Analysis of Blood Culture Collection and Laboratory Processing Practices in Israel.

Importance: Blood culturing is a critical diagnostic procedure affecting patient outcomes and antibiotic stewardship. Although there are standards for blood culturing, the process is not often measured. Objectives: To evaluate processes related to the diagnosis of bloodstream infection and compare them with best practices. Design, Setting, and Participants: A quality improvement study using laboratory data from January 1 to June 30, 2019, was conducted in 28 (96.6%) Israeli acute care hospitals. All blood cultures (BCs) performed on samples from adults and children in a period of 147 hospital-months were analyzed. Data analysis was performed from April 12, 2021, to September 9, 2022. Main Outcomes and Measures: True pathogen detection rate, contamination rate, proportion of adults with blood cultures performed, proportion of adult culturing episodes with only 1 set or bottle used, and median time of steps from sample collection to pathogen identification. Results: The data set consisted of 348 987 BC bottles. Bloodstream infection was detected in a median of 6.7% (IQR, 5.8%-8.2%) of adult culturing episodes and 1.1% (IQR, 0.7%-1.9%) of pediatric episodes. Eleven of 27 hospitals (40.7%) with adult patients met the standard of a contamination rate of less than 3% and only 2 hospitals (7.4%) met the more stringent standard of less than or equal to 1% contamination rate. The percentage of adults with blood cultures ranged from 2.7% to 29.0% (mean [SD], 15.7% [6.0%]). There was an association between sampling rate and pathogen detection until BCs were performed in 17% of adult admissions. The percentage of solitary BCs ranged from 47.8% to 94.4%. An estimated 1745 of 7436 (23.5%) adult bloodstream infections went undetected because solitary BCs were performed, anaerobic bottles were not used, or BCs were not performed. Median processing time was 51.2 (IQR, 33.9-78.0) hours, 3 times the optimal time: 4.4 (IQR, 1.7-12.5) hours for the preanalytical stage, 15.9 (IQR, 10.2-23.6) hours from incubation to growth detection, 4.5 (IQR, 1.5-10.7) hours from detection to Gram stain, and 30.9 (IQR, 22.0-41.9) hours from detection to isolate identification. An 8.6-hour delay was related to off-hours operating of laboratories. Conclusions and Relevance: The findings of this study suggest that the multistep process of blood culturing is not managed comprehensively in Israel, leading to poor clinical practices and delayed results.

An Exploratory Study Using Electronic Medical Records to Assess the Feasibility of Establishing Cohorts of Patients with Genetic Causes of Parkinson's Disease.

BACKGROUND: More efficient screening methods are needed to improve the ability to identify and follow genetic cohorts in Parkinson's disease (PD). OBJECTIVE: To explore the use of the electronic medical records (EMRs) to identify participants with PD. METHODS: Using an algorithm previously developed in collaboration with Maccabi Healthcare Services (MHS), approximately 5,200 participants with PD were identified, more than 3,200 were screened, and 837 participants were enrolled and genotyped for leucine-rich repeat kinase 2 (LRRK2) and beta-glucocerebrosidase (GBA) variants. Questionnaires were completed to ascertain Ashkenazi Jewish (AJ) ancestry and family history of PD. RESULTS: Among 837 participants with PD, 82% were 65 years and older and 72% had a family history of AJ ancestry. Among those with AJ ancestry, 15.6% reported having relatives with PD. The frequency of observed mutations for LRRK2 and GBA genes combined was approximately 15.4%. The frequency of observed LRRK2 mutation was 6.1% overall and 7.2% from those with AJ ancestry; and for GBA mutation was 9.3% overall and 11.2% from those with AJ ancestry. CONCLUSION: Although the frequency of observed mutations in this study was lower than anticipated, mutation carriers were enriched among those with a family history of AJ ancestry increasing nearly 2-3-fold, from 3% -7% (LRRK2) and 4% -11% (GBA). The identification (and selection) of PD patients through EMRs prior to genotyping is a viable approach, to establish a genetically defined cohort of patients with PD for clinical research.

Antibiotic exposure and the risk of hospital-acquired diarrhoea and Clostridioides difficile infection: a cohort study.

