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Context: Among numerous knee-related patient-reported outcome measures, the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) has been used across a wide variety of knee pathologies. However, traditional validation procedures (classical test theory) and existing studies (estimating item parameters) have limitations in establishing the measurement properties of the IKDC-SKF. Rasch analysis reveals a strong validation approach to improve IKDC-SKF clinical interpretation with larger samples. Objective: To assess psychometric properties, including differential item functioning, of the IKDC-SKF as a patient-reported measure of knee function. Design: Cross-sectional study. Setting: Secondary data. Data were extracted from the cloud-based orthopedic and sports medicine global registry Surgical Outcome System (Arthrex). Patients: A total of 1725 individuals who underwent an arthroscopic knee procedure and completed all items on the IKDC-SKF. Main Outcome Measure(s): Rasch analysis including model-data fit, rating scale's function, item-person map (distribution of item difficulty and person ability), and differential item functioning (sex and age groups) was used to evaluate the psychometric properties of the IKDC-SKF. Results: Ten misfit items were found and removed. The 5-point Likert scale of the 9-item IKDC-SKF worked well. Item difficulty ranged from 0.58 to 0.81 logits, and person's knee function had ranged from –5.56 to 4.86 logits, with a wide distribution. The IKDC-SKF was found to function similarly for sex (male vs female) and age. Conclusions: Rasch analysis identified a unidimensional structure retaining 9 of the original IKDC-SKF items; however, a more comprehensive inventory is necessary to assess a wider range of knee function and improve measurement validity. [ABSTRACT FROM AUTHOR]

Background: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. Methods: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. Results: During 2006–2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. Conclusions: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis. [ABSTRACT FROM AUTHOR]

Health information management is a vital and constructive component of the health system, refers to the process of producing and collecting, organising and storing, analysing, disseminating and using information. The aim of this study was to evaluate the strengths and weaknesses of the information management system in epidemic infectious diseases in Iran, specifically focusing on the registration, reporting, quality, confidentiality, and security of infectious disease data. This assessment was conducted from the perspective of policymakers and experts responsible for data registration and reporting. After examining the processes of registering and reporting infectious disease data and interviewing experts, a researcher-designed questionnaire was prepared to evaluate the infectious disease information management system. To assess the content validity of the Content Validity Index and Content Validity Ratio Index, a questionnaire was utilized. The reliability of the questionnaire was confirmed using Cronbach's alpha. By employing purposeful sampling and adhering to the inclusion criteria, 150 participants were included in the study. Questionnaires were distributed via email, WhatsApp, or Telegram to employees at various levels of Iran's health and treatment systems who were responsible for registering and reporting infectious disease data. The study encompassed 100 participants who successfully concluded the research. The results highlight that the key strength of healthcare data registration lies in its ability to "depict the epidemic curve during outbreaks of infectious diseases." Conversely, a notable weakness was the "insufficient collaboration from non-academic sectors (e.g., clinics, private laboratories) in registering and reporting infectious diseases. The present study's findings suggest that the issue lies not in the framework itself, but rather in the execution and functionality of the strategies. We can cultivate a repository of reliable and beneficial data by incorporating initiatives like training programs, enforcing regulations with consequences for inadequate data documentation, offering both material and motivational rewards, and streamlining all data collection and reporting systems. [ABSTRACT FROM AUTHOR]

Objective To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005–2010 and 2017–2021 inception cohorts. Methods Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan–Meier survival analysis and multivariable Cox regression. Results The 2005–2010 and 2017–2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005–2010 and 26% (23, 30) in the 2017–2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10). Conclusion Although baseline disease characteristics were comparable in the 2005–2010 and 2017–2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity. [ABSTRACT FROM AUTHOR]

