Glucose-6-phosphate dehydrogenase deficiency and long-term risk of immune-related disorders

IntroductionGlucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study aimed to assess the long-term health risks associated with G6PD deficiency.MethodsA retrospective cohort study was conducted using data from a national healthcare provider in Israel (Leumit Health Services). A total of 7,473 G6PD-deficient individuals were matched with 29,892 control subjects in a 1:4 ratio, based on age, gender, socioeconomic status, and ethnic groups. The exposure of interest was recorded G6PD diagnosis or positive G6PD diagnostic test. The main outcomes and measures included rates of infectious diseases, allergic conditions, and autoimmune disorders between 2002 and 2022.ResultsSignificantly increased rates were observed for autoimmune disorders, infectious diseases, and allergic conditions in G6PD-deficient individuals compared to the control group. Specifically, notable increases were observed for rheumatoid arthritis (odds ratio [OR] 2.41, p<0.001), systemic lupus erythematosus (OR 4.56, p<0.001), scleroderma (OR 6.87, p<0.001), pernicious anemia (OR 18.70, p<0.001), fibromyalgia (OR 1.98, p<0.001), Graves’ disease (OR 1.46, p=0.001), and Hashimoto’s thyroiditis (OR 1.26, p=0.001). These findings were supported by elevated rates of positive autoimmune serology and higher utilization of medications commonly used to treat autoimmune conditions in the G6PD-deficient group.DiscussionIn conclusion, individuals with G6PD deficiency are at a higher risk of developing autoimmune disorders, infectious diseases, and allergic conditions. This large-scale observational study provides valuable insights into the comprehensive association between G6PD deficiency and infectious and immune-related diseases. The findings emphasize the importance of considering G6PD deficiency as a potential risk factor in clinical practice and further research is warranted to better understand the underlying mechanisms of these associations

The World Federation of ADHD International Consensus Statement:208 Evidence-based conclusions about the disorder

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.</p

The Association of Previous Vaccination with Live-Attenuated Varicella Zoster Vaccine and COVID-19 Positivity: An Israeli Population-Based Study

The Bacillus Calmette&ndash;Gu&eacute;rin (BCG) vaccine affords indirect protection against COVID-19, which is presumably due to priming of the innate immune system. It was hypothesized that the live attenuated Varicella Zoster (LAVZ) vaccine, recommended for the elderly population, would also protect against COVID-19 infection. A retrospective population-based cross-sectional study was conducted using the Leumit Health Services (LHS) database. LAVZ-vaccinated patients were matched with controls based on a propensity score model using 1:9 nearest-neighbor matching. Matching was based on age, gender, and the presence of some chronic disorders, which were selected according to their association with COVID-19 infection. Multivariate logistic regression analyses, adjusted for sex, age, smoking status, comorbidities, and chronic medications associated with COVID-19 risk, were used to estimate the association between LAVZ vaccination and COVID-19 RT-PCR results. Subjects (625) vaccinated with LAVZ and RT-PCR-tested for COVID-19 were identified. After 1:9 matching of subjects who received the LAVZ vaccine, 6250 subjects were included in the study. Multivariate logistic regression analysis demonstrated a significant and independent negative association between having received the LAVZ vaccine and the likelihood of COVID-19 infection (adjusted OR = 0.47 (95% CI 0.33&ndash;0.69, p &lt; 0.001)). This association was further strengthened after separate analysis based on the time of LAVZ vaccination before COVID-19 RT-PCR testing. Individuals aged &ge;50 years vaccinated with LAVZ had a decreased likelihood of being tested positive for COVID-19

The association of previous influenza vaccination and coronavirus disease-2019

Studies have shown similarities in the structure of influenza and coronaviruses, in their binding receptors and in patterns of immune responses; and that influenza vaccine can induce cross-immunity. We examined the association of previous influenza vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, resulting in coronavirus disease-2019 (COVID-19), among 715,164 members of a health maintenance organization. In a multivariate regression model, the odds ratios for SARS-CoV-2 infection among individuals vaccinated for influenza in 2018–2019, 2019–2020, and in both seasons, compared to non-vaccinated individuals, were 0.82 (95% CI 0.68–0.99, p = .048), 0.79 (95% CI 0.67–0.98, p = .005), and 0.76 (95% CI 0.61–0.97, p = .004), respectively. Based on our findings, administration of influenza vaccine before the influenza season is highly recommended to reduce the burden of influenza, which is critical in scenarios of outbreaks of both influenza and SARS-CoV-2 infections, and also regarding its association with reduced rate of COVID-19

The Effect of Antibiotic Treatment of Early Childhood Shigellosis on Long-Term Prevalence of Attention Deficit/Hyperactivity Disorder

It has recently been shown that children with early shigellosis are at increased risk of attention deficit/hyperactivity disorder (ADHD). This study aimed to evaluate the association between antibiotic treatment of shigellosis with long-term ADHD rates. A retrospective cohort study was conducted that included all the Leumit Health Services (LHS) enrollees aged 5–18 years between 2000–2018 with a documented Shigella-positive gastroenteritis before the age of 3 years. Of the 5176 children who were positive for Shigella gastroenteritis before the age of 3 years, 972 (18.8%) were treated with antibiotics early (&lt;5 days), 250 (4.8%) were treated late (≥5 days), and 3954 children (76.4%) were not prescribed antibiotics. Late antibiotic treatment was associated with significantly increased rates of ADHD (adjusted OR = 1.61; 95% CI, 1.1–2.3). Early treatment with antibiotics was not associated with increased ADHD rates (adjusted OR = 1.02; 95% CI, 0.8–1.3). In conclusion, late antibiotic treatment of early childhood shigellosis was associated with increased rates of ADHD

