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עמוד בית
Thu, 29.10.26

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May 2014
Donato Rigante MD PhD, Aurora Rossodivita MD PhD and Luca Cantarini MD PhD
Cassandra Ocampo MD, Molebedi L. Segwagwe MB ChB MRCP, Julian Deonarain MB ChB FCPath, Francesca Cainelli MD and Sandro Vento MD
Ilan Ben-Zvi MD and Avi Livneh MD
Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease characterized by spontaneous short attacks of fever, elevated acute-phase reactants, and serositis. Approximately 5%–10% of FMF patients do not respond to colchicine treatment and another 5% are intolerant to colchicine because of side effects. Recently, following the discovery of the inflammasome and recognition of the importance of interleukin-1β (IL-1β) as the major cytokine involved in the pathogenesis of FMF, IL-1β blockade has been suggested and tried sporadically to treat FMF, with good results. To date, case reports and small case series involving colchicine-resistant FMF patients and showing high efficacy of IL-1β blockade have been reported. At the Israel Center for FMF at the Sheba Medical Center the first double-blind randomized placebo-controlled trial of anakinra in FMF patients who are resistant or intolerant to colchicines is underway. In this report we discuss the mechanism of colchicine resistance in FMF patients, the data in the literature on IL1β blockade in these patients, and the anakinra trial inclusion criteria and study protocol.

Miriam E. Pepys Vered MB BS and Mark B. Pepys MD PhD FRCP FRCPath FRS FMedSci
Bonaguri Chiara PHD, Orsoni Jelka Gabriella MD, Russo Annalisa PHD, Rubino Pierangela MD, Bacciu Salvatore MD, Lippi Giuseppe MD Melegari Alessandra PHD, Zavota Laura MD, Ghirardini Stella AO and Mora Paolo MD

Background: Cogan’s syndrome (CS) is a rare autoimmune vasculitis characterized by ocular inflammation and sensorineural hearing loss. CS is divided into a “typical” form with non-syphilitic interstitial keratitis and audiovestibular symptoms, and an “atypical” form with ocular involvement affecting structures other than the cornea. Anti-Hsp70 antibodies were found at variable levels in patients presenting with various forms of autoimmune sensorineural hearing loss (ASNHL).

Objectives: To assess the correlation between anti-Hsp70 antibodies and specific ASNHL subgroups.

Methods: We divided 112 subjects into four groups: 14 subjects with typical CS, 24 with atypical CS, 55 with ASNHL, and 19 control subjects (healthy subjects and patients with systemic autoimmune diseases but no sensorineural hearing or audiovestibular alterations). Patients were tested for serological autoimmunity markers including anti-Hsp70.

Results: Positivity of the anti-Hsp70 antibody test was highest in the typical CS group (92.9%) and lowest in the control group (5.2%). The test was positive in 52.7% of patients in the ASNHL group and 16.6% in the atypical CS group. The paired comparison analysis between groups showed that sensitivity of anti-Hsp70 in the typical CS group was significantly higher, as compared to the other three study groups.

Conclusions: Anti-Hsp70 antibodies can be considered a serological marker of “typical” CS. “Atypical” CS is conceivably a sort of “melting pot” of different forms of autoimmune diseases still characterized by ocular inflammation and sensorineural hearing loss but whose antigenic characteristics need to be further defined.

Yael Zenziper BPharm, Daniel Kurnik MD, Noa Markovits MD, Amitai Ziv MD MHA, Ari Shamiss MD MPA, Hillel Halkin MD and Ronen Loebstein MD

Background: Prescription errors are common in hospitalized patients and result in significant morbidity, mortality and costs. Electronic prescriptions with computerized physician order entry systems (CPOE) and integrated computerized decision support systems (CDSS providing online alerts) reduce prescription errors by approximately 50%. However, the introduction of CDSS is often met by opposition due to the flood of alerts, and most prescribers eventually ignore even crucial alerts (“alert fatigue”). 

Objectives: To describe the implementation and customization of a commercial CDSS (SafeRx®) for electronic prescribing in Internal Medicine departments at a tertiary care center, with the purpose of improving comprehensibility and substantially reducing the number of alerts to minimize alert fatigue. 

Methods: A multidisciplinary expert committee was authorized by the hospital administration to customize the CDSS according to the needs of six internal medicine departments at Sheba Medical Center. We assessed volume of prescriptions and alert types during the period February–August 2012 using the statistical functions provided by the CDSS. 

Results: A mean of 339 ± 13 patients per month per department received 11.2 ± 0.5 prescriptions per patient, 30.1% of which triggered one or more CDSS alerts, most commonly drug-drug interactions (43.2%) and dosing alerts (38.3%). The review committee silenced or modified 3981 alerts, enhancing comprehensibility, and providing dosing instructions adjusted to the patient’s renal function and recommendations for follow-up. 

Conclusions: The large volume of drug prescriptions in internal medicine departments is associated with a significant rate of potential prescription errors. To ensure its effectiveness and minimize alert fatigue, continuous customization of the CDSS to the specific needs of particular departments is required.

 

Lidia V. Gabis MD and John Pomeroy MD
Background:  Autism spectrum disorders (ASD) represent a common phenotype related to multiple etiologies, such to genetic, brain injury (e.g., prematurity), environmental (e.g., viral, toxic), multiple or unknown causes. 

Objectives: To devise a clinical classification of children diagnosed with ASD according to etiologic workup.

Methods: Children diagnosed with ASD (n=436) from two databases were divided into groups of symptomatic, cryptogenic or idiopathic, and variables within each database and diagnostic category were compared.