Objectives To describe the clinical features and treatment outcomes of children with juvenile psoriatic arthritis (JPsA) and compare the distinct patterns of the disease between early-onset and late-onset age groups. Methods Patients with JPsA followed regularly for at least 6 months between 2010 and 2020 in seven paediatric rheumatology centres in Turkey were included in the study. The demographic features, clinical manifestations, treatment strategies and outcomes of the patients were evaluated retrospectively. Results A total of 87 (46 male/41 female) patients were included in the study. The mean age at diagnosis was 11.9 years (s. d. 4.5). Fifty-seven (65.5%) patients had psoriasis at the time of diagnosis and arthritis preceded psoriasis in 10 (11.5%) patients. Thirty (34.5%) patients had dactylitis, 28 (32.2%) had nail pitting, 36 (41.4%) had involvement of the small joints and 20 (23%) had enthesitis. Sacroiliitis was detected in 11 (12.6%) patients by MRI. ANA was positive in 35 (40.2%) patients. Twelve children (13.8%) were in the early-onset (<5 years) group. Uveitis and ANA positivity were more common in the early-onset group. Active joint counts and activity scores of our patients showed significant improvement at month 6 and at the last control compared with baseline. Conclusion About one-third of patients with JPsA do not have psoriasis at the time of diagnosis. In some patients, no skin lesion is seen during the course of the disease. Children with PsA seem to display two different phenotypes. Younger children have a female predominance, ANA positivity and uveitis, while older children have more axial involvement. [ABSTRACT FROM AUTHOR]

Background: Research on incidence and characteristics of Out-of-Hospital Cardiac Arrest (OHCA) in the Middle East is limited. We assessed the incidence, prehospital characteristics, and outcomes of OHCA in Qatar, a Middle Eastern country. Subsequently, we performed gender-specific analysis. Methods: This was a retrospective examination of data obtained from the OHCA registry at Hamad Medical Corporation (HMC) in Qatar from 2017 to 2022. We included adults, non-traumatic, EMS-treatment OHCA. We calculated the incidence of adult OHCA and conducted descriptive analyses for prehospital characteristics, and prehospital outcomes presented by return of spontaneous circulation (ROSC). We evaluated gender differences in prehospital characteristics and ROSC using Student's t-test and the Chi-Square test as appropriate. Furthermore, we conducted a multivariable logistic regression analysis to investigate the correlation between gender and achieving ROSC. Results: We included 4,306 adult OHCA patients, with 869 (20.2%) being females. The mean annual incidence of adult OHCA was 27.4 per 100,000 population-year. Males had a higher annual incidence of OHCA than females. Among all cases, 36.3% occurred in a public location, 25.8% had an initial shockable rhythm, and 28.8% achieved ROSC. Males had a higher proportion of bystander CPR, arrests in public locations, and initial shockable rhythms. While unadjusted analysis showed no significant gender differences in achieving ROSC, adjusted analysis revealed that male gender was associated with higher odds of achieving ROSC (adjusted OR male vs. female 1.38, 95% CI 1.15–1.66, p < 0.001). Conclusions: Approximately 720 adults undergo non-traumatic OHCA in Qatar every year, with a higher incidence observed in males. Male gender was associated with higher odds of achieving ROSC. Further gender-specific research in OHCA intervention and outcome in the Middle East is required. [ABSTRACT FROM AUTHOR]

Whole genome and exome sequencing are reporting on hundreds of thousands of missense mutations. Taking a pan-disease approach, we explored how mutations in intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created a peptide-phage display library tiling ~57,000 peptides from the IDRs of the human proteome overlapping 12,301 single nucleotide variants associated with diverse phenotypes including cancer, metabolic diseases and neurological diseases. By screening 80 human proteins, we identified 366 mutation-modulated interactions, with half of the mutations diminishing binding, and half enhancing binding or creating novel interaction interfaces. The effects of the mutations were confirmed by affinity measurements. In cellular assays, the effects of motif-disruptive mutations were validated, including loss of a nuclear localisation signal in the cell division control protein CDC45 by a mutation associated with Meier-Gorlin syndrome. The study provides insights into how disease-associated mutations may perturb and rewire the motif-based interactome. Synopsis: Hundreds of mutations in the intrinsically disordered regions of the human proteome that break, diminish, enhance or create motif-based interactions are uncovered by mutational proteomic peptide-phage display. A novel peptide-phage display library that combines disease-associated amino acid changing mutations with the intrinsically disordered regions of the human proteome is described. 275 mutations associated with various diseases are reported to affect 279 motif-based protein-protein interactions. About 50% of the mutations enhance or create binding motifs, and the rest disrupt or diminish interactions. The study provides novel insights into how disease-associated mutations perturb and rewire the motif-based interactome. Hundreds of mutations in the intrinsically disordered regions of the human proteome that break, diminish, enhance or create motif-based interactions are uncovered by mutational proteomic peptide-phage display. [ABSTRACT FROM AUTHOR]

