Israel Medical Association Journal

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.

Background: With advances in myelodysplastic syndromes (MDS), patient cohorts from different time periods might be different.

Objectives: To compare presentation and outcomes between two cohorts.

Methods: Data were collected from George Washington University Medical Center, Washington, DC, USA 1986–1987 (DC), and Tel Aviv Medical Center, Israel 1999–2009 (TA).

Results: The study comprised 227 patients (139 TA, 88 DC). TA patients were older (75.4 ± 9.8 vs. 63.8 ± 14.3 years, P < 0.001) and had more cardiovascular diseases (56.8% vs. 14.8%, P < 0.001), fewer cytopenias (1.67 ± 0.82 vs. 2.0 ± 0.93, P = 0.003), and lower mean corpuscular volume (94.3 ± 9.9 fl vs. 100.5 ± 15.3 fl, P < 0.001). Hemoglobin, leukocyte, neutrophil, and platelet counts were similar. More TA patients had dysplasias. Bone marrow cellularity and cytogenetics were similar, but more TA patients had blasts < 5% (73.4% vs. 50.6%, P = 0.003). More TA patients had early French-American-British (FAB) disease (66.9% vs. 40.9%, P < 0.001) and lower risk disease per International Prognostic Scoring System (81% vs. 50%, P < 0.001). The 5 year survival (5YS) of TA patients was not significantly greater (62% vs. 55%). 5YS by FAB was also slightly greater for TA patients (77% vs. 65% for early FAB; 43% vs. 37% for advanced FAB, P > 0.05).

Conclusions: Although patients diagnosed with MDS at a later period were older and had more cardiovascular co-morbidities, they had fewer cytopenias, tended to have earlier disease, and had minimally greater, but not significant, 5YS.

Background: Magnesium is an essential intracellular cation. Magnesium deficiency is common in the general population and its prevalence among patients with cirrhosis is even higher. Correlation between serum levels and total body content is poor because most magnesium is intracellular. Minimal hepatic encephalopathy is a subclinical phase of hepatic encephalopathy with no overt symptoms. Cognitive exams can reveal minor changes in coordination, attention, and visuomotor function, whereas language and verbal intelligence are usually relatively spared.

Objectives: To assess the correlation between intracellular and serum magnesium levels and minimal hepatic encephalopathy.

Methods: Outpatients with a diagnosis of compensated liver cirrhosis were enrolled in this randomized, double-blinded study. Patients were recruited for the study from November 2013 to January 2014, and were randomly assigned to a control (placebo) or an interventional (treated with magnesium oxide) group. Serum and intracellular magnesium levels were measured at enrollment and at the end of the study. Cognitive function was assessed by a specialized occupational therapist.

Results: Forty-two patients met the inclusion criteria, 29 of whom were included in this study. Among these, 83% had abnormal cognitive exam results compatible with minimal hepatic encephalopathy. While only 10% had hypomagnesemia, 33.3% had low levels of intracellular magnesium. Initial intracellular and serum magnesium levels positively correlated with cognitive performance.

Conclusions: Magnesium deficiency is common among patients with compensated liver cirrhosis. We found an association between magnesium deficiency and impairment in several cognitive function tests. This finding suggests involvement of magnesium in the pathophysiology of minimal hepatic encephalopathy.

Background: Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology. Its occurrence in the general population is 1/100,000, and 20/100,000 among overweight women of childbearing age. Familial occurrence is reportedly uncommon and not well-characterized.

Objectives: To describe a familial association with IIH.

Methods: We conducted a retrospective chart review of all familial cases of IIH examined in the neuro-ophthalmology clinic of our medical center between January 2006 and June 2013.

Results: Of a total of 520 patients with IIH, 15 had other family members with IIH (from seven different families). The family relation was a mother and daughter in two families, a brother and sister in four families, and an aunt and two first-degree cousins in the seventh family. Symptoms, course of disease, and risk factors were similar among the relatives of all seven families, except for the age at diagnosis, which was different in one family. All of the adult patients of six families were obese (body mass index 25–35 kg/m²), and all of the members of the other family were morbidly obese. There was no association between other systemic risk factors and IIH.

Conclusions: IIH occurrence within a family is more common than previously believed, and its incidence in families is more common than in the general population. The clinical course appears to be similar in family members. Our findings suggest a genetic predisposition. Further investigation of familial cases may yield useful information on the pathogenesis and genetic nature of this condition.

Background: Ptyalism gravidarum (PG) is a condition of hypersalivation that affects pregnant women early in gestation. Symptoms include massive saliva volumes (up to 2 liters per day), swollen salivary glands, sleep deprivation, significant emotional distress, and social difficulties.

Objectives: To examine maternal and fetal characteristics and pregnancy outcomes of patients with PG.

Methods: Patients diagnosed with PG in our clinic during the years 2001–2016 were identified and contacted. Demographic data were extracted from patient charts and clinical and outcome data was collected via telephone interviews.

Results: The incidence of PG was 1/963 (0.09%) in our sample. Eleven out of 22 women (40%) with PG were also diagnosed with hyperemesis gravidarum. Fetal gender did not increase the risk. Of the mothers presenting with PG, 37% had a positive family history for this condition. There was no associated increase in the rate of fetal or maternal complications. Two women reported a resolution of the symptoms immediately following hypnosis with acupuncture treatment.

Conclusions: Although PG represents an unpleasant mental and physical condition, it does not pose any specific risk to the health of the mother or increase adverse perinatal outcomes for the fetus. Alternative medicine could play a role in the treatment of PG.

Background: The incidence, characteristics, and clinical significance of catheter-induced mechanical suppression (trauma) of ventricular arrhythmias originating in the outflow tract (OT) area have not been thoroughly evaluated.

Objectives: To determine these variables among our patient cohort.

