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Despite increasing awareness for diagnosing autism spectrum disorder (ASD) and initiating treatments early in life, many children and adolescents continue to be diagnosed at a relatively older age. Focusing on children who first received an ASD diagnosis at age six or older, this study aimed to describe the symptoms that parents reported when ASD was diagnosed, follow the patients' clinical trajectory prior to receiving the diagnosis, and describe differences in symptoms and prior diagnoses between males and females cases. We included 258 children (205 males and 53 females) who were first diagnosed with autism at age 6–18 in 2017–2018. We retrieved demographic information, neurologic and developmental symptoms, diagnoses, and medications dispensing history from the children's electronic medical charts. The data indicated that prior diagnoses of language delays and attention deficit hyperactivity disorder were common among children with a late ASD diagnosis. Two thirds of the children were prescribed one or more medications to treat psychosocial and behavioral conditions before receiving a late ASD diagnosis. Difficulties in social relationships with peers were the leading reported symptoms by parents at the time of ASD diagnosis. Across these different domains, some differences were found between males and females, including a somewhat higher cognitive level in males, who were also more likely to present aggressive behavior. Lay Summary: Despite the high vigilance for diagnosing autism, a subgroup of children and adolescents continue to be diagnosed late. These children are often diagnosed with several neurodevelopmental conditions prior to receiving a final autism spectrum disorder (ASD) diagnosis and are often also treated with various medications for psychosocial difficulties, with some differences across sexes. It is important that clinicians continue to monitor children diagnosed with developmental disabilities age to identify the characteristics of autism as early as possible and to enable proper treatment. [ABSTRACT FROM AUTHOR]

Background The short-term effectiveness of a 2-dose regimen of the BioNTech/Pfizer BNT162b2 vaccine for adolescents has been demonstrated. However, little is known about the long-term effectiveness in this age group. It is known, however, that waning of vaccine-induced immunity against infection in adult populations is evident within a few months. Methods Leveraging the database of Maccabi Healthcare Services (MHS), we conducted a matched case-control design for evaluating the association between time since vaccination and the incidence of infections, where 2 outcomes were evaluated: documented SARS-CoV-2 infection (regardless of symptoms) and symptomatic infection (COVID-19). Cases were defined as individuals aged 12–16 with a positive polymerase chain reaction (PCR) test occurring between 15 June and 8 December 2021, when the Delta variant was dominant in Israel. Controls were adolescents who had not tested positive previously. Results We estimated a peak vaccine effectiveness between 2 weeks and 3 months following receipt of the second dose, with 85% (95% confidence interval [CI]: 84–86%) and 90% (95% CI: 89–91%) effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19), respectively. However, in line with findings for adults, waning effectiveness was evident. Long-term protection was reduced to 73% (95% CI: 68–77%) against infection and 79% (95% CI: 73–83%) against COVID-19 3–5 months after the second dose and waned to 53% (95% CI: 46–60%) against infection and 66% (95% CI: 59–72%) against COVID-19 after 5 months. Conclusions Although vaccine-induced protection against both infection and COVID-19 continues over time in adolescents, the protection wanes with time since vaccination, starting 3 months after inoculation and continuing for more than 5 months. [ABSTRACT FROM AUTHOR]

