Ambient temperature and preeclampsia: A historical cohort study.

Previous studies found inconsistent associations between ambient temperature during pregnancy and the risk of preeclampsia. If such associations are causal, they may impact the future burden of preeclampsia in the context of climate change. We used a historical cohort of 129,009 pregnancies (5074 preeclampsia cases) from southern Israel that was merged with temperature assessments from a hybrid satellite-based exposure model. Distributed-lag and cause-specific hazard models were employed to study time to all preeclampsia cases, followed by stratification according to early (≤34 weeks) and late (>34 weeks) onset disease and identify critical exposure periods. We found a positive association between temperature and preeclampsia during gestation, which was stronger in the 3rd trimester. For example, during week 33, compared to the reference temperature of 22.4 °C, the cause-specific hazard ratio (HRCS) of preeclampsia was 1.01 (95% confidence interval (CI): 1.01-1.02) when exposed to 30 °C, 1.05 (95%CI: 1.03-1.08) at 35 °C, and 1.07 (95%CI: 1.04-1.10) at 37 °C. The associations existed with both early- and late-onset preeclampsia; however, the associations with the early-onset disease were somewhat stronger, limited to the first weeks of pregnancy and the third trimester, and with larger confidence intervals. The HRCS for early preeclampsia onset, when exposed to 37 °C compared to 22.4 °C during week 33, was 1.12 (95%CI: 0.96-1.30), and for late-onset preeclampsia, the HRCS was 1.09 (95%CI: 1.05-1.13). To conclude, exposure to high temperatures at the beginning and, particularly, the end of gestation is associated with an increased risk of preeclampsia in southern Israel.

Air Pollution and Meteorological Conditions Significantly Associated With Vernal Keratoconjunctivitis Exacerbations.

Purpose: Vernal keratoconjunctivitis (VKC) is a severe chronic allergic inflammation of the ocular surface with episodes of acute exacerbations, that primarily affects children and young adults. Although the etiology and pathogenesis of VKC remain unclear, studies have suggested that environmental factors may be involved. This study aims to investigate the association between exposure to meteorological and environmental factors and the incidence of VKC exacerbations. Methods: This study was conducted in southern Israel, which is a semi-arid, hot, and dry climate with frequent dust storms. Patients diagnosed with VKC were recruited for the study. VKC exacerbations were identified as the need for medical intervention. Pollutants measured included nitrogen dioxide (NO2), ozone (O3), particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), relative humidity (RH), temperature, and solar radiation (SR). To assess the association between VKC exacerbations and exposure to different pollutants, a case-crossover analysis was conducted. We also stratified the analysis by sex, age, ethnicity, immigration status, and social state score. Results: Our results demonstrated that the pollutants NO2, O3, and PM10 were associated with VKC exacerbations with odds ratio (OR) = 2.17 (95% confidence interval [CI] =1.40 to 3.04), OR = 2.28 (95% CI = 1.30 to 3.39), and OR = 1.89 (95% CI = 1.06 to 2.74). Other pollutants PM2.5, temperature, and solar radiation were also independently associated with incidence of exacerbations with OR = 1.15 (95% CI = 0.87 to 1.50), OR = 1.75 (95% CI = 1.16 to 2.65), and OR = 1.37 (95% CI = 1.01 to 1.63) and had varying effects in different demographic strata. Conclusions: The environmental parameters, NO2, O3, PM10, PM2.5, temperature, and solar radiation were found to be significantly associated with VKC exacerbations, with NO2, O3, and PM10 showing the strongest associations. Our findings suggest that environmental factors should be considered when developing strategies to prevent and manage VKC exacerbations.

Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2.

Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates of protection (COP) in a multicenter prospective study following 607 healthy individuals who received three doses of the Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 individuals who received a fourth dose to 365 who did not. Within 90 days of enrollment, 239 individuals contracted COVID-19, 45% of the 3-dose group and 30% of the four-dose group. The fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple VOCs reducing the risk of symptomatic infection by 37% [95%CI, 15%-54%]. However, a group of individuals, characterized by low baseline titers of binding antibodies, remained susceptible to infection despite significantly increased neutralizing antibody titers upon boosting. A combination of reduced IgG levels to RBD mutants and reduced VOC-recognizing IgA antibodies represented the strongest COP in both the 3-dose group (HR = 6.34, p = 0.008) and four-dose group (HR = 8.14, p = 0.018). We validated our findings in an independent second cohort. In summary combination IgA and IgG baseline binding antibody levels may identify individuals most at risk from future infections.

