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.

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.

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.

Utilising patient-reported outcomes for goal-directed therapy of hip fracture patients: a sequential controlled trial.

BACKGROUND: Hip fracture patients (HFPs) frequently have multiple underlying conditions, necessitating that agreed-upon goals take these complications into consideration. Communication regarding goals between medical-personnel and patients is not always effective. Patient-reported outcomes (PROs) can outline personal goals and help promote quality health care in HFPs. Few studies have been published on this topic. The study's aim was to outline the process of using PROs for goal-directed therapy among HFPs. METHODS: This sequential controlled trial was conducted among HFPs from two medical centres. The control and the intervention group received integrative rehabilitation. PROs were measured in both groups using the SF36 questionnaire three times postsurgery: 24-48 hours, 2 weeks and 3 months. During the first round of questioning, only the intervention group was asked 'what matters most to you?' during the rehabilitative process. Accordingly, agreed-upon goals that were determined by the SF36's eight topics and were incorporated into the HFP's rehabilitative process. A Likert scale of 1-5, '1' indicating no-achievement and '5' full-achievement, was used to assess the goal achievement 4-6 months post-fracture. RESULTS: 84 HFPs participated in the study: 40 and 44 in the intervention and control group, respectively. In both groups, PROs declined after the HF, then improved somewhat 3 months later, but did not return to prefracture scores. Among the intervention group, 39% reached their specific goals (Likert level 5). Patients who achieved their goals had better PROs in comparison to others. The intervention group indicated PROs helped them articulate their desires and introduced them to new areas of care. CONCLUSIONS: Shifting from asking 'what's the matter?' to 'what matters most to you?' can improve the understanding of HFPs' own priorities, promote quality outcomes and enhance patient-centred care. Using PROs as a guide for goal-directed therapy can create a more inclusive process that includes the patients' most important health determinants and needs.

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.

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.

Risk assessment of human mpox infections: retrospective cohort study.

OBJECTIVES: The global supply of vaccines against mpox (previously called monkeypox virus infection) was significantly lower than the demand. Therefore, evidence-based vaccine prioritization criteria, based on risk assessment were needed. Our objective was therefore to identify the characteristics of individuals at the highest risk for mpox. METHODS: This population-based cohort study included all Clalit Health Services (CHS) subjects assumed to be at risk for mpox. The eligibility criteria for inclusion were determined based on known characteristics of people with infection worldwide and insights of lesbian, gay, bisexual, transgender, queer+ (LGBTQ+) -specialized CHS clinicians. Cox hazards models were used to identify the risk factors for mpox within the study cohort. The study commenced on 6 June 2022, the date of the first known mpox in CHS members, until 31 July 2022, when the mpox vaccination campaign started. RESULTS: A total of 8088 individuals of 4.7 million CHS members (0.18%) were identified according to the study inclusion criteria. Of those, 69 (0.85%) developed infection during the study period. Risk factors for mpox were birth in 1980 or later (hazard ratio, 5.04; 95% CI, 2.11-12.02), history of syphilis (2.62; 1.58-4.35), registration to primary healthcare clinics in the Tel Aviv district (2.82; 1.44-5.54), HIV-pre-exposure prophylaxis medication use (3.96; 2.14-7.31), PDE5 inhibitors use (2.92; 1.77-4.84), and recent sexually transmitted infections (STIs) within the last 18 months (2.27; 1.35-3.82). No infections were observed in individuals with none of the factors. Individuals with three or more risk factors had a 20.30-fold (10.39-39.69) higher risk for mpox compared with those with 0-2, with 85.5% (75.0-92.8%) sensitivity and 77.8% (76.9-78.7%) specificity. DISCUSSION: Weighting individuals' risk levels based on validated risk factors against vaccine availability can assist health systems in the equitable prioritization of vaccine allocation in various future outbreaks, given supply-demand gaps.

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.

Viral and Bacterial Respiratory Pathogens during the COVID-19 Pandemic in Israel.

BACKGROUND: previous worldwide reports indicated a substantial short-term reduction in various respiratory infections during the early phase of the SARS-CoV-2 pandemic. AIMS: exploring the long-term impact of the COVID-19 pandemic on respiratory pathogens. METHODS: retrospective analysis of bacterial and viral positivity rate in respiratory samples, between 1 January 2017-30 June 2022 in a tertiary hospital in Jerusalem, Israel. RESULTS: A decline in overall respiratory tests and positivity rate was observed in the first months of the pandemic. Respiratory isolations of Hemophilus influenza and Streptococcus pneumoniae were insignificantly affected and returned to their monthly average by November 2020, despite a parallel surge in COVID-19 activity, while Mycoplasma pneumoniae was almost eliminated from the respiratory pathogens scene. Each viral pathogen acted differently, with adenovirus affected only for few months. Human-metapneumovirus and respiratory-syncytial-virus had reduced activity for approximately a year, and influenza A virus resurged in November 2021 with the elimination of Influenza-B. CONCLUSIONS: After an immediate decline in non-SARS-CoV-2 respiratory infections, each pathogen has a different pattern during a 2-year follow-up. These patterns might be influenced by intrinsic factors of each pathogen and different risk reduction behaviors of the population. Since some of these measures will remain in the following years, we cannot predict the timing of return to pre-COVID-19 normalcy.