The contribution of splicing variants to molecular diagnostics of inherited diseases is reported to be less than 10%. This figure is likely an underestimation due to several factors including difficulty in predicting the effect of such variants, the need for functional assays, and the inability to detect them (depending on their locations and the sequencing technology used). The aim of this study was to assess the utility of Nanopore sequencing in characterizing and quantifying aberrant splicing events. For this purpose, we selected 19 candidate splicing variants that were identified in patients affected by inherited retinal dystrophies. Several in silico tools were deployed to predict the nature and estimate the magnitude of variant-induced aberrant splicing events. Minigene assay or whole blood-derived cDNA was used to functionally characterize the variants. PCR amplification of minigene-specific cDNA or the target gene in blood cDNA, combined with Nanopore sequencing, was used to identify the resulting transcripts. Thirteen out of nineteen variants caused aberrant splicing events, including cryptic splice site activation, exon skipping, pseudoexon inclusion, or a combination of these. Nanopore sequencing allowed for the identification of full-length transcripts and their precise quantification, which were often in accord with in silico predictions. The method detected reliably low-abundant transcripts, which would not be detected by conventional strategies, such as RT-PCR followed by Sanger sequencing. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is an economically costly cancer, especially in Brazil, where treatment and diagnosis vary greatly across regions. This study revealed that, after the age of 50, mortality from this disease increases, and is more common among white people and residents of the southern region of Brazil. The lack of health professionals and the lower investment in health actions and services contributed to this increase in mortality. In addition, the performance of basic procedures, such as punctures and cystoscopy examinations, was lower in regions with higher mortality rates; however, more complex surgeries failed to reduce mortality rates. These results underscore the need to improve public health policies and ensure better access to healthcare for cancer, especially in Brazilian regions with fewer resources. Bladder cancer is one of the most economically costly types of cancer, but few studies have evaluated its mortality considering the factors that impact this outcome. This study aimed to investigate the impact of sociodemographic factors, period, cohort, and health services on bladder cancer mortality. This ecological study analyzed bladder cancer mortality data in Brazil from 2000 to 2022 and evaluated sociodemographic variables (race, region of residence), socioeconomic variables (gross domestic product per capita, Gini index of household income per capita, number of health professionals per inhabitant, expenditure on public health services, and consultations per inhabitant), and bladder cancer diagnosis and treatment procedures. These data were subjected to statistical analysis, which revealed that after the age of 50, there was a progressive increase in the risk of bladder cancer. Indigenous people had the lowest mortality rate, while white people had a significantly greater mortality rate than black and brown people. The North Region and Northeast Region presented the lowest mortality rates, whereas the South Region presented the highest mortality rates. In the South and Southeast Regions, a higher GDP was related to lower mortality. In the South, higher mortality was associated with a lower number of consultations per inhabitant per region. Fewer bladder punctures/aspirations and bladder biopsies were associated with higher mortality rates. In oncology, more procedures, such as total cystectomy, cystoenteroplasty, and total cystectomy with a single shunt, do not reduce the mortality rate. These results can serve as guidelines for adjusting public health policies. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the association of immune-related adverse events during atezolizumab therapy with better outcomes for patients with advanced non-small-cell lung cancer who had already received chemotherapy in previous lines of treatment. This study found that patients who experienced an immune-related adverse event while undergoing atezolizumab treatment had longer median progression-free survival compared to those who did not. Specifically, patients that experienced side effects had a median progression-free survival of 13.03 months, compared to just 3.4 months for those without side effects. Additionally, these side effects were more common in patients who were in better overall health when they started the treatment. The findings suggest that immune-related adverse events could be predictive in this patient population. Immune checkpoint inhibitors (ICIs) are pivotal in managing metastatic non-oncogene addicted non-small-cell lung cancer (NSCLC). They have unique toxicities known as immune-related adverse events (irAEs). Previous studies have linked irAEs during atezolizumab-based first-line treatments in advanced NSCLC with improved outcomes. This study explored the association between irAEs and the efficacy of atezolizumab in advanced NSCLC patients who had previously received platinum-based chemotherapy. The study involved 105 advanced NSCLC patients who received atezolizumab monotherapy after progressing on at least one line of platinum-based chemotherapy from a single academic institution in Serbia. Data were obtained from a hospital lung cancer registry. Among the participants, 63.8% were male, with the majority being current (53.3%) or former smokers (37.1%). About half had a good performance status (ECOG PS 0–1) at the start of atezolizumab treatment. irAEs occurred in 23 patients (21.9%). The median progression-free survival (mPFS) was significantly longer for patients with irAEs (13.03 months) compared to those without (3.4 months) (HR 0.365 [95% CI, 0.195–0.681], p = 0.002). irAEs and ECOG PS 0–1 were predictors of longer mPFS, with irAEs being more common in patients with good performance status (p = 0.01). irAEs were linked to improved mPFS in NSCLC patients treated with atezolizumab after multiple lines of platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The platelet count is an established marker of cancer. In healthy populations, platelet count varies by age and sex; despite that variation, a single reference range is used. This study aimed to identify age- and sex-specific upper thresholds for platelet count at which cancer should be considered in primary care, using audits of primary care-based clinical data in England, Canada, and Australia. Across all three cohorts, there was a clear upwards trend in cancer incidence with increasing platelet count for both sexes and at all age groups. The appropriate threshold will vary by country and will depend on local healthcare needs and priorities. As colorectal and lung cancers predominate, initial investigation may target these sites. Further investigation, depending on the patient's symptoms, could be CT imaging, endoscopy, or CA125. The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/L; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England, Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of the test date was estimated from linked registry data. In all three countries, there was a clear upwards trend in cancer incidence with increasing platelet count for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determining appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit. [ABSTRACT FROM AUTHOR]

