Gender-affirming hormone therapy effect on cortisol levels in trans males and trans females.

PURPOSE: Previous studies have shown differences in baseline and stimulated cortisol levels between men and women. Whether this difference is secondary to sex hormones or to other factors, such as genetic or epigenetic changes, is unknown. We investigated the effect of gender-affirming hormone treatment (GAHT) on the hypothalamo-pituitary-adrenal axis of transgender subjects in an effort to throw light on this question. METHODS: Ten transgender males (TM) and eight transgender females (TF) underwent a low-dose (1 µg) adrenocorticotropic hormone (ACTH) stimulation test before and 6 months after GAHT initiation. Serum total, free and salivary cortisol (SC) levels were measured at baseline and at 20, 30 and 40 min. RESULTS: For the TM, all three levels were significantly lower at several time points after ACTH injection compared to pretreatment levels following 6 months of treatment (p < .05). Likewise, the overall SC response as calculated by the area under the curve was significantly lower (p = .0053). For the TF, the basal total cortisol (TC) level increased after 6 months of treatment (p < .01) while ACTH-stimulated SC levels decreased significantly. The basal ACTH levels were significantly lower following hormonal therapy (p < .001). CONCLUSION: Stimulated salivary cortisol levels decreased significantly after 6 months of GAHT in both male and female transgender subjects, possibly reflecting a decreased state of anxiety associated with treatment initiation. Additionally, basal and stimulated serum TC levels increased after hormonal treatment in the TF, probably secondary to the effect of oestrogen on cortisol-binding globulin.

Characterization of Cannabis users and products and the experience of negative mental emotions following Cannabis use.

There is a potential link between cannabis and mental disorders. Cannabis exposure involves in many cases negative mental emotions, which are unpleasant sensations or thoughts. Whereas mild cases of negative mental emotions inflict patient's quality of life, more severe cases lead to therapy discontinuations, or even hospitalizations and death. This study characterizes cannabis users who experienced negative mental emotions after cannabis exposure. The Releaf App database was utilized to evaluate the association between personal and cannabis use characteristics on reporting a negative mental emotion during cannabis exposure. This global mobile lets individuals track real-time cannabis experience use with cannabinoid-based products, containing data points such as gender, age, reasons for use, product type, cannabis composition, and feelings and emotions experienced after cannabis use. Multivariable logistic regression models were constructed, adjusting for potential confounders such as gender and previous experience with cannabis use. The study population comprised 4,435 users, and 34,279 sessions were collected from various countries, mainly from North America, and included in the primary analysis. Reporting on negative mental emotions was associated with users in the age group of 18-30 years. Using cannabis for a mental purpose was associated with a small increase in reporting on negative mental emotions (OR = 1.10, 95%CI [1.03-1.19]). Oral products were associated with reporting on negative mental emotions. THC-dominant products were associated with reporting negative mental emotions compared to balanced products (OR = 1.21, 95%CI [1.06-1.38]). This study suggests that some characteristics of cannabis use, such as young age and oral consumption are associated with negative mental emotions. Further studies should examine the interface between cannabis consumption, characteristics of consumers, and negative emotional experience or even long-term mental disorders.

The effect of systemic acetazolamide administration on intraocular pressure in healthy horses-A preliminary study.

OBJECTIVES: In equine glaucoma, topical treatment with carbonic anhydrase inhibitors (CAIs) is recommended. Oral acetazolamide, a systemic CAI, is used in horses with hyperkalemic periodic paralysis. Information regarding its effect on equine intraocular pressure (IOP) is scarce. The aim of the study was to determine the effect of oral acetazolamide treatment on IOP in horses, in a case-control study. ANIMALS: Ten healthy horses. PROCEDURES: Horses were treated with oral acetazolamide (4.4 mg/kg) BID for 1 week. Serum acetazolamide concentrations were determined by liquid chromatography/tandem mass spectrometry, and IOP were measured before treatment, daily during treatment, and at 48 and 72 h after treatment. RESULTS: Acetazolamide serum levels reached steady state at 72 h after the first oral dose. In a mixed effect model logistic regression, there was a significant decrease in IOP on the third treatment day, of 2.4 mmHg (p = .012) and 2.7 mmHg (p = .006) in the left (OS) and right eye (OD), respectively. On the seventh day, there was a decrease in 2.5 mmHg (p = .008) and 2.7 mmHg (p = .007) OS and OD, respectively. A significant increase occurred 48 h following treatment discontinuation (3.6 mmHg, p < .001 and 3.5 mmHg, p < .001 OS and OD, respectively). The area under the concentration versus time curve (AUC(0-10h)) was 1.1 ± 0.5 µg/mL*h, mean residence time 6.7 ± 4.3 h, peak plasma concentration (Cmax) 0.4 ± 0.4 µg/mL and time to reach Cmax 1.8 h. There was a significant increase in serum concentrations 1, 2, 48, 72, and 156 h following the first drug administration (p < .05). CONCLUSIONS: Further studies are required to determine whether acetazolamide is a potential treatment for equine glaucoma.

