Association between obstructive sleep apnea (OSA) and COVID-19 severity.

Obstructive sleep apnea and sleep-related hypoxia have been associated with higher rates of hospitalization and mortality among patients with Coronavirus disease 2019 (COVID-19). We further explored the association between obstructive sleep apnea, COVID-19 severity and related mortality. In addition, we examined the effects of clinical and demographic parameters on COVID-19. In this retrospective study, we included adult patients who were diagnosed with COVID-19 prior to the Omicron variant identification. We compared the severity of COVID-19 and mortality with the diagnosis of obstructive sleep apnea. The study population included 44,275 patients who tested positive for COVID-19. Of these, 97% had mild or asymptomatic disease, 1.2% had moderate disease, and 1.8% had severe disease. Obstructive sleep apnea was diagnosed in 980 (2.2%) patients. In a multivariate analysis, obstructive sleep apnea diagnosis increased the risk of severe COVID-19 by 1.6 (95% confidence interval: 1.1-2.4) compared with mild disease. However, no increase in mortality was associated with obstructive sleep apnea. Interestingly, patients with moderate and high socioeconomic status had a 1.6 times higher risk for severe COVID-19 than patients from the low socioeconomic status group (95% confidence interval: 1.2-2.1 and 95% confidence interval: 1.1-2.3, respectively). The risk of dying due to COVID-19 was 1.6 (95% confidence interval: 1.1-2.5) and 3.1 (95% confidence interval: 1.8-5.3) times higher in patients with medium and high socioeconomic status, respectively, compared with patients with low socioeconomic status. Diagnosis of obstructive sleep apnea was found to be an independent risk factor for severe COVID-19. The higher the socioeconomic status, the higher the risk of severe COVID-19 morbidity and mortality.

The association of medical, social, and normative factors with the implementation of end-of-life care practices.

BACKGROUND: End-of-life (EoL) care practices (EoLCP) are procedures carried out at the EoL and bear directly on this stage in the patient's life. Public support of these practices in Israel is far from uniform. Previous studies show that while ∼30% of participants support artificial respiration or feeding of terminally ill patients, 66% support analgesic treatment, even at the risk of shortening life. This study aimed to create a typology of six end-of-life care practices in Israel and assess the association of medical, social, and normative factors with the implementation of those practices. These practices included mechanical ventilation, artificial feeding, deep sedation, providing information to the patient and family caregivers, including family caregivers in EoL decision-making, and opting for death at home. METHODS: This cross-sectional study was performed as an online survey of 605 adults aged 50 or more in Israel, of which ~ 50% (n = 297) reported supporting a dying terminally ill relative in the last 3 years. Participants were requested to provide their account of the EoL process of their relative dying from a terminal illness in several aspects, as well as the EoL care practices utilized by them. RESULTS: The accounts of the 297 interviewees who supported a dying relative reveal a varied EoL typology. The utilization of end-of-life care practices was associated with the socio-normative beliefs of family caregivers but not with their socioeconomic status. Strong correlations were found between family caregiver support for three key practices (mechanical ventilation, artificial feeding, and family involvement in EoL) and the actual utilization of these practices in the care of dying patients. CONCLUSIONS: The findings portray an important image of equity in the utilization of EoLCP in Israel, as the use of these practices was not associated with socioeconomic status. At the same time, the study found substantial diversity in family caregivers' preferences regarding EoL care practices use not related to socioeconomic status. We believe that differences in preferences that do not lead to problems with equity or other important societal values should be respected. Accordingly, policymakers and health system leaders should resist calls for legislation that would impose uniform EoL practices for all Israelis. Instead, they should take concrete steps to preserve and enhance the widespread current practice of practitioners to adapt EoL care to the varied needs and preferences of Israeli families and cultural, social, and religious subgroups. These steps should include providing frameworks and tools for family caregivers to support their loved ones close to their deaths, such as educational programs, seminars, supportive care before and during the end of life of their loved ones, etc.

Polarization in public attitudes toward end-of-life decisions in Israel - A cross-sectional study.