Background Although BNT162b2 vaccine-efficacy analyses have been published, the effectiveness of the vaccine in preventing coronavirus disease 2019 given confirmed exposure has not been previously demonstrated, even though it has policy implications, such as the need for self-quarantine when exposure has occurred. Methods In a retrospective cohort study, we used data collected between 20 December 2020 and 17 March 2021 from the second largest healthcare provider in Israel to analyze the probability of an additional household infection occurring within 10 days after an index infection. In model 1, vaccine effectiveness was described for Fully Vaccinated individuals (7 or more days from second dose) vs either Unvaccinated individuals or those Recently Vaccinated Once (0–7 days from the first dose, presumably still unprotected). Secondary analyses included correction for differing testing rates. In model 2, we conducted a separate analysis of households comprised of only adults with the same vaccination status. Results A total of 173 569 households were included, of which 6351 had an index infection (mean [standard deviation] age, 58.9 [13.5] years); 50% were women. Adjusted vaccine effectiveness of Fully Vaccinated compared with Unvaccinated participants was 80.3% (95% confidence interval [CI], 73.5–85.4) and 82.0% (95% CI, 75.6–86.8) compared with those Recently Vaccinated Once. Conclusions The BNT162b2 vaccine is effective in high-risk real-life exposure scenarios, but the protection afforded in these settings is lower than that previously described. Individuals with a confirmed significant exposure to severe acute respiratory syndrome are still at risk of being infected even if fully vaccinated. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality. Methods This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1–7 after the first dose, where no protection by the vaccine is assumed (reference-period). Results Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD = 18.1], 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval [CI]: 26.1–115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5–8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%–95%) and 94% (95% CI: 88%–97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%–87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI:.36–1.88), 0.45 (95% CI:.23–.90), and 0.56 (95% CI:.36–.89) in the age groups 16–44, 45–64. and ≥75 years, respectively. Conclusions The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial. [ABSTRACT FROM AUTHOR]

Introduction: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide [Gut Liver. 2017;11(1):27–37]. The use of PPI has become a common practice and is overprescribed for all patients with cancer including patients with hematological malignancies. In the current study, we aimed to explore retrospectively the effect of PPI, on time to first treatment (TTFT) in a large cohort of patients with chronic lymphocytic leukemia (CLL) who were under watch-and-wait approach. Methods: The cohort is based on anonymized data obtained from electronic medical records of Maccabi Healthcare Services (MHS) members, who is the second-largest healthcare organization in Israel, with 2.5 million insured patients, and received a diagnosis of CLL during this period. Results: Our cohort included 3,474 patients with CLL who are treatment-naïve, and the median follow-up was 1,745 days (602–3,700). A total of 1,061 patients (30.5%) received a PPI agent, for a minimum of 3 months during the watch-and-wait period. The intake of PPI was found to be associated with a shorter TTFT: among PPI users, the 10-year treatment-free ratio is 79.2%, while among non-PPI users it is 90.6%. Conclusion: Routine use of PPI in CLL patients may negatively impact their clinical course. Biology of this primary observation requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Ferritin, an iron storage protein and acute phase reactant, has been implicated in various aspects of human health and disease, including cancer. Previous studies have identified elevated serum ferritin (SF) levels in several cancer types, but a comprehensive examination across different malignancies remains lacking. This study aims to fill this gap by utilizing anonymized data from Maccabi Health Services (MHS), one of Israel's largest health organizations, to explore the association between elevated SF levels and the diagnosis of different malignancies., Methods: An extensive dataset from MHS, comprising 2.7 million members, including 1.3 million individuals who underwent SF level testing, was analyzed. Odds Ratios (OR) and 95% confidence intervals (CI) were calculated to assess the association between high SF levels and cancer diagnosis. Subgroup analysis was conducted to investigate variations across different malignancies., Results: The analysis revealed a significant association between elevated SF levels and cancer diagnosis among MHS members, with an OR of 1.9 (95% CI 1.71-2.15). Sub- group analysis unveiled differences in the association across malignancy types, with hematological, hepatobiliary and respiratory malignancies more strongly associated with high SF levels., Conclusions: This study provides further support for the link between elevated SF levels and malignancy, leveraging a vast dataset from MHS, underscoring potential utilities of elevated SF levels as a potential indicator for cancer with a variable role among different malignancy types., Impact: The identification of elevated SF levels as a potential indicator for underlying malignancy for seemingly-healthy individuals.