Levels of PFAS concentrations in the placenta and pregnancy complications.

BACKGROUND: Recent research has raised concerns about the potential health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure, particularly during critical periods of development such as pregnancy. In this study, we sought to investigate the presence and potential impacts of PFAS in the placenta. METHODS: We measured 13 PFAS compounds in placental tissue samples among 50 women who gave birth at a tertiary medical center in southern Israel. The sample comprised of 10 women with pregnancy-related complications (preterm birth, preeclampsia, gestational diabetes or small-for-gestational age) and 40 women without complications individually matched to cases by age. RESULTS: For five (5) out of 13 PFAS compounds (Perfluorooctane Sulfonate (PFOS), perfluorooctanoic acid (PFOA), Perfluorohexanesulphonic acid (PFHxS), Perfluorononanoic acid (PFNA), Perfluorodecanoic acid (PFDA)) median concentrations were lower or comparable to placental measurements in different international populations. Geometric mean was estimated at 0.09 ng/g (90%CI:0.07;0.10) for PFOA, 0.05 ng/g for PFNA (90%CI:0.04;0.07), 0.03 ng/g for PFDA (90%CI:0.01;0.03), 0.06 ng/g for PFHxS (90%CI:0.05;0.07), 0.23 ng/g for PFOS linear measurement (90%CI:0.20;0.26) and 0.25 ng/g (90%CI:0.22;0.30) for PFOS summed concentrations that included non-linear isomers. Composite outcome of pregnancy-related complications was associated with elevated PFOA placental concentrations at an odds ratio (OR)= 1.82 (90%CI:1.06;3.13) for an increase of one quintile of PFOA value and adjusted to maternal gravidity in a conditional logistic regression. CONCLUSION: This pilot study indicates a widespread exposure to multiple PFAS compounds in placental tissue of pregnant women in Israel. These findings warrant further validation through comprehensive national human biomonitoring initiatives.

Linking between ambient pollution and metals concentration in blood. Nationwide study based on the national blood banking system.

This study was aimed to describe the chemical traces of air pollution in blood of residents and evaluate the association between ambient pollution and its dose absorbed internally by a human body. The national Magen David Adom Blood Services blood donation collection platform and the National Public Health Laboratory's testing services were utilized to conduct a human biomonitoring study among blood donors in Israel. The donors' residential addresses and donations sites' locations were geocoded and merged with the levels of pollutants recorded by the nearby monitoring stations. Pollutants included nitrogen dioxide (NO2), sulfate dioxide (SO2), ozone (O3), carbon monoxide (CO) and particulate matter of size <10 and 2.5 µm in diameter (PM10 & PM2.5). Metal concentrations were statistically analyzed by ratio t-test and a lognormal regression, and adjusted to age, gender and smoking (defined based on Cadmium values). The findings indicate an independent positive association between pollutants and metals' concentrations in blood. Specifically, an increase in interquartile range (IQR) of NO2 was associated with 9.5 % increase in As in blood. The increase in one IQR of PM10 and SO2 was associated with an increase in Pb, of 16.6 % and 12.4 %, respectively. SO2 was also adversely associated with Cd concentrations, by increasing its levels by 5.7 %. The donors' proximity to quarries was related to the Pb blood levels higher 1.47 times compared to donors without quarries close to their residence (p-value = 0.013). To conclude, ambient pollution levels are associated with internal metals' concentrations, reaffirming the link between the two in the pathological pathway from air pollution to morbidity.

National blood bank services as a platform for national human biomonitoring - A proof-of-concept study.

