Showing papers by "Gideon Koren published in 2022"
TL;DR: It is found that treatment-induced emergence of resistance could be predicted and minimized at the individual-patient level and machine learning–personalized antibiotic recommendations were developed, offering a means to reduce the emergence and spread of resistant pathogens.
Abstract: Treatment of bacterial infections currently focuses on choosing an antibiotic that matches a pathogen’s susceptibility, with less attention paid to the risk that even susceptibility-matched treatments can fail as a result of resistance emerging in response to treatment. Combining whole-genome sequencing of 1113 pre- and posttreatment bacterial isolates with machine-learning analysis of 140,349 urinary tract infections and 7365 wound infections, we found that treatment-induced emergence of resistance could be predicted and minimized at the individual-patient level. Emergence of resistance was common and driven not by de novo resistance evolution but by rapid reinfection with a different strain resistant to the prescribed antibiotic. As most infections are seeded from a patient’s own microbiota, these resistance-gaining recurrences can be predicted using the patient’s past infection history and minimized by machine learning–personalized antibiotic recommendations, offering a means to reduce the emergence and spread of resistant pathogens. Description Personal histories of past resistance A serious infection may initially be diagnosed as antibiotic susceptible but subsequently become drug resistant—and life threatening. Rather than de novo resistance mutation occurring, it is more likely that a resistant strain or species persisting in the patient’s gut or skin replaced the susceptible strain. From this starting point, Stracy et al. built machine-learning models that predict individual risks of gaining resistance to specific antibiotics using 8 years of records on more than 200,000 patients’ microbiome profiles (see the Perspective by Lugagne and Dunlop). Data on antibiotic use for urinary tract and wound infections were used to train the algorithms and to develop personalized antibiotic treatment strategies. For most patients, there was an alternative susceptibility-matched antibiotic that had a lower predicted risk of resistance emerging compared with the antibiotic prescribed by the physician. —CA Machine learning can help to identify personalized alternative antibiotic treatments.
65 citations
TL;DR: The objective of this meta‐analysis was to determine whether maternal exposure to statins is associated with increased rates of major congenital malformations and other adverse pregnancy outcomes.
Abstract: The objective of this meta‐analysis was to determine whether maternal exposure to statins is associated with increased rates of major congenital malformations and other adverse pregnancy outcomes.
6 citations
TL;DR: In this article , a multilevel logistic regression with random effects for maternal locality of residence, administrative census area (ACA) and mother was used to assess the association between exposure to particulate matter with diameter ≤ 2.5 μm during pregnancy and birth outcomes.
Abstract: A growing body of literature reports associations between exposure to particulate matter with diameter ≤2.5 μm (PM2.5) during pregnancy and birth outcomes. However, findings are inconsistent across studies.To assess the association between PM2.5 and birth outcomes of fetal growth in a cohort with high prevalence of siblings by multilevel models accounting for geographical- and mother-level correlations.In Israel, we used Maccabi Healthcare Services data to establish a population-based cohort of 381,265 singleton births reaching 24-42 weeks' gestation and birth weight of 500-5000 g (2004-2015). Daily PM2.5 predictions from a satellite-based spatiotemporal model were linked to the date of birth and maternal residence. We generated mean PM2.5 values for the entire pregnancy and for exposure periods during pregnancy. Associations between exposure and birth outcomes were modeled by using multilevel logistic regression with random effects for maternal locality of residence, administrative census area (ACA) and mother.In fully adjusted models with a mother-level random intercept only, a 10-μg/m3 increase in PM2.5 over the entire pregnancy was positively associated with term low birth weight (TLBW) (Odds ratio, OR = 1.25, 95% confidence interval, CI: 1.09,1.43) and small for gestational age (SGA) (OR = 1.15, 95% CI: 1.06,1.26). Locality- and ACA-level effects accounted for <0.4% of the variance while mother-level effects explained ∼50% of the variability. Associations varied by exposure period, infants' sex, birth order, and maternal pre-pregnancy BMI.Consideration of mother-level variability in a region with high fertility rates provides new insights on the strength of associations between PM2.5 and birth outcomes.
3 citations
TL;DR: In a large sample of elderly in Israel, findings indicate a decrease in referrals to medical care during the first COVID-19 lockdown period, yet an increase in ambulance orders, physician visits and service refusals.