Results: By analyzing the two separate databases, 5.4% of the children were classified as symptomatic, 27% as cryptogenic and 67.75% as idiopathic. Among other findings, the entire symptomatic group demonstrated language delays, but almost none showed evidence for regression. Our results indicate similarities between the idiopathic and cryptogenic subgroups in most of the examined variables, and mutual differences from the symptomatic subgroup. The similarities between the first two subgroups support prior evidence that most perinatal factors and minor physical anomalies do not contribute to the development of core symptoms of autism. Conclusions: Differences in gender and clinical and diagnostic features were found when etiology was used to create subtypes of ASD. This classification could have heuristic importance in the search for an autism gene(s).

May 2014
Lior Koren MD, Adi Barak RN, Doron Norman MD, Ofer Sachs MD and Eli Peled MD
Background: Proximal hip fractures in the elderly are common and have serious implications for health resources. Researching the timing of these fractures could contribute to diverting resources towards peaks in incidence and investing in prevention at certain times.

Objectives: To examine the effect of seasonality, weather and holidays on hip fracture incidence in older adults. The study population comprised 2050 patients aged 65 years or more who sustained a proximal hip fracture.

Methods: The computerized files of the patients were reviewed for trends in incidence by season, precipitation, minimum and maximum temperatures, day of the week, and certain Jewish festivals.

Results: Hip fractures were more likely to occur in the winter than in the summer (P < 0.0001). Factors that significantly correlated with hip fracture were the maximum daily temperature (r = -0.746, P = 0.005) followed by the minimum daily temperature (r = -0.740, P = 0.006) and precipitation (r = 0.329, P = 0.02). There were fewer fractures on Saturdays (the Sabbath) as compared to other days of the week (P = 0.045). Researching the incidence on Jewish festivals, we found an elevated incidence on Passover (P < 0.0001) and a reduced incidence on the Day of Atonement (Yom Kippur) (P = 0.013).

Conclusions: In older people there is an elevated incidence of proximal hip fractures during the winter and on the Jewish festivals. On weekends and on the Day of Atonement the incidence of proximal hip fractures was reduced.

April 2014
Eyal Bercovich MD, Lital Keinan-Boker MD PhD and Shaul M. Shasha MD
 Background: Previous studies suggest that exposure to starvation and stress between conception and early infancy may have deleterious effects on health later in life; this phenomenon is termed fetal origin of adult disease.

Objectives: To determine whether exposure to the Holocaust from preconception to early infancy is a cause of chronic morbidity in adulthood.

Methods: This pilot study involved 70 European Jews born in countries under Nazi rule (exposed group) during the period 1940–1945 who were interviewed to determine the presence of chronic diseases. A control group of 230 Israeli-born individuals of the same descent, age, and gender distribution were extracted from the Israel National Health Interview Survey-2 (unexposed group). The prevalence of selected risk factors and chronic diseases was compared between the groups.

Results: The prevalence of cardiovascular risk factors and morbidity was significantly higher in the exposed group: body mass index (BMI) (29.06 ± 3.2 vs. 26.97 ± 4.42, P = 0.015), hypertension (62.9% vs. 43%, P = 0.003), dyslipidemia (72.9% vs. 46.1%, P < 0.001), diabetes (32.9% vs. 17.4%, P = 0.006), angina pectoris (18.6% vs. 4.8%, P = 0.001) and congestive heart failure (8.6% vs. 1.7%, P = 0.013). The prevalence of cancer (30.0% vs. 8.7% P < 0.001), peptic ulcer disease (21.4% vs. 7%, P = 0.001), headaches/migraines (24.3% vs. 12.6%, P < 0.001) and anxiety/depression (50.0% vs. 8.3%, P < 0.001) was also higher in the exposed group.

Conclusions: These results suggest that exposure to Holocaust conditions in early life may be associated with a higher prevalence of obesity, dyslipidemia, diabetes, hypertension, cardiovascular morbidity, malignancy and peptic diseases in adulthood. These findings set the stage for further research, which might define those exposed as a high risk group for chronic morbidity.

Tessa Chelouche MD
 Born in Czechoslovakia, psychiatrist Leo Eitinger (1912-1996) became internationally recognized for research on his fellow concentration camp inmates. He graduated as an MD in 1937, but being Jewish was prohibited from practicing as a doctor. When the Nazis moved into the area he was forced to flee to Norway, where in 1940 he was again deprived of his right to practice medicine. In 1942 he was arrested and deported to Auschwitz. There, as a physician inmate, he was able to help and in many cases save his fellow prisoners, not only with his medical skills but by falsifying prisoners' documents and hiding them from their Nazi captors. One of his patients was Elie Wiesel. Eitinger survived the camps but was forced to join a "death march." After the war he resumed medical practice in Norway, specializing in psychiatry. With his personal experience and knowledge of the suffering of camp survivors, he dedicated his life to studying the psychological effects of traumatic stress in different groups. Eitinger's academic contributions were crucial in the development of this area of research on the effects of excessive stress, laying the foundations for the definition of post-traumatic stress disorder and the post-concentration camp syndrome, thus facilitating recognition of the medical and psychological post-war conditions of the survivors and their resultant disability pensions. 

George M. Weisz MD FRACS MA and William R. Albury BA PhD
 Reinhard Heydrich, architect of the “Final solution of the Jewish problem,” had a meteoric career in the SS. He organized the Wannsee Conference and created the SS killing squads. Under his leadership as Reich Protector of Bohemia and Moravia, the suppression of the Czech community was brutal. An attempt on his life in Prague was unsuccessful but it left him severely injured and he died eight days later. Reviewing the available information on his hospital treatment and the autopsy report, it is suggested that Heydrich received substandard medical treatment, quite likely a result of political interference from rival members of the SS hierarchy.

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