OBJECTIVES: End-of-life (EoL) processes are a complex socio-normative and ethical phenomenon. This study aimed to generate a database of public opinion in Israel concerning EoL processes and decisions and to identify differences in attitudes across subgroups in the population, particularly based on experience as a family caregiver of a dying patient. METHODS: This cross-sectional study was performed in late March 2022. The study utilized an online sample of 605 adults over the age of 50 including those who accompanied a loved one to their death in the last 3 years. Participants were requested to provide their opinions and attitudes on several aspects of EoL decisions, including truth-telling, medically assisted dying, EoL procedures, pre-death actions, and family caregivers' engagement. RESULTS: While only 27% and ∼30% of participants support artificial respiration or feeding (respectively) of terminally ill patients, 66% support analgesic treatment, even at the risk of shortening life. The data show an association between religiosity and agreement with life-extending procedures. For example, while 83% of seculars support medically assisted dying, only 59% and 26% of traditional and religious respondents support it. However, no statistically significant differences were observed in support of family involvement in EoL process in any sociodemographic variable. SIGNIFICANCE OF RESULTS: The results of this study suggest that the Israeli public is relatively polarized on several issues about EoL processes, specifically patient autonomy and medically assisted dying. Yet, at the same time, there is a consensus among the Israeli public about certain EoL elements, particularly the importance of family caregivers in the EoL decision-making process.

Benign transient hyperphosphatasemia in infants and children: a retrospective database study.

Benign transient hyperphosphatasemia is a condition characterized by greatly increased serum alkaline phosphatase (ALP) without laboratory or clinical evidence of underlying bone or liver disease. It is usually identified incidentally during routine blood testing. We describe the demographic and clinical characteristics of benign transient hyperphosphatasemia in a cohort of healthy infants and children. We performed a retrospective review of electronic medical records on all children aged 1 day to 18 years with a diagnosis of benign transient hyperphosphatasemia, who were registered at 3 central districts in Israel from January 1, 2000, to December 31, 2020. The demographic and clinical characteristics were retrieved from the medical files. The study group comprised 382 infants and children aged from 2 months to 14 years who had serum ALP > 1000 U/L (mean 2557 U/L, range 1002-14,589 U/L). The majority of participants (87%) were aged up to 24 months (median age 14 months, IQR 10-18 months). Fifty-four percent of the study participants were male. In many patients, there was a history of recent fever, gastroenteritis or diarrhea, acute otitis media, and viral infection. A seasonal peak was observed in autumn-early winter, but this may be a detection bias. CONCLUSION: Benign transient hyperphosphatasemia seems to be a disorder described among otherwise healthy infants and children, which resolves spontaneously. Other known causes of markedly elevated serum ALP should be excluded, especially bone and liver disease. Higher awareness and recognition of this benign condition are important in order to avoid unnecessary tests and parental anxiety. WHAT IS KNOWN: • Benign transient hyperphosphatasemia is a benign condition characterized by greatly increased serum alkaline phosphatase without laboratory or clinical evidence of underlying bone or liver disease, which usually resolves spontaneously, with no intervention. WHAT IS NEW: • In the case of an incidental finding of high serum alkaline phosphatase in an otherwise healthy infant or child with no other clinical or laboratory suspicion of bone or liver disease, we recommend repeating the alkaline phosphatase level within a few months in order to confirm the resolution of this condition. • When benign transient hyperphosphatasemia is suspected, a "wait and see" approach is optimal in order to avoid unnecessary investigations and parental anxiety.

Predictors and Adverse Outcomes of Acute Kidney Injury in Hospitalized Renal Transplant Recipients.

Data about in-hospital AKI in RTRs is lacking. We conducted a retrospective study of 292 RTRs, with 807 hospital admissions, to reveal predictors and outcomes of AKI during admission. In-hospital AKI developed in 149 patients (51%). AKI in a previous admission was associated with a more than twofold increased risk of AKI in subsequent admissions (OR 2.13, p < 0.001). Other major significant predictors for in-hospital AKI included an infection as the major admission diagnosis (OR 2.93, p = 0.015), a medical history of hypertension (OR 1.91, p = 0.027), minimum systolic blood pressure (OR 0.98, p = 0.002), maximum tacrolimus trough level (OR 1.08, p = 0.005), hemoglobin level (OR 0.9, p = 0.016) and albumin level (OR 0.51, p = 0.025) during admission. Compared to admissions with no AKI, admissions with AKI were associated with longer length of stay (median time of 3.83 vs. 7.01 days, p < 0.001). In-hospital AKI was associated with higher rates of mortality during admission, almost doubled odds for rehospitalization within 90 days from discharge and increased the risk of overall mortality in multivariable mixed effect models. In-hospital AKI is common and is associated with poor short- and long-term outcomes. Strategies to prevent AKI during admission in RTRs should be implemented to reduce re-admission rates and improve patient survival.

