Adherence to diabetes quality indicators in primary care and all-cause mortality: A nationwide population-based historical cohort study.

BACKGROUND: In the last three decades, much effort has been invested in measuring and improving the quality of diabetes care. We assessed the association between adherence to diabetes quality indicators and all-cause mortality in the primary care setting. METHODS: A nationwide, population-based, historical cohort study of all people aged 45-80 with pharmacologically-treated diabetes in 2005 (n = 222,235). Data on annual performance of quality indicators (including indicators for metabolic risk factor management and glycemic control) and vital status were retrieved from electronic medical records of the four Israeli health maintenance organizations. Cox proportional hazards and time-dependent models were used to estimate hazard ratios (HRs) for mortality by degree of adherence to quality indicators. RESULTS: During 2,000,052 person-years of follow-up, 35.8% of participants died. An inverse dose-response association between the degree of adherence and mortality was shown for most of the quality indicators. Participants who were not tested for proteinuria or did not visit an ophthalmologist during the first-5-years of follow-up had HRs of 2.60 (95%CI:2.49-2.69) and 2.09 (95%CI:2.01-2.16), respectively, compared with those who were fully adherent. In time-dependent analyses, not measuring LDL-cholesterol, blood pressure, HbA1c, or HbA1c>9% were similarly associated with mortality (HRs ≈1.5). The association of uncontrolled blood pressure with mortality was modified by age, with increased mortality shown for those with controlled blood pressure at older ages (≥65 years). CONCLUSIONS: Longitudinal adherence to diabetes quality indicators is associated with reduced all-cause mortality. Primary care professionals need to be supported by health care systems to perform quality indicators.

Association of common maternal infections with birth outcomes: a multinational cohort study.

PURPOSE: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. METHODS: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. RESULTS: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02-1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09-1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02-1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. CONCLUSION: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis.

Membrane stripping in group B streptococcus carriers does not impede adequate intrapartum antibiotic prophylaxis: a retrospective study.

Objective: Membrane stripping in group B streptococcus (GBS) carriers poses an increased risk of inadequate antibiotic prophylaxis, potentially due to accelerated labor, thereby potentially impacting the management of GBS colonization during delivery. We compared the adequacy of intrapartum antibiotic prophylaxis between pregnant women colonized with GBS, who underwent membrane stripping and those who did not. The study aimed to determine whether the performance of membrane stripping, by potentially shortening labor duration, increases the risk of inadequate antibiotic prophylaxis dispensation. Study design: A retrospective cohort study was conducted on GBS screen-positive women with a full-term singleton pregnancy in cephalic presentation, who were eligible for vaginal delivery. The exposed group consisted of women who underwent membrane stripping, while the unexposed group consisted of women who did not undergo membrane stripping. The primary outcome was defined as inadequate duration of antibiotic prophylaxis during labor, wherein less than 4 h of beta-lactam antibiotics were administered prior to delivery. Neonatal outcome was compared between the groups. Results: This retrospective cohort study comprised 1,609 women, with 129 in the exposed group (stripping group) and 1,480 in the unexposed group (no stripping group). Adequate intrapartum antibiotic prophylaxis was received by 64.3% (83/129) of the exposed group, compared to 46.9% (694/1,480) of the unexposed group (p = 0.003). Membrane stripping was associated with increased odds of receiving adequate prophylaxis (OR 1.897, 95% CI 1.185-3.037, p = 0.008). After excluding women who presented to the labor ward in active labor and delivered in less than 4 h, both the exposed and unexposed groups had similarly high rates of adequate intrapartum antibiotic prophylaxis (87.5% vs. 85.8%, respectively). No significant difference was observed in adverse neonatal outcomes between the groups. Conclusion: The provision of membrane stripping did not impede adequate intrapartum antibiotic prophylaxis and was correlated with a higher rate of sufficient prophylaxis in comparison to non-swept patients. These observations suggest that membrane stripping can be considered a safe option for ensuring adequate antibiotic prophylaxis in women colonized with GBS.

Home Versus Hospital Rehabilitation of Older Adults Following Hip Fracture Yields Similar Patient-Reported Outcome Measures.