BACKGROUND: Human biomonitoring (HBM) is crucial for identifying potential risks to human health from exposure to environmental hazards. However, it is an expensive and labor-intensive endeavor. To save on samples' collection process we suggested using a national blood banking system as a platform for a national HBM program. For the case study, we used a comparison of blood donors from heavily industrialized Haifa Bay region, northern Israel, with donors from the rest of the country. METHODS: The study population comprised a random sample of blood donors donating blood all over Israel. Samples of whole blood were tested for arsenic (As), cadmium (Cd), chromium (Cr) and lead (Pb). Donors' donations sites and residential locations were geocoded. Smoking status was verified based on Cd levels, after calibrating their concentrations vs Cotinine in a sub-sample of 45 subjects. Metal concentrations were compared between regions using a lognormal regression, while controlling for age, gender, and predicted probability of smoking. RESULTS: During Mar 2020-Feb 2022, we collected 6230 and tested 911 samples. Concentrations of most of the metals were modified by age, gender, and smoking. Cr and Pb appeared to be 1.08-1.10 times higher among Haifa Bay residents than in the rest of the country (although with borderline significance of 0.069 for Cr). Cr and Pb were 1.13-1.15 times higher for those who donated blood in the Haifa Bay region, but not necessarily resided in the area. Donors from Haifa Bay had lower levels of As and Cd as compared to other donors in Israel. CONCLUSIONS: Using a national blood banking system for HBM proved to be feasible and efficient. Blood donors from Haifa Bay area were characterized by elevated levels of Cr and Pb and lower levels of As and Cd. An extensive investigation of industries in the area is warranted.

Contribution of Solar Radiation and Pollution to Parkinson's Disease.

Background. Parkinson's disease (PD) is believed to develop from epigenetic modulation of gene expression through environmental factors that accounts for up to 85% of all PD cases. The main objective of this study was to examine the association between PD onset and a cumulative exposure to potentially modifiable ambient exposures. Methods. The study population comprised 3343 incident PD cases and 31,324 non-PD controls in Southern Israel. The exposures were determined based on the monitoring stations and averaged per year. Their association with PD was modeled using a distributed lag non-linear model and presented as an effect of exposure to the 75th percentile as compared to the 50th percentile of each pollutant, accumulated over the span of 5 years prior to the PD. Results. We recorded an adverse effect of particulate matter of size ≤10 µm in diameter (PM10) and solar radiation (SR) with odds ratio (OR) = 1.06 (95%CI: 1.02; 1.10) and 1.23 (95%CI: 1.08; 1.39), respectively. Ozone (O3) was also adversely linked to PD, although with a borderline significance, OR: 1.12 (95%CI: 0.99; 1.25). Immigrants arriving in Israel after 1989 appeared to be more vulnerable to exposure to O3 and SR. The dose response effect of SR, non-existent for Israeli-born (OR = 0.67, 95%CI: 0.40; 1.13), moderate for immigrants before 1989 (OR = 1.17, 95%CI: 0.98; 1.40) and relatively high for new immigrants (OR = 1.25, 95%CI: 1.25; 2.38) indicates an adaptation ability to SR. Conclusions. Our findings supported previous reports on adverse association of PD with exposure to PM10 and O3. Additionally, we revealed a link of Parkinson's Disease with SR that warrants an extensive analysis by research groups worldwide.

Fourth dose of BNT162b2 vaccine for patients with autoimmune rheumatic diseases in a nationwide setting.

OBJECTIVE: The effectiveness of COVID-19 vaccinations wanes due to immune evasion by the B.1.1.529 (Omicron) variant and diminished antibody titres over time. We aimed to evaluate the benefit of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARDs). METHODS: This retrospective analysis included ARD patients aged 18 years or older and members of Clalit Health Services in Israel (which at the time of the study insured 52% of the entire population), and covered the period from 16 January 2022 to 31 March 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who had received three doses of the BNT162b2 vaccine (the control group) with those who had received the fourth dose. The primary outcome was COVID-19 infection, which was analysed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19-related hospitalizations and COVID-19-related death. RESULTS: We included 43 748 ARD patients, of whom 27 766 and 15 982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6942 (25.0%) of the control group and 1754 (11.0%) of the fourth dose group (P < 0.001). Patients vaccinated with the fourth dose had a lower risk of COVID-19 infection than the entire cohort [Hazard Ratio (HR) 0.54, 95% CI 0.52, 0.58] and throughout every subgroup regardless of the baseline characteristic or medical treatment, except for rituximab. A similar association was observed for risk of COVID-19-related hospitalization (HR 0.36, 95% CI 0.22, 0.61) and of COVID-19-related death (HR 0.41, 95% CI 0.24, 0.71). CONCLUSION: A fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared with three doses among patients with no history of COVID-19 infection.

Ability to adapt to seasonal temperature extremes among atrial fibrillation patients. A nation-wide study of hospitalizations in Israel.

