the trunk were the most common causes for over triage. However, a penetrating injury to the trunk had been the only clue that the victim needed an emergent operation in five cases. 128 patients had a pre-hospital Glasgow coma score (GCS) ≤12. Altered mental status was the most common and a significant predictor of both major trauma (RR of 3.00 with a 95% confidence interval (CI) of 1.98-4.53) and a need for an emergent operation (RR, 95% CI: 4.43, 2.28-8.58). Also, a systolic blood pressure ≤90 mmHg was highly associated with an emergent operation (RR, 95% CI: 11.69, 5.85-23.36). Conclusion: For determining the evacuation priority, we suggest a triage system based on three major criteria: mental status, hypotension and a penetrating injury to the trunk. Overall, the set of trauma alert criteria system can be further simplified and enable better utilisation of resources. © 2010 Elsevier Ltd. All rights reserved.
May K.,University of Greifswald |
Goldstein L.H.,Haemek Medical Center
European Journal of Clinical Pharmacology | Year: 2010
Background: Neurologic adverse events reported in premarketing clinical trials of azithromycin have been mild, occurring in less than 1% of the patients, and include dizziness, headache, vertigo, and somnolence. Serious adverse neuropsychiatric effects of azithromycin have never been reported in the pediatric population and only seldom in adults. Case report: We report two brothers aged 6 and 15 years with severe and prolonged complex neuropsychiatric manifestations associated with azithromycin treatment. Both brothers experienced visual and auditory hallucinations, and one brother additionally experienced multiple partial complex seizures, severe headaches, and recurrent cortical blindness. All symptoms commenced within 24 h after the initial dose of azithromycin and resolved slowly, within 2-4 weeks. Discussion: Possible genetic and environmental explanations are discussed, such as polymorphism in uptake of efflux transporters at different levels, particularly at the blood brain barrier level. © 2010 Springer-Verlag.
Vardizer Y.,Haemek Medical Center
Pediatric endocrinology reviews : PER | Year: 2010
This review follows the process of evaluation of thyroid related orbitopathy (TRO) patients from diagnosis to treatment decision. We will attempt to define the criteria for referring TRO patients to the ophthalmologist and establish a common basis for orbital examination and TRO patient assessment. This should help classify TRO patients and achieve the best treatment regime. Thyroid related orbitopathy (TRO) is an endocrine disorder with orbital manifestations. Though most patients are first seen by an endocrinologist because of thyroid function disturbance symptoms, approximately 10% will first be seen by an ophthalmologist due to orbitopathy symptoms and signs (1). In the majority of cases the time interval between the appearance of dysthyroid symptomatology and orbital signs is less than a year. Among patients with thyroid endocrine dysfunction, 25% to 50% will gradually develop TRO. Most will have mild orbital manifestations, 28% will develop moderate to severe signs and only 3-5% will have the severe form (2). In this review we will follow the TRO patient through his first steps in the orbital clinic and emphasize the importance of clinical assessment as a crucial phase in determining the appropriate therapeutic approach.
Barak E.C.,Haemek Medical Center |
Kerner M.,Haemek Medical Center |
Rozenman D.,Haemek Medical Center |
Ziv M.,Haemek Medical Center
Dermatologic Therapy | Year: 2015
Combination therapy has become important in treating psoriasis, using synergism between different mechanisms to maximize efficacy and minimize toxicity. Little has been published on the combination of cyclosporine and anti-tumor necrosis factor (TNF) α agents. In this study, a retrospective chart review was made of the effects of this combination therapy in 10 patients with recalcitrant psoriasis. Treatment included a conditioning phase with cyclosporine, 3.14 ± 0.37 mg/kg for 4.6 ± 2 weeks, and a combination phase during which etanercept/adalimumab were initiated and cyclosporine was tapered over 10.2 ± 3.7 weeks. Treatment success, evaluated after each phase, was classified as complete recovery (CR, more than 75% improvement), partial response (PR, 25-75% improvement), and no response (NR, less than 25% improvement). All patients reached CR at the end of the combination therapy. Two were still on combination therapy after 12 and 20 weeks. Adverse event occurred in three cases, all in the conditioning phase. We conclude that combination therapy with cyclosporine and anti-TNF α appears to offer an effective and safe approach to treatment of psoriasis. © 2015 Wiley Periodicals, Inc.