The increase in hip fractures (HF) due to aging of the population and the rise in attractiveness of services provided at home following the COVID-19 pandemic, emphasize the need to compare outcomes of home versus hospital HF rehabilitation. To date, studies comparing the 2 services have focused primarily on clinical outcomes rather than patient-reported outcomes (PROs). This longitudinal observational study evaluated PROs of older adults with HF in the 2 settings. The SF36 questionnaire was used to measure PROs 3 times after surgery. The first PRO was retrospective and reflected pre-fracture health status. Descriptive statistics and mixed-effect logistic regression were used. Of 86 patients participating in the study, 41 had home rehabilitation and 45 had hospital rehabilitation. In both groups, the mental and physical scores plummeted 2 weeks after the HF, compared to pre-fracture status. The difference in improvement from pre-fracture status to recovery in both groups, were not significantly (P < .05) different, except for the pain domain. PROs of home versus hospital rehabilitation were similar, suggesting that rehabilitation at home can be as effective as hospital rehabilitation for suitable patients. This knowledge can improve quality of care in an aging global population.

Assessing the diagnostic utility of the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system using real-world data.

BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive condition associated with clinical features such as splenomegaly, hepatomegaly, anemia, thrombocytopenia, and bone abnormalities. Three clinical forms of GD have been defined based on the absence (type 1, GD1) or presence (types 2 and 3) of neurological signs. Early diagnosis can reduce the likelihood of severe, often irreversible complications. The aim of this study was to validate the ability of factors from the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system to discriminate between patients with GD1 and controls using real-world data from electronic patient medical records from Maccabi Healthcare Services, Israel's second-largest state-mandated healthcare provider. METHODS: We applied the GED-C scoring system to 265 confirmed cases of GD and 3445 non-GD controls matched for year of birth, sex, and socioeconomic status identified from 1998 to 2022. The analyses were based on two databases: (1) all available data and (2) all data except free-text notes. Features from the GED-C scoring system applicable to GD1 were extracted for each individual. Patients and controls were compared for the proportion of the specific features and overall GED-C scores. Decision tree and random forest models were trained to identify the main features distinguishing GD from non-GD controls. RESULTS: The GED-C scoring distinguished individuals with GD from controls using both databases. Decision tree models for the databases showed good accuracy (0.96 [95% CI 0.95-0.97] for Database 1; 0.95 [95% CI 0.94-0.96] for Database 2), high specificity (0.99 [95% CI 0.99-1]) for Database 1; 1.0 [95% CI 0.99-1] for Database 2), but relatively low sensitivity (0.53 [95% CI 0.46-0.59] for Database 1; 0.32 [95% CI 0.25-0.38]) for Database 2). The clinical features of splenomegaly, thrombocytopenia (< 50 × 109/L), and hyperferritinemia (300-1000 ng/mL) were found to be the three most accurate classifiers of GD in both databases. CONCLUSION: In this analysis of real-world patient data, certain individual features of the GED-C score discriminate more successfully between patients with GD and controls than the overall score. An enhanced diagnostic model may lead to earlier, reliable diagnoses of Gaucher disease, aiming to minimize the severe complications associated with this disease.

Perinatal exposures and adolescence overweight: The role of shared maternal-offspring pathways.

BACKGROUND AND AIMS: Early life exposures affect offspring health across the life-course. We aimed to examine whether prevalent perinatal exposures and obstetric complications are independently associated with offspring overweight in adolescence. We then assessed whether shared maternal-offspring pathways drive the association of perinatal exposures with offspring overweight. METHODS: Using data from the Jerusalem Perinatal Study birth cohort, two perinatal scores were constructed: obstetric complications (OC) and prevalent perinatal exposures (PPE) scores. PPE score, generated by principal component analysis, included three primary components. Logistic regressions were used to assess associations of scores with offspring overweight, with and without adjustment for maternal life-course survival. RESULTS: OC and PPE scores were independently associated with offspring overweight (OROC = 1.15, 95%CI:1.07,1.25; ORPPE1- SEP and lifestyle = 0.85, 95%CI:0.79,0.91; ORPPE2- Maternal body size = 1.20, 95%CI: 1.13,1.28; ORPPE3-Fetal growth = 1.18, 95%CI:1.11,1.26). Maternal survival was associated with offspring overweight (OR = 1.38, 95%CI:1.08,1.76), yet introducing PPE score to the same model attenuated this association (OR = 1.16, 95%CI:0.90, 1.49). When OC score and maternal survival were included in the same model, their associations with offspring overweight remained unchanged. CONCLUSIONS: Mother-offspring shared factors, captured by maternal life-course survival, underlie the effect of prevalent perinatal exposures on offspring overweight. However, the effect of obstetric complications was independent, highlighting the contribution of additional pathways.