Clinical characteristics and healthcare utilisation associated with undiagnosed cognitive impairment in elderly patients with diabetes in a primary care setting: a population-based cohort study

Objectives The objective of this study is to report the prevalence, clinical characteristics and healthcare utilisation of patients with type 2 diabetes (T2DM) and previously undiagnosed cognitive impairment who were identified as having a low Montreal Cognitive Assessment (MoCA) score.Design A population-based cohort study comparing clinical characteristics, medications, outpatient and inpatient care of patients with a MoCA score &lt;19 to MoCA &gt;26 using descriptive statistics, linear regression and multivariate logistic regression.Setting Electronic medical records of a large health maintenance organisation in Israel.Participants 350 patients, age &gt;65 with T2DM who participated in a cognitive function screening initiative using MoCA, and had a follow-up visit during the 12 months after screening.Results 130 (37.1%) had a MoCA score &gt;26 and 68 (19.4%) &lt;19. Patients with MoCA&lt;19 had more diabetes-related complications, poorer glycaemic and lipid control, fewer visits to their main primary care physician (PCP; 3.9±3.2 vs 7.3±4.2 visits/year p=0.008), shorter duration of PCP visits (8.3±4.5 vs 4.0±3.5 min, p=0.007), fewer nutritionist and endocrinologist visits, and lower participation in diabetes or smoking cessation workshops. They were less likely to be treated with glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 inhibitor (DPP-4), or sodium-glucose transport protein 2 (SGLT-2) inhibitors and more likely to receive insulin or sulfonylurea. Moreover, they had more emergency room visits (ER; 15 (11.5%) vs 16 (23.5%), p=0.019), hospitalisations (8 (6.2%) vs 22 (32.4%), p=0.001), and longer hospital stays (4.3±3.2 vs 14.5±9.8, p=0.001). Using statistical models, MoCA&lt;19 was identified as a risk factor for fewer and shorter PCP visits and more ER visits and hospitalisations.Conclusions This study highlights the high prevalence of undiagnosed severe cognitive impairment in elderly patients with T2DM and its association with poor outpatient care. Appropriate interventions are needed to improve outcomes and prevent hospitalisation in this high-risk population

Patient-level predictors of temporal regularity of primary care visits

Abstract Background Patients with chronic diseases should meet with their primary care doctor regularly to facilitate proactive care. Little is known about what factors are associated with more regular follow-up. Methods We studied 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease), cared for by Leumit Health Services, an Israeli health maintenance organization. Patients were divided into the quintile with the least temporally regular care (i.e., the most irregular intervals between visits) vs. the other four quintiles. We examined patient-level predictors of being in the least-temporally-regular quintile. We calculated the risk-adjusted regularity of care at 239 LHS clinics with at least 30 patients. For each clinic, compared the number of patients with the least temporally regular care with the number predicted to be in this group based on patient characteristics. Results Compared to older patients, younger patients (age 40–49), were more likely to be in the least-temporally-regular group. For example, age 70–79 had an adjusted odds ratio (AOR) of 0.82 compared to age 40–49 (p < 0.001 for all findings discussed here). Males were more likely to be in the least-regular group (AOR 1.18). Patients with previous myocardial infarction (AOR 1.07), atrial fibrillation (AOR 1.08), and current smokers (AOR 1.12) were more likely to have an irregular pattern of care. In contrast, patients with diabetes (AOR 0.79) or osteoporosis (AOR 0.86) were less likely to have an irregular pattern of care. Clinic-level number of patients with irregular care, compared with the predicted number, ranged from 0.36 (fewer patients with temporally irregular care) to 1.71 (more patients). Conclusions Some patient characteristics are associated with more or less temporally regular patterns of primary care visits. Clinics vary widely on the number of patients with a temporally irregular pattern of care, after adjusting for patient characteristics. Health systems can use the patient-level model to identify patients at high risk for temporally irregular patterns of primary care. The next step is to examine which strategies are employed by clinics that achieve the most temporally regular care, since these strategies may be possible to emulate elsewhere

Large-Scale Study of Antibody Titer Decay following BNT162b2 mRNA Vaccine or SARS-CoV-2 Infection

Immune protection following either vaccination or infection with SARS-CoV-2 is thought to decrease over time. We designed a retrospective study, conducted at Leumit Health Services in Israel, to determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals. Antibody titers were measured between 31 January 2021, and 31 July 2021 in two mutually exclusive groups: (i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and (ii) SARS-CoV-2 convalescents who had not received the vaccine. A total of 2653 individuals fully vaccinated by two doses of vaccine during the study period and 4361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8&ndash;5644.6]) after the second vaccination than in convalescent individuals (median 355.3 AU/mL IQR [141.2&ndash;998.7]; p &lt; 0.001). In vaccinated subjects, antibody titers decreased by up to 38% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of &lt;50 AU/mL, while only 10.8% of convalescent patients were below &lt;50 AU/mL threshold after 9 months from SARS-CoV-2 infection. This study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group