Objective Previous epidemiological data of JIA in Finland are from the turn of the millennium. We aimed to determine the recent annual incidence of JIA in several consecutive years in Finland and to explore the differences in incidence between sexes, age groups and regions. Methods We analysed all children <16 years of age who met the ILAR classification criteria for JIA. Cases from 2000–2020 were identified from two national registers: the Care Register for Health Care of the Finnish Institute for Health and Welfare and the Reimbursement Register containing medication data from the Social Insurance Institution of Finland; cases from 2016–2020 were identified from the Finnish Rheumatology Quality Register. Results The incidence of JIA was 31.7 per 100 000 (95% CI 30.2, 33.1), according to the Care Register in 2000–2020 and peaked in 2010–2014. No considerable differences in incidence rates were observed among registers. In all age groups, incidence in girls was predominant compared with boys. The incidence in girls peaked at the ages of 2 years and 14–15 years. Decreasing incidence was observed among boys 0–3 years old during the entire study period, whereas increasing incidence was observed among teenage girls and boys 4–7 years old in 2000–2013. Conclusion The incidence of JIA is not only very high with respect to that in other parts of the world but also higher than previously reported in Finland. The incidence varied by region and year but was not higher at the end than the beginning of the study period. [ABSTRACT FROM AUTHOR]

Objective To present the characteristics of patients with potential difficult-to-treat (D2T) PsA. Methods We used data from the Greek multicentre registry of PsA patients. D2T PsA was defined as follows: patients with at least 6 months' disease duration, who have failed to at least one conventional synthetic DMARD and at least two biologic DMARDs/targeted synthetic DMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA (Disease Activity index in PSoriatic Arthritis) >14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. Results Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (P  < 0.0001) and were more likely to have higher BMI (P  = 0.023) and a history of IBD (P  = 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (P  = 0.001 and P  = 0.008, respectively). Moreover, female gender (P  = 0.034) in the MODA analysis and axial disease (P  = 0.040) in the MDA analysis were independent variables for D2T PsA. Conclusion Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial disease and history of IBD were also associated with D2T PsA. [ABSTRACT FROM AUTHOR]

