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Chronic kidney disease (CKD) is a major public health challenge, affecting as much as 8 to 18% of the world population. Identifying childhood risk factors for future CKD may help clinicians make early diagnoses and initiation of preventive interventions for CKD and its attendant comorbidities as well as monitoring for complications. The purpose of this review is to describe childhood risk factors that may predict development of overt kidney disease later in life. Currently, there are multiple childhood risk factors associated with future onset and progression of CKD. These risk factors can be grouped into five categories: genetic factors (e.g., monogenic or risk alleles), perinatal factors (e.g., low birth weight and prematurity), childhood kidney diseases (e.g., congenital anomalies, glomerular diseases, and renal cystic ciliopathies), childhood onset of chronic conditions (e.g., cancer, diabetes, hypertension, dyslipidemia, and obesity), and different lifestyle factors (e.g., physical activity, diet, and factors related to socioeconomic status). The available published information suggests that the lifelong risk for CKD can be attributed to multiple factors that appear already during childhood. However, results are conflicting on the effects of childhood physical activity, diet, and dyslipidemia on future renal function. On the other hand, there is consistent evidence to support follow-up of high-risk groups.

This study showed that a history of clinically evident kidney disease in childhood was associated with an increased risk of end-stage renal disease in adulthood, even if renal function was apparently normal in adolescence.

Importance To assess the differential effects of pre-infection glucose levels on the risk for severe COVID-19 amongst patients with and without diabetes. National state-mandated HMO. All adult patients with a positive SARS-COV2 test between March-October 2020. 37,121 patients with a positive SARS-COV2 test were identified; 707 defined as severe (1.9%). Unadjusted risk factors for severe disease were age (OR = 1.1 for every year increase; 95% CI 1.09-1.11, p < 0.001), male gender (OR = 1.34, 95% CI 1.06-1.68, p = 0.012); BMI (OR = 1.02 for 1 kg/m.sup.2 increase, 95% CI 1.00-1.04, p = 0.025). Controlling for these factors, we found an association between pre-infection FBG and the risk of severe COVID-19, with a differential effect in patients with and without a diagnosis of diabetes. For patients without diabetes, elevated FBG in the pre-diabetes range (106-125 mg/dl) was associated with severe COVID-19 (OR 1.55 95% CI 1.04-2.26 p = 0.027). For patients with a diagnosis of diabetes, we found a J-shaped association between pre-infection glucose control and the risk for severe COVID-19 where the lowest risk for was for patients with FBG 106-125 mg/dl; the risk increased with higher pre-infection glucose levels but strikingly also for patients with a low pre-infection FBG (<100mg/dl) or HbA1C (<5.7%). Elevated pre-infection blood glucose is a risk factor for severe COVID-19 even in non-diabetics. For patients with a diagnosis of diabetes both high as well as low pre-infection glucose levels are risk factors for severe COVID-19. Further research is required to assess whether these associations are causal, but we believe these findings can already have clinical implications for COVID-19 risk assessment and stratification.

The Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses’ vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy during two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022). Time-dependent Cox proportional-hazards regression models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,659 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83–96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26–99%), and 48% (95% CI 37–57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes. Data on the effectiveness of a third dose of COVID-19 vaccine in pregnant women are limited. In this observational study, the authors report that a third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy enhances protection against maternal adverse COVID-19-related outcomes.

Hybrid immunity, acquired through vaccination followed or preceded by a COVID-19 infection, elicits robust antibody augmentation. We hypothesize that maternal hybrid immunity will provide greater infant protection than other forms of COVID-19 immunity in the first 6 months of life. We conducted a case-control study in Israel, enrolling 661 infants up to 6 months of age, hospitalized with COVID-19 (cases) and 59,460 age-matched non-hospitalized infants (controls) between August 24, 2021, and March 15, 2022. Infants were grouped by maternal immunity status at delivery: Naïve (never vaccinated or tested positive, reference group), Hybrid-immunity (vaccinated and tested positive), Natural-immunity (tested positive before or during the study period), Full-vaccination (two-shot regimen plus 1 booster), and Partial-vaccination (less than full three shot regimen). Applying Cox proportional hazards models to estimate the hazard ratios, which was then converted to percent vaccine effectiveness, and using the Naïve group as the reference, maternal hybrid-immunity provided the highest protection (84% [95% CI 75-90]), followed by full-vaccination (66% [95% CI 56-74]), natural-immunity (56% [95% CI 39-68]), and partial-vaccination (29% [95% CI 15-41]). Maternal hybrid-immunity was associated with a reduced risk of infant hospitalization for Covid-19, as compared to natural-immunity, regardless of exposure timing or sequence. These findings emphasize the benefits of vaccinating previously infected individuals during pregnancy to reduce COVID-19 hospitalizations in early infancy. Maternal anti-SARS-CoV-2 antibodies can provide protection against severe COVID-19 in infants, but the relative protection conferred by maternal infection, vaccination, and hybrid immunity is unknown. Here, the authors use data from Israel and show that infants born to mothers with hybrid immunity had lowest rates of COVID-19 hospitalisation.