Background: Treatment approach for metastatic non-small cell lung cancer (mNSCLC) has revolutionized in the recent decade with the introduction of immunotherapy and targeted medications in first-line (1L) therapy. We present real-world data on clinical outcomes and direct healthcare resource utilization (HCRU) and cost in a 2.7-million-member Israeli health provider., Patients and Methods: Newly diagnosed mNSCLC patients between January 2017 and December 2020 were categorized by 1L treatment: platinum-based chemotherapy, targeted therapy, or immunotherapy. HCRU and costs were calculated based on the Ministry of Health Prices and were assessed at a minimum of 6 months' follow-up (cutoff: 30 June 2021)., Results: A total of 886 patients were included in the study: 40.6% female, median age 68 years (IQR 61-74), 24.3% never smokers, 80.6% with adenocarcinoma, and 54% with a 0-1 performance status. The median follow-up was 27.12 months (95% CI, 24.7-29.6) and the median duration of first-line (1L) treatment was 2.3 months for platinum-based chemotherapy (n = 177), 12.3 months for targeted therapy (n = 255), and 4.8 months for immunotherapy (n = 463). The median overall survival was 9.09, 27.68, and 12.46 months, respectively. Total 1L costs were driven by radiotherapy for platinum-based chemotherapy and medication for targeted therapy or immunotherapy. Total costs for deceased patients over the entire follow-up were €121 155, €129 458, and €110 716, respectively., Conclusion: The treatment of mNSCLC carries a high economic burden, primarily driven by first-line therapy, especially with targeted and immune therapies. Further studies are needed to evaluate the impact of innovative treatments on the disease management costs of mNSCLC., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Ocular manifestations (OMs) in patients with inflammatory bowel disease (IBD) are uncommon, particularly in children. We aimed to explore the prevalence and characteristics of IBD-associated OM in a large cohort study., Methods: A cross-sectional study was performed using the Maccabi Healthcare Services (MHS) database. The eligible population included all patients diagnosed with IBD as children (<18 years) between January 2005 and July 2023., Results: Out of 2567 children with IBD (males 55%, Crohn's disease 64%), 78 (3%) were diagnosed with OM at any time during the disease course. In 54 patients (69%), the ocular disease occurred after IBD diagnosis with a median time of 2.6 (0.47-7) years between the 2 events, whereas in 24 patients (31%), ocular involvement preceded IBD diagnosis with a median time of 2.1 (0.6-5.7) years. The presence of ocular involvement was associated with increased usage of systemic corticosteroids (P < .001) and biologic agents (P = .04). There were 55 patients with ocular involvement during childhood who were ever diagnosed with IBD. In this population, ocular involvement was also associated with increased usage of systemic corticosteroids (P < .001). The prevalence of OM among patients with IBD did not change significantly over time (P = .75), with a prevalence of 2.3% at the end of the study period., Conclusions: The prevalence of ocular involvement in children with IBD is rare and steady; it is also associated with a greater usage of systemic corticosteroids and biologic agents, potentially representing a more severe disease course., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Despite increasing awareness for diagnosing autism spectrum disorder (ASD) and initiating treatments early in life, many children and adolescents continue to be diagnosed at a relatively older age. Focusing on children who first received an ASD diagnosis at age six or older, this study aimed to describe the symptoms that parents reported when ASD was diagnosed, follow the patients' clinical trajectory prior to receiving the diagnosis, and describe differences in symptoms and prior diagnoses between males and females cases. We included 258 children (205 males and 53 females) who were first diagnosed with autism at age 6-18 in 2017-2018. We retrieved demographic information, neurologic and developmental symptoms, diagnoses, and medications dispensing history from the children's electronic medical charts. The data indicated that prior diagnoses of language delays and attention deficit hyperactivity disorder were common among children with a late ASD diagnosis. Two thirds of the children were prescribed one or more medications to treat psychosocial and behavioral conditions before receiving a late ASD diagnosis. Difficulties in social relationships with peers were the leading reported symptoms by parents at the time of ASD diagnosis. Across these different domains, some differences were found between males and females, including a somewhat higher cognitive level in males, who were also more likely to present aggressive behavior., (© 2022 International Society for Autism Research and Wiley Periodicals LLC.)

Background: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality., Methods: This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1-7 after the first dose, where no protection by the vaccine is assumed (reference-period)., Results: Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD = 18.1], 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval [CI]: 26.1-115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5-8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%-95%) and 94% (95% CI: 88%-97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%-87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI: .36-1.88), 0.45 (95% CI: .23-.90), and 0.56 (95% CI: .36-.89) in the age groups 16-44, 45-64. and ≥75 years, respectively., Conclusions: The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)