Nationwide Evaluation of Quality of Care Indicators for Individuals with Severe Mental Illness and Diabetes Mellitus, Following Israel's Mental Health Reform.

Diabetes Mellitus (DM) is more common among individuals with severe mental illness (SMI). We aimed to assess quality-of-care-indicators in individuals with SMI following the 2015 Israel's Mental-Health-reform. We analyzed yearly changes in 2015-2019 of quality-of-care-measures and intermediate-DM-outcomes, with adjustment for gender, age-group, and socioeconomic status (SES) and compared individuals with SMI to the general adult population. Adults with SMI had higher prevalences of DM (odds ratio (OR) = 1.64; 95% confidence intervals (CI): 1.61-1.67) and obesity (OR = 2.11; 95% CI: 2.08-2.13), compared to the general population. DM prevalence, DM control, and obesity rates increased over the years in this population. In 2019, HbA1c testing was marginally lower (OR = 0.88; 95% CI: 0.83-0.94) and uncontrolled DM (HbA1c > 9%) slightly more common among patients with SMI (OR = 1.22; 95% CI: 1.14-1.30), control worsened by decreasing SES. After adjustment, uncontrolled DM (adj. OR = 1.02; 95% CI: 0.96-1.09) was not associated with SMI. Cardio-metabolic morbidity among patients with SMI may be related to high prevalences of obesity and DM rather than poor DM control. Effective screening for metabolic diseases in this population and social reforms are required.

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.

Cancer Risk in Patients with Gaucher Disease Using Real-World Data.

The association between GD and cancer has been uncertain due to ascertainment bias in previously published studies. We analyzed cancer incidence using the Maccabi Healthcare Service (MHS) electronic health records among 264 patients with GD compared to 3440 matched controls. We ascertained cancers diagnosed before and after the index date (i.e., the first documentation of GD in cases and the corresponding date for controls). Before the index date, cancers were diagnosed in 18 individuals, with 11 (4.2%) in the GD group and 7 (0.2%) in the control group. After the index date, cancers were diagnosed in 57 individuals, with 20 (7.9%) in the GD group and 37 (1.1%) in the control group, with a median follow-up of almost 13 years in both groups. The most common cancers diagnosed in GD were non-melanoma skin cancer (NMSC) and hematological malignancies, with a clustering of diagnoses around the time of GD diagnosis. The incidence of cancers (excluding MNSC) was 4.1 (95% CI 2.2-7.1) and 0.7 (95% CI 0.4-0.9) per 1000 patient-years in the GD and control groups, respectively, with an incidence rate ratio of 6.37 (95% CI 3-12.7). Patients with GD underwent more cancer screening tests than their counterparts in the control group. While our study revealed an increased occurrence of cancers in patients with GD, this finding might be partly attributed to the more rigorous surveillance procedures employed in this patient population.

Active Lifestyle and Mobility of Adults with Vision Impairment: A Multiphase Mixed-Methods Study.

Individuals with vision impairment (VI) are less physically active than their sighted peers, heightening their risk of chronic illness. This study aimed to explore real and perceived barriers and promoters of an active lifestyle among adults with VI. We used mixed-methods, including a quantitative analysis of spatial data and a qualitative analysis of input from focus groups. The data were analyzed using descriptive statistics, graphical and thematic analysis. The spatial analysis highlighted frequent impediments, including high proportions of inaccessible crosswalks and stairs, a high density of obstacles (12/km) and almost inexistent guidance markings (0.1/km). Factors influencing active lifestyle of individuals with VI reported in the focus groups included: VI severity and self-confidence; accessibility of the physical environment as well as support and consideration of the society; use of behavioral strategies, striving for good health and willpower. Combined psychosocial, behavioral and infrastructural modifications could enhance active lifestyles among adults with VI. Consideration of the needs of individuals with VI is critical among environmental planners. Sustainable solutions for improving accessibility and mobility in the city for individuals with VI will influence not only their social integration but will enable them to adopt an active lifestyle and reduce their risk of chronic illness.

Attitude, Perceived Barriers, and Challenges Toward Implementing Resource-Appropriate Guidelines for Hematologic Malignancies: Physicians' Survey in Ethiopia.

