Avi Livneh MD and Ilan Ben-Zvi 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.
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).
Mihai Meirovitz MD, Dvir Gatt BSc, Jacob Dreiher MD MPH and Ruthy Shaco-Levy MD
Background: The "see and treat" approach, proceeding without a biopsy directly to uterine cervix conization in women diagnosed with high grade squamous intraepithelial lesion (HGSIL) on Pap smear, shortens the treatment duration, lessens patient anxiety, and reduces health care costs.
Objectives: To evaluate the level of diagnostic accuracy and the over-treatment rate in the "see and treat" versus conventional management of women diagnosed with HGSIL.
Methods: We retrospectively reviewed all women with HGSIL who had undergone the "see and treat" approach during 2001–2011 at Soroka University Medical Center. Similar cohorts, who were managed conventionally with a cervical biopsy prior to the conization, served as a comparison group.
Results: The study population consisted of 403 women: 72 (18%) had undergone the "see and treat" approach and 331 (82%) conventional management. The false positive rate was 11% for the "see and treat" group, compared to 6% for the conventional management group (P = 0.162). Similarly, no statistically significant difference was observed when comparing the positive predictive value (PPV) of high grade dysplasia diagnosed on Pap smear (PPV 88.9%) versus cervical biopsy (PPV 93.8%) (P = 0.204). Moreover, both the false positive rate and PPV remained similar in subgroups of patients, according to age, menopausal status, number of births, and colposcopy findings.
Conclusions: The accuracy level of HGSIL diagnosis on Pap smear is similar to that of high grade dysplasia on a cervical biopsy. We therefore recommend referring patients with HGSIL directly to conization. Skipping the biopsy step was not associated with significant over-treatment or other adverse effects.
Dorit Blickstein MD, Rima Dardik PhD, Esther Rosenthal MsC, Judith Lahav PhD, Yair Molad MD and Aida Inbal MD
Background: A 75 year old patient presenting with mucocutaneous bleeding was diagnosed with acquired thrombastheniaThe diagnosis was based on lack of platelet aggregation with adenosine diphosphate (ADP), arachidonic acid and collagen, and normal aggregation induced by ristocetin.
Objective: To study the mechanism of platelet function inhibition in a patient with acquired thrombasthenia.
Methods: Aggregation assays of platelets from the patient and healthy controls were performed. In addition, anti-glycoprotein (GP) IIbIIIa antibodies binding to normal platelets in the presence or absence of the patient’s serum was studied by flow cytometry.
Results: Aggregation of normal platelets in the presence of patient's plasma was inhibited four- and 2.5-fold in the presence of ADP and arachidonic acid respectively, while collagen-induced aggregation was completely abolished. Ristocetin-induced aggregation was normal. The patient's serum inhibited binding of commercial anti-glycoprotein IIbIIIa antibodies to normal platelets twofold by flow cytometry. Treatment with anti-CD20 monoclonal antibody (rituximab) normalized the patient's platelet aggregation.
Conclusions: These results suggest that the patient developed inhibitory anti-GPIIbIIIa autoantibodies that caused acquired thrombasthenia.
Eyal Lotan MD MSc, David Orion MD, Mati Bakon MD, Rafael Kuperstein MD and Gahl Greenberg MD
Juraj Dubrava MD PhD, Ivan Vulev MD PhD and Denis Richter MD
Timna Agur MD MSc, Yair Levy MD, Eleonora Plotkin MD and Sydney Benchetrit MD
Zeeshan Ramzan MD and Florian Anzengruber MD
Cassandra Ocampo MD, Molebedi L. Segwagwe MB ChB MRCP, Julian Deonarain MB ChB FCPath, Francesca Cainelli MD and Sandro Vento MD