The effect of physical activity on the primary prevention of chronic kidney disease (CKD) is unclear. We assessed walking and running as exercise behaviors and their associations with individual-level risk for kidney function decline. We conducted a historical cohort study in which we followed 20,976 young adults. Participants were interviewed periodically about their lifestyle, and clinical parameters were assessed. The decline in estimated glomerular filtration rate (eGFR) over time was divided into quartiles. Using logistic regressions, we estimated the odds ratio (OR) for being in the slowest declining quartile by consistency of running or walking. We also used Cox proportional hazards models to estimate the associations of physical activity with future eGFR < 90 ml/min/1.73m2. All models were adjusted for age, sex, smoking status, family history of kidney diseases, BMI, blood-pressure, baseline eGFR and serum cholesterol. During 9.5 years of follow-up, the eGFR decreased by 0.97 ml/min/1.73m2 per year. Participants who reported in two consecutive questionnaires on walking as a leisure time activity had an OR of 1.21 (95% confidence interval: 1.03-1.41) to have slow eGFR decline compared to those who were physically inactive. Participants who predominantly reported on running as their physical activity were less likely to be slow eGFR decliners (OR:0.81, 95% CI:0.71-0.93). Similarly, consistent walking was associated with decreased risk for future eGFR < 90 ml/min/1.73m2 in contrast to consistent running which was associated with an increased risk for reduced eGFR. All associations showed dose dependent effects in terms of the number of weekly activity sessions. Consistent walking, as opposed to consistent running, was associated with slower eGFR decline compared to inactive participants. These associations start already within the normal GFR range.

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. 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. 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). 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.

To study the association between mode of delivery and offspring BMI in late adolescence in a large cohort that predated the obesity epidemic, and assess the role of maternal pre-pregnancy BMI (ppBMI) in this association. We conducted a historical prospective study in the setting of the Jerusalem Perinatal Study (JPS), a population-based cohort that includes all 17,003 births to residents of West Jerusalem, between 1974 and 1976. Offspring's BMI at age 17 was obtained upon army recruitment and was available for 11,001 of cohort participants. The associations were examined using logistic regressions, adjusting for socio-demographic characteristics and for proxies for indication for C-Section birth. Analyses were then stratified by quartiles of ppBMI. C-Section was associated with offspring overweight/obesity, with adjusted OR of 1.44 (95%CI:1.14-1.82). Significant interaction of ppBMI with mode of delivery was observed, such that the associations of C-Section with overweight/obesity were limited to the upper quartile of ppBMI (adjusted OR = 1.70, 95%CI:1.18-2.43). Restricting the analyses to singleton first births and excluding pregnancies complicated with toxemia and gestational diabetes yielded similar findings. C-Section was positively associated with being overweight/obese at age 17. Importantly, ppBMI modified this association, with a significant association between C-Section and overweight/obesity evident only among offspring born to mothers in the highest ppBMI quartile. In light of the growing rates of obesity in women of reproductive age, these results should be considered in patient-doctor shared decisions related to selection of mode of delivery, in the absence of a clear medical indication.

Background The age at first delivery is rising leading to an increasing proportion of women with advanced maternal age (AMA) which is defined as greater than or equal to 35 years at time of delivery. Previous studies have associated AMA with adverse maternal and neonatal outcomes leading to an arbitrary increased rate of cesarean sections amongst AMA women without clear medical indications. Objective To determine the associations between AMA and adverse maternal and neonatal outcomes in nulliparous women in a large cohort. Methods Our retrospective cohort study looked at 44,295 nulliparous women (39,496 < 35years and 4,799 ≥ 35years) with term singleton gestation who delivered in the obstetrical units of Hadassah Medical Organization in Jerusalem, Israel, between 2003 and 2017. Data on maternal characteristics and outcomes, and neonatal outcomes were extracted from the electronic database. Outcomes were compared between women with AMA and women < 35 using Chi square, Fisher exact and t-tests. Multivariable logistic regressions estimated odds ratios (OR) for outcomes, controlling for confounders. We reported two-sided p-values, adjusted odds ratio (aOR), and 95% confidence intervals (CI). Results Women with AMA were more likely to have c-sections compared to women < 35 years in the whole study population ( aOR:2.29 , 95% CI: 2.13–2.47 , p  < 0.0001) including women having inductions ( aOR:1.38 , 95% CI:1.25–1.53 , p  < 0.0001). Self-requested c-sections were significantly higher among women with AMA ( 16.8% vs. 2.8% , OR:6.9 , 95% CI:5.5–8.8 ). AMA did not increase the risk of postpartum hemorrhage ( aOR: 0.82 , 95% CI: 0.72–0.94 ) and decreased likelihood of instrumental delivery ( aOR:0.81 , 95% CI: 0.73–0.89 , p  < 0.0001). Fewer women with AMA had 3rd- and 4th-degree tears (0.35% for ≥ 35years vs. 0.71% for < 35 years , RR:0.50 , 95% CI:0.29–0.87 , p  = 0.012). Women with AMA were more than three times likely to have an intrauterine fetal demise ( RR:3.53 , 95% CI:2.54–4.90 , p  < 0.0001), but were not more likely to have low neonatal 5-minute APGAR scores (RR:0.79, 95% CI: 0.43–1.46, p value:0.44) or NICU admissions ( RR:0.84 , 95% CI: 0.61–1.17 , p  = 0.30). Conclusions Management of nulliparous AMA patients should be based on obstetric considerations and not solely on AMA status. Shared decision making is preferred to reduce the risks associated with AMA.

The authors regret that the name of the author Michal Stern-Zimmer was incorrectly rendered as “Michal Stern Zimmer.”