EClinicalMedicine最新文献

Background: Older people account for a growing proportion of unplanned hospital admissions and many have complex conditions. However, there are few data on cognitive morbidity (delirium, dementia and low cognitive test score) by specialty to plan services and guide policy. We therefore determined the occurrence of cognitive morbidity hospital-wide in older hospital patients using electronic patient record (EPR) data.

Methods: The Oxford and Reading Cognitive Comorbidity, Frailty and Ageing Research Database (ORCHARD-EPR) includes data on consecutive patients aged ≥70 years with length of stay of ≥1 day (1st January 2017-31st December 2019) admitted to four hospitals covering Oxfordshire, UK. ORCHARD-EPR includes information from a mandatory on-admission cognitive screen comprising the 10-point Abbreviated Mental Test (AMT), dementia history and documentation of delirium where delirium diagnosis is based on a holistic assessment incorporating the AMT, Confusion Assessment Method (CAM) and clinical notes. Delirium and dementia diagnosis from the cognitive screen was supplemented by discharge ICD-10 coding. Prevalence of cognitive morbidity was determined hospital-wide and then by specialty.

Findings: Among 51,202 admissions (mean/SD age = 82/7 years), any cognitive morbidity was present in 18,225 (35.6%, 95% CI 35.2-36.0%): delirium occurred in 24.0% (n = 12,289, of which 14.3% (n = 7332) had delirium only and 9.7% (n = 4957) had delirium + dementia) dementia only in 8.7%, (n = 4450), AMTS <8 in 2.9% (n = 1486). The prevalence of cognitive morbidity was highest in geriatrics (44.5%; n = 134/301), general medicine (42.8%; n = 14,346/33,512), trauma/orthopaedics (36.4%; n = 1337/3673), palliative care (36.0%; n = 128/356), stroke (30.8%; n = 144/468), infectious disease (27.6%; n = 42/152), neurosurgery (22.9%; n = 161/702) and general surgery (21.5%; n = 822/3819) and was 10-20% in all other specialties except two. Delirium was the most prevalent cognitive morbidity subtype in 24/29 specialties.

Interpretation: Cognitive morbidity was common in older people with unplanned hospital admission across a broad range of specialties, with delirium accounting for most cases. Findings support the need for hospital-wide delirium screening and access to multidisciplinary team input for all specialties.

Funding: Rhodes Trust, Canadian Institutes of Health Research, National Institutes for Health Research.

The World Health Organization's Access, Watch, and Reserve (AWaRe) classification promotes appropriate antibiotic use and is widely adopted as a global indicator of antimicrobial use (AMU) quality. This paper highlights key limitations of the AWaRe classification system, using Japan as a case study. The global targets for the proportional use of "Access" antibiotics (60%-70%) lack epidemiological justification and may not fully capture regional disease patterns to reflect regional disease patterns. Furthermore, inconsistencies in drug classification and the influence of long-term prescriptions can distort Access category percentages. As most countries do not monitor prescription duration in AMU surveillance, global comparisons using the current AWaRe framework may be misleading. This paper suggests a careful reassessment of AMU surveillance methodology or the AWaRe classification itself to ensure meaningful evaluation of antibiotic stewardship efforts worldwide.

Funding: This article was funded by a research grant from the Ministry of Health, Labour and Welfare (JP23HA2002) and JSPS KAKENHI grant number JP23K18396 and the funders did not play any role in writing the manuscript.

Background: Childhood cancer survivors face physical, psychological, and neurological symptoms that contribute to risky health behaviors and increased healthcare utilization. Traditional survivorship care models overlook risk associated with this symptom burden. The current study examined symptoms phenotypes to identify high-risk groups.

Methods: Five-year survivors (N = 17,231; Mean [standard deviation] age = 27.4 [5.98]; 80% non-Hispanic White; 48% female) from the Childhood Cancer Survivor Study (NCT01120353) self-reported symptoms and risky behavior at baseline and first follow-up (original cohort data collection: baseline 1994-1998 and follow-up 2002-2004; expansion cohort: baseline 2008-2010 and follow-up 2014-2016). Medical records were extracted through chart review. Chronic health conditions (CHCs) were graded according to common terminology criteria for adverse events criteria. Latent class analysis derived symptom phenotypes.