Objective Excess mortality has been demonstrated in patients with SLE compared with the general population. We aimed to investigate the 5-year and 10-year all-cause mortality in patients with SLE compared with the general population in recent decades. Methods This was a Danish nationwide population-based exposure-matched cohort study. Incident cases of SLE diagnosed between 1996 and 2015 were identified using administrative health registries and followed until 2020, allowing for 5 and 10 years of follow-up. Patients with SLE were matched 1:5 on age and sex with individuals from the Danish general population. Time-to-event analyses were performed using the pseudo-observation approach. Results In total, 1351 incident cases of SLE and 6755 matched controls were identified. The crude risk difference (RD) for 5-year mortality decreased over the study period, from 10.3% (95% CI 6.5–14.1%) to 4.6% (95% CI 1.4–7.8%) for patients with SLE compared with controls. The relative risk (RR) for 5-year mortality decreased similarly in the same period. Adjustment for comorbidities revealed lower RD and RR for mortality in patients with SLE compared with controls, but the decreasing trend remained. The crude and adjusted RD and RR for 10-year mortality did not change over the calendar period. The 10-year RR was highest in young patients with SLE (<50 years of age). Conclusion The 5-year mortality risk decreased over time for both patients with SLE and matched controls. However, excess 5-year mortality for patients with SLE in the most recent calendar period and excess mortality late in their disease course remained. Continued focus on preventing disease progression and comorbidity is required. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Kidney transplantation with minimal or no dialysis exposure provides optimal outcomes for children with end-stage kidney disease. We sought to understand disparities in timely access to transplant waitlisting. METHODS: We conducted a retrospective, registry-based cohort study of candidates ages 3 to 17 added to the US kidney transplant waitlist 2015 to 2019. We defined "preemptive waitlisting" as waitlist addition before receiving dialysis and compared demographics of candidates based on preemptive status. We used competing risk regression to determine the association between preemptive waitlisting and transplantation. We then identified waitlist additions age >18 who initiated dialysis as children, thereby missing pediatric allocation prioritization, and evaluated the association between waitlisting with pediatric prioritization and transplantation. RESULTS: Among 4506 pediatric candidates, 48% were waitlisted preemptively. Female sex, Hispanic ethnicity, Black race, and public insurance were associated with lower adjusted relative risk of preemptive waitlisting. Preemptive listing was not associated with time from waitlist activation to transplantation (adjusted hazard ratio 0.94, 95% confidence interval 0.87-1.02). Among transplant recipients waitlisted preemptively, 68% had no pretransplant dialysis, whereas recipients listed nonpreemptively had median 1.6 years of dialysis at transplant. Among 415 candidates initiating dialysis as children but waitlisted as adults, transplant rate was lower versus nonpreemptive pediatric candidates after waitlist activation (adjusted hazard ratio 0.54, 95% confidence interval 0.44-0.66). CONCLUSIONS: Disparities in timely waitlisting are associated with differences in pretransplant dialy- sis exposure despite no difference in time to transplant after waitlist activation. Young adults who experience delays may miss pediatric prioritization, highlighting an area for policy intervention. [ABSTRACT FROM AUTHOR]

