Continuous admission to primary school and mental health problems

Background: Younger children in a school class have higher rates of mental health problems if admission to primary school occurs once a year. This study examines whether this relative age effect also occurs if children are admitted to school continuously throughout the year. Methods: We assessed mental health problems based on parent-reports (using the Child Behavior Checklist, CBCL) and on professional assessments, among two Dutch national samples of in total 12,221 children aged 5-15 years (response rate: 86.9%). Results: At ages 5-6, we found a higher occurrence of mental health problems in relatively young children, both for mean CBCL scores (p = 0.017) and for problems assessed by child health professionals (p < 0.0001). At ages 7-15, differences by relative age did not reach statistical significance. Conclusion: Continuous admission to primary school does not prevent mental health problems among young children, but may do so at older ages. Its potential for the prevention of mental problems deserves further study

Continuous admission to primary school and mental health problems

Background: Younger children in a school class have higher rates of mental health problems if admission to primary school occurs once a year. This study examines whether this relative age effect also occurs if children are admitted to school continuously throughout the year. Methods: We assessed mental health problems based on parent-reports (using the Child Behavior Checklist, CBCL) and on professional assessments, among two Dutch national samples of in total 12,221 children aged 5-15 years (response rate: 86.9%). Results: At ages 5-6, we found a higher occurrence of mental health problems in relatively young children, both for mean CBCL scores (p = 0.017) and for problems assessed by child health professionals (p <0.0001). At ages 7-15, differences by relative age did not reach statistical significance. Conclusion: Continuous admission to primary school does not prevent mental health problems among young children, but may do so at older ages. Its potential for the prevention of mental problems deserves further study

Variations in presentation, management, and patient outcomes of urinary tract infection: a prospective four-country primary care observational cohort study

Background Regional variations in the presentation of uncomplicated urinary tract infection (UTI) and pathogen sensitivity to antibiotics have been cited as reasons to justify differences in how the infections are managed, which includes the prescription of broad-spectrum antibiotics. Aim To describe presentation and management of UTI in primary care settings, and explore the association with patient recovery, taking microbiological findings and case mix into account. Design and setting Prospective observational study of females with symptoms of uncomplicated UTI presenting to primary care networks in England, Wales, the Netherlands, and Spain. Method Clinicians recorded history, symptom severity, management, and requested mid-stream urine culture. Participants recorded, in a diary, symptom severity each day for 14 days. Time to recovery was compared between patient characteristics and between countries using two-level Cox proportional hazards models, with patients nested within practices. In total, 797 females attending primary care networks in England (n = 246, 30.9% of cohort), Wales (n = 213, 26.7%), the Netherlands (n = 133, 16.7%), and Spain (n = 205, 25.7%) were included. In total, 259 (35.8%, 95% confidence interval 32.3 to 39.2) of 726 females for whom there was a result were urine culture positive for UTI. Pathogens and antibiotic sensitivities were similar. Empirical antibiotics were prescribed for 95.1% in England, 92.9% in Wales, 95.1% in Spain, and 59.4% in the Netherlands There were no meaningful differences at a country network level before and after controlling for severity, prior UTIs, and antibiotic prescribing. Conclusion Variation in presentation and management of uncomplicated UTI at a country primary care network level is clinically unwarranted and highlights a lack of consensus concerning optimal symptom control and antibiotic prescribing. Result

Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC4 E): the ALIC4 E protocol

INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48-72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products

The antitumor activity of adoptive T cell therapies (ACT) is highly dependent on the expansion, persistence, and continued activity of adoptively transferred cells. Clinical studies using ACTs have revealed that products that possess and maintain less differentiated phenotypes, including memory and precursor T cells, show increased antitumor efficacy and superior patient outcomes owing to their increased expansion, persistence, and ability to differentiate into effector progeny that elicit antitumor responses. Strategies that drive the differentiation into memory or precursor-type T cell subsets with high potential for persistence and self-renewal will enhance adoptively transferred T cell maintenance and promote durable antitumor efficacy. Because of the high costs associated with ACT manufacturing, ACTs are often only offered to patients after multiple rounds of systemic therapy. An essential factor to consider in producing autologous ACT medicinal products is the impact of the patient’s initial T cell fitness and subtype composition, which will likely differ with age, disease history, and treatment with prior anti-cancer therapies. This study evaluated the impact of systemic anti-cancer therapy for non-small cell lung cancer treatment on the T cell phenotype of the patient at baseline and the quality and characteristics of the genetically modified autologous T cell therapy product after manufacturing

Variations in presentation, management, and patient outcomes of urinary tract infection: A prospective four-country primary care observational cohort study

Aim: To describe presentation and management of urinary tract infection in primary care settings, and explore the association with patient recovery, taking microbiological findings and case mix into account. Design and setting: Prospective observational study of women with symptoms of uncomplicated UTI presenting to primary care networks in England, Wales, the Netherlands, and Spain. Method: Clinicians recorded history, symptom severity, management, and requested mid-stream urine culture. Participants recorded symptom severity each day for 14 days in a diary. Time to recovery was compared between patient characteristics and between countries using two-level Cox proportional hazards models, with patients nested within practices. Results: 797 women attending primary care networks in England (246 (30·9%)), Wales (213 (26·7%)), the Netherlands (133 (16·7%)) and Spain (205 (25·7%)) were included. 259 (35·7%, 95% CI 32·3 to 39·2) were urine culture positive for UTI. Pathogens and antibiotic sensitivities were similar. Empirical antibiotics were prescribed for &gt; 90% of women in England, Wales and Spain, but lower in the Netherlands. There were no meaningful differences at a country network level before and after controlling for severity, prior UTIs, and antibiotic prescribing. Conclusion: Variation in presentation and management of uncomplicated UTI at a country primary care network level is clinically unwarranted and highlights lack of consensus concerning optimal symptom control and antibiotic .prescribing