Eyal Zimlichman MD, Itai Gueta MD, Daniella Daliyot RN Msc, Amitai Ziv MD, Bernice Oberman Msc, Ohad Hochman MD, Ofer Tamir MD, Orna Tal MD and Ronen Loebstein MD
Background: Adverse drug events (ADEs) are a major cause of morbidity and mortality worldwide. Hence, identifying and monitoring ADEs is of utmost importance. The Trigger Tool introduced by the Institute of Healthcare Improvement in the United States has been used in various countries worldwide, but has yet to be validated in Israel.
Objective: To validate the international Trigger Tool in Israel and to compare the results with those generated in various countries.
Methods: A retrospective descriptive correlative analysis surveying four general hospitals in Israel from different geographical regions was conducted. Patient medical charts (n=960) were screened for 17 established triggers and confirmed for the presence of an ADE. Trigger incidence was compared to the actual ADE rate. Further comparison among countries was conducted using published literature describing Trigger Tool validation in various countries.
Results: A total of 421 triggers in 279 hospitalizations were identified, of which 75 ADEs in 72 hospitalizations (7.5%) were confirmed. In addition, two ADEs were identified by chart review only. Mean positive predictive value was 17.81% and overall sensitivity was 97%. We found 1.54 ADEs for every 100 hospitalization days, 7.8 ADEs per 100 admissions, and 1.81 ADEs for every 1000 doses of medication. Of the 77 ADEs identified, 22.7% were defined as preventable.
Conclusions: Our results support the Trigger Tool validity in Israel as a standardized method. Further studies should evaluate between hospital and region differences in ADE rate, in particular for the preventable events.
Eliyahu Zaig MD, Odile Cohen-Ouaknine MD, Anat Tsur MD, Sheila Nagar MD, Gherta Bril MD, Lior Tolkin MD, Avivit Cahn MD, Mozhgan Heyman and Benjamin Glaser MD
Background: Reduced sensitivity to thyroid hormone (RSTH) syndrome describes a group of rare heterogeneous genetic disorders. Precise diagnosis is essential to avoid unnecessary treatment.
Objectives: To identify and characterize previously undiagnosed patients with RSTH in Israel.
Methods: Patients with suspected RSTH throughout Israel were referred for study. After clinical evaluation, genomic DNA was obtained and all coding exons of the thyroid hormone receptor beta (THRB) gene were sequenced. If mutations were found, all available blood relatives were evaluated. The common polymorphism rs2596623, a putative intronic regulatory variant, was also genotyped. Genotype/phenotype correlations were sought, and the effect of mutation status on pregnancy outcome was determined.
Results: Eight mutations (one novel; two de-novo, six dominant) were identified in eight probands and 13 family members. Clinical and genetic features were similar to those reported in other populations. Previous suggestions that rs2596623 predicts clinical features were not confirmed. There was no evidence of increased risk of miscarriage or fetal viability. Mothers carrying a THRB mutation tended to have increased gestational hypertension and low weight gain during pregnancy. Their affected offspring had increased risk of small-for-gestational age and poor postnatal weight gain.
Conclusions: Clinical heterogeneity due to THRB mutations cannot be explained by the variant rs2596623. Mothers and newborns with THRB mutations seem to be at increased risk of certain complications, such as gestational hypertension and poor intrauterine and postnatal growth. However, these issues are usually mild, suggesting that routine intervention to regulate thyroid hormone levels may not be warranted in these patients.
Vered Nir MD, Michal Gur MD, Yazeed Toukan MD, Fahed Hakim MD, Arcadi Vachyan MD and Lea Bentur MD
Background: Recurrence of tracheoesophageal fistula (TEF) is reported in 8–20% patients. Factors that may influence recurrence of fistula beyond the postoperative period are not clear.
Objectives: To evaluate possible factors associated with recurrence of TEF beyond the immediate postoperative period.
Methods: A single center, retrospective comparison of patients with and without recurrence of TEF was conducted. Medical records of patients previously operated for TEF who were followed in our pediatric pulmonary institute between January 2007 and December 2016 were reviewed.
Results: The medical records of 74/77 patients previously operated for TEF were evaluated. Nine patients (12%) had a recurrence of TEF and 65 did not. These groups had similar age and gender distribution and similar prevalence of VACTERL association. In addition, they had similar length of atretic gap, rates of thoracoscopic surgery, rates of prolonged need for respiratory assistance post-surgery, and frequency of gastrointestinal symptoms. Notably, the patients who had recurrent TEF had significantly more hospitalizations for respiratory symptoms (P = 0.011) and significantly more episodes of clinical bronchiolitis per patient (P < 0.0001). In addition, the patients with recurrent TEF had significantly more episodes of positive polymerase chain reaction for viruses (P = 0.009).