Background and aims: Studies on cancer incidence and mortality among people with opioid use‐related disorders are lacking. We aimed to measure cancer‐specific incidence, mortality and survival among people diagnosed with opioid use‐related disorders in Norway during 2010–18. Design and setting: This was a cohort study conducted in Norway during 2010–18. Participants: Individuals (n = 20 710) diagnosed with opioid use‐related disorders. Measurements: We conducted a cohort study utilizing a data‐linkage of national health and population registers. Information on opioid use‐related disorders was extracted from specialized healthcare, malignancies from the Cancer Registry of Norway and deaths from Cause of Death Registry. Cancer incidence and mortality were compared with the general population by calculating sex‐specific age‐standardized incidence (SIR) and mortality (SMR) ratios. One‐year survival rates were computed. Findings Compared with the general population, people with opioid use‐related disorders were at an increased risk of developing cancer overall [SIR = 1.2, 95% confidence interval (CI) = 1.1–1.3] with a higher than twofold cancer mortality rate (SMR = 2.3, 95% CI = 2.0–2.7). Excess risk was observed for liver (12.6, 95% CI = 9.1–17.0), larynx (4.7, 95% CI = 1.7–10.2), lung (3.5, 95% CI = 2.8–4.3) and pancreas cancer (2.6, 95% CI = 1.6–4.0), whereas reduced risk was found for melanoma (0.5, 95% CI = 0.3–0.9), breast (0.6, 95% CI = 0.4–0.9) and prostate cancers (0.3, 95% CI = 0.1–0.4). Site‐specific SMRs were significantly elevated for liver (12.3, 95% CI = 8.5–17.2), lung (3.9, 95% CI = 3.0–5.0), pancreas (3.0, 95% CI = 1.7–4.8) and colon cancers (1.9, 95% CI = 1.1–3.1). The average 1‐year survival rate after a cancer diagnosis was low in liver, pancreas and colon cancer, ranging from 10 to 15% less than that of the general population. Conclusions: In Norway, cancer incidence and cancer‐related mortality appear to be elevated among individuals with opioid use‐related disorders. [ABSTRACT FROM AUTHOR]

Background: Charcot–Marie–Tooth disease (CMT) is one of the most common inherited neuropathies. The disease is generally characterized by sensory loss most prominent in distal extremities, muscle weakness, and muscle wasting. There is still no effective therapy for Charcot–Marie–Tooth disease. Case presentation: The patient is a 6-year-old Iranian girl, of Fars ethnicity, who was admitted with a chief complaint of hoarseness and an impression of Charcot–Marie–Tooth disease type 4B. She was initially treated with noninvasive ventilation and, after a year, electively underwent cordotomy as a novel therapeutic approach. Conclusions: Charcot–Marie–Tooth disease type 4B is a less common but important cause of stridor. Noninvasive ventilation treatment and unilateral posterior cordotomy can be utilized for hereditary neuropathies. [ABSTRACT FROM AUTHOR]

Background: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods. Methods: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits – measured with three scales from the Child Behavior Checklist – from childhood to adulthood. Results: Autism heritability was comparable from childhood, (96% [95% CI, 76–99%]) to adulthood (87% [67–96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35–0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8–9 to 19–20, and unique nonshared environmental influences at each age. Conclusions: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted. [ABSTRACT FROM AUTHOR]

Background: India is a vast and diverse country with existing variations in the frequency and distribution of cancers across its various parts. In regions lacking population-based cancer registries (PBCRs) in a vast country like India, hospital-based cancer registry (HBCR) data become an important source of information on the trends and patterns of a region. To determine the numerical trends of cases of the top ten cancer sites reporting to HBCR of a tertiary care cancer center in Bihar from 2014 to 2021. Materials and Methods: The details of all histopathologically confirmed cancer cases registered in the HBCR department of radiation oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, India between January 2014 and December 2021 were included in this retrospective observational study. All these cases were grouped site-wise and listed in descending order of the total number of cases reported in each group. Cross-tabulation with age and sex distribution was done. The frequency distribution of the top ten leading cancers for every consecutive calendar year was plotted in line diagrams for time trend analysis. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). was used for analysis. Annual percent change (APC) was determined for the number of cases of all ten cancer sites using joinpoint regression analysis (Joinpoint Regression Software, Version 4.0.4--May 2013; Statistical Methodology and Applications Branch, Surveillance Research Program of the US National Cancer Institute; Bethesda, MD, USA). Results: Out of 32,057 total cancer cases registered between Jan 2014 and Dec 2021, 21,848 patients (68.2%) cases constituted the top ten cancers. The top ten cancers among both sexes were cancer gallbladder (n = 4204, 13.1%), head and neck (n = 3395, 10.6%), breast (n = 3392, 10.6%), lung (n = 2069, 6.5%), cervix (n = 2039, 6.4%), hematolymphoid (n = 1930, 6.0%), liver (n = 1572, 4.9%), stomach (n = 1116, 3.5%), ovary (n = 1103, 3.4%), and colon-rectum (n = 1028, 3.2%). Except for cervical and hematolymphoid cancers, the rest all showed a rising trend over consecutive years. Conclusion: Cancer of the gallbladder continues to be among the most common cancers in the region. Focused research in all aspects of this deadly disease is needed. Strengthening of prevention and screening programs for common cancers and upliftment of the existing infrastructure for diagnosis and treatment of cancer in the region are necessitated. [ABSTRACT FROM AUTHOR]

