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: Sepsis is a common cause of hospitalization, particularly in intensive care units (ICUs), and is a major cause of morbidity and mortality. Diagnosis is often difficult due to the absence of characteristic clinical signs (e.g., fever and leukocytosis); therefore, additional markers, in addition to C-reactive protein (CRP) and white blood cell (WBC) count, are needed.

Objectives: To prospectively link resting energy expenditure (REE) with CRP, WBC count, and sequential organ failure assessment (SOFA) scores in ICU patients. Such a correlation may suggest REE measurement as an additional parameter for sepsis diagnosis.

Methods: Our study comprised 41 ventilated consecutive patients > 18 years of age. Patient demographic data, height, actual body weight, and SOFA scores were collected at admission. REE was measured by indirect calorimetry. REE, CRP, and WBC measurements were collected at admission, on day three after admission, and 1 week later or as clinically indicated.

Results: Comparison of the REE and CRP changes revealed a significant correlation between REE and CRP changes (r = 0.422, P = 0.007). In addition, CRP changes also correlated with the changes in REE (r = 0.36, P = 0.02). Although no significant correlations in REE, WBC count, and SOFA score were found, a significant trend was observed.

Conclusions: To the best of our knowledge, this is the first study to link REE and CRP levels, indicative of severe infection. Further study is needed to establish these findings.

Background: Unlike the elective treatment of metastatic colorectal cancer (MCRC), sufficient data and consensual guidelines on acute care are lacking.

Objectives: To analyze a cohort of MCRC patients who required urgent surgery due to acute abdomen and to identify risk factors contributing to the patient's perioperative mortality and morbidity.

Methods: A retrospective analysis was conducted of patients diagnosed with stage IV colorectal cancer who required urgent laparotomy at the Rabin Medical Center. Comparative analysis was performed using Pearson’s chi-square and Student`s t-test.

Results: Between 2010 and 2015, 113 patients underwent urgent laparotomy due to colorectal cancer complications, of which 62 patients were found to have a metastatic, stage IV, disease. Large bowel obstruction was the most common indication for urgent laparotomy. In-hospital mortality was 30% (n=19), and overall 30 day mortality was 43%. Fifteen patients (24%) required more than one surgery. The average length of hospital stay was 21 days. Age and lactate levels at presentation were the only prognostic factor found for mortality (P < 0.05).

Conclusions: MCRC laparotomy patients incur a significant burden of care and have a relatively high incidence of early mortality. Our data suggest high, verging on unacceptable, mortality and complication rates in this subgroup of patients. This finding is further accentuated in the subgroup of older patients presenting with lactatemia. These data should be considered by surgeons when discussing treatment options with patients and families.

Background: Mortality and decrease in function after hip fracture are significantly related to patient factors including age, gender, co-morbidities, and mental status. Several studies demonstrated ethnic disparities in incidence, mortality, and functional outcome after hip fractures in the United States.

Objectives: To assess the relationship between ethnicity and hip fracture incidence and outcomes of mortality, functional change, and perioperative complications in the Israeli population.

Methods: We reviewed our institutional hip fracture registry for all patients from 2014–2015. Patients with incomplete data, < 60 years of age, or pathologic and periprosthetic fractures were excluded. Our study comprised 693 patients. Ethnicity was based on country of birth. Specifically, for those born in Israel, the nationality of either Jewish or Arab was further dichotomized. Perioperative complications, mortality, and mobility status at 1 year follow-up were recorded. The ethnicities of 27,130 patients admitted to the medicine and surgical wards during the same time interval served as a control group for the hip fracture cohort.

Results: Immigrants from Europe and America had the highest incidence of hip fractures. Fracture types varied in incidence in groups with 70% of extracapsular hip fractures occurring in Arabs and immigrants from Eastern countries, compared to 60% in immigrants from Western countries and the former Soviet Union. Mortality, perioperative complications, and mobility at 1 year were similar in all ethnic groups.