Greater temporal regularity of primary care visits was associated with reduced hospitalizations and mortality, even after controlling for continuity of care.

BACKGROUND: Previous studies have shown that more temporally regular primary care visits are associated with improved patient outcomes. OBJECTIVE: To examine the association of temporal regularity (TR) of primary care with hospitalizations and mortality in patients with chronic illnesses. Also, to identify threshold values for TR for predicting outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: We used data from the electronic health record of a health maintenance organization in Israel to study primary care visits of 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease). MAIN MEASURES: We calculated TR for each patient during a two-year period (2016-2017), and divided patients into quintiles based on TR. Outcomes (hospitalization, death) were observed in 2018-2019. Covariates included the Bice-Boxerman continuity of care score, demographics, and comorbidities. We used multivariable logistic regression to examine TR's association with hospitalization and death, controlling for covariates. KEY RESULTS: Compared to patients receiving the most regular care, patients receiving less regular care had increased odds of hospitalization and mortality, with a dose-response curve observed across quintiles (p for linear trend < 0.001). For example, patients with the least regular care had an adjusted odds ratio of 1.40 for all-cause mortality, compared to patients with the most regular care. Analyses stratified by age, sex, ethnic group, area-level SES, and certain comorbid conditions did not show strong differential associations of TR across groups. CONCLUSIONS: We found an association between more temporally regular care in antecedent years and reduced hospitalization and mortality of patients with chronic illness in subsequent years, after controlling for covariates. There was no clear threshold value for temporal regularity; rather, more regular primary care appeared to be better across the entire range of the variable.

Mothers' Knowledge of Infants' Fever Management: A National Prospective Study.

OBJECTIVES: The aim of this study was to describe mothers' knowledge of infant fever management after birth and six months later and its association with sociodemographic characteristics, perceived support, sources of consultation and health education; and to assess determinants of change in mother's knowledge from birth to six months. METHODS: Mothers (n = 2804) answered a self-reporting questionnaire after giving birth in maternity wards in six hospitals in Israel; six months later follow- up interviews were conducted by telephone. RESULTS: The mothers' knowledge level of infant fever management was low after birth (mean = 50.5, range 0-100, SD = 16.1), and rose to a moderate level six months later (mean = 65.2, SD = 15.0). Mothers having their first born, with lower household income or education were less knowledgeable about infant fever management after birth. However, these mothers showed the largest improvement after six months. Mothers' perceived support or sources of consultation and health education (partner, family, friends, nurses, and physicians) were not associated with their knowledge at either time. Moreover, mothers stated self-learning from internet and other media as often as receiving health education by health professionals. CONCLUSIONS FOR PRACTICE: Public health policy for health professionals in hospitals and community clinics is essential to promote clinical interventions promoting mothers' knowledge of infant fever management. Efforts should focus at first time mothers, those with non-academic education, and those with a moderate or low household income. Public health policy enhancing communication with mothers regarding fever management in hospitals and community health settings, as well as accessible means of self-learning is warranted.

Effect of anesthetic induction with propofol, alfaxalone or ketamine on intraocular pressure in cats: a randomized masked clinical investigation.

