Risk Factors for Neonatal Clavicular Fractures: A Population-Based Case-Control Study.

BACKGROUND: Neonatal clavicular fractures represent the most common fracture during delivery. We aimed to define risk factors associated with these fractures in a large population-based database. METHODS: Data were extracted from Clalit Health Services' electronic health records from 2000 to 2020. Newborns with clavicular fractures were compared with a healthy control group. The following parameters were compared-for the newborns: sex, birth weight, birth height, and head circumference; for the delivery process: assisted delivery, cesarean section, use of epidural, birth week, and number of fetuses; and for the mother: age at delivery, socioeconomic status, height, weight, and body mass index (BMI). RESULTS: We found a rate of 0.28% for neonatal clavicular fractures (5015 clavicular fractures/1 755 660 deliveries). Male gender and heavier birth weight were found to be significantly associated with clavicular fractures (P < .001). Increased risk was also associated with lower socioeconomic status, baseline weight, and maternal BMI (P < .001 for all). Assisted delivery increased the risk of clavicular fracture (OR = 2.274; 95% CI, 1.661-3.115; P < .0001), while cesarean section and use of epidural were found to be protective (OR = 0.149; 95% CI, 0.086-0.26; P < .0001; and OR = 0.687; 95% CI, 0.0531-0.89; P < .004, respectively). CONCLUSIONS: This study provides insight into the risk factors associated with neonatal clavicular fractures on the largest group of patients reported to date.

Comparative evaluation of Sensititre YeastOne and CLSI M38-Ed3 reference method for determining echinocandin minimum effective concentrations against Aspergillus isolates.

The minimum inhibitory concentration (MIC) of echinocandins against Aspergillus spp. does not represent the actual inhibition threshold of echinocandins. Therefore, the recommended method to evaluate their activity is determining the minimum effective concentration (MEC) in broth microdilution, a method that is less common in clinical settings. This study aimed to assess a user-friendly commercial method, Sensititre YeastOne (SYO), to determine the effectiveness of echinocandins (caspofungin, anidulafungin and micafungin) against Aspergillus spp. Echinocandins MEC was determined against 23 isolates of Aspergillus spp. using SYO and the reference Clinical and Laboratory Standards Institute (CLSI) method. MECs were read with an inverted microscope and a reading mirror. Essential agreement (EA) between the tested methods was defined as a ±twofold dilution difference. There was a high EA (91%-100%) between the reference method and SYO in determining echinocandins MEC against Aspergillus isolates using inverted microscopy. A high EA was also observed between SYO MEC determined by inverted microscopy and a reading mirror, but different incubation times were required. SYO is a reliable, simple method for determining the MEC of echinocandins against Aspergillus isolates, preferably with an inverted microscope, and can be easily used in clinical laboratories when echinocandin susceptibility testing is required.IMPORTANCEUsing a commercial method such as Sensititre YeastOne (SYO) to determine the minimum effective concentration (MEC) of echinocandins against Aspergillus spp. has been shown to be a reliable alternative to the Clinical and Laboratory Standards Institute (CLSI) reference method. This makes it more suitable for high-volume clinical laboratories. SYO provides accurate results comparable to the standard method and could potentially improve patient care by guiding more optimal antifungal treatment choices for patients with Aspergillus infections.

Serological follow-up after syphilis diagnosis in Israel.

The global incidence of syphilis is increasing. Continuity of care challenges the control of sexually transmitted diseases. In this study, we assessed the follow-up and serological decline differences between community- and hospital-diagnosed patients in Israel. A historical cohort study was conducted using the Israel National Syphilis Center (NSC) repository. Patients with a positive non-specific Venereal Disease Research Laboratory (VDRL) test between 2011 and 2020 were included. Rates of serological follow-up and serological titre decreases were compared between hospital- and community-diagnosed patients. The study included 4,445 patients, 2,596 (58.4%) were diagnosed in community clinics and 1,849 (41.6%) in hospitals. Of community-diagnosed patients, 1,957 (75.4%) performed follow-up testing, compared with 834 (51.2%) hospital-diagnosed patients (p < 0.001). On multivariate analysis, the odds ratio of serology follow-up among community-diagnosed patients was 2.8 (95 per cent confidence interval (95% CI): 2.2-3.5) that of hospital-diagnosed patients. There were 1,397 (71.4%) community-diagnosed patients with serological titre decrease, compared with 626 (74.9%) hospital-diagnosed patients (p = 0.03). On multivariate analysis, this difference diminished. Serological follow-up testing is suboptimal and was performed more often among patients initially diagnosed in the community compared to hospitals. Continuity of care should be improved to promote successful patient care and prevent disease spread.