PURPOSE: Cancer care in low-income countries poses formidable challenges. Care may be facilitated by resource-adapted guidelines, such as the National Comprehensive Cancer Network (NCCN) harmonized guidelines for sub-Saharan Africa (NCCN-HG). Understanding physicians' attitudes and knowledge toward guidelines, as well as patient- and resource-related barriers, is essential for promoting their effective implementation. METHODS: We conducted an online survey among oncologists, hematologists, internists, residents/fellows, and generalists treating hematologic malignancies in Ethiopia. We assessed attitudes toward the use of guidelines, institutional capacity, and barriers/determinants to effective care. RESULTS: Among the 47 physicians completing the survey (representing 64% of Ethiopian professionals treating hematologic malignancies), the majority (85%) reported using guidelines; however, only 22.7% (n = 10) used the NCCN-HG. While overall attitudes toward guidelines were favorable, 57.8% of physicians familiar with the NCCN-HG were either undecided or believed that it lowers the standard of care. Perceived lack of institutional regulation was negatively associated with guideline use (B = -3.23; P = .004). Lack of diagnostic facilities including immunohistochemistry and flow cytometry, supportive care, and poor utilization of guidelines were reported to be determinants of poor patient outcome. Regarding patient factors, 57.4% respondents identified treatment abandonment as an important contributor to poor outcome. Availability of chemotherapy/radiotherapy (89.4%), financial status (85.1%), distance from the hospital (74.5%), and harvest season (65%) had major influences on treatment decisions. Over 80% reported that targeted therapies were unavailable or rarely available. CONCLUSION: Awareness and usage of the NCCN-HG are limited among Ethiopian physicians. Lack of facilities, therapies, and regulation, in addition to patient-related factors, was identified as barriers to guideline adherence and determinants of poor outcome.

Perception of Goals and Expected Outcomes in Older Hip Fracture Patients and Their Medical Staff: A Cross Sectional Study.

Background: Goal-oriented patientcare is a key element in qualityhealthcare. Medical-caregiver's (MC) are expected to generate a shared decision-making process with patients regarding goals and expected health-outcomes. Hip-fracture patients (HFP) are usually older-adults with multiple health-conditions, necessitating that agreed-upon goals regarding the rehabilitation process, take these conditions into consideration. This topic has yet to be investigated by pairing and comparing the perception of expected outcomes and therapeutic goals of multidisciplinary MCs and their HF patient's. Our aim was to assess in a quantitative method whether HFPs and their multidisciplinary MCs agree upon target health-outcomes and their most important goals as they are reflected in the SF12 questionnaire. Methods: This was a cross-sectional, multi-center, study of HFPs and their MCs. Patients and MCs were asked to rate their top three most important goals for rehabilitation from the SF12 eight subscales: physical functioning, physical role limitation, bodily pain, general health, vitality, social functioning, emotional role limitation and mental health, and indicate their expected outcome. Descriptive statistics and mixed effect logistic-regression were used to compare concordance of the ratings. Agreement between patients and MCs was assessed using interclass coefficients (ICCs). Results: A total of 378 ratings were collected from 52 patients, 12 nurses, 12 physicians and 6 paramedical personnel. Each patient had between 3 and 9 raters. Patients considered physical functioning and physical role limitation more important than did MCs. Physicians and nurses emphasized the importance of bodily pain while patients referred to it as relatively less significant. The total ICC was low (2%) indicating poor agreement between MCs and patients. With the exception of physical-functioning, MCs predicted a less optimistic outcome in all of the SF12's subscales in comparison to HFPs. Conclusion: Effective intervention in HFPs requires constructive communication between MCs and patients. The study suggests that caregivers have an insufficient understanding of the expectations of HFPs. More effective communication channels are required in order to better understand HFPs' needs and expectations.

Pediatric overweight and obesity increased in Israel during the COVID-19 period.

Reports from many settings suggest that pediatric overweight and obesity increased in 2020 and 2021, presumably due to lifestyle changes associated with the COVID-19 pandemic. Many of these previous reports have relied on convenience samples or subsets of the population. Here, we present results of a longitudinal study of the entire population of Israel, a nation of approximately 9 million people, with the proportion with underweight, normal weight, overweight, and obesity at age 7 and at age 14-15, across the years 2017-2021. Our results show that the prevalence of overweight and obesity, which had been steady or improving through 2019, increased relatively quickly in 2020 and 2021. For example, among 7-year-olds, the percentage of children with obesity in 2019 was 6.8% (99% CI: 6.69-7.05), and by 2021, it had increased to 7.7% (99% CI: 7.53-7.93). There were important disparities in overweight and obesity based on SES; for example, the rate ratio for obesity comparing the poorest with the wealthiest 14-15-year-olds in 2019 was 1.63 (99% CI: 1.55-1.72). However, these disparities did not change meaningfully in 2020 and 2021, implying that while obesity did become more prevalent, this increase in prevalence was not differential across socioeconomic status. Like many other nations, Israel too experienced considerable increases in pediatric overweight and obesity in 2020-2021, erasing the improvements of the previous years among younger children.

Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis.

BACKGROUND: Therapeutic options for intermediate- or high-risk pulmonary embolism (PE) include anticoagulation, systemic thrombolysis and catheter-directed thrombolysis (CDT); however, the role of CDT remains controversial. We sought to compare the efficacy and safety of CDT with other therapeutic options using network meta-analysis. METHODS: We searched PubMed (MEDLINE), Embase, ClinicalTrials.gov and Cochrane Library from inception to Oct. 18, 2022. We included randomized controlled trials and observational studies that compared therapeutic options for PE, including anticoagulation, systemic thrombolysis and CDT among patients with intermediate- or high-risk PE. The efficacy outcome was in-hospital death. Safety outcomes included major bleeding, intracerebral hemorrhage and minor bleeding. RESULTS: We included data from 44 studies, representing 20 006 patients. Compared with systemic thrombolysis, CDT was associated with a decreased risk of death (odd ratio [OR] 0.43, 95% confidence interval [CI] 0.32-0.57), intracerebral hemorrhage (OR 0.44, 95% CI 0.29-0.64), major bleeding (OR 0.61, 95% CI 0.53-0.70) and blood transfusion (OR 0.46, 95% CI 0.28-0.77). However, no difference in minor bleeding was observed between the 2 therapeutic options (OR 1.11, 95% CI 0.66-1.87). Compared with anticoagulation, CDT was also associated with decreased risk of death (OR 0.36, 95% CI 0.25-0.52), with no increased risk of intracerebral hemorrhage (OR 1.33, 95% CI 0.63-2.79) or major bleeding (OR 1.24, 95% CI 0.88-1.75). INTERPRETATION: With moderate certainty of evidence, the risk of death and major bleeding complications was lower with CDT than with systemic thrombolysis. Compared with anticoagulation, CDT was associated with a probable lower risk of death and a similar risk of intracerebral hemorrhage, with moderate certainty of evidence. Although these findings are largely based on observational data, CDT may be considered as a first-line therapy in patients with intermediate- or high-risk PE. PROTOCOL REGISTRATION: PROSPERO - CRD42020182163.

The rate of occupational noise-induced hearing loss among male workers in Israel and implication on hearing surveillance frequency.

OBJECTIVES: To investigate the annual rate of NIHL in Israel, a modern economy with relatively low industrial hazardous noise exposure. To review international protocols of hearing surveillance. To recommend an effective, efficient, hearing screening frequency protocol. METHODS: A historical cohort study was conducted. Audiometric surveillance data from the Jerusalem occupational medicine registry of male employees in various industries from 2006 to 2017 were used. Mean individual annual threshold shifts simulating 1-8 checkup interval years were calculated. Joinpoint regression analysis was used to assess the interval in which the slope of the calculated ATS variability moderates significantly. RESULTS: A total of 263 noise-exposed workers and 93 workers in the comparison group produced 1913 audiograms for analysis. Among the noise-exposed workers, using the 1-4 kHz average, threshold shifts stabilized from 3 years onwards at around 1 dB per year in all age groups and 0.83 dB in the stratum younger than 50 years. No enhanced decline was detected in the first years of exposure. CONCLUSION: Although most countries conduct annual hearing surveillance, hearing threshold shifts of noise-exposed workers become more accurate and show less variability when calculated at 3-year checkup intervals onwards than shorter intervals. Since margins of errors of the test method are much larger than the annual shift found, screening schedule that enables each subsequent test to identify a real deterioration in hearing is necessary. Triennial audiometric screening would be a better surveillance frequency for noise-exposed workers younger than 50 years of age in the category of 85-95 dBLAeq,8 h without other known risk factors.

Evaluation of Maternal Infection During Pregnancy and Childhood Leukemia Among Offspring in Denmark.