OBJECTIVE: To compare the effect of propofol, alfaxalone and ketamine on intraocular pressure (IOP) in cats. STUDY DESIGN: Prospective, masked, randomized clinical trial. ANIMALS: A total of 43 ophthalmologically normal cats scheduled to undergo general anesthesia for various procedures. METHODS: Following baseline IOP measurements using applanation tonometry, anesthesia was induced with propofol (n = 15), alfaxalone (n = 14) or ketamine (n = 14) administered intravenously to effect. Then, midazolam (0.3 mg kg-1) was administered intravenously and endotracheal intubation was performed without application of topical anesthesia. The IOP was measured following each intervention. Data was analyzed using one-way anova and repeated-measures mixed design with post hoc analysis. A p-value <0.05 was considered significant. RESULTS: Mean ± standard error IOP at baseline was not different among groups (propofol, 18 ± 0.6; alfaxalone, 18 ± 0.7; ketamine, 17 ± 0.5 mmHg). Following induction of anesthesia, IOP increased significantly compared with baseline in the propofol (20 ± 0.7 mmHg), but not in the alfaxalone (19 ± 0.8 mmHg) or ketamine (16 ± 0.7 mmHg) groups. Midazolam administration resulted in significant decrease from the previous measurement in the alfaxalone group (16 ± 0.7 mmHg), but not in the propofol group (19 ± 0.7 mmHg) or the ketamine (16 ± 0.8 mmHg) group. A further decrease was measured after intubation in the alfaxalone group (15 ± 0.9 mmHg). CONCLUSIONS AND CLINICAL RELEVANCE: Propofol should be used with caution in cats predisposed to perforation or glaucoma, as any increase in IOP should be avoided.

Predicting factors for complications in peripheral intravenous catheters in the pediatric population.

AIM: To characterise the association between peripheral intravenous catheter (PIVC) gauge (G), the patient's age, insertion site and complication incidence. METHODS: This prospective study was performed in Hadassah Medical Center, Jerusalem, Israel, between June 2018 and March 2019. Children with PIVC admitted to the paediatric departments were included. PIVCs were evaluated daily. RESULTS: A total of 113 children with 132 PIVCs were included in the study. The most common site of insertion was the antecubital fossa (43.9%). PIVCs were most commonly used for intravenous (IV) antibiotics (46.6%). Complications were observed for 40.9% PIVCs. Dislodgement was the most common complication. The complication rate was higher for the lower limbs (60%) and external jugular veins (100%) p = 0.002. In infants younger than 12 months, the complication rate was higher for 22 G PIVCs or larger (58.7% versus 27.5%; p = 0.05). In contrast, for the 1-6 years age group, PIVCs smaller than 24 G had a higher complication rate (p = 0.004). Patients with comorbidities had a higher complication rate (p = 0.003). CONCLUSION: Risk factors for complications are comorbidities and sites of insertion other than the upper limbs. In infants, 24 G PIVC or smaller should be inserted, whereas 22 G PIVC or larger are superior for 1- to 6-year-old children.

Extended spectrum ß lactamase-producing Enterobacteriaceae shedding by race horses in Ontario, Canada.

BACKGROUND: We aimed to investigate the prevalence, molecular epidemiology and prevalence factors for Extended Spectrum ß-Lactamase-producing Enterobacteriaceae (ESBL-E) shedding by race horses. A cross-sectional study was performed involving fecal samples collected from 169 Thoroughbred horses that were housed at a large racing facility in Ontario, Canada. Samples were enriched, plated on selective plates, sub-cultured to obtain pure cultures and ESBL production was confirmed. Bacterial species were identified and antibiotic susceptibility profiles were assessed. E. coli sequence types (ST) and ESBL genes were determined using multilocus sequence type (MLST) and sequencing. Whole genome sequencing was performed to isolates harboring CTX-M-1 gene. Medical records were reviewed and associations were investigated. RESULTS: Adult horses (n = 169), originating from 16 different barns, were sampled. ESBL-E shedding rate was 12% (n = 21/169, 95% CI 8-18%); 22 ESBL-E isolates were molecularly studied (one horse had two isolates). The main species was E. coli (91%) and the major ESBL gene was CTX-M-1 (54.5%). Ten different E. coli STs were identified. Sixty-four percent of total isolates were defined as multi-drug resistant. ESBL-E shedding horses originated from 8/16 different barns; whereas 48% (10/21) of them originated from one specific barn. Overall, antibiotic treatment in the previous month was found as a prevalence factor for ESBL-E shedding (p = 0.016, prevalence OR = 27.72, 95% CI 1.845-416.555). CONCLUSIONS: Our findings demonstrate the potential diverse reservoir of ESBL-E in Thoroughbred race horses. Multi-drug resistant bacteria should be further investigated to improve antibiotic treatment regimens and equine welfare.