Real-world effectiveness of a single dose of mpox vaccine in males.

The recent global outbreak of the monkeypox (mpox) virus in humans was declared a public health emergency by the World Health Organization in July 2022. The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox. However, the efficacy of MVA-BN against mpox has never been demonstrated in clinical trials to date. Due to the limited supply of vaccines, the World Health Organization has recommended prioritizing the vaccination of high-risk groups. We evaluated the real-world effectiveness of a single, subcutaneous dose of MVA-BN in this observational, retrospective cohort study, which included the analysis of electronic health records of all members of Clalit Health Services eligible for the vaccine on 31 July 2022. We used a Cox proportional hazards regression model with time-dependent covariates to estimate the association between vaccination and mpox while adjusting for sociodemographic and clinical risk factors. In an analysis of 2,054 male individuals who met vaccine eligibility criteria, 1,037 (50%) were vaccinated during the study recruitment period and completed at least 90 d of follow-up. During the study period, 5 and 16 infections were confirmed in vaccinated and unvaccinated individuals, respectively. The adjusted vaccine effectiveness was estimated at 86% (95% confidence interval, 59-95%). Our results suggest that a single dose of subcutaneous MVA-BN in this high-risk cohort is associated with a significantly lower risk of MPXV infection.

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.

Prevalence and Molecular Characterization of Extended-Spectrum ß-Lactamase Producing Enterobacterales in Healthy Community Dogs in Israel.

BACKGROUND: antimicrobial resistance is a global problem in human and veterinary medicine. We aimed to investigate the extended spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) gut colonization in healthy community dogs in Israel. METHODS: Rectal swabs were sampled from 145 healthy dogs, enriched, plated on selective plates, sub-cultured to obtain pure cultures, and ESBL production was confirmed. Bacterial species and antibiotic susceptibility profiles were identified. WGS was performed on all of the ESBL-PE isolates and their resistomes were identified in silico. Owners' questionnaires were collected for risk factor analysis. RESULTS: ESBL-PE gut colonization rate was 6.2% (n = 9/145, 95% CI 2.9-11.5). Overall, ten isolates were detected (one dog had two isolates); the main species was Escherichia coli (eight isolates), belonging to diverse phylogenetic groups-B1, A and C. Two isolates were identified as Citrobacter braakii, and C. portucalensis. A phylogenetic analysis indicated that all of the isolates were genetically unrelated and sporadic. The isolates possessed diverse ESBL genes and antibiotic-resistance gene content, suggesting independent ESBL spread. In a multivariable risk factor analysis, coprophagia was identified as a risk factor for ESBL-PE gut colonization (p = 0.048, aOR = 4.408, 95% CI 1.014-19.169). CONCLUSIONS: healthy community dogs may be colonized with ESBL-PE MDR strains, some of which were previously reported in humans, that carry wide and diverse resistomes and may serve as a possible source for AMR.

Bacteremia with Carbapenemase-Producing Enterobacterales in Immunocompromised Patients Colonized with These Bacteria.

We aimed to analyze rates and risk factors for carbapenemase-producing Enterobacterales (CPE) bloodstream infection (BSI) in CPE-colonized patients with malignancies or following hematopoietic cell transplantation. We retrospectively collected data on demography, underlying disease, colonizing CPE, treatment, intensive care unit (ICU) hospitalization, CPE-BSI, and mortality in CPE-colonized immunocompromised patients (2014-2020). Two hundred twenty-one patients were colonized with 272 CPE: 254 (93.4%) carried one carbapenemase [KPC (50.4%), NDM (34.6%), OXA-48-like (5.2%), and VIM (3.3%)]; 18 (6.6%) carried two carbapenemases. Twenty-eight (12.7%) patients developed CPE-BSI. Univariate analysis revealed CPE-BSI-associated factors: younger age, carbapenem or aminoglycoside exposure, ICU admission, neutropenia, carrying serine carbapenemase-producing, and specifically KPC-producing bacteria, colonization with several CPE, and detection of several carbapenemases. None of 23 auto-HSCT recipients developed CPE-BSI. In multivariate analysis, ICU hospitalization was significantly associated with CPE-BSI (odds ratio [OR] 2.82, 95% CI 1.10-7.20; p = 0.042); solid tumor diagnosis was protective (OR 0.21, 95% CI 0.05-1.01; p = 0.038). One-year crude mortality was 108/221 (48.8%), including 19/28 (67.9%) and 89/193 (46.1%) in patients with and without CPE-BSI, p = 0.104. To conclude, CPE-BSI is rare in CPE-colonized patients with solid tumors and following auto-HSCT. ICU hospitalization increased CPE-BSI risk. These data can help to guide empirical anti-CPE antibiotic therapy in patients colonized with these bacteria.

Long-term respiratory outcomes in early-term born offspring: a systematic review and meta-analysis.