COVID-19 lockdown impact on quality of treatment and outcomes of STEMI and stroke patients in a large tertiary medical center: an observational study.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic affected health-care systems worldwide, leading to fewer admissions and raising concerns about the quality of care. The objective of this study was to investigate the early effects of the COVID-19 pandemic on quality of care among stroke and ST-elevation myocardial infarction (STEMI) patients, focusing on clinical outcomes and direct treatment costs. METHOD: This retrospective, observational study was based on the 10-week period that included the first wave of the COVID-19 pandemic in Israel (15 February 2020-30 April 2020). Emergency department admissions for stroke and STEMI were compared with parallel periods in 2017-2019, focusing on demographics, risk and severity scores, and the effect of clinical outcomes on hospitalization costs. RESULTS: The 634 stroke and 186 STEMI cases comprised 16% and 19% fewer admissions, respectively, compared to 2019. No significant changes were detected in demographics, most disease management parameters, readmission and mortality outcomes. The mean door-to-balloon time increased insignificantly by 33%, lowering the health quality indicator (HQI) for treatment in <90 min from 94.7% in 2017-2019 to 83% in 2020 (P = 0.022). Among suspected stroke patients, 97.2% underwent imaging, with 28% longer median time from admission (P = 0.05). Consequently, only 24.3% met the HQI of imaging in <29 min, compared to 45.5% in 2017-2019 (P < 0.01). Increased length of stay and more intensive care unit admissions were the leading causes of 6.5% increased mean cost of STEMI patients' initial hospitalization, which totaled $29 300 in the COVID-19 period (P = 0.008). CONCLUSION: The initial pandemic period caused a decline in HQIs linked to diagnostic and treatment protocols, without changes in outcomes, but with increased hospitalization costs. Medical information and awareness of life-threatening conditions among patients and caregivers should be increased to enable proper diagnosis and management.

Duplicate Prescription Rates of Long-Acting Bronchodilator Inhalers.

Background: Long-acting bronchodilator inhalers are widely used with or without inhaled corticosteroids (ICs) by patients with lung diseases. In Israel alone, there are 21 inhalers containing long-acting ß2 agonists (LABAs) and/or long-acting muscarinic antagonists (LAMAs). Some patients are treated incorrectly with several inhalers of the same pharmacologic group. Methods: Electronic data of LABA and/or LAMA inhalers purchased during a period of 1 year were extracted in one district of Clalit Health Services in Israel. Patients who were treated with two or more inhalers from the same pharmacologic group were compared with patients without duplicate treatment. Inhaler purchases during the 12 months before and after the first duplicate purchase were compared with the purchases by patients without duplication of treatment. New diagnoses were compared to identify possible side effects. Results: Of the 13,528 patients who were treated with LABA and/or LAMA inhalers, 244 (1.8%) purchased at least two different inhalers from the same pharmacologic group. Inhaler purchases were 3.8 times higher in the duplication group during the 12 months before the first duplication. Inhaler purchase increased by 28% in the duplication group compared with a 4.5% increase in the nonduplication group (p < 0.001) during the following year. The risk for duplicated consumption was significantly higher in patients with a chronic obstructive pulmonary disease (COPD) diagnosis, males, and persons aged between 61 and 80 years. Conclusions: Nearly 2% of the patients treated with long-acting bronchodilators consumed different medications of the same pharmacologic group even when adherence was satisfactory. COPD patients are at higher risk for inhaler duplication. Clinical Trial Registration Number: 0151-20-COM1.

Fermented Wheat Germ Extract (FWGE) as a Treatment Additive for Castration-Resistant Prostate Cancer: A Pilot Clinical Trial.

Castration-resistant prostate cancer (CRPC) is a devastating and incurable disease. Combined therapy using conventional anticancer drugs and a proprietary medical nutriment, fermented wheat germ extract (FWGE), also known as Avemar, has been suggested as a treatment for progressing prostate cancer (PCa) patients, who have become resistant to first line hormonal therapy (gonadotropin releasing hormone, GnRH). The primary aim of this study was to test if this combined therapy would slow down disease progression in CRPC patients. We tested the nontoxic, readily available, inexpensive FWGE, together with the conventional treatment, GnRH analogue, in 36 CRPC patients. Although this is a pilot study, with the drawback of a statistically small sample size, some anticancer clinical activity of FWGE could be seen in the CRPC patients, as measured by prostate specific antigen doubling time (PSADT). We found that the intake of GnRH with FWGE for at least 4 months, improved the overall health as well as the quality of life (QOL) in 4 patients (11%) and was instrumental in extending the PSADT in about 17 (out of 26) patients (65.4%), six of whom were significant. Since no mentionable adverse events were noticed, this treatment may permit the postponement of chemotherapy for these patients.