BACKGROUND: Hospital-acquired diarrhoea (HAD) and Clostridioides difficile infection (CDI) may be triggered by antibiotic use. OBJECTIVES: To determine the effect of specific antibiotic agents and duration of therapy on the risk of HAD and CDI. PATIENTS AND METHODS: A single-centre retrospective cohort study was conducted between May 2012 and December 2014 in the internal medicine division. HAD was defined based on documentation of diarrhoea in the medical record or an uncancelled C. difficile test in the laboratory database. CDI was diagnosed using a two-step test (initial glutamate dehydrogenase and toxin A/B EIA, with PCR for discrepant results). Outcomes first occurred on hospital Day 4 or later. Treatment with antibiotics and days of therapy were modelled. RESULTS: In 29 063 hospitalizations there were 970 HAD events [incidence rate per 10 000 patient days (IR) = 38.5] and 105 CDI events (IR = 3.9). Any antibiotic treatment increased the risk of HAD [adjusted relative risk (aRR) 2.79; 95% CI 2.27-3.43] and CDI (aRR 5.31; 95% CI 2.23-12.69). Each day of ß-lactam/ß-lactamase inhibitors (ßL/ßLIs), carbapenems, IV glycopeptides and metronidazole increased the risk of HAD. Each day of ßL/ßLIs, third- and fourth-generation cephalosporins and carbapenems increased the risk of CDI by over 2%. CONCLUSIONS: Preventing HAD and CDI should focus on reducing the overall use of antibiotics and shortening antibiotic exposure, rather than focusing on specific agents.

A COVID-19 call center for healthcare providers: dealing with rapidly evolving health policy guidelines.

BACKGROUND: Communication between health authorities and healthcare providers is an essential element of the response to public health emergencies. Although call centers can facilitate such communication, no published reports describing their outcomes exist. In advance of the expected COVID-19 outbreak in Israel, the Israel Center for Disease Control established a call center dedicated to queries from healthcare professionals. METHODS: The call center operated from February 5, 2020 (week 6) to May 14, 2020 (week 20). Data on calls received, including date and time, caller characteristics, questions and responses were recorded in a database designed for this purpose. The volume, sources and content of queries were analyzed. RESULTS: In 15 weeks of operation, the call center responded to 6623 calls. The daily number of calls ranged from 1 to 371 (mean 79.8, median 40), peaking on week 12, 2 weeks prior to a peak in new COVID-19 cases. Callers were predominantly physicians (62.4%), nurses (18.7%) and administrators (4.4%). Most worked in primary care clinics (74.2%) or hospitals (8.7%). Among physicians, 42.3% were family physicians or internists, and 10.0% were pediatricians. The issues most commonly addressed were home quarantine (21.6%), criteria for suspected cases (20.6%), and SARS-CoV2 testing (14.1%). Twenty-five percent of questions involved requests for clarifications of MOH guidelines regarding travel restrictions, clinic management, triage of symptomatic patients, routine medical and dental care, recommended precautions for health care workers with preexisting medical conditions, and other matters. A total of 119 queries were not resolved on the basis of existing guidelines and were referred to MOH headquarters. CONCLUSIONS: This is the first report of a call center established to serve the needs of healthcare providers seeking guidance on COVID-19 management, and to facilitate communication of providers' concerns to the central health authority. Our work indicates that a central call center for healthcare providers can facilitate the development, implementation and amendment of guidelines and should be an integral element of the early response to public health emergencies. Real-time analysis of the call data may reveal important trends requiring prompt attention.

Elderly bedridden patients with dementia use over one quarter of resources in internal medicine wards in an Israeli hospital.

BACKGROUND: Elderly bedridden patients with dementia (EBRPD) are a growing segment of the population. We aimed to describe acute care hospitalization of EBRPD in internal medicine wards: the prevalence of EBRPD, their impact on hospital resources and hospital ecology, one-year survival, and one-year readmission-free survival. METHODS: The study setting was the internal medicine division of one tertiary care hospital in Israel. We conducted a point-prevalence survey to measure the prevalence of EBRPD and the prevalence of multidrug-resistant organism (MDRO) carriage. We also conducted a retrospective chart review of EBRPD who were hospitalized in the internal medicine division in order to assess resource use, survival, and readmission. RESULTS: In the point prevalence surveys (N = 1667 patients), EBRPD comprised 24.3% of patients and 59.0% of mechanically ventilated patients. EBRPD were twice as likely to be colonized or infected by MDROs as other patients (39.3% vs. 18%, p < 0.001); thus, 41% of MDRO carriers during the survey days were EBRPD. In the retrospective study (N = 517 EBRPD), 80% of EBRPD received antibiotics; on average, they received an antibiotic on 87.7% of their hospital days. One-year survival was 35.6% and one-year readmission-free survival was 16.4%. CONCLUSIONS: Acute care hospitalization of EBRPD accounted for a high proportion of bed occupancy and ventilator use in internal medicine wards. EBRPD significantly increase the potential for MDRO transmission. Policymakers should seek alternatives to acute care hospitalization for EBRPD.