Findings: Five phenotypes emerged: 1) Low Burden (63.1%); 2) Cardio-Pulmonary-Pain (5.3%) 3); Neurologic-Pain (10.6%); 4) Psychological Distress-Pain (13.3%); 5) Global burden (7.7%). Compared to survivors with Low Burden, those in other symptom phenotypes were older, female, had lower education, no health insurance, smoked cigarettes, were physically inactive, and had ≥ grade 3 CHC (all ps < 0.05). Survivors in symptom phenotypes were at-risk for future emergency room use (all ps < 0.05). Risk for future physical inactivity was higher in Cardio-Pulmonary-Pain (OR = 1.19, CI = 1.09, 1.31), Global (OR = 1.12, CI = 1.02, 1.22), and Neurologic-Pain (OR = 1.18, CI = 1.10, 1.27) phenotypes. Cigarette use was higher in Cardio-Pulmonary-Pain (OR = 1.62, CI = 1.08, 2.42) and (Global OR = 1.65, CI = 1.17, 2.31) phenotypes.

Interpretation: Symptom phenotyping identified groups at-risk for future risky health behaviors, which was not explained alone by diagnosis or CHCs. Integrating symptom assessments may guide interventions to improve health outcomes.

Funding: The work was supported by the National Cancer Institute (U24 CA055727, PI: GT Armstrong). Support to St. Jude Children's Research Hospital was also provided by the National Cancer Institute Cancer Center Support grant (P30 CA021765, PI: CWM Roberts) and by the American Lebanese Syrian Associated Charities.

Background: Studies where urine is typically obtained via invasive methods, show dipstick urinalysis can accurately screen for urinary tract infection (UTI) in febrile infants under 90 days old. However, evidence is limited in settings where clean catch urine collection is standard practice. This study assessed the accuracy of dipstick for UTI in a prospective cohort of febrile infants presenting to UK and Ireland emergency departments, where clean catch is the predominant urine collection method.

Methods: Post-hoc analysis of the Febrile Infant Diagnostic Assessment and Outcome study, a prospective multicentre observational cohort study. Febrile infants ≤90 days old were recruited from 35 Paediatric Emergency Research in the UK and Ireland (PERUKI) sites (NCT05259683) between 6th July 2022 and the 31st August 2023. Accuracy of dipstick urinalysis testing for detecting UTI was reported with sensitivity, specificity and predictive values.

Findings: In this multicentre prospective study of 1821 febrile infants ≤90 days, point-of-care dipstick urinalysis was performed in 57.1% of cases. Diagnostic accuracy varied significantly by age, sex, and method of dipstick assessment. Sensitivity was lowest in neonates (≤28 days; 53.3%) and if dipsticks were user-inspected (57.1%), highlighting limitations in these subgroups. In contrast, automated dipstick testing in infants >28 days achieved high sensitivity (87.5%) and moderate specificity (73.4%) at a cut-off of ≥trace leukocytes and/or ≥trace nitrites. Specificity was notably lower in female infants (60.3%) than males (85.0%), likely due to higher contamination rates in clean catch samples.

Interpretation: Automated dipstick urinalysis offers a reliable method for excluding UTI in infants >28 days and can guide selective urine culture use when clean catch urine sampling is used. However, dipstick testing of samples obtained by clean catch should not be used to rule out UTI in neonates or when relying on manual interpretation due to poor sensitivity.

Funding: Royal College of Emergency Medicine Doctoral Fellowship (RCEM 02/03/2021), the funders played no part in study conception or design.

Background: Omadacycline is a first-in-class aminomethylcycline antibiotic approved to treat adults with community-acquired bacterial pneumonia (CABP). This trial was conducted as a postmarketing regulatory commitment to confirm the efficacy and safety of omadacycline.

Methods: This phase 3b, randomised, double-blind, multicentre, noninferiority trial enrolled adults in Eastern Europe between February 2021 (first patient enrolled) and March 2024 (last patient follow-up visit) who had CABP (NCT04779242). Participants with Pneumonia Severity Index (PSI) class III or IV CABP were randomised 1:1 to omadacycline (100 mg IV every 12 h for two doses, then 100 mg IV QD) or moxifloxacin (400 mg IV QD), with an oral option after ≥2 days of treatment (omadacycline, 300 mg QD; or moxifloxacin, 400 mg QD), for a total of 7-10 days. Primary efficacy endpoint was early clinical response (ECR), assessed 72-120 h after first dose, with a noninferiority margin of 10%. Key secondary endpoint was investigator's assessment of clinical response at post-therapy evaluation (PTE), 5-10 days after last dose. Microbiological response was determined by subject and pathogen. Treatment-emergent adverse events (TEAEs) were reported through 30-37 days after first dose.

Findings: Of 670 participants randomised (omadacycline, n = 336; moxifloxacin, n = 334), approximately half were aged >65 years, and 76% had PSI class III disease. Omadacycline was noninferior to moxifloxacin at ECR and PTE (ECR, 89.6% versus 87.7%, treatment difference [95% CI]: 1.9 [-3.0, 6.8]; PTE, 86.0% versus 87.7%, treatment difference [95% CI]: -1.7 [-6.9, 3.4]). Clinical success rates were consistently high across select pathogens: 74.4-100% for omadacycline, 75.0-97.4% for moxifloxacin. Omadacycline was generally safe and well tolerated. Most commonly reported TEAEs (≥2%) in the omadacycline and moxifloxacin groups, respectively, were headache (3.6%, 4.5%), AST increase (2.1%, 0%), insomnia (0.6%, 2.1%), and diarrhoea (0%, 3.0%).