Summary: This multicentre, prospective cohort study measured the effect of romosozumab for 12 months on bone mineral density, taking into account prior therapies. Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip. Introduction: In Switzerland, romosozumab is administered to high-risk osteoporosis patients. Our study aimed to assess the effect of romosozumab on bone mineral density (BMD), taking into account prior therapies. Methods: This multicentre, prospective cohort study measured the effect of romosozumab for 12 months in patients in a nationwide Swiss osteoporosis registry. BMD and bone turnover marker (P1NP and CTX) changes were measured and compared between pre-treated and treatment naïve patients. Results: Ninety-nine patients (92 women and 7 men, median age 71 years [65, 76]) were enrolled from January 2021 to December 2023. Among them, 22 had no prior treatment before romosozumab, while 77 had previous therapy (including 23 with a history of prior teriparatide therapy), with a median duration of 6 years [4, 11] of cumulative antiresorptive treatment. Over 12 months, romosozumab led to BMD changes of 10.3% [7.5, 15.5] at the lumbar spine, 3.1% [1.1, 5.8] at the total hip and 3.1% [0.5, 5.3] at the femoral neck, indicating notable variability. Significantly lower BMD responses were observed in pre-treated patients, with the duration of prior antiresorptive therapy inversely associated with BMD increases at the lumbar spine and hip. Other predictors of BMD changes at the total hip included baseline T-scores at the hip, body mass index and baseline CTX level, while the BMD response at the lumbar spine was associated with the lumbar spine T-score at baseline, age and baseline CTX level. Conclusion: Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip. [ABSTRACT FROM AUTHOR]

Theobroma cacao is primarily cultivated for its seeds. In the Philippines, where cacao yields are decreased by pod rots and vascular streak dieback (VSD)-like symptoms, the fungus Lasiodiplodia theobromae (Botryospaheriaceae) is the only reported species of Lasiodiplodia reported to cause disease in cacao. Here to identify and determine the pathogenicity of Lasiodiplodia isolates from cacao trees, we isolated Lasiodiplodia from from a leaf with blight (isolate PH22-080), stem with vascular streak (PH22-060), pod rot (PH22-120), an asymptomatic stem (PH22-014), and leaf litter (PH22-007). All strains were pathogenic on wounded leaves and stems and infected pods even without wounds. On the basis of molecular analysis of combined sequence data for ITS, rpb2, tef1-α and tub2 and morphological characteristics, the strains were identified as L. pseudotheobromae (PH22-080), L. theobromae (PH22-120), and Lasiodiplodia sp. (PH22-060), which were confirmed to be pathogenic on cacao leaves, stems, and pods. L. theobromae (PH22-007) and L. hormozganensis (PH22-014) showed potential to cause disease in cacao but further investigation is needed. [ABSTRACT FROM AUTHOR]