Abstract: Purpose: The COVID-19 pandemic has led to the isolation of the population in Israel, including the elderly, some of whom are chronically ill. The present study examines the consumption of medical services among adults over the age of 65 in Israel at the time of the first COVID-19 lockdown relative to the corresponding period the year before, according to various socio-demographic variables: gender, age, marital status, ethnicity, degree of religiosity and socioeconomic status. Methods: A retrospective longitudinal observational quantitative research based on the Natali Healthcare Solutions Israel database of subscribers. Company subscribers over the age of 65 (N=103,955) were included in the sample (64.5% women) in two time periods, before the COVID-19 outbreak-P1, in 2019, and during the first COVID-19 lockdown- P2 in 2020. Medical needs included referrals to a medical or emergency services, ordering an ambulance, physician home visits and service refusal. Results: The average number of referrals to services was lower during the COVID-19 lockdown period (M=0.3658, SD=0.781) compared to the corresponding period the previous year (M=0.5402, SD=0.935). At the time of the COVID-19 lockdown, the average number of referrals to medical services was lower, but the average number of ambulance orders, physician visits and service refusals was higher compared to the same period in the previous year. During both time periods, women (P1- M=0.5631, SD=0.951; P2- M=0.3846, SD=0.800) required significantly more (p<.000) services than men (P1- M=0.5114, SD=0.910; P2- M=0.3417, SD=0.753). In both time periods, subscribers who were older, widowed, living in non-Jewish/mixed localities or in average or below average socioeconomic status localities required more services relative to younger, married people living in Jewish localities, or in above-average socioeconomic localities (p<.000). Summary and Conclusions: In a large sample of elderly in Israel, findings indicate a decrease in referrals to medical care during the first COVID-19 lockdown period, yet an increase in ambulance orders, physician visits and service refusals. There were no significant differences between the periods according to different socio-demographic characteristics. The period of the first COVID-19 lockdown was characterized by a higher incidence of medical service refusals compared to routine times. The incidence of requiring medical service at the time of the first COVID-19 lockdown was 2.5 times higher among those who required services during the previous year, 1.7 times higher among unmarried seniors, and 1.4 times higher among the older age group of 85 and over in comparison to the younger seniors.
1 citations
TL;DR: There is no significant association between maternal post-partum depression and uptake of child immunization, according to a retrospective cohort study of Maccabi Healthcare Services members comparing immunization rates between children born between 2006 and 2019 to mothers with post- partum depression
Abstract: Background Maternal post-partum depression is one of the most common medical complications around childbirth. One of its consequences is a possible association with children's receipt of preventive health care, including immunization. This study aimed to explore the association between maternal postpartum depression and children's immunization rates. Methods A retrospective cohort study of Maccabi Healthcare Services (HMO) members comparing immunization rates between children born between 2006 and 2019 to mothers with post-partum depression and children born to mothers with no documented depression. Post-partum depression was assessed by Edinburgh Postnatal Depression Scale, a 10-item questionnaire considered the screening tool of choice in Israel for early Post-partum detection. 1:1 matching was conducted according to criteria: age of the mother ± 2 years, child's year of birth, the newborn baby's gender, the baby's birth order and socioeconomic index. The primary outcome was defined as non-vaccination and the exposure was defined as depression. A sub-analysis was performed, comparing immunization rates of children born to mothers treated with antidepressant medications to rates of children born to untreated mothers. Results A total of 709 subjects in the exposed cohort (children born to mothers with post-partum depression symptoms) and 681 subjects in the matched cohort were analyzed. The relative risks among children born to depressed mothers compared with children born to healthy mothers for not receiving any vaccine at 2 months, three doses of pertussis vaccine up to 7 months and four doses of DTaP-Hib-IPV vaccine up to 18 months were 1.15 (95% CI 0.74–1.78), 1.11 (95% CI 0.94–1.31) and 0.82 (95% CI 0.56–1.95), respectively. The relative risks among 139 infants born to treated mothers compared with 570 infants born to untreated mothers for not receiving any vaccine at 2 months, three doses of pertussis vaccine up to 7 months and four doses of DTaP-Hib-IPV vaccine up to 18 months were 1.28 (0.64–2.54), 0.78 (0.57–1.06) and 0.42 (0.17–1.03), respectively. Conclusion We found no significant association between maternal post-partum depression and uptake of child Immunization.
TL;DR: The arrhythmogenic cardiac consequences and molecular mechanisms underlying tissue remodeling changes in impaired or accelerated cardiac myofibroblast (CMF) senescence and the pro‐inflammatory SASP during post‐MI wound healing process in genetically engineered mice are characterized.
Abstract: Cellular senescence is a stress response involving permanent replicative arrest. It is accompanied by a complex senescence‐associated secretory phenotype (SASP), which is characterized by the presence of pro‐inflammatory cytokines and chemokines, growth factors, and tissue‐remodeling metalloproteinases. Little is known regarding the role of senescence and the SASP in the context of arrhythmias post myocardial infarction (MI). Here, we characterized the arrhythmogenic cardiac consequences and molecular mechanisms underlying tissue remodeling changes in impaired or accelerated cardiac myofibroblast (CMF) senescence and the pro‐inflammatory SASP during post‐MI wound healing process in genetically engineered mice.