Methods: All consecutive patients with right ventricular OT (RVOT) and left ventricular OT (LVOT) arrhythmias ablated at two medical centers from 1998 to 2014 were included. Patients were observed for catheter-induced trauma during ablation procedures. Procedural characteristics, as well as response to catheter-induced trauma and long term follow-up, were recorded.

Results: During 288 ablations of OT arrhythmias in 273 patients (RVOT n=238, LVOT n=50), we identified 8 RVOT cases (3.3%) and 1 LVOT (2%) case with catheter-induced trauma. Four cases of trauma were managed by immediate radiofrequency ablation (RFA), three were ablated after arrhythmia recurrence within a few minutes, and two were ablated after > 30 minutes without arrhythmia recurrence. Patients with catheter-induced trauma had higher rates of repeat ablations compared to patients without: 3/9 (33%) vs. 12/264 (0.45%), P = 0.009. The three patients with arrhythmia recurrence were managed differently during the first ablation procedure (immediate RFA, RFA following early recurrence, and delayed RFA). During the repeat procedure of these three patients, no catheter trauma occurred in two, and in one no arrhythmia was observed.

Conclusions: Significant catheter-induced trauma occurred in 3.1% of OT arrhythmias ablations, both at the RVOT and LVOT. Arrhythmia suppression may last > 30 minutes and may interfere with procedural success. The optimal mode of management following trauma is undetermined.

Background: Door-to-balloon time (DTBT) ≤ 90 minutes has become an important quality indicator in the management of ST-elevation myocardial infarction (STEMI). We identified three specific problems in the course from arrival of STEMI patients at our emergency department to initiation of balloon inflation and determined an intervention comprised of specific administrative and professional steps. The focus of the intervention was on triage within the emergency department (ED) and on increasing the efficiency and accuracy of electrocardiography interpretation.

Objectives: To examine whether our intervention reduced the proportion of patients with DTBT > 90 minutes.

Methods: We compared DTBT of patients admitted to the ED with STEMI during the year preceding and the year following implementation of the intervention.

Results: Demographic and clinical characteristics at presentation to the ED were similar for patients admitted to the ED in the year preceding and the year following intervention. The year preceding intervention, DTBT was > 90 minutes for 19/78 patients (24%). The year after intervention, DTBT was > 90 minutes for 17/102 patients (17%). For both years, the median DTBT was 1 hour. Patients with DTBT > 90 minutes tended to be older and more often female. Diagnoses in the ED were similar between those with DTBT ≤ 90 minutes and > 90 minutes. In-hospital mortality was 17% (13/78) and 14% (14/102) for the respective time periods.

Conclusions: An intervention specifically designed to address problems identified at one medical center was shown to decrease the proportion of patients with DTBT > 90 minutes.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) (such as canagliflozin, empagliflozin, and dapagliflozin) are widely used to treat patients with type 2 diabetes mellitus (T2DM) to improve glycemic, cardiovascular and renal outcomes. However, based on post-marketing data, a warning label was added regarding possible occurrence of acute kidney injury (AKI).

Objectives: To describe the clinical presentation of T2DM patients treated with SGLT2i who were evaluated for AKI at our institution and to discuss the potential pathophysiologic mechanisms.

Methods: A retrospective study of a computerized database was conducted of patients with T2DM who were hospitalized or evaluated for AKI while receiving SGLT2i, including descriptions of clinical and laboratory characteristics, at our institution.

Results: We identified seven patients in whom AKI occurred 7–365 days after initiation of SGLT2i. In all cases, renin-angiotensin-aldosterone system blockers had also been prescribed. In five patients, another concomitant nephrotoxic agent (injection of contrast-product, use of nonsteroidal anti-inflammatory drugs or cox-2 inhibitors) or occurrence of an acute medical event potentially associated with AKI (diarrhea, sepsis) was identified. In two patients, only the initiation of SGLT2i was evident. The mechanisms by which AKI occurs under SGLT2i are discussed with regard to the associated potential triggers: altered trans-glomerular filtration or, alternatively, kidney medullary hypoxia.

Conclusions: SGLT2i are usually safe and provide multiple benefits for patients with T2DM. However, during particular medical circumstances, and in association with usual co-medications, particularly if baseline glomerular filtration rate is decreased, patients treated with SGLT2i may be at risk of AKI, thus warranting caution when prescribed.

Background: Behçet’s disease (BD) is an inflammatory disorder potentially leading to life- and sight-threatening complications. No laboratory marker correlating with disease activity or predicting the occurrence of disease manifestations is currently available.

Objectives: To determine an association between serum amyloid-A (SAA) levels and disease activity via the BD Current Activity Form (BDCAF), to evaluate disease activity in relation to different SAA thresholds, to examine the association between single organ involvement and the overall major organ involvement with different SAA thresholds, and to assess the influence of biologic therapy on SAA levels.

Methods: We collected 95 serum samples from 64 BD patients. Related demographic, clinical, and therapeutic data were retrospectively gathered.

Results: No association was identified between SAA levels and BD disease activity (Spearman's rho = 0.085, P = 0.411). A significant difference was found in the mean BDCAF score between patients presenting with SAA levels < 200 mg/L and those with SAA levels > 200 mg/L (P = 0.027). SAA levels > 200 mg/L were associated with major organ involvement (P = 0.008). A significant association was found between SAA levels > 150 mg/dl and ocular (P = 0.008), skin (P = 0.002), and mucosal (P = 0.012) manifestations. Patients undergoing biologic therapies displayed more frequently SAA levels < 200 mg/L vs. patients who were not undergoing biologic therapies (P = 0.012).

Conclusions: Although SAA level does not represent a biomarker for disease activity, it might be a predictor of major organ involvement and ocular disease relapse at certain thresholds in patients with BD.