Conclusions: Hospitalizations for respiratory symptoms as well as clinical and/or viral bronchiolitis are associated with recurrence of TEF. Even though cause and effect cannot be established, these patients should undergo meticulous evaluation for the possibility of recurrence of TEF.
Shlomit Koren MD, Michael Yoshpa MD, Ronit Koren MD, Dror Cantrell MD and Micha J. Rapoport MD
Background: Basal-bolus (BB) insulin treatment is increasingly used in poorly controlled diabetes patients during hospitalization and is commonly recommended at discharge; however, the extent of adherence with this recommendation is unknown.
Objectives: To determine short-term adherence of type 2 diabetes mellitus (T2DM) patients discharged from internal medicine wards with recommendation for BB insulin treatment.
Methods: Prescription (primary physician adherence) and purchase (patient adherence) of long-acting and short-acting insulins during the first month following discharge from internal medicine wards was determined in 153 T2DM patients. Adherence was defined as full if prescription/purchase of both basal (long-acting) and bolus (short-acting) insulin was completed, and as partial if only one kind of insulin (basal or bolus) was prescribed/purchased. Association between demographic and clinical parameters and adherence was determined.
Results: Full adherence with discharge instructions was higher for primary physicians than for patients )79.1% vs. 69.3%, respectively, P = 0.0182). Pre-hospitalization hemoglobin A1C was significantly associated with adherence by both patients and primary physicians (full-adherence group 9.04% ± 2.04%; no-adherence group 7.51% ± 1.35%, P = 0.002). Age was negatively associated with adherence of both primary physicians and patients; however, this association did not reach statistical significance. Patients with certain background diseases such as atrial fibrillation, coronary heart disease, and chronic heart failure had significantly worse adherence (P < 0.05). When the sole cause of admission was diabetes, full adherence (100%) of both primary physicians and patients was found.
Conclusions: Short-term adherence with discharge recommendation for BB insulin treatment is associated with pre-hospitalization patient characteristics.
Naim Abu Freha MD MHA, Wafi Badarna MD, Muhammad Abu Tailakh RN MPH PhD, Heba Abu Kaf MD, Alex Fich MD, Doron Schwartz MD, Arik Segal, Jabir Elkrinawi and Amir Karban MD
Background: Inflammatory bowel disease (IBD) prevalence is increasing among Bedouin Arabs in Israel. This population is known to have a high rate of consanguinity. NOD2/CARD15 mutations are well-studied in IBD.
Objectives: To investigate the frequency of NOD2/CARD15 mutations in IBD Bedouin patients and their relevance to disease phenotype.
Methods: The IBD-Arab cohort in southern Israel included 68 patients, of which 25 Crohn's disease (CD) patients and 25 ulcerative colitis (UC) patients consented to participate (72%). Blood samples were obtained from all participants who were genotyped for NOD2/CARD15 variants Arg702Trp, Gly908Arg, and Leu1007fsinsC.
Results: The NOD2/CARD15 mutation frequency was higher in Crohn's disease than in ulcerative colitis patients. Carrier frequency for the Gly908Arg mutation in CD and UC patients was 8/25 (32%) and 3/25 (12%), respectively (P = 0.08). Neither the Arg702Trp nor Leu1007fsinsC mutation was found in our cohort. No homozygous/compound heterozygote mutations were found. Genotype-phenotype analysis revealed that CD patients carrying the Gly908Arg mutation were younger at diagnosis, 22.8 ± 4.5 vs. 28.82 ± 9.1 years (P = 0.04). All carriers were males, compared with 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 ± 24.5 years compared with 41.2 ± 12.3 years (P = 0.006). No other associations regarding disease localization or other clinical parameter were found.
Conclusions: The frequency of NOD2/CARD15 gene mutations is high in CD and UC among Bedouin Arab IBD patients and is associated with younger age at onset in CD and male gender.
Christoph Robier MD, Omid Amouzadeh-Ghadikolai MD, Mariana Stettin MD and Gerhard Reicht MD
Elena Chertok Shacham MD, Elena Chervinsky and Avraham Ishay MD
Igor Snast MD, Iris Ostfeld MD, Lev Pavlovsky MD PhD, Emmilia Hodak MD and Anat Gafter-Gvili MD
Roberta Fenoglio MD, Irene Cecchi MD and Dario Roccatello MD
Nir Hod MD MHA, Reut Anconina MD, Daniel Levin MD, Ekaterina Tiktinsky MD, Dina Ezroh Kazap MD, Itai Levi MD, Maria Zektser MD, Vered Stavi MD, Gilbert Sebbag MD and Sophie Lantsberg MD
Florian Rey MD, Thibault Ronchard MD PharD, Jawad Chaara MD and Stéphane Noble MD
Vardit M. Kalamaro PharmD, Karen Harshkop RN PhD, Rose Lipner and Orly Tamir MHA PhD