BACKGROUND: In recent years, temperature fluctuations and adverse weather events have become major concerns, influencing overall mortality and morbidity. While the association between extreme temperatures and atrial fibrillation (AF) has been supported by research, there is limited evidence on the ability of AF patients to adapt to the changing temperatures. We explored this question among AF patients in Israel featured by extreme temperature conditions. METHODS: We examined the association between exposure to extreme temperatures and hospitalizations related to AF in a nationwide cohort in Israel. A case-crossover design with a distributed nonlinear model (DLNM) was applied to assess possible effects of temperature fluctuations during each season. We considered the 7 days prior to the event as the possible window period. RESULTS: During 2004-2018 we recorded a total of 54,909 hospitalizations for AF. Low temperatures in winter and high in summer adversely affected AF-related hospitalizations. The effect recorded for the first few weeks of each season was of higher magnitude and decreased or faded off completely as the seasons progressed (OR in winter: from 1.14, 95%CI 0.98, 1.32 to 0.90, 95%CI: 0.77, 1.06;OR in summer: from 1.95, 95%CI: 1.51, 2.52 to 1.22, 95%CI: 0.90, 1.65). Patients living in the south region and patients with low socioeconomic status were more susceptible to extreme temperatures. CONCLUSIONS: Although extreme hot and cold temperatures are associated with an increased risk of hospitalization for AF, the patients are likely to adapt to temperature change over the course of the first weeks of the season.

SARS-CoV-2 infection among patients with autoimmune rheumatic diseases; comparison between the Delta and Omicron waves in Israel.

OBJECTIVE: The Omicron variant of the coronavirus SARS-CoV-2 (COVID-19) had milder clinical impacts than prior variants. This study aimed to describe the impact of COVID-19 on Autoimmune Rheumatic Disease (ARD) patients during the Delta and Omicron variants waves. METHODS: We used data from Clalit Health Services (CHS), the largest health service in Israel. ARD patients diagnosed with COVID-19 between July 1, 2021, to December 1, 2021, were included in the Delta group. Patients diagnosed between December 2, 2021, to March 31, 2022, were included in the Omicron group based on the predominance of COVID-19 in Israel. The study outcomes were COVID-19-related hospitalization or death. RESULTS: The final study cohort included 8443 actively treated ARD patients diagnosed with COVID-19. 1204 patients were positive during the predefined Delta variant period, and 7249 were positive during the predefined Omicron variant period). Compared to the Delta group, the Omicron group showed a lower rate of COVID-19-related hospitalization (3.9% vs. 1.3% for the Delta Vs. Omicron accordingly, p<0.001) and COVID-19-related death (3.2% vs. 1.1% for the Delta Vs. Omicron accordingly, p<0.001). After applying multivariable regression models, the Omicron group showed a lower risk for COVID-19-related hospitalization (Relative risk 0.4, 95% CI 0.27-0.59) and COVID-19-related mortality (RR 0.48, 95% CI 0.31-0.75). CONCLUSION: ARD patients infected with the COVID-19 Omicron variant had a lower risk of developing COVID-19-related adverse outcomes compared to the Delta variant.

Perceived Stress, Resilience, and Wellbeing in Seasoned Isha Yoga Practitioners Compared to Matched Controls During the COVID-19 Pandemic.

Background: Yoga practices, including breathing, meditation, and posture protocols (asanas), have been shown to facilitate physical and mental wellbeing. Methods: Seasoned yoga practitioners were recruited from the Isha Foundation. Recruitment of the comparison group was achieved using snowball sampling and were not yoga practitioners. Participants in the non-yoga group were randomized to a 3-min Isha practice or a comparator group asked to perform 15-min of daily reading. Participants completed a series of web-based surveys (REDCap) at baseline, 6, and 12 weeks. These surveys include validated scales and objective questions on COVID-19 infection and medical history. The validated questionnaires assess for: perceived stress (PSS), mood states [anxiety and depression (PHQ-4), joy (DPES-Joy subscale)], mindfulness attention and awareness (MAAS), resilience (BRS), mental wellbeing (WEMWBS) and recovery from traumatic event (PTGI). Weekly activity diaries were employed as a tool for collecting compliance information from study participants. Perceived stress scale scores were identified as primary outcome for this study. Findings: The median Perceived Stress Scale (PSS) score for the yoga practitioners compared to the active and placebo comparators was significantly lower at all time-points: baseline: 11 [IQR 7-15] vs. 16 [IQR 12-21] in both the active and placebo comparators (p < 0.0001); 6 weeks: 9 [IQR 6-13] vs. 12 [IQR 8-17] in the active comparator and 14 [IQR 9-18] in the placebo comparator (p < 0.0001); and 12 weeks: 9 [IQR 5-13] vs. 11.5 [IQR 8-16] in the active comparators and 13 [IQR 8-17] in the placebo comparator (p < 0.0001). Among the randomized participants that were compliant for the full 12 weeks, the active comparators had significantly lower median PSS scores than the placebo comparators 12 weeks [10 (IQR 5-14) vs. 13 (IQR 8-17), p = 0.017]. Further, yoga practitioners had significantly lower anxiety at all three-time points (p < 0.0001), lower depression at baseline and 6 weeks (p < 0.0003), and significantly higher wellbeing (p < 0.0001) and joy (p < 0.0001) at all three-time points, compared to the active and placebo comparator groups. Interpretation: The lower levels of stress, anxiety, depression, and higher level of wellbeing and joy seen in the yoga practitioners compared to the active and placebo comparators illustrate the impact of regular yoga practices on mental health even during the pandemic. Trial Registration: ClinicalTrials.gov, identifier: NCT04498442.