Shalev E.,Haemek Medical Center
Obstetrics and Gynecology | Year: 2011
Objective: To investigate the effect of a decidual incision on trophoblastic invasion potential in vitro. Methods: Human trophoblast cells were obtained from first-trimester legal terminations of pregnancy. Decidual tissue was retrieved from healthy, low-risk women who underwent an elective cesarean delivery at term. Each dissected decidual sample was divided into four similar-sized samples. The first slice was not treated, the second was incised with a surgical blade to mimic an in vivo injury, the third was incised and immediately repaired with medical adhesive material. This model was used to investigate trophoblastic invasion through a fully repaired decidua. The fourth slice was covered with medical adhesive material only, to exclude any effect of the adhesive material on the decidua. The percent of invasion was calculated as: absorbance of invaded cell×100=invasion index (%). Invasion was expressed as invasion index. The mean and standard deviation of the invasion index were then calculated. Results: Eight decidual samples were retrieved from eight women. Incised decidua showed a significantly higher mean invasion index (83.3% [±8.1%], P=.012) than the other three models (intact decidua, 69.9% [±5.1%]; incised decidua repaired with adhesive, 66.6% [±8.2%]; intact decidua with adhesive, 58.3% [±11.3%]. There was no significant difference in the invasion index between the other models (P=.4). Conclusion: Induced decidual injury significantly increased the invasion potential of trophoblastic cells compared with intact decidua. Complete re-approximation of the incised edges reversed this effect in vitro. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.
Saliba W.,Technion - Israel Institute of Technology |
Saliba W.,Haemek Medical Center |
Barnett O.,Technion - Israel Institute of Technology |
Rennert H.S.,Technion - Israel Institute of Technology |
And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012
Context and Objectives: Vitamin D plays a key role in maintaining bone health, but evidence for its nonskeletal effects is inconsistent. This study aims to examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and all-cause mortality in a large general population cohort. Design, Participants, and Setting: Using the computerized database of the largest health care provider in Israel, we identified a cohort of subjects 20 years old or older with serum 25(OH)D levels measured between January 2008 and December 2009. Vital status was ascertained through August 2011. Results: Median follow-up was 28.5 months (interquartile range 23.8-33.5 months); 7,247 of 182,152 participants (4.0%) died. Subjects who died had significantly lower serum 25(OH)D levels (mean 44.8 ± 24.2 nmol/liter) than those alive at the end of follow-up (51.0 ± 23.2 nmol/liter), P <0.001. After adjustment for age, gender, ethnicity, and seasonality, the hazard ratio (HR) for all-cause mortality was 2.02 [95% confidence interval (CI) 1.89-2.15] for the lowest serum 25(OH)D quartile (<33.8 nmol/liter) compared with the highest. After further adjustment for comorbidity, use of vitamin D supplements and statins, smoking, socioeconomic status, and body mass index, the HR was 1.81 (95% CI 1.69-1.95). This remained, even after adjustment for serum low-density lipoprotein, high-density lipoprotein, calcium level (corrected for serum albumin levels), and glomerular filtration rate, 1.85 (95% CI 1.70-2.01). The fully adjusted HR associated with being in the second 25(OH)D quartile (33.8-49.4 nmol/liter) was 1.25 (95% CI 1.16-1.34). Conclusions: All-cause mortality is independently and inversely associated with serum 25(OH)D levels at levels less than 50 nmol/liter. Copyright © 2012 by The Endocrine Society.
Saliba W.,Technion - Israel Institute of Technology |
Barnett-Griness O.,Technion - Israel Institute of Technology |
Elias M.,Haemek Medical Center |
Rennert G.,Technion - Israel Institute of Technology |
Rennert G.,Clalit Health Services Headquarters
Journal of Thrombosis and Haemostasis | Year: 2015
Background: The neutrophil to lymphocyte ratio (NLR) is associated with increased risk of cardiovascular morbidity and mortality. We aimed to assess the association between NLR and first episode of stroke in patients with atrial fibrillation. Methods: Using the computerized database of the largest HMO in Israel, we identified a cohort of adults, aged 20 years or older, with atrial fibrillation diagnosed before 1 January 2012. Eligible subjects had no prior stroke or TIA, were not on anticoagulants at baseline, and had at least one blood cell count performed in 2011. The cohort (32 912 subjects) was followed for the first event of stroke or TIA until 31 December 2012. Results: Overall 981 subjects developed stroke during a follow-up of 30 961 person-years (stroke rate, 3.17 per 100 person-years). The incidence rate of stroke increased across NLR quartiles: 2.27, 2.72, 3.26 and 4.54 per 100 person-years, respectively. Cox proportional hazard regression analysis adjusting for the individual CHA2DS2-VASc score risk factors showed that, compared with the lowest NLR quartile, the HR for stroke was 1.11 (95% CI, 0.91-1.35), 1.25 (1.03-1.51) and 1.56 (1.29-1.88) for the second, third and highest quartile, respectively. On stratified analysis, NLR refined the risk of stroke across all CHA2DS2-VASc score strata. Adding NLR to the CHA2DS2-VASc score increased the AUC from 0.627 (95% CI, 0.612-0.643) to 0.635 (0.619-0.651) (P = 0.037). Conclusions: The neutrophil to lymphocyte ratio is directly associated with the risk of stroke in patients with atrial fibrillation. Future studies are needed to replicate these findings. © 2015 International Society on Thrombosis and Haemostasis.