Importance: Maternal infection is common during pregnancy and is an important potential cause of fetal genetic and immunological abnormalities. Maternal infection has been reported to be associated with childhood leukemia in previous case-control or small cohort studies. Objective: To evaluate the association of maternal infection during pregnancy with childhood leukemia among offspring in a large study. Design, Setting, and Participants: This population-based cohort study used data from 7 Danish national registries (including the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Cancer Registry, and others) for all live births in Denmark between 1978 and 2015. Swedish registry data for all live births between 1988 and 2014 were used to validate the findings for the Danish cohort. Data were analyzed from December 2019 to December 2021. Exposures: Maternal infection during pregnancy categorized by anatomic locations identified from the Danish National Patient Registry. Main Outcomes and Measures: The primary outcome was any leukemia; secondary outcomes were acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Offspring childhood leukemia was identified in the Danish National Cancer Registry. Associations were first assessed in the whole cohort using Cox proportional hazards regression models, adjusted for potential confounders. A sibling analysis was performed to account for unmeasured familial confounding. Results: This study included 2 222 797 children, 51.3% of whom were boys. During the approximately 27 million person-years of follow-up (mean [SD], 12.0 [4.6] years per person), 1307 children were diagnosed with leukemia (ALL, 1050; AML, 165; or other, 92). Children born to mothers with infection during pregnancy had a 35% increased risk of leukemia (adjusted hazard ratio [HR], 1.35 [95% CI, 1.04-1.77]) compared with offspring of mothers without infection. Maternal genital and urinary tract infections were associated with a 142% and 65% increased risk of childhood leukemia, with HRs of 2.42 (95% CI, 1.50-3.92) and 1.65 (95% CI, 1.15-2.36), respectively. No association was observed for respiratory tract, digestive, or other infections. The sibling analysis showed comparable estimates to the whole-cohort analysis. The association patterns for ALL and AML were similar to that for any leukemia. No association was observed for maternal infection and brain tumors, lymphoma, or other childhood cancers. Conclusions and Relevance: In this cohort study of approximately 2.2 million children, maternal genitourinary tract infection during pregnancy was associated with childhood leukemia among offspring. If confirmed in future studies, our findings may have implications for understanding the etiology and developing preventive measures for childhood leukemia.

Timing, extent and outcomes of public health measures in the first wave of the COVID-19 pandemic in Israel and a comparative analysis by socioeconomic indices.

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, governments implemented exceptional public health measures (PHMs) in the face of uncertainty. This study aimed to compare mitigation policies implemented by Israel and their timing in the first wave of the pandemic to those of other countries, and to assess whether country characteristics such as democracy, trust, education, economic strength and healthcare reserve were associated with decision-making. METHODS: PHMs and pre-pandemic characteristics, using internationally accepted indices, of 50 countries were collected from 1/1/2020-30/06/2020; and associations between them were assessed. Time to implementation of these measures was compared among the Organisation for Economic Co-operation (OECD) nations. Log-rank test was used for univariate analysis. Cox regression was performed to assess the independent contribution of pre-pandemic characteristics to time-to-implementation of measures. Correlations between timing of specific measures and COVID-19 mortality at 60 days were assessed. RESULTS: Israel ranked in the upper third of the OECD in swiftness to implementation of eight of the ten measures compared. In univariate survival analysis, countries with an education level below the OECD median were more likely to implement a lockdown (p-value = 0.043) and to close restaurants and entertainment venues (p-value = 0.007) when compared to countries above the OECD median. In Cox regression models, controlling for geographic location, democracy level above the OECD median was associated with a longer time-to-implementation of a lockdown (HR=0.35, 95% CI=0.14-0.88, p-value=0.025). Similarly, a high level of GDP per capita was inversely associated with closing schools; and a high level of education inversely associated with closure of restaurants and entertainment venues. Earlier initiation of all PHMs was associated with lower mortality at 60 days, controlling for geographic location. CONCLUSIONS: Israel's initial response to the pandemic was relatively quick, and may have been facilitated by its geographic isolation. Countries with lower pre-pandemic socio-economic indices were quicker to initiate forced social distancing. Early initiation of PHMs was associated with reduced mortality in the short run. Timing of initiation of measures relative to the country-specific spread of disease is a significant factor contributing to short-term early local pandemic control, perhaps more than the exact measures implemented. It is important to note that this study is limited to the initial pandemic response. Furthermore, it does not take into account the broader long-term effects of certain PHMs, which should be a focus of further research.