Sedative polypharmacy mediates the effect of mechanical ventilation on delirium in critically ill COVID-19 patients: A retrospective cohort study.

BACKGROUND: Polypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium. METHODS: Retrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels. RESULTS: A total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16-12.52]) and PP (OR 7.38 [2.4-22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%-94%) of the effect of mechanical ventilation on delirium was mediated through PP. CONCLUSION: PP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium. IMPLICATION STATEMENT: PP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.

The roles of personal interview and cognitive abilities at admission to medical school in predicting performance of medical students in their internal medicine sub-internship.

BACKGROUND: The medical school admission process is complicated, perhaps reflecting unresolved debates concerning the most important skills necessary to become an ideal physician. The Goldman Medical School at Ben-Gurion University in Israel is known for placing great emphasis on the personal attributes of candidates in addition to their academic excellence. To this end, 1-h consecutive interviews are embedded in the admission process. This study aims to determine whether there is an association between candidates' personal interview ratings and the ratings assigned to these students at the conclusion of their 6th year internal medicine sub-internship. METHODS: Our study sample included 136 students who were admitted to the medical school in 2015, and who completed their 6th year internal medicine sub-internship in 2019-2020. Our data were derived from the admissions information for each candidate and from structured interviews concerning medical competence and personal traits, which were completed by medical personnel who were in contact with these students during their clinical rounds. RESULTS: Higher interview ratings of candidates during the admission process were associated with a higher probability that students would be evaluated as top-rated internists 6 years later (Odds Ratio (OR) = 9.4, p-value = 0.049), independent of gender (OR for male vs female = 0.2, p-value = 0.025) and age (OR = 1.3 per each year, p-value = 0.115). Although significant, the numeric difference in interview rating was relatively small (median 9.5 and 9.4 for top-rated and not top-rated internists, respectively). CONCLUSIONS: Our study shows that high personal interview ratings assigned to candidates as part of the medical school admission process are predictive of high performance ratings of students after they complete their 6th year internal medicine sub-internships. These findings demonstrate the value and importance of using semi-structured personal interviews in the medical school admission process.

Short Term Effects of Inner Engineering Completion Online Program on Stress and Well-Being Measures.