Questionnaire-based study showed that neonatal chest radiographs could be reliably interpreted using the WhatsApp messaging application.

AIM: We surveyed whether clinicians used the WhatsApp messaging application to view neonatal chest radiographs and asked a sub-sample to compare them with computer screen viewings. METHODS: The study was conducted at three university-affiliated medical centres in Israel from June-December 2016. Questionnaires on using smartphones for professional purposes were completed by 68/71 paediatric residents and 20/28 neonatologists. In addition, 11 neonatologists viewed 20 chest radiographs on a computer screen followed by a smartphone and 10 viewed the same radiographs in the opposite order, separated by a washout period of 2 months. After another 2 months, five from each group viewed the same radiographs on a computer screen. Different interpretations between viewing modes were assessed. RESULTS: Most respondents used WhatsApp to send chest radiographs for consultation: 82% of the paediatric residents and 80% of the neonatologists. The mean number of inconsistencies in diagnosis was 3.7/20 between two computer views and 2.9/20 between computer and smartphone views (p = 0.88) and the disease severity means were 3.7/20 and 2.85/20, respectively (p = 0.94). Neonatologists using WhatsApp only determined umbilical line placement in 80% of cases. CONCLUSION: WhatsApp was reliable for preliminary interpretation of neonatal chest radiographs, but caution was needed when assessing umbilical lines.

[ANTIBIOTIC USE IN COMMUNITY HEALTHCARE IN ISRAEL AS REFLECTED IN THE NATIONAL PROGRAM FOR QUALITY INDICATORS].

AIMS: We sought to evaluate the extent of overall and second-line systemic antibiotic use in the Israeli community, to compare them to international data and to monitor temporal trends. BACKGROUND: Antibiotic overuse is prevalent and has grave implications, primarily the emergence of resistant pathogens - an urgent public health concern worldwide. METHODS: The Israel National Program for Quality Indicators in Community Healthcare (QICH) obtains data from electronic medical records from the 4 health-plans, covering the entire civilian population. We assessed 2 quality indicators, compatible with those of the OECD: 1. Overall volume of antibiotics for systemic use dispensed. 2. Volume of second-line antibiotics as a proportion of all systemic antibiotics. Analysis was stratified by gender, age and socio-economic position (SEP). RESULTS: The volume of systemic antibiotics dispensed in 2016 was 20.76 DDD/1000 person/day, with second-line antibiotics comprising 22.0% of the total. These values have been stable since 2014, and are higher compared with the OECD averages (20.61 DDD/1000 person/day, and 17.02% in 2015). Both overall volume and the proportion of second-line antibiotics rose with age and were higher among women especially in the 20-40 years age bracket (overall volume of 23.98 DDD/1000 person/day, proportion of second-line antibiotics of 23.98% VS 17.41 and 19.17% in men). Higher overall use was observed among patients of low SEP. CONCLUSIONS: The observed volume of systemic antibiotics and the proportion of second-line antibiotics dispensed in the Israeli community were stable and high. Higher use was observed among older individuals, women and patients of low SEP. Our results call for the implementation of a national-level, community-based antibiotic stewardship program. QICH might serve to monitor such a program.

Use of tidal breathing curves for evaluating expiratory airway obstruction in infants.

OBJECTIVE: To evaluate tidal breathing (TB) flow-volume and flow-time curves for identification of expiratory airway obstruction in infants. METHODS: Pulmonary function tests were analyzed retrospectively in 156 infants aged 3-24 months with persistent or recurrent respiratory complaints. Parameters derived from TB curves were compared to maximal expiratory flow at functional residual capacity ( V˙ maxFRC) measured by rapid thoracoabdominal compression technique. Analyzed parameters were: inspiratory time (tI), expiratory time (tE), tidal volume, peak tidal expiratory flow (PTEF), time to peak tidal expiratory flow (tPTEF), expiratory flow when 50% and 25% of tidal volume remains in the lungs (FEF50, FEF25, respectively), and the ratios tPTEF/tE, tI/tE, FEF50/PTEF, and FEF25/PTEF. Statistical comparisons between flow indices and TB parameters were performed using mean squared error and Pearson's sample correlation coefficient. The study population was also divided into two groups based on severity of expiratory obstruction (above or below z-score for V˙ maxFRC of -2) to generate receiver operating characteristic (ROC) curves and calculate discriminatory values between the groups. RESULTS: TB parameters that were best correlated to V˙ maxFRC were: tPTEF/tE, FEF50/PTEF, and FEF25/PTEF, with r = 0.61, 0.67, 0.65, respectively (p < 0.0001 for all). ROC curves for FEF50/PTEF, FEF25/PTEF and tPTEF/tE showed areas under the curve of 0.813, 0.797, and 0.796, respectively. Cutoff value z-scores of -0.35, -0.34, and -0.43 for these three parameters, respectively, showed an 86% negative predictive value for severe airway obstructions. CONCLUSION: TB curves can assist in ruling out severe expiratory airway obstruction in infants.