Conclusion: Our study demonstrated significant differences in incidence and fracture characteristic among ethnicities, but no difference in patient outcome. These findings differed from the available North American studies.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a challenging nosocomial pathogen in the last 50 years.

Objectives: To describe an investigation and containment of an MRSA outbreak in a neonatal intensive care unit (NICU).

Methods: Our NICU is a 25-bed level III unit. Almost 540 neonates are admitted yearly. The index case was an 8 day old term baby. MRSA was isolated from his conjunctiva. Immediate infection control measures were instituted, including separation of MRSA+ carriers, strict isolation, separate nursing teams, and screening of all infants for MRSA. Healthcare workers and parents of positive cases were screened and re-educated in infection control measures. New admissions were accepted to a clean room and visiting was restricted. MRSA isolates were collected for molecular testing.

Results: MRSA was isolated from five infants by nasal and rectal swabs, including the index case. Screening of healthcare workers and families was negative. Two MRSA+ patients already known in the pediatric intensive care unit (PICU) located near the NICU were suspected of being the source. All NICU isolates were identical by pulsed-field gel electrophoresis but were different from the two PICU isolates. The NICU and one of the PICU isolates were defined as ST-5 strain by multilocus sequence typing. One PICU isolate was ST-627. All NICU isolates were Panton–Valentine leukocidin negative and SCCmec type IV. No further cases were detected, and no active infections occurred.

Conclusions: A strict infection control policy and active screening are essential in aborting outbreaks of MRSA in the NICU.

Background: Nail-patella syndrome (NPS) is characterized by changes in the nails, knees, and elbows, as well as the presence of iliac horns detected by X-ray of the pelvis. A higher occurrence of psychiatric disorders has also been suggested in NPS. Heterozygous mutations in the gene encoding the LIM-homeodomain transcription factor (LMX1B) are identified in most patients with typical clinical findings of NPS.

Objective: To report on the association between NPS and schizophrenia.

Methods: Genomic DNA were isolated from a patient's venous blood and collected on ethylenediaminetetraacetic 5% with the Gentra Puregene Blood Kit. All exons and flanking regions of the LMX1B gene (LMX1B: NM_001174146.1) were amplified by standard polymerase chain reaction and analyzed by direct DNA sequencing with BigDye Terminators on an ABI 3100 sequencer. Sequence chromatograms were analyzed using SeqScape software version 1.1. Mutation analysis and characterization of variants was performed with the Alamut Software Version 2.1.

Results: We report a patient presenting to the psychiatry department with schizophrenia. Clinical examination revealed characteristic findings consistent with NPS. Since NPS was suspected, based on clinical findings, sequencing of all coding exons of LMX1B gene was completed. Results revealed a novel heterozygous mutation in the proband: c.546_547insACCG(het); p.Glu183Thrfs*11.

Conclusions: Based on LMX1B expression in brain regions that are implicated in neuropsychiatric illness, and especially in the development of dopaminergic neurons, we hypothesize that schizophrenia may be part of the clinical spectrum of NPS.

Background: Abnormal gestational weight gain (GWG) has been associated with adverse outcomes for mothers and their offspring.

Objectives: To compare the achievement of recommended GWG and lifestyle factors in women with high-risk versus normal-risk pregnancies.

Methods: Pregnant women hospitalized in a gynecological and obstetrics department and pregnant women who arrived at a community clinic for a routine checkup were interviewed and completed questionnaires relating to weight gain and lifestyle factors (e.g., smoking, diet, exercise). Recommended GWG was defined by the American Congress of Obstetricians and Gynecologists (ACOG).

Results: GWG higher than ACOG recommendations was reported by 52/92 women (57%) with normal pregnancies and by 43/86 (50%) with high-risk pregnancies. On univariate analysis, characteristics associated with greater GWG were: current or past smoking, age > 40 years, pre-gestational body mass index (BMI) > 25 kg/m², low fruit intake, and high snack intake. High-risk pregnancies were associated with pre-gestational BMI > 25 kg/m² (48% vs. 27%, P = 0.012), consumption of vitamins (84% vs. 63%, P = 0.001), avoidance of certain foods (54% vs. 21%, P = 0.015), receiving professional nutritionist consultation (65% vs. 11%, P = 0.001), and less physical activity (9% vs. 24%, P = 0.01).