Introduction: The Covid-19 pandemic has been a major disruptor of routine life, resulting in increased stress and predisposing people to negative outcomes, such as insomnia, anxiety and hopelessness. Mind-body interventions have improved concentration, emotional balance, and positive emotions, with an enhanced sense of productivity, and self-confidence. We therefore hypothesized that exposure to an online mind-body intervention, "Inner Engineering Completion Online (IECO)," would reduce stress and promote well-being. Methods: This prospective cohort study enrolled participants registered for the IECO courses, which for the first time were delivered remotely, online. Participants learned a 21-min meditation practice called Shambhavi Mahamudra Kriya during the course, which incorporates controlled breathing and mediation techniques. Each enrolled participant was asked to complete self-reported electronic surveys at three key time points: at the time of consent, immediately after completing IECO, and 6 weeks after IECO completion. Effects of IECO practice were assessed using four well-validated neuropsychological scales: Perceived Stress Scale (PSS), Positive Emotion/Relationship/Engagement Scale (PERMA) Profiler, Pittsburgh Sleep Quality Index (PSQI), and Mindful Attention Awareness Scale (MAAS). A Signed Rank test was used to analyze the survey data and P-values of < 0.05 were considered statistically significant. Results: Of the 375 participants interested in participation, 164 participants were eligible. Sixty-eight participants completed surveys at all time points and were identified as compliant participants. The baseline median score for PSS in compliant participants (n = 95) was 13.5 (IQR 9, 18); immediate post-IECO median PSS score was 12 (IQR 8, 16) demonstrating a 1.5 unit decrease in PSS scores (p-value = 0.0023). Similarly, comparing PSS scores in compliant participants (n = 68) for immediate Post IECO [11.5 (IQR 8, 15.5)] to PSS scores at six weeks [8 (IQR 4.5, 12.5)] showed a statistically significant 3.5-unit decrease, indicating a reduction in stress upon routine practice of the intervention (p < 0.0001). Conclusion: Incorporating the remotely delivered mind-body intervention Shambhavi Mahamudra Kriya into daily life via the IECO program over as few as 6 weeks produced a significant stress reduction, improvement in sleep quality and mindfulness. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04189146].

BNT162b2 mRNA COVID-19 vaccine and booster in patients with autoimmune rheumatic diseases: a national cohort study.

INTRODUCTION: Emerging evidence supports the immunogenic response to mRNA COVID-19 vaccine in patients with autoimmune rheumatic diseases (ARD). However, large-scale data about the association between vaccination, and COVID-19 outcomes in patients with ARD is limited. METHODS: We used data from Clalit Health Services, which covers more than half of the population in Israel. Patients with ARD older than 18 were included between 20 December 2020 and 30 September 2021, when the BNT162b2 mRNA COVID-19 vaccine, and later a third booster dose, were available. The primary outcome was a documented positive SARS-CoV-2 PCR test. We used a Cox regression models with vaccination status as time-dependent covariate and calculated the HR for the study outcome. RESULTS: We included 127 928 patients with ARD, of whom, by the end of the study follow-up, there were 27 350 (21.3%) unvaccinated patients, 31 407 (24.5%) vaccinated patients and 69 171 (54.1%) patients who also received a third booster-dose. We identified 8470 (6.6%) patients with a positive SARS-CoV-2 PCR test during the study period. The HR for SARS-CoV-2 infection among the vaccination group was 0.143 (0.095 to 0.214, p<0.001), and among the booster group was 0.017 (0.009 to 0.035, p<0.001). Similar results were found regardless of the type of ARD group or antirheumatic therapy. CONCLUSION: Our results indicate that both the BNT162b2 mRNA COVID-19 vaccine and the booster are associated with better COVID-19 outcomes in patients with ARD.

In vivo strains at the middle and distal thirds of the tibia during exertional activities.

There is a known variance in the incidence and anatomical site of tibial stress fractures among infantry recruits and athletes who train according to established uniform training programs. To better understand the biomechanical basis for this variance, we conducted in vivo axial strain measurements using instrumented bone staples affixed in the medial cortex, aligned along the long axis of the tibia at the level of the mid and distal third of the bone in four male subjects. Strain measurements were made during treadmill walking, treadmill running, drop jumps from a 45 cm height onto a force plate and serial vertical jumps on a force plate. Significance levels for the main effects of location, type of activity and their interaction were determined by quasi-parametric methodologies. Compared to walking, running and vertical jumping peak axial tensile strain (µÎµ) was 1.94 (p = 0.009) and 3.92 times (p < 0.001) higher, respectively. Peak axial compression strain (µÎµ) values were found to be greater at the distal third than at the mid tibia for walking, running and vertical jumping (PR = 1.95, p-value<0.001). Peak axial compression and tension strains varied significantly between the subjects (all with p < 0.001), after controlling for strain gauge location and activity type. The study findings help explain the variance in the anatomical location of tibial stress fractures among participants doing the same uniform training and offers evidence of individual biomechanical susceptibility to tibial stress fracture. The study data can provide guidance when developing a generalized finite element model for mechanical tibial loading. For subject specific decisions, individualized musculoskeletal finite element models may be necessary.

Five-Year Clinical Outcomes of the COBRA Polyzene F NanoCoated Coronary Stent System.