Short-acting bronchodilators purchase as a marker for asthma control.

Background: Administrative data has been used to quantify the amount of medication use in order to identify at-risk asthma patients. In our previous study we used short-acting beta-agonists (SABA) inhalers as a marker for asthma control.Methods: We further analyzed patient data from the SABA inhalers study in which asthma control was classified by GINA guidelines, physician assessment and the patients overall estimation. We identified all short-acting bronchodilator purchases (SABA and anticholinergic inhalers and solutions) in the year prior to administering the questionnaire relating to asthma control, and compared inhaled and systemic steroid use.Results: Of 241 asthma patients, 83 completed questionnaires. Using the GINA guidelines criteria, 26 were symptom controlled, 46 were partially controlled and 11 were uncontrolled. Using patients' overall impression of their asthma control, mean annual short-acting bronchodilator purchases were significantly higher in the partially controlled and uncontrolled patients (10 and 8.9 respectively) than in the controlled patients (2, p = 0.005). Most asthma patients purchase less than half of the controller medications prescribed to them.Conclusion: When using administrative data, 3 or more -of all types of short-acting bronchodilator purchases in one year should alert the physician to evaluate asthma control and purchase alerts should notify both physicians and patients when controller consumption is low.

Improved transplant outcomes with myeloablative conditioning for hemophagocytic lymphohistiocytosis in HLA-matched and mismatched donors: a national multicenter retrospective study.

We report the results of national retrospective study of 45 children with hemophagocytic lymphohistiocytosis (HLH) who underwent allogeneic hematopoietic stem-cell transplantation (HSCT) in Israel between the years 2000-2018. Donors were either HLA-matched (n = 26), partially mismatched (n = 7), haploidentical (n = 8), or cord-blood (n = 4). Myeloablative conditioning (MAC) was used in 20 procedures, and reduced-intensity conditioning (RIC) in 25. Forty-two patients engrafted, two had primary graft failure (one successfully retransplanted), one died prior to engraftment, and two developed secondary graft failure. Of the eight patients who had mixed donor chimerism at day 30 (5-95%), five achieved stable mixed or full donor chimerism. The 5-year probabilities of overall survival and event-free survival (EFS) were 86% and 82%, respectively. Five-year EFS was lower for patients receiving RIC compared to MAC (72% vs. 100%, p = 0.018) and following alternative-donor transplant (68% vs. 92% for HLA-matched donors, p = 0.034), mostly due to increased transplant-related mortality (TRM). Thus, both HLA-matched and alternative donor transplant procedures may benefit form a myeloablative conditioning regimen.

Sick Euthyroid Syndrome on Presentation of Patients With COVID-19: A Potential Marker for Disease Severity.

OBJECTIVE: Precise risk stratification and triage of coronavirus disease 2019 (COVID-19) patients are essential in the setting of an overwhelming pandemic burden. Clinical observation has shown a somewhat high prevalence of sick euthyroid syndrome among patients with COVID-19. This study aimed to evaluate the predictive value of free triiodothyronine (FT3) at the clinical presentation of COVID-19 for disease severity and death. METHODS: This retrospective cohort study was based on electronic medical records. The study was conducted at Sheba Medical Centre, a tertiary hospital where several acute and chronic wards have been dedicated to the treatment of patients with COVID-19. The primary outcome measure was death during hospitalization; secondary outcomes included hospitalization in intensive care, mechanical ventilation, and length of hospitalization. RESULTS: Of a total of 577 polymerase chain reaction-positive patients with COVID-19 hospitalized between February 27 and July 30, 2020, 90 had at least 1 measurement of thyroid-stimulating hormone, free thyroxine, and FT3 within 3 days of presentation. After applying strict exclusion criteria, 54 patients were included in the study. Patients in the lowest tertile of FT3 had significantly higher rates of mortality (40%, 5.9%, and 5.9%, P = .008), mechanical ventilation (45%, 29.4%, and 0.0%; P = .007) and intensive care unit admission (55%, 29.4%, and 5.9%, P = .006). In multivariate analyses adjusted for age, Charlson comorbidity index, creatinine, albumin, and white blood cell count. FT3 remained a significant independent predictor of death. CONCLUSION: FT3 levels can serve as a prognostic tool for disease severity in the early presentation of COVID-19.