OBJECTIVE: Newborns exhibit the lowest immediate respiratory morbidity rates when born at full term (39-40 completed weeks of gestation). We evaluated whether early-term deliveries (37 0/7 to 38 6/7 weeks of gestation) bear a substantial impact on overall and specific long-term respiratory outcomes of offspring up to the age of 18 years compared with full-term or later deliveries. DATA SOURCES: We searched PubMed, Medline, Embase, and relevant reference lists from January 2012 to May 2020. STUDY ELIGIBILITY CRITERIA: This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews guidelines and was registered on International Prospective Register of Systematic Reviews. Any observational or randomized human trials addressing the association between early-term delivery and long-term respiratory outcomes in the offspring, restricted to studies published in English, were included. The search included terms relating to gestational age, pediatric morbidity, and respiratory outcomes. We included studies assessing long-term respiratory disease (1-18 years) of offspring born early term compared with offspring born full term and later. METHODS: Here, 2 independent reviewers extracted data and assessed the risk of bias. Using a random-effect meta-analysis, pooled relative risk with their 95% confidence intervals and heterogeneity were determined. Publication bias was assessed using funnel plots with Egger regression line and contours, and sensitivity analyses were performed using Baujat plots. RESULTS: Overall, 14 studies were included after screening nearly 2500 abstracts. These studies included nearly 8 million patients and were subjected to qualitative and quantitative analyses. Early-term delivery significantly increased the risk of total respiratory morbidity in the offspring (relative risk, 1.20; 95% confidence interval, 1.16-1.26) compared with full-term delivery. The increased respiratory morbidity was attributed to obstructive airway diseases (relative risk, 1.19; 95% confidence interval, 1.12-1.27) and infectious respiratory diseases (relative risk, 1.22; 95% confidence interval, 1.17-1.29). Most studies were of acceptable quality. CONCLUSION: This comprehensive meta-analysis suggested that early-term delivery poses a risk of long-term pediatric respiratory morbidity compared with full-term delivery. Other factors throughout the years cannot be accounted for. Our study has added an important perspective to be considered when balancing the fetal, maternal, and neonatal risks associated with delivery timing.

Comparison of three regional anaesthetic techniques for infraorbital or maxillary nerve block in cats: a cadaveric study.

OBJECTIVES: The maxillary nerve courses very close to the globe, rendering cats - with their large eyes - at risk of globe penetration during infraorbital or maxillary nerve blocks. Therefore, the goals of the study were to compare the distribution and potential complications of three infraorbital or maxillary regional injection techniques. METHODS: Twenty-three bilateral maxillae of cat cadavers were used in a randomised blinded trial. Each maxilla was injected with a 0.2 ml 1:1 mixture of lidocaine 2% and a contrast medium by one of three injection techniques: infraorbital foramen (IOF; n = 14); infraorbital canal (IOC; n = 16); or maxillary foramen (MF; transpalpebral approach; n = 16) using a 25 G 1.6 cm needle. CT imaging of each cadaver head was performed before and after injections. A radiologist scored injectate distribution (none [0], mild [1], moderate [2], large [3]) in four locations: rostral, central and caudal IOC, and at the MF, for which the distribution side was also determined. Comparisons were performed with ordinal logistic mixed effects (P <0.05). RESULTS: The median (range) total distribution score of the IOC and MF technique were significantly higher compared with the IOF technique (6.5 [4-12], 4 [2-8] and 0 [0-10], respectively). The total IOC score was also significantly higher compared with the MF technique. Injectate distribution at the MF was significantly more central following IOC injection compared with MF injection, which distributed centrolaterally. None of the techniques resulted in intraocular injection. CONCLUSIONS AND RELEVANCE: The IOC and MF techniques produced a satisfactory spread of the mixture that could result in effective maxillary anaesthesia in cats. Further studies are required to determine the effectiveness and safety of these techniques.

Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses.

The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 µg/mL) for 24 h. Ten (n = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9% NaCl for a total volume of 100 mL. Synovial fluid and blood samples were obtained immediately before IVRLP and at 0.25, 0.5, 2, 6, 12 and 24 h after the initiation of IVRLP. Trimethoprim and sulphadiazine concentrations were determined using a method based on liquid chromatography/tandem mass spectrometry. The Cmax (peak drug concentration) values were 36 ± 31.1 and 275.3 ± 214.4 µg/mL (TMP and SDZ). The respective tmax (time to reach Cmax) values were 20 ± 7.8 and 26.4 ± 7.2 min. The initial synovial fluid concentrations were high but decreased quickly. No horse had synovial concentrations of trimethoprim-sulphadiazine above the MIC at 12 h. Severe vasculitis and pain shortly after IVRLP, lasting up to one week post-injection, occurred in five out of 10 horses. In conclusion, IVRLP with trimethoprim-sulphadiazine cannot be recommended due to the low concentrations of synovial fluid over time and the frequent severe adverse effects causing pain and discomfort in treated horses. Thus, in cases of septic synovitis with bacteria sensitive to trimethoprim-sulphadiazine, other routes of administration should be considered.

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.