Environmental exposures and fetal growth: the Haifa pregnancy cohort study.

BACKGROUND: The developing fetus is susceptible to environmental insults. Studying the effects of environmental exposures on fetal growth is essential for understanding the causal pathway between prenatal exposures and pregnancy outcomes. Here we describe the Haifa Pregnancy Cohort Study (HPCS) and discuss challenges and opportunities in applying "big data" paradigm. METHODS: Maccabi Healthcare Services (MHS), is the second largest Israeli health maintenance organization (HMO) providing care services to two million beneficiaries. The HPCS cohort potentially includes ~750,000 newborns born between 1998 and 2017. We will estimate daily exposures to air pollutants, temperature and greenness, using satellite-based data and models. We hypothesize that residents of Haifa have higher exposures to environmental pollutants and that in pregnant women this higher exposure is associated with poorer fetal growth. We will evaluate outcomes such as birth-weight, head-circumference and gestational age at birth. We will adjust for pregnancy complications such as pre-eclampsia and gestational diabetes and parental variables, such as maternal weight, age and smoking habits as potential confounders. In addition, we will conduct a multi-tiered field study, nested within this population, among 150 pregnant women residing in two geographical regions-one in the polluted Haifa area, and one in a relatively unpolluted area in central Israel. Blood and urinary samples will be collected, as well as personal and indoor exposure to air pollution. DISCUSSION: Evaluating environmental exposures of pregnant women and assessing in utero growth over the course of the pregnancy during different exposure windows, is of great scientific and public health interest. Recent advances in data collection and analysis pose great promise to provide insights into contribution of environment to the health of the developing fetus, but also pose major challenges and pitfalls, such as data management, proper statistical framework and integration of data in the population-based study and selectiveness in the nested field study. Yet the continuing follow-up of the study cohort, integrating data from different services, health-promotion, and eventually, application later in real life of our main promises. Our study aims to meet these challenges and to provide evidence of the environmental exposures associated with fetal growth.

Using anaerobic blood cultures for infants younger than 90 days rarely showed anaerobic infections but increased yields of bacterial growth.

AIM: The use of anaerobic blood cultures in infants suspected of bacteraemia is controversial. Our children's hospital uses both aerobic and anaerobic media, regardless of the risk of anaerobic infection, and the aim of this study was to re-evaluate the use of anaerobic cultures in infants. METHODS: We collected retrospective data from 2002 to 2016 on all blood cultures taken from infants younger than 90 days in the Hadassah-Hebrew University Medical Centre, Jerusalem, Israel. The incidence and characteristics of infants with positive anaerobic blood cultures were assessed. RESULTS: During the study period, 51 035 blood cultures were drawn from 44 304 infants. Of these, 1496 (2.9%) were clinically significant positive cultures. Pathogenic obligatory anaerobic bacteraemia was extremely rare, with only 37 positive cultures (0.07%) from all of the cultures drawn. No specific risk factors for obligatory anaerobic bacteraemia could be defined, but as many as 174 (11.6%) clinically significant isolates were only detected in the anaerobic culture bottle. CONCLUSION: True anaerobic bacteraemia was extremely rare in neonates. Nevertheless, using anaerobic culture media may increase the overall yield of bacterial culture growth by isolating anaerobic-facultative bacteria. This should be weighed up against increasing the volume of blood used for the aerobic culture.

Socioeconomic disparities in breast cancer incidence and survival among parous women: findings from a population-based cohort, 1964-2008.