Interpretation: This trial demonstrates the safety and efficacy of omadacycline in CABP. Omadacycline offers a once-daily monotherapy oral and IV option to treat CABP, including in patients with comorbidities.

Funding: This study was sponsored by Paratek Pharmaceuticals, Inc. This study described herein has been funded in whole or in part with federal funds from the U.S. Department of Health and Human Services (HHS), Administration for Strategic Preparedness and Response (ASPR), Biomedical Advanced Research and Development Authority (BARDA), under Contract No. 75A50120C00001. The contract and federal funding are not an endorsement of the study results, products, or company.

Background: While ethnic differences in IBD phenotype are recognised, the comparative efficacy and safety of common IBD therapies across ethnically diverse populations remain uncertain. This multicentre cohort study aimed to compare the efficacy and safety of these therapies between White (WH) and South Asian (SA) IBD cohorts.

Methods: Demographic, phenotypic and outcome data from the UK IBD BioResource were utilised (BioResource inception date: 1st January 2016; data lock for analysis: 12th May 2023). The primary outcome was treatment response (defined as treatment persistence free of discontinuation or failure) to 5-aminosalicylates (5-ASAs), thiopurines and anti-TNFs. The secondary outcome was the occurrence of treatment-related adverse events (AEs). Ethnic differences in treatment response were evaluated using propensity score weighting and Cox proportional hazards regression. AE occurrence was assessed through logistic regression analysis.

Findings: In total, 26,530 patients were included [51.2% females; median age at diagnosis 30 years (IQR 21-43); 96.1% WH, 3.9% SA]. SA were diagnosed at a younger age, began treatment younger than WH, and demonstrated baseline phenotypic differences including more perianal disease in CD. However, no significant differences in treatment response between WH and SA were identified in either CD (reference group WH; thiopurines, HR 0.82 (95% CI 0.53-1.27), p = 0.37; anti-TNFs, HR 1.07 (95% CI 0.34-3.37), p = 0.91] or UC [thiopurines, HR 0.98 (95% CI 0.95-1.02), p = 0.36; anti-TNFs, HR 0.98 (95% CI 0.92-1.04), p = 0.54]. SA were at significantly increased risk of pancreatitis [HR 2.34 (95% CI 1.37-3.75), p = 0.001] and leucopenia [HR 1.76 (95% CI 1.02-2.84), p = 0.03] with thiopurines, and renal dysfunction with anti-TNFs [HR 4.75 (95% CI 1.55-12.07), p = 0.002].

Interpretation: Treatment efficacy in similar WH and SA IBD patients recruited to the UK IBD BioResource is unaffected by ethnicity but patients from SA ethnic backgrounds are at increased risk of developing pancreatitis and leucopenia with thiopurines, and renal dysfunction with anti-TNFs. These findings highlight the importance of comprehensive risk assessment and counselling by clinicians, and emphasise the importance of improving ethnic representation in IBD research.

Funding: Bowel Research UK; NIHR Imperial Biomedical Research Centre (BRC); NIHR Cambridge BRC.

In high-transmission settings, up to 70% of school-aged children (SAC; 5-15 years) harbour malaria parasites, mostly asymptomatically. This contributes significantly to school absenteeism (13-50%) and anaemia (61%), impairing cognitive development and academic performance. Despite this burden, SAC are often excluded from malaria-targeted interventions and act as a key reservoir for transmission. Intermittent Preventive Treatment for school-aged children (IPTsc), recommended by the World Health Organization (WHO), involves administering a full antimalarial treatment course at regular intervals to prevent infection. This policy brief follows a successful clinical trial and large-scale implementation research in Tanzania that demonstrated IPTsc's operational feasibility and effectiveness. Administering Dihydroartemisinin-Piperaquine (DP) through school-based delivery proved safe, cost-effective, acceptable to communities, and led to significant reductions in malaria prevalence. These findings support IPTsc as a complementary malaria control strategy in endemic areas with moderate to high transmission. Countries with similar epidemiological profiles are encouraged to adopt IPTsc as part of their national malaria control strategies.

Funding: The Global Fund, via the Ministry of Health, Tanzania (implementation research pilot of IPTsc), and Flemish Interuniversity Council (VLIR-UOS), Belgium, TEAM initiative, grant TZ2017TEA451A102 (clinical trial).