BACKGROUND/PURPOSE: The COBRA Polyzene F™ NanoCoated Coronary Stent System (PzF coated stent) stent demonstrated favorable clinical outcomes at 9 months but late results have not been reported. We sought to assess the late safety and effectiveness of the PzF coated stent for treatment of de novo coronary artery lesions. METHODS: Patients with de novo coronary artery lesions meeting eligibility criteria were enrolled in a non-randomized, prospective clinical trial and followed for 5 years. The primary endpoint was target vessel failure (TVF, cardiac death, myocardial infarction [MI], or clinically-driven target vessel revascularization [TVR]) at 9 months. Secondary endpoints included major adverse clinical events (MACE, cardiac death, MI, or clinically driven TLR), clinically driven target lesion revascularization (TLR) and definite or probable stent thrombosis during 5-year follow-up. Endpoints at 5 years were analyzed as cumulative incidence accounting for competing risk of death. RESULTS: Of 296 enrolled patients, 290 (98%) were evaluable at 5 years. By 5 years, MACE had occurred in 61 (21.3%), cardiac death in 11 (4.2%), MI in 25 (8.6%), and TLR in 34 (12.0%) subjects. Between follow-up years 1 and 5, a first MACE occurred in 17 (6.2%), including 10 (4.0%) cardiac death, 4 (1.6%) MI, and 7 (2.9%) TLR events. There were no definite or probable stent thromboses. CONCLUSIONS: The PzF coated stent demonstrated continued safety and effectiveness through 5 years with low to very low incident rates of MACE, MI, TLR and stent thrombosis between 1 and 5 years after stent placement.

Relieving pain and distress symptoms in the outpatient burn clinic: The contribution of a medical clown.

CONTEXT: High levels of pain and emotional distress characterize the experience of patients, at burn outpatient clinic and reflect on their accompanying persons and the medical personal. OBJECTIVES: To examine the effect of a medical clown presence on: the patients' pain and distress levels as perceived by the patient and by their accompanying persons, and the emotional response of healthcare personnel. METHODS: A yearlong prospective observational comparative study in the burn outpatient clinic, operating twice a week, with a medical clown's presence once a week [Exposure Group - EG] versus clinic without clown presence [Non exposure Group- NEG]. Patients and accompanying persons filled pain [WBS, VAS] and emotional distress [SUDS] questionnaires regarding the patient's experience: before (T1) and after treatment (T2). The clinic personnel filled SUDS at the beginning and the end of the clinic working hours. RESULTS: Significantly lower WBS, VAS, and SUDS scores were reported at T2 in the EG as compared to the NEG both in patients and in the accompanying persons' evaluations. Personnel SUDS were affected in a similar manner. CONCLUSION: Presence of a medical clown induced a positive atmosphere in the clinic. It is possible that the effect of humor through stress reduction mechanism lessened agony. Furthermore, the distraction the clown evoked played a role in the decrease of pain and emotional distress. We recommend implementing psychosocial oriented interventions such as those performed by a medical clown to improve the emotional atmosphere in the ambulatory clinic of patients, accompanying persons and healthcare personnel.

Efficacy of Biologic Drugs in Short-Duration Versus Long-Duration Inflammatory Bowel Disease: A Systematic Review and an Individual-Patient Data Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD). METHODS: This was a systematic review and individual-patient data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (October 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction of remission in patients with short-duration (≤18 months) vs long-duration disease (>18 months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome. RESULTS: We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab (6168 patients with CD and 3227 patients with UC). In CD, remission induction rates were higher in pooled placebo and patients in active arms with short-duration disease of ≤18 months (41.4% [244 of 589]) compared with disease duration of >18 months (29.8% [852 of 2857], meta-analytically estimated odds ratio, 1.33; 95% confidence interval, 1.09-1.64). The primary outcome, proportional biologic/placebo treatment effect on induction of remission, was not different in short-duration disease of ≤18 months (n = 589, odds ratio, 1.47; 95% confidence interval, 1.01-2.15) compared with longer disease duration (n = 2857, odds ratio, 1.43; 95% confidence interval, 1.19-1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable, regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cutoffs and when modeled for individual patient's covariates, including prior anti-tumor necrosis factor exposure. CONCLUSIONS: There are higher rates of induction of remission with biologics and with placebo in early CD, resulting in a treatment to placebo effect ratio that is similar across disease durations. No such relationships between disease duration and outcomes was found in UC. PROSPERO registration: CRD42018041961.