The Effects of Publicized Suicide Deaths on Subsequent Suicide Counts in Israel.

This study investigated associations between indiscriminate media reporting of suicides and later inflated suicide counts among Israel's general population between the years 2008 and 2012. Self-inflicted deaths that received post-suicide media exposure (referred to as "publicized suicides") were selected via Google news search-hit appraisals. Distributions of suicides were inspected and risk ratios (RRs) estimated by comparing population suicide rates 4 weeks before and 4 weeks after each publicized suicide ("reference" vs. "affected" periods, respectively). Poisson time series regression was employed to account also for secular trends and seasonality. A total of 2,119 people died by suicide, 13 of whom received noticeable media attention throughout the study. No meaningful impact following the 13 deaths on subsequent suicide counts during the observation window (affected vs. reference phase) was found. Poisson regression confirmed that suicide counts following publicized suicides were independent of media coverage. Given the pronounced search hits following the publicized suicides developing regulation practices that constrain indiscreet media reporting should officially be included as part of suicide prevention practices. Future research should focus on imitation suicide effects as a function of post-suicide media exposure, while including both risk and protective factors.

The tip of the iceberg: postpartum suicidality in Israel.

BACKGROUND: Postpartum suicidality, a result of extreme distress or depression, is a tragedy for the woman, infant, and family. Screening for postpartum depression (PPD) is mandatory in Israel, including a question on suicidal ideation. This study presents and analyzes data regarding rates, trends and characteristics of postpartum women who considered, attempted, or completed suicide, to help direct services aimed at preventing these occurrences. METHODS: Suicidal ideation data based on PPD screening was drawn from various publications and databases. Suicide attempt data was obtained from the Emergency Department database for 2006-2015 and matched with the National Birth Registry. Cause of death from the national database for those years were similarly linked to births to identify postpartum suicides and deaths. Postpartum and non-postpartum suicide attempt rates were computed by year, and by age and ethnic/immigrant group. A multivariate logistic model was used to estimate relative risk for postpartum attempts, controlling for age and ethnic group. RESULTS: Suicidal ideation in recent years has been reported as 1% or less, with higher rates found in studies of Arab women. Suicide attempt rates for non-postpartum women were 3-5 times that of postpartum women, rising over the years, while remaining relatively stable for postpartum women. Adjusted risk of suicide attempt for non-postpartum women was significantly higher; adjusted odds ratio was 4.08 (95% CI 3.75-4.44). It was also significantly higher for Arabs and immigrants from the Former Soviet Union, compared to Israeli-born Jews/veteran immigrants, and for younger women compared to those aged 35-44. Seven postpartum suicides were recorded during 2006-2015, a rate of 0.43 per 100,000 births. CONCLUSION: Postpartum suicidality in Israel is low relative to other countries. Although relatively rare and lower than among non-postpartum women, health professionals should be attentive to risk factors, such as past psychiatric disorders, suicide attempts and current emotional distress, particularly among higher-risk populations. The universal screening program for PPD is a valuable opportunity for this, but increased resources should be allotted to implement and utilize it optimally. Prenatal screening should be added as an Israeli Quality Indicator, and postpartum completed suicides should be thoroughly investigated to guide prevention efforts.

Risk Factors for Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae (CP-CRE) Acquisition Among Contacts of Newly Diagnosed CP-CRE Patients.