Receipt of prescription opioid medication is associated with increased mortality in an Israeli population.

BACKGROUND: Despite Israel's increased use of prescription opioids, reported deaths resulting or associated with opioids have decreased, in fact dramatically, since 2005. This contrast is unique and difficult to explain. We sought to examine whether higher prescribed opioid dosages among adults without oncologic diagnoses were associated with higher all-cause mortality rates. METHODS: A historical cohort study in Clalit Health Services, using a data repository including all adult patients prescribed opiates between 2010 and 2020, excluding patients with oncologic diagnoses. Patients were classified into three groups according to opioid use: below 50 Morphine milligram equivalents (MME) per day, 50 to 90 MME per day, and above 90 MME per day. Sex, Charlson comorbidity score, age and socioeconomic status were recorded. Mortality rates were compared between the dosage groups and compared to age-standardized mortality rates in the general population. RESULTS: On multivariate analysis, patients receiving 90 or more MME per day were 2.37 (95%CI 2.1 to 2.68) more likely to have died compared to patients receiving below 50 MME per day. The respective hazard ratio among patients receiving between 50 and 90 MME per day was 2.23 (2.01 to 2.46). Among patients aged 18 to 50, standardized mortality ratios (SMRs) compared to the general population ranged between 5.4 to 8.6 among women, receiving between 50 and 90 MME per day, and between 8.07 and 10.7 among women receiving 90 or more MME per day. The respective SMRs among men were 1.2 to 3.8 and 2.7 to 5.4. CONCLUSION: Increased opioid use is independently associated with increased all-cause mortality among non-oncological patients. This result is most notable among young adults with little or no known comorbidities. These findings are consistent with results in other countries and seem more credible than previous Israeli reports. Healthcare regulators and providers should, therefore, act to curtail the increasing opioid prescriptions and devise and enhance controls in the healthcare system, which, until 2020, had very limited mechanisms in place.

Gradual dosing of ursodeoxycholic acid in mothers with intrahepatic cholestasis of pregnancy may improve composite neonatal outcome.

INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is often accompanied by fetal and maternal complications. MATERIALS AND METHODS: Retrospective review of the clinical course of women with ICP and their neonates treated at our medical center over a 10-year period. Special attention was paid to the maternal and neonatal response to 2 different modes of ursodeoxycholic acid (UDCA) administration. RESULTS: Neonates of mothers with high total bile acid levels had a poorer composite neonatal outcome. Twenty-seven women who presented at an advanced stage of their pregnancies did not receive UDCA. UDCA was administered in 2 modes: either a full dose at admission (76 women) or a gradually increasing dose until the desired dosage was reached (25 women). The mean gestational age at delivery for the 94 neonates that were exposed to full UDCA dose was the lowest (36±2.3 weeks for the full dose, 37±1.4 weeks for the 30 neonates from the gradually increasing dose, 38±1.6 weeks for the 29 neonates from the no treatment group, p<0.001). The group of neonates that were exposed to full UDCA dose had the highest rate of unfavorable composite neonatal outcome (53% for full dose, 30% for gradually increasing dose, 24% for the no treatment group, p=0.006). CONCLUSIONS: Compared to the administration of a full UDCA dose, the administration of a gradually increasing dose of UDCA may be associated with a greater gestational age at delivery and fewer events of unfavorable composite neonatal outcomes. These novel findings should be retested prospectively in a large cohort of patients.

Trends in Israeli community-based opioid prescribing, 2010-2020, an observational study of the country's largest HMO.

BACKGROUND: Prescription opioids are widely used for pain control and palliative care but have been associated with a variety of untoward effects, including opioid use disorder, addiction, and increased mortality. Patterns of opioid use in Israel are to date poorly described. METHODS: Using a community-based database, the authors performed a retrospective analysis of filled opioid prescriptions of Israeli HMO members 18 years of age or older during the years of 2010-2020 that filled at least one opioid prescription. Morphine milligram equivalent (MME) calculations were stratified by presence or absence of oncology diagnosis and by specific opioid medication. RESULTS: The percentage of HMO members who filled at least one opioid prescription increased every year from 2.1% in 2010 to 4.2% in 2020. There was an increase in the MME per prescription (44.2%), daily MME per capita (142.1%) and MME per prescription-filling patient (39%) from 2010 to 2020. Increased prescription opioid use is driven by a small group of non-oncological patients, which is less than 1.5% of opioid-prescribed patients and 0.1% of the adult population, primarily owing to fentanyl use. CONCLUSION: Supervision and control of opioid prescriptions in Israel should be a focused effort directed at patients prescribed uniquely high dosages rather than a population-wide strategy that focuses on all patients prescribed opioids. This should be complemented by improved physician training and access to non-opioid therapies, as well as improved data collection and analysis.