Associations of physicians' prescribing experience, work hours, and workload with prescription errors.

OBJECTIVE: We aimed to assess associations of physician's work overload, successive work shifts, and work experience with physicians' risk to err. MATERIALS AND METHODS: This large-scale study included physicians who prescribed at least 100 systemic medications at Sheba Medical Center during 2012-2017 in all acute care departments, excluding intensive care units. Presumed medication errors were flagged by a high-accuracy computerized decision support system that uses machine-learning algorithms to detect potential medication prescription errors. Physicians' successive work shifts (first or only shift, second, and third shifts), workload (assessed by the number of prescriptions during a shift) and work-experience, as well as a novel measurement of physicians' prescribing experience with a specific drug, were assessed per prescription. The risk to err was determined for various work conditions. RESULTS: 1 652 896 medical orders were prescribed by 1066 physicians; The system flagged 3738 (0.23%) prescriptions as erroneous. Physicians were 8.2 times more likely to err during high than normal-low workload shifts (5.19% vs 0.63%, P < .0001). Physicians on their third or second successive shift (compared to a first or single shift) were more likely to err (2.1%, 1.8%, and 0.88%, respectively, P < .001). Lack of experience in prescribing a specific medication was associated with higher error rate (0.37% for the first 5 prescriptions vs 0.13% after over 40, P < .001). DISCUSSION: Longer hours and less experience in prescribing a specific medication increase risk of erroneous prescribing. CONCLUSION: Restricting successive shifts, reducing workload, increasing training and supervision, and implementing smart clinical decision support systems may help reduce prescription errors.

Factors associated with disparities in out-of-pocket expenditure on dental care: results from two cross-sectional national surveys.

BACKGROUND: Socioeconomic differences in oral health and dental care utilization are a persistent problem in many high-income countries. We evaluated demographic, geographic and socioeconomic factors associated with disparities in households' out-of-pocket expenditure (OOPE) on dental care, and the effect of ongoing dental health reform on these disparities. METHODS: This cross-sectional analysis used data collected in two Israeli Household Expenditure Surveys conducted in 2014 and 2018. OOPE for dental care was estimated using a two-part multivariable model. A logistic regression was used to examine the likelihood of reporting any OOPE, and a log-transformed linear regression model examined the level of expenditure among those who reported any OOPE. RESULTS: In 2018, OOPE on dental care accounted for 22% of total health expenditure for all households, whereas among those who reported dental OOPE it reached 43%. Households with children up to age 14 years reported lower OOPE, regardless of ownership of supplementary health insurance. Owning supplementary health insurance had a heterogeneous effect on the level of OOPE, with a significant increase among those with 0-8 years of education, compared to households without such insurance, but not among those of higher educational level. In 2014, Arab ethnic minority and residence in the country periphery were associated with a greater likelihood for any OOPE and higher amounts of OOPE on dental care. While the gaps between Jewish and Arab households persisted into 2018, those between peripheral and non-peripheral localities seem to have narrowed. CONCLUSIONS: The burden of dental OOPE on Israeli households remains heavy and some disparities still exist, even after the implementation of the dental health reform. Expanding the dental health reform and addressing barriers to preventive dental care, especially among Arabs and those of lower educational level, may help in reducing households' private expenses on dental care.

Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study.

BACKGROUND: VB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM). METHODS: Patients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS). RESULTS: VB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease. CONCLUSIONS: Patients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study.

Incidence and Risk Factors for Anastomotic Leakage in Colorectal Surgery: A Historical Cohort Study.