BACKGROUND: Socioeconomic position (SEP) has been associated with breast cancer incidence and survival. We examined the associations between two socioeconomic indicators and long-term breast cancer incidence and survival in a population-based cohort of parous women. METHODS: Residents of Jerusalem who gave birth between 1964-1976 (n = 40,586) were linked to the Israel Cancer Registry and Israel Population Registry to determine breast cancer incidence and vital status through mid-2008. SEP was assessed by husband's occupation and the woman's education. We used log ranks tests to compare incidence and survival curves by SEP, and Cox proportional hazard models to adjust for demographic, reproductive and diagnostic factors and assess effect modification by ethnic origin. RESULTS: In multivariable models, women of high SEP had a greater risk of breast cancer compared to women of low SEP (Occupation: HR 1.18, 95 % CI 1.03-1.35; Education: HR 1.39, 95 % CI 1.21-1.60) and women of low SEP had a greater risk of mortality after a breast cancer diagnosis (Occupation: HR 1.33, 95 % CI 1.04-1.70; Education: HR 1.37, 95 % CI 1.06-1.76). The association between education and survival was modified by ethnic origin, with a gradient effect observed only among women of European origin. Women of Asian, North African and Israeli origin showed no such trend. CONCLUSIONS: SEP was associated with long-term breast cancer incidence and survival among Israeli Jews. Education had a stronger effect on breast cancer outcomes than occupation, suggesting that a behavioral mechanism may underlie disparities. More research is needed to explain the difference in the effect of education on survival among European women compared to women of other ethnicities.

Gum chewing and gastrointestinal function following caesarean delivery: a systematic review and meta-analysis.

AIMS AND OBJECTIVES: The aims of this systematic review and meta-analysis were to summarise current knowledge regarding gum chewing intervention for activation of the gastrointestinal (GI) system following caesarean delivery. BACKGROUND: GI symptoms such as nausea, vomiting and defecatory difficulties are bothersome for women following a caesarean delivery. There is category A recommendation to not withhold oral intake postoperatively. However, current practice guidelines vary widely on time to initiate oral feeding post caesarean delivery, and additional research is needed. Gum chewing has been shown to stimulate the GI system in other postoperative patient populations. DESIGN: A systematic review and meta-analysis. METHODS: An electronic review was undertaken using the following resources: PubMed (Medline), CINAHL, EMBASE and ClinicalTrials.gov databases. Key words used in various combinations included cesarean section; cesarean delivery; postoperative chewing gum; bowel movement; bowel function and complications. RESULTS: A total of 171 articles were found of which 166 were excluded: 157 were duplicates and the remainder did not meet the inclusion criteria. Five randomised control trials were included in the meta-analysis, focusing on gum chewing as an intervention as compared with a nongum chewing intervention, with a total of 846 participants. Compared with the nongum chewing group, gum chewing showed a beneficial impact on the major outcomes of digestive system activation, including bowel sound, gas passage and defecation. CONCLUSIONS: This meta-analysis supports the effectiveness of gum chewing post caesarean delivery as a noninvasive/nonpharmacological intervention for reactivation of bowel movement. RELEVANCE TO CLINICAL PRACTICE: Gum chewing in the immediate postoperative period following caesarean delivery may provide a socially acceptable, low-cost and safe intervention to reduce postcaesarean delivery GI complications and restore GI function.

Meta-analysis of fine particulate matter exposure during pregnancy and birth weight: Exploring sources of heterogeneity.

BACKGROUND: Several meta-analyses assessed the relationship between exposure to PM with aerodynamic diameter ≤ 2.5 µm (PM2.5) during pregnancy and birth weight (BW), but results were inconsistent and substantial unexplained heterogeneity was reported. We aimed to investigate the above association and to explore sources of heterogeneity across studies. METHODS: We systematically reviewed the current worldwide evidence examining the association between PM2.5 and BW. The review protocol was registered on the PROSPERO website (CRD42020188996) and followed PRISMA guidelines. We extracted association measures for BW and low birth weight (LBW, BW < 2500 g) from each study to evaluate pooled summary measures and to explore sources of between-study heterogeneity. FINDINGS: Of the 2677 articles identified, 84 met the inclusion criteria (~42 M births). Our random effects meta-analyses revealed substantial heterogeneity among included studies (I2 = 98.4 % and I2 = 77.7 %, for BW and LBW respectively). For LBW, the heterogeneity decreased (I2 = 59.7 %) after excluding four outlying studies, with a pooled odds ratio 1.07 (95 % confidence interval, CI: 1.05, 1.09) per a 10-µg/m3 increase in mean PM2.5 exposure over the entire pregnancy. Further subgroup analysis revealed geographic heterogeneity with higher association in Europe (1.34, (1.16, 1.55)) compared to Asia (1.06, (1.03, 1.10)) and US (1.07, (1.04, 1.10)). CONCLUSION: The association between PM2.5 and birth weight varied depending on several factors. The sources of heterogeneity between studies included modifiers such as study region and period. Hence, it is advisable not to pool summary measures of PM2.5-BW associations and that policy would be informed by local evidence.