Conclusions: A minority of pregnant women met the recommended GWG. No difference was noted between normal and high-risk pregnancies. High-risk population tended to have a less healthy lifestyle. Counseling to follow a healthy, balanced diet should be recommended, regardless of pregnancy risk, with particular attention to women at high risk of extra weight gain.

Background: Skin colonization of microorganisms in blood cultures (BCs) are generally considered clinically non-significant and can be the source of a true infection, particularly in immunosuppressed patients.

Objectives: To study the epidemiology and risk factors for bacteremia caused by contaminants.

Methods: This retrospective, descriptive study is based on adult BCs collected (2004–2013) and categorized as positive (True bacteremia [TrueB] or contamination) or negative. Clinical, demographic, and laboratory characteristics of BCs positive for the six most common potential contaminant pathogens (PCPs) that can cause TrueB and contamination (Coagulase-negative Staphylococcus [CoNS], Streptococcus viridans, Propionibacterium acnes, Corynebacterium spp., Bacillus spp., Clostridium spp.) were assessed. Ninety-two TrueB were identified vs. 196 contaminations (1:2 ratio).

Results: From 74,014 BCs, PCPs were found in 3735 samples, of which 3643 (97.5%) were contaminations and 92 (2.5%) were TrueB. The overall rate of BC contamination decreased during the study period from 6.7% to 3.8%. CoNS was the most common PCP. Bacillus spp. were only contaminants. Clostridium spp. and Streptococcus viridans were more often TrueB. In a multivariate model, predictors of TrueB included high creatinine levels, Streptococcus viridans in BC, and multiple positive BCs. A single culture of CoNS was strongly predictive of contamination.

Conclusions: Ten years of data on BCs, focusing on six PCPs, demonstrates a significant, yet insufficient reduction in the rate of contamination. High creatinine level, isolation of Streptococcus viridans, and multiple positive BCs were predictors of TrueB, while growth of CoNS was strongly predictive of contamination. This model could assist in diagnostic and therapeutic decision making.

Background: Fractures of the distal radius are the most common fractures in the upper extremity, and their incidence is increasing with the aging of the population. Despite anatomical reduction of the bones, many patients complain of residual pain. A reason for this may be ligament injury not addressed during surgery or conservative treatment. Radiographic measurements may allow assessment of ligament integrity but they may be population specific and differ among races.

Objectives: To assess radiographic wrist measurements in an Israeli population and to compare them to existing values.

Methods: Demographic data, previous diagnosis of osteoporosis, fracture classification, and radiologic measurements (radial height, radial inclination, ulnar variance, volar tilt, and d2/w2) were measured and compared.

Results: The study was comprised of 53 females and 27 males, mean age 64 years, with wrist radiographs following surgery. Of these, 13% were smokers and 38.5% had osteoporosis. According to the Arbeitsgemeinschaft für Osteosynthesefragen classification system, most of the fractures were comminuted and intra-articular. The mean values for all measurements did not differ significantly from values in the literature. The average d2/w2 ratio (describing the radiocarpal ligaments) was 0.42, significantly differing from this measurement in normal wrists as described in the literature, but similar to a population following surgery (P = 0.002).

Conclusions: Our population had more fragility fractures than other populations. Otherwise, our demographics and measurements did not differ from normal values described in the literature. This study supports the validity of any wrist radiographic study performed in our population.

Background: Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease with poor prognosis despite intensive therapy.

Objectives: To discuss the ideal therapy of EBV-associated HLH for adults.

Methods: We retrospectively studied 23 adult patients with EBV-associated HLH at our institution between January 2000 and June 2015. The clinical characteristics, treatment, and prognosis of adult EBV-associated HLH were analyzed. The median age was 38 years (range 18–72).