Payer reimbursement practices and incentives for improving interpretation of germline genetic testing.

Germline genetic testing for inherited cancer risk has shifted to multi-gene panel tests (MGPTs). While MGPTs detect more pathogenic variants, they also detect more variants of uncertain significance (VUSs) that increase the possibility of harms such as unnecessary surgery. Data sharing by laboratories is critical to addressing the VUS problem. However, barriers to sharing and an absence of incentives have limited laboratory contributions to the ClinVar database. Payers can play a crucial role in the expansion of knowledge and effectiveness of genetic testing. Current policies affecting MGPT reimbursement are complex and create perverse incentives. Trends in utilization and coverage for private payers and Medicare illustrate opportunities and challenges for data sharing to close knowledge gaps and improve clinical utility. Policy options include making data sharing (i) a condition of payment, and (ii) a metric of laboratory quality in payment contracts, yielding preferred coverage or enhanced reimbursement. Mandating data sharing sufficient to verify interpretations and resolve discordance among labs under Medicare and federal health programs is an option for the US Congress. Such policies can reduce the current waste of valuable data needed for precision oncology and improved patient outcomes, enabling a learning health system.

Incidence of Invasive Infections Among Hemato-Oncology Patients with Significant Burden of Candida in Stool.

Candidemia is a serious infection associated with increased mortality. It is unclear whether a high concentration of Candida in stool in patients with hematologic malignancies is associated with a higher risk for developing candidemia. In this observational historical study in patients hospitalized in hemato-oncology departments, we describe the association between gastrointestinal Candida colonization and the risk for candidemia and other severe outcomes. Data from 166 patients with heavy burden of Candida in stool were collected and compared to a control group of 309 patients with minimal or no Candida in stool, from 2005 to 2020. Severe immunosuppression and recent use of antibiotics were more common in heavily colonized patients. Outcomes of heavily colonized patients were worse as compared to the control group with statistical significance in 1-year mortality (53% vs. 37.5%, p = 0.001) and borderline statistical significance in candidemia rate (12.6% vs. 7.1%, p = 0.07). Risk factors for 1-year mortality were significant colonization of Candida in stool, older age and recent use of antibiotics. In conclusion, significant stool burden of Candida among hospitalized hemato-oncology patients may pose a risk for 1-year mortality and increased candidemia rate.

Sources of primary bloodstream infections in internal medicine patients - a cohort study.

PURPOSE: To describe the sources of bloodstream infections (BSIs) in internal-medicine patients, on admission and during hospitalization, and to determine the proportion of BSIs in which no secondary cause could be defined (i.e., primary-BSI). METHODS: We analyzed all BSIs at the internal-medicine wards of the two campuses of the Hadassah Hebrew-University Medical Center, during 2017-2018. We defined the BSI source of each event (secondary, Central-line associated BSI (CLABSI) or primary non-CLABSI) and compared BSIs present on admission (POA) to hospital acquired (HA). RESULTS: There were 595 patient-unique BSI events, 316 (53.1%) POA-BSI and 279 (46.9%) HA-BSI. Overall, 309 (51.9%) were secondary, 194 (32.6%) primary non-CLABSI and 92 (15.5%) CLABSI. Primary non-CLABSI in the POA-BSI group was 20.6% vs. 46.2% in the HA-BSI group (p = 0.001). The length of hospital stay (LOS) of the HA-BSI group was longer than in the POA-BSI group (mean LOS, 19 days vs. 13.6 days, p = 0.01) and mortality rate was higher (48.7% vs. 19%, p = 0.001). Staphylococcus aureus was more common in primary non-CLABSI than in CLABSI and secondary BSI (29.5%, 12.8% and 16.2%, respectively). CONCLUSIONS: The proportion of primary non-CLABSI among HA-BSI events is very high (46.2%). The absence of any plausible source for these BSIs, and the fact that in our hospital more than 90% of patients in medicine wards have peripheral lines, suggests that these may be a possible source for primary non-CLABSIs. Measures to prevent peripheral-line associated BSI (PLABSI), like those implemented successfully for the prevention of CLABSI, should be considered.