OBJECTIVE Carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are extremely drug-resistant pathogens. Screening of contacts of newly identified CP-CRE patients is an important step to limit further transmission. We aimed to determine the risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient. METHODS A matched case-control study was performed in a tertiary care hospital in Israel. The study population was comprised of patients who underwent rectal screening for CP-CRE following close contact with a newly identified CP-CRE index patient. Cases were defined as positive tests for CP-CRE. For each case patient, 2 matched controls were randomly selected from the pool of contacts who tested negative for CP-CRE following exposure to the same index case. Bivariate and multivariate analyses were conducted using conditional logistic regression. RESULTS In total, 53 positive contacts were identified in 40 unique investigations (896 tests performed on 735 contacts) between October 6, 2008, and June 7, 2012. bla KPC was the only carbapenemase identified. In multivariate analysis, risk factors for CP-CRE acquisition among contacts were (1) contact with an index patient for ≥3 days (odds ratio [OR], 9.8; 95% confidence interval [CI], 2.0-48.9), (2) mechanical ventilation (OR, 4.1; 95% CI, 1.4-11.9), and (3) carriage or infection with another multidrug-resistant organism (MDRO; OR, 2.6; 95% CI, 1.0-7.1). Among patients who received antibiotics, cephalosporins were associated with a lower risk of acquisition. CONCLUSIONS Patient characteristics (ventilation and carriage of another MDRO) as well as duration of contact are risk factors for CP-CRE acquisition among contacts. The role of cephalosporins requires further study. Infect Control Hosp Epidemiol 2016;1-7.

Prevalence and risk factors for carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae among patients prior to bowel surgery.

Prophylactic antibiotics are an important measure in preventing perioperative infection, Failure to cover multidrug-resistant pathogens may place carriers at increased risk of infection. We conducted a prospective, cross-sectional study in patients prior to bowel surgery to measure the carriage prevalence of extended-spectrum ß-lactamase-producing Enterobacteriaceae and identify risk factors for carriage in this population. During an 11-month period, 150 patients were eligible for inclusion. 27 patients (18%) were found to be carriers of extended-spectrum ß-lactamase-producing Enterobacteriaceae. Factors independently associated with carriage were immunosuppressive therapy (OR, 4.09; 95% CI 1.55-10.81; P = 0.005) and receipt of antibiotics in the prior 3 months (OR, 2.59; 95% CI 1.08-6.24; P = 0.033). Detection of a population at risk for carriage may help in devising and modifying appropriate antibiotic regimens for surgical prophylaxis in carriers of multidrug-resistant bacteria.

The postmortem proxy-based interview--future directions.

The present study aims to provide an overview of the procedural and methodological challenges that need to be addressed when determining the content and application of postmortem proxy-based interviews and recommendations for meeting these challenges in future death investigations are outlined. Preliminary interview considerations are discussed and a step-by-step procedural algorithm for applying proxy-based interview protocol is supplied. A vulnerability-stress model is used for organizing the conceptualization of risk and protective factors into domains of theoretically similar factors. Techniques to improve data collected about mental disorders and stressful life events-variables addressed in nearly all psychological autopsy studies-are suggested, and the importance of examining certain understudied constructs (e.g., psychological factors, family history, select situational factors, childhood adversity, and protective factors) is emphasized. Given the convergence of findings across postmortem proxy-based interviews, whereby extracting postmortem psychiatric diagnoses is the rule, the next generation of studies must offer a point of departure from univariate models, by studying how and why well known exposures interact to produce suicide. In practical terms, targeting specific sub-populations and high-risk individuals can serve as the basis for constructing and testing different clinical hypothesis, which in turn may yield insights into the underlying etiological heterogeneity of suicide.

The accuracy of suicide statistics: are true suicide deaths misclassified?

PURPOSE: Official suicide statistics often produce an inaccurate view of suicide populations, since some deaths endorsed as being of uncertain manner are in fact suicides; it is common, therefore, in suicide research, to account for these deaths. We aimed to test the hypothesis that non-suicide death categories contain a large potential reservoir of misclassified suicides. METHODS: Data on undetermined intent and ill-defined death causes, and official suicide deaths recorded in the district of Tel Aviv for the years 2005 and 2008 were extracted. Based on supplementary data, cases regarded as probable suicides ("suicide probable") were then compared with official suicides ("suicide verdicts") on a number of socio-demographic variables, and also in relation to the mechanism of death. RESULTS: Suicide rates were 42 % higher than those officially reported after accounting for 75 probable suicides (erroneously certified under other cause-of-death categories). Both death classifications ("suicide probable" and "suicide verdicts") had many similarities, significantly differing only with respect to method used. Logistic regression confirmed that the most powerful discriminator was whether the mechanism of death was considered "less active" or "more active" (p < 0.001). Indeed, deaths among the less active group were 4.9 times as likely to be classified as "suicide probable" than were deaths among the more active group. CONCLUSIONS: Caution is needed when interpreting local area data on suicide rates, and undetermined and ill-defined deaths should be included in suicide research after excluding cases unlikely to be suicides. Improving suicide case ascertainment, using multiple sources of information, and uniform reporting practices, is advised.