Results: All patients were found to have high fever, thrombocytopenia, abnormal liver function, elevated ferritin, and lactate dehydrogenase. Leukopenia, anemia, coagulopathy, hypofibrinogenemia, and splenomegaly were found in more than 80% of patients. Ten patients were treated with HLH-2004 protocol. Eventually, 95.7% of patients died of EBV-associated HLH. Non-HLH-2004 treatment and bone marrow suppression may predict early relapse independently, and the poor performance status and high lactate dehydrogenase level can be poor prognostic factors. It was also validated in comprehensive analysis of published articles.

Conclusions: Adult EBV-associated HLH occurs most often in people of Asian descent who are older than 35 years. These patients had a disappointing outcome despite intensive treatment, especially with high lactate dehydrogenase levels, poor performance status, and bone marrow suppression. HLH-2004 protocol has shown a glimmer of hope in the adult populations.

Background: The Epstein-Barr virus (EBV) is one of the most common viruses found in humans, causing lifelong infection in up to 95% of the world population.

Objectives: To analyze the seroprevalence of EBV infection in different population groups in Croatia.

Methods: During a 2 year period (2015–2016), a total of 2022 consecutive serum samples collected from Croatian residents were tested for the presence of EBV-specific viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies using an enzyme-linked immunoassay. IgM/IgG-positive samples were further tested for IgG avidity.

Results: The overall prevalence of EBV IgG antibodies was 91.4%. Females had significantly higher IgG seroprevalence than males (93.1% vs. 89.9%, P = 0.008). According to age, IgG seropositivity increased progressively from 59.6% in children age < 9 years to 98.3% in 30–39 year olds, and remained stable thereafter (P < 0.001). The IgG seroprevalence differed significantly among groups: 68.1% in children/adolescents and 95.9% in adults; multiple sclerosis (100%), hemodialysis patients (97.7%), heart transplant recipients (93.8%), hematological malignancies (91.2%), and Crohn’s disease (88.5%), P < 0.001. IgM antibodies were detected in 9% of participants. Using IgG avidity, recent primary EBV infection was documented in 83.8% of IgM-positive subjects < 9 years old, 69.2% age 10–19, 33.3% age 20–29, and 3.6–4.2% > 40. All IgM positive participants > 40 years showed high IgG avidity. Logistic regression showed that age is associated with EBV IgG seropositivity.

Conclusions: EBV is widespread in the Croatian population. Older age appears to be the main risk factor for EBV seropositivity.

Background: Ureaplasma species (Usp) are the most prevalent genital Mycoplasma isolated from the urogenital tract of both men and women. Usp may be commensals in the genital tract but may also be contributors to a number of pathological conditions of the genital tract. Because they can also just colonize the genital tract of healthy people, their pathogenic role can be difficult to prove.

Objectives: The aim of the study was to evaluate the efficacy of a quantitative polymerase chain reaction (qPCR) method for the discrimination between infection and colonization by measuring prevalence of Usp in asymptomatic versus symptomatic patients.

Methods: Urine samples were tested for U. parvum and U. urealyticum using a semi-quantitative multiplex PCR technique for sexually transmitted diseases (Anyplex™ STI-7 Detection Kit, Seegene, South Korea). A total of 250 symptomatic and 250 asymptomatic controls were included.

Results: A strong positive result for U. parvum was significantly more prevalent in symptomatic compared to asymptomatic patients. This finding was observed especially in women and in the young group (15–35 years of age). No significant differences were observed between the prevalence in symptomatic and asymptomatic patients of U. parvum with low strength of positivity and for U. urealyticum in all groups by age, gender, and strength of positivity.

Conclusions: The significant difference between the symptomatic and asymptomatic group in the highest positivity group for U. parvum using the Anyplex™ STI-7 detection kit in urine may indicate a high probability of infection rather than colonization, especially in women and young patients.