Trends in Pregabalin Use and Prescribing Patterns in the Adult Population: A 10-Year Pharmacoepidemiologic Study.

BACKGROUND AND OBJECTIVE: Pregabalin is steadily gaining popularity worldwide, with epidemiological studies indicating an increase in labeled, off-labeled, and recreational uses. In Israel, pregabalin prescriptions are not regulated by the controlled substances legislations, prompting a need to examine its usage trends for potential policy adjustments. The objective of this study was to assess trends in pregabalin prescribing during a 10-year period, to characterize demographic and clinical characteristics of individuals prescribed pregabalin, and to identify risk factors associated with high-intensity pregabalin use. METHODS: This retrospective, longitudinal study examined trends in pregabalin prescribing from 2010 to 2019 based on data extracted from the Clalit Health Services (CHS) electronic database. Annual pregabalin prescribing rate was calculated individually for each reporting year. A univariable analysis was conducted to compare the demographic and clinical characteristics of pregabalin users in 2019 with those in 2010. Multivariable regression analysis was performed to assess dose-related patterns by specific demographic and clinical characteristics. RESULTS: Pregabalin prescription rate more than doubled over 10 years [odds ratio (OR) 2.3, p = 0.001], reaching 7.2 [95% confidence interval (CI) 7.18-7.28] prescriptions per 100 CHS members in 2019. The highest prescription rates were observed among the elderly population (13.2 and 24.1 prescriptions per 100 CHS members for those aged 55-74 and over 75 years old, respectively). Same-year administration of pregabalin with opioids, benzodiazepines, and Z-drugs was common; however, the percentage of patients using these drugs together declined in 2019 compared with 2010 (p < 0.001). Males, patients with low socioeconomic status, patients aged 35-54 years, and those who consumed opioids, benzodiazepines, and Z-drugs received higher pregabalin doses. CONCLUSION: Pregabalin use has increased significantly in the Israeli adult-based CHS population, consistent with worldwide data. A growing use over time may indicate overprescription. More studies are needed on misuse patterns to identify populations most susceptible to high-dose and high-intensity pregabalin use.

Trends in the Incidence of Cardiovascular Diagnoses and Procedures over the Years 2012-2021 in Israel: The Impact of the COVID-19 Pandemic.

Prior studies found reduced incidences of cardiovascular diagnoses and treatments in the initial phase of the COVID-19 pandemic. However, these studies included a limited number of outcomes and did not consider pre-pandemic trends. This study aimed to describe trends in the incidence of cardiovascular diagnoses and treatments over the years 2012-2021 in Israel and to compare the two years of the COVID-19 period with the preceding 8 years. In this retrospective, population-based study, carried out within Clalit Health Services, the incidence rates of cardiovascular outcomes were calculated for individuals aged ≥ 25 (~2.7 million adults per year) during the first (Y1, 3/2020-2/2021) and second (Y2, 3/2021-2/2022) years of COVID-19 and the 8 years prior (3/2012-2/2020). Declines were observed in Y1 compared to 2019 in all diagnoses and treatments: STEMI (-16.3%; 95% CI: -16.6, -16.1), non-STEMI (-16.4%; -16.6, -16.2), AF (-14.1%; -14.2, -14.0), CHF (-7.8%; -7.9, -7.7), CVA (-5.0%; -5.0, -4.9), catheterization (-64.7%; -65.2, -64.2), CABG (-77.7%; -79.2, -76.2), ablation (-21.2%; -22.0, -20.4), pacemaker implantation (-39.3%; -40.7, -37.9), and defibrillator insertion (-12.5%; -13.1, -12.0). Compared with expected rates based on pre-pandemic trends, observed rates were within expected ranges (CHF, CVA, and ablation), less than expected (STEMI, non-STEMI, AF, catheterization, CABG, and pacemaker insertion), or more than expected (defibrillator insertion). In Y2, STEMI, catheterization, and CABG returned to expected rates; non-STEMI and AF were lower than expected; and CHF, CVA, ablation, and pacemaker and defibrillator implantations were higher than expected. Several cardiovascular diagnoses and treatment trends were interrupted by COVID-19. The long-term consequences of these changes should be considered by health policymakers.