Characteristics of suicide completers with a psychiatric diagnosis before death: a postmortem study of 98 cases.

The objective of this research was to classify the deaths of 98 victims of suicide in Tel Aviv, Israel between the years 2007 and 2010. This was done by examining background features and clinical characteristics among suicide completers with histories of a prior psychiatric hospitalization using logistic regression modeling. 34% of the sample (33/98) was given at least one psychiatric diagnosis upon discharge from a prior psychiatric hospitalization. Throughout their lifetime, those with psychiatric diagnoses were significantly more likely to have histories of mental health treatment (psychotherapy and psychotropic medication), psychopathology and suicidality among family members, prior suicide attempts and familial or emotional crisis as compared with those without a psychiatric diagnosis. During their last life phase, those with prior psychiatric diagnoses were also significantly more likely to have received psychotherapeutic treatment, expressed a lack of desire to live and presented with affective symptoms (e.g. depression, anxiety, adaptation difficulty and nervousness) as compared with those without such histories. Thus, focusing on high risk populations, such as those with psychiatric illnesses and deciphering the role of mental health treatment, familial predisposition, prior suicide attempt and sub-clinical symptoms in relation to suicide can inform future prevention practices.

Lack of severe long-term outcomes of acute, subclinical B1 deficiency in 216 children in Israel exposed in early infancy.

BACKGROUND: A vitamin B(1)-deficient soy-based infant formula was marketed in Israel in 2003, exposing infants to clinical or subclinical B(1) deficiency. We investigated whether subclinical B(1) deficiency in early infancy had medical, neurodevelopmental, or cognitive effects at 3-5 y of age. METHODS: A historical prospective cohort study was conducted consisting of four groups: "exposed," consuming a B(1)-deficient soy-based formula exclusively for four consecutive weeks or longer; "control," consuming no soy-based formula; "mixed," consuming the formula nonexclusively or exclusively for less than four consecutive weeks; and "other," consuming soy-based formulas other than Remedia. Participants were evaluated by medical examination, Stanford-Binet (SB) intelligence test, sensory profile evaluation, and Conners scales (attention deficit disorder/attention deficit and hyperactivity disorder (ADD/ADHD)). RESULTS: Following adjustment for gender, age, and maternal education, there were no significant differences among the four groups on the mean SB scores, on the verbal and nonverbal scores, or in the proportion of children in each group with scores <90. A significantly higher proportion of exposed children as compared with control children had an impaired sensory profile and scores on the Conners scales (ADD/ADHD), but these proportions were also high in the "other" and "mixed" groups. CONCLUSION: The results do not support an association between subclinical B(1) deficiency in infancy and long-term development.

Expression of Bcl-x(S) in Xenopus oocytes induces BH3-dependent and caspase-dependent cytochrome c release and apoptosis.

The mechanism of action of pro-apoptotic proteins is difficult to study in vivo because of their death effect, which makes it problematic to obtain sufficient homogeneous experimental material for biochemical analysis. We show here that pro-apoptotic genes expressed in Xenopus oocytes constitute a useful in vivo system for studying their mechanism of action. In the present study, we used this system to study the death effects of Bcl-x(S), a pro-apoptotic member of the Bcl-2 family. The results showed that expression of Bcl-x(S) in oocytes induces oocyte death by a caspase-dependent mechanism, which includes BH3-dependent cytochrome c release and is inhibited by co-expression of the anti-apoptotic proteins Bcl-2 and Bcl-x(L). The release of cytochrome c was found to be dependent on caspase activity. Bcl-x(S) was localized mainly in the mitochondria, and Bcl-x(S) transmembrane and BH3 domains were required for its apoptotic effect. These findings suggest that Bcl-x(S) induces apoptosis in Xenopus oocytes mainly by its presence in the mitochondria, where it induces BH3- and caspase-dependent release of cytochrome c, which leads to oocyte death.