BACKGROUND: Anastomotic leakage (AL) is a major complication following colorectal surgery, with many risk factors established to date. The incidence of AL varies in the medical literature and is dependent on research inclusion criteria and diagnostic criteria. OBJECTIVES: To determine the incidence of and the potential risk factors for AL following colorectal surgery at a single academic medical center. METHODS: We retrospectively reviewed all operative reports of colorectal procedures that included bowel resection and primary bowel anastomosis performed at Sheba Medical Center during 2012. AL was defined according to the 1991 United Kingdom Surgical Infection Study Group criteria. Data were assessed for leak incidence within 30 days. In addition, 17 possible risk factors for leakage were analyzed. A literature review was conducted. RESULTS: This cohort study comprised 260 patients, and included 261 procedures performed during the study period. The overall leak rate was 8.4%. In a univariate analysis, male sex (odds ratio [OR] 3.37, 95% confidence interval [95%CI] 1.21-9.43), pulmonary disease (OR 3.99, 95%CI 1.49-10.73), current or past smoking (OR 2.93, 95%CI 1.21-7.10), and American Society of Anesthesiologist score ≥ 3 (OR 3.08, 95%CI 1.16-8.13) were associated with an increased risk for anastomotic leakage. In a multivariate analysis, male gender (OR 3.62, 95%CI 1.27-10.33) and pulmonary disease (OR 4.37, 95%CI 1.58-12.10) were associated with a greater risk. CONCLUSIONS: The incidence of AL in the present study is similar to that found in comparable series. Respiratory co-morbidity and male sex were found to be the most significant risk factors.

Adverse Drug Event Rate in Israeli Hospitals: Validation of an International Trigger Tool and an International Comparison Study.

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. OBJECTIVES: 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.

Determination of asthma control using administrative data regarding short-acting beta-agonist inhaler purchase.

BACKGROUND: Symptom control is a primary goal in asthma. We hypothesized that administrative data regarding rescue inhaler purchases may correlate with asthma symptom control. METHODS: We identified all patients who purchased short-acting beta-agonist (SABA) inhalers during the course of one year in the database of a Health Maintenance Organization (HMO). Primary physicians identified asthma patients and classified their asthma symptom control into three groups according to the Global Initiative for Asthma (GINA) guidelines. Asthma patients were asked to answer symptom questionnaires and grade their asthma control. SABA inhaler purchases were compared between asthma control groups as classified by the guidelines, the physicians and the patients. We also compared the agreement on asthma control between the three methods of classification. RESULTS: Of 241 asthma patients, 83 completed the questionnaires. Using the GINA guidelines criteria, 26 were symptom controlled, 46 were partially controlled and 11 were uncontrolled. SABA inhaler purchases were not significantly lower in the controlled group. Using patients' overall impression of their asthma control, the mean numbers of SABA inhalers purchased were 1.5, 4.4 and 6.4 per year in the controlled, partially controlled and uncontrolled groups, respectively (p = 0.03). Patients' classification of asthma control had better agreement (kappa = 0.34) with GINA guidelines than physician's' agreement (kappa = 0.05). CONCLUSION: When using administrative data for asthma patients, 2 or more SABA inhaler purchases in one year should alert the physician for the need for asthma control evaluation. Purchase of at least 4 SABA inhalers a year may be regarded as a marker for asthma that is not controlled.

Adult Arabs have higher risk for diabetes mellitus than Jews in Israel.

OBJECTIVE: Diabetes mellitus is an emerging epidemic in the Arab world. Although high diabetes prevalence is documented in Israeli Arabs, information from cohort studies is scant. METHODS: This is a population study, based on information derived between 2007-2011, from the electronic database of the largest health fund in Israel, among Arabs and Jews. Prevalence, 4-year-incidence and diabetes hazard ratios [HRs], adjusted for sex and the metabolic-syndrome [MetS]-components, were determined in 3 age groups (<50 years, 50-59 years, and ≥60 years). RESULTS: The study cohort included 17,044 Arabs (males: 49%, age: 39.4±17.3) and 16,012 Jews (males: 50%, age: 40.5 ±17.6). The overall age and sex-adjusted diabetes prevalence rates were much higher among Arabs 18.4% (95%CI: 17.6-19.1); and 10.3% (95%CI: 9.7-10.9) among Jews. Arab females had higher prevalence rates 20.0% (95%CI: 19-21) than Arab males 16.7% (95%CI: 15.7-17.8). Annual incidence rates were also significantly higher among Arabs 2.9% (95%CI: 2.7-3.1) than among Jews 1.7% (95%CI: 1.6-1.8). This held true across all age and sex subgroups. Adjustment for body mass index [BMI] attenuated HR estimates associated with Arab ethnicity across all age subgroups, mainly in the <50yrs age group from HR 2.04 (95%CI: 1.74-2.40) to 1.64 (95%CI: 1.40-1.92). BMI at incident diabetes among females was higher in Arabs than Jews. Males, however, did not differ by ethnicity. CONCLUSION: Arabs, mainly female, have high incidence and prevalence of diabetes. This excess risk is only partially explained by the high prevalence of obesity. Effective culturally-congruent diabetes prevention and treatment and an effective engagement partnership with the Arab community are of paramount need.