Effectiveness and safety of molnupiravir in the intended-use population: an observational cohort study.

OBJECTIVES: Previous research reported inconsistent results on the efficacy of molnupiravir in treating COVID-19. Moreover, efficacy was not assessed in the intended-use population (IUP), as defined by the FDA. Therefore, we aimed to evaluate the effectiveness and safety of molnupiravir for the treatment of COVID-19 in the IUP. METHODS: We performed a retrospective cohort study on all IUP in Israel's Clalit Health Services from January 16, 2022, to February 16, 2023. The effectiveness outcome was the incidence of hospitalization or death due to COVID-19, and the safety outcome was the incidence of all-cause mortality within 35 days of SARS-CoV-2 infection. Cox-proportional hazard models were used to analyse the data after 1:5 propensity-score matching. RESULTS: A total of 49 515 patients met the eligibility criteria. Of them, 3957 molnupiravir-treated patients were matched to 19 785 untreated patients. In molnupiravir-treated patients, 70 out of 3957 (5.1 per 10 000 person per day) experienced COVID-19-related hospitalization or death, compared with 699 out of 19 785 untreated patients (10.4 per 10 000 person per day); RR: 0.50 (95% CI, 0.39-0.64). All-cause mortality was also lower in the treated group, with 41 out of 3957 (3.0 per 10 000 person per day) experiencing mortality compared with 414 out of 19 785 untreated patients (6.1 per 10 000 person per day); RR: 0.50 (0.36-0.68). DISCUSSION: In a real-world cohort of IUP, molnupiravir therapy was associated with a significant reduction in hospitalizations or deaths due to COVID-19 and all-cause mortality.

Therapeutic efficacy and pharmacokinetics of liposomal-cannabidiol injection: a pilot clinical study in dogs with naturally-occurring osteoarthritis.

Introduction: Osteoarthritis is a common disease in dogs resulting in chronic pain and decreased wellbeing. Common analgesics such as non-steroidal anti-inflammatories may fail to control pain and can produce major adverse effects. Study objectives were to evaluate pharmacokinetics, therapeutic efficacy, and safety of subcutaneous liposomal-cannabidiol (CBD) as an additional analgesic therapy in dogs suffering from naturally-occurring osteoarthritis. Methods: Six such dogs were recruited following ethics approval and owner consent. Dogs were administered a single subcutaneous injection of 5 mg/kg liposomal-CBD. Plasma concentrations of CBD, blood work, activity monitoring collar data, wellbeing questionnaire (owners) and pain scoring (veterinarian) were performed at baseline and monitored up to six weeks following intervention. Data overtime were compared with baseline using linear-regression mixed-effects. P-value was set at 0.05. Results: CBD plasma concentrations were observed for 6 weeks; median (range) peak plasma concentration (Cmax) was 45.2 (17.8-72.5) ng/mL, time to Cmax was 4 (2-14) days and half-life was 12.4 (7.7-42.6) days. Median (range) collar activity score was significantly increased on weeks 5-6; from 29 (17-34) to 34 (21-38). Scores of wellbeing and pain evaluations were significantly improved at 2-3 weeks; from 69 (52-78) to 53.5 (41-68), and from 7.5 (6-8) to 5.5 (5-7), respectively. The main adverse effect was minor local swelling for several days in 5/6 dogs. Conclusion: Liposomal-CBD administered subcutaneously produced detectable CBD plasma concentrations for 6 weeks with minimal side effects and demonstrated reduced pain and increased wellbeing as part of multimodal pain management in dogs suffering from osteoarthritis. Further placebo-controlled studies are of interest.