Rituximab maintenance improves overall survival of patients with follicular lymphoma-Individual patient data meta-analysis.

BACKGROUND: Randomised trials of rituximab maintenance (MR) for patients with follicular lymphoma support improved progression-free survival (PFS), but the effect on overall survival has been inconclusive. To evaluate the effect of MR on overall survival according to patient and disease characteristics, and to explore certain adverse events, we performed an individual patient data (IPD) meta-analysis. METHODS: All investigators of randomised controlled trials that compared MR therapy with observation or treatment only at relapse (no MR) for patients with follicular lymphoma were invited to participate in an IPD meta-analysis. We obtained baseline patient and disease characteristics and time to progression and death for each patient. All analyses took into account the trial and original randomised treatment group. We analysed data in two ways: a two-stage analysis and a multivariate model including patient and disease characteristics. FINDINGS: Seven trials including 2315 patients were analysed. Overall survival of patients improved with MR compared with no MR (hazard ratio [HR] 0.79, 95% CI 0.66-0.96). We could not detect any patient or disease characteristics that were associated with a survival benefit with MR. In all of the models, MR had a beneficial effect on overall survival compared with observation for all types of patients, which was not shown in a particular subgroup in which the patient had already received rituximab in the induction phase and received first-line therapy. MR improved PFS compared with observation (HR 0.57, 95% CI 0.51-0.64). The risk of adverse events was higher with MR, specifically infection of any grade and grade 3-4 infections. INTERPRETATION: Based on IPD from randomised controlled trials, MR improves overall survival consistently in all patients, regardless of patient and disease characteristics when compared with observation, and should be prescribed after a successful induction with R-CVP or R-CHOP for patients with follicular lymphoma. It is still uncertain if that holds when the patient has already received rituximab in his/hers first induction. The effect of MR after bendamustine-rituximab induction compared with rituximab at progression should be further explored.

Chromatic Multifocal Pupillometer for Objective Perimetry and Diagnosis of Patients with Retinitis Pigmentosa.

PURPOSE: To assess visual field (VF) defects and retinal function objectively in healthy participants and patients with retinitis pigmentosa (RP) using a chromatic multifocal pupillometer. DESIGN: Cross-sectional study. PARTICIPANTS: The right eyes of 16 healthy participants and 13 RP patients. METHODS: Pupil responses to red and blue light (peak, 485 and 625 nm, respectively) presented by 76 light-emitting diodes, 1.8-mm spot size at different locations of a 16.2° VF were recorded. Subjective VFs of RP patients were determined using chromatic dark-adapted Goldmann VFs (CDA-GVFs). Six healthy participants underwent 2 pupillometer examinations to determine test-retest reliability. MAIN OUTCOME MEASURES: Three parameters of pupil contraction were determined automatically: percentage of change of pupil size (PPC), maximum contraction velocity (MCV; in pixels per second), and latency of MCV (LMCV; in seconds). The fraction of functional VF was determined by CDA-GVF. RESULTS: In healthy participants, higher PPC and MCV were measured in response to blue compared with red light. The LMCV in response to blue light was relatively constant throughout the VF. Healthy participants demonstrated higher PPC and MCV and shorter LMCV in central compared with peripheral test points in response to red light. Test-retest correlation coefficients were 0.7 for PPC and 0.5 for MCV. In RP patients, test point in which the PPC and MCV were lower than 4 standard errors from the mean of healthy participants correlated with areas that were indicated as nonseeing by CDA-GVF. The mean absolute deviation in LMCV parameter in response to the red light between different test point was significantly higher in RP patients (range, 0.16-0.47) than in healthy participants (range, 0.02-0.16; P < 0.0001) and indicated its usefulness as a diagnostic tool with high sensitivity and specificity (area under the receiver operating characteristic curve (AUC), 0.97, Mann-Whitney-Wilcoxon analysis). Randomly reducing the number of test points to a total of 15 points did not significantly reduce the AUC in RP diagnosis based on this parameter. CONCLUSIONS: This study demonstrates the feasibility of using a chromatic multifocal pupillometer for objective diagnosis of RP and assessment of VF defects.