Hyperoxia has been suggested as a mechanism for secondary injury following adult traumatic brain injury (TBI), but its effects have not been well described in pediatric patients. Pediatric (≤18yo) TBI patients were identified in a prospective institutional registry from October 2008 to April 2022. The first, highest, and the Area Under the Curve (AUC) PaO2 in the first 24 hours were collected and calculated for each patient from arterial blood gas reports after admission to the ICU. Neurological outcome after 6 months was measured using dichotomized modified Rankin Scale (mRS) and Glasgow Outcome Scale – Extended (GOS-E). Multivariable logistic regression models were used to determine if the three measurements for hyperoxia predicted an unfavorable outcome after controlling for well-established clinical and imaging predictors of outcome. We identified 98 pediatric patients with severe accidental TBI during the study period. Hyperoxia (PaO2 > 300 mmHg) occurred in 33% of the patients. The presence of elevated PaO2 values, determined by all three evaluations of hyperoxia, was not associated with unfavorable outcome after 6 months. Utilizing multiple methods to assess exposure, hyperoxia was present in a substantial number of patients with severe TBI but was not associated with an unfavorable outcome. [ABSTRACT FROM AUTHOR]

Formal infectious disease surveillance in Ukraine has been disrupted by Russia’s 2022 invasion, leading to challenges with tracking and containing epidemics. To analyze the effects of the war on infectious disease epidemiology, we used open-source data from EPIWATCH, an artificial intelligence early-warning system. We analyzed patterns of infectious diseases and syndromes before (November 1, 2021–February 23, 2022) and during (February 24–July 31, 2022) the conflict. We compared case numbers for the most frequently reported diseases with numbers from formal sources and found increases in overall infectious disease reports and in case numbers of cholera, botulism, tuberculosis, HIV/AIDS, rabies, and salmonellosis during compared with before the invasion. During the conflict, although open-source intelligence captured case numbers for epidemics, such data (except for diphtheria) were unavailable/underestimated by formal surveillance. In the absence of formal surveillance during military conflicts, open-source data provide epidemic intelligence useful for infectious disease control. [ABSTRACT FROM AUTHOR]

Background: There has been a notable decrease in antibiotic prescribing in the last thirty years in Sweden. Little is known about factors influencing antibiotic prescribing over several years. Objective: To compare primary care physicians who, over time, reduced their antibiotic prescribing for respiratory tract infections with those who remained either high or low prescribers regarding potentially influencing factors. Design and setting: A register-based study including all RTI visits in primary care in Region Kronoberg, Sweden 2006–2014. The data were divided into three 3-year periods. Subjects: The data comprised all physicians who had diagnosed at least one RTI for each of the three-year periods. The antibiotic prescribing rate adjusted for the patients' sex and age group was calculated for each physician and period, and based on the change between the first and the third period, the physicians were divided into three prescriber groups: The High Prescribing Group, the Decreasing Prescribing Group, and the Low Prescribing Group. Main outcome measures: For the three prescriber groups, we compared factors influencing antibiotic prescribing such as the characteristics of the physicians, their use of point-of-care tests, their choice of diagnoses, and whether the patients returned and received antibiotics. Results: The High Prescribing Group ordered more point-of-care tests, registered more potential bacterial diagnoses, prescribed antibiotics at lower C-reactive protein levels, and prescribed antibiotics more often despite negative group A Streptococci test than in the Low Prescribing Group. The Decreasing Prescribing Group was between the High Prescribing Group and the Low Prescribing Group regarding these variables. The lower prescription rate in the Low Prescribing Group did not result in more return visits or new antibiotic prescriptions within 30 days. Conclusion: Point-of-care testing and its interpretation differed between the prescriber groups. Focus on interpreting point-of-care test results could be a way forward in antibiotic stewardship. KEY POINTS: High prescribers used antibiotics at lower CRP levels and were more likely to identify a potential bacterial diagnosis. Many physicians reduced their antibiotic prescribing during the study period. Nine out of ten low prescribers remained low prescribers. Seeing a low-prescribing physician did not lead to more return visits or antibiotic changes. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to compare quality of diabetes care in people with type 2 diabetes by ethnicity, in Scotland. Methods: Using a linked national diabetes registry, we included 162,122 people newly diagnosed with type 2 diabetes between 2009 and 2018. We compared receipt of nine guideline indicated processes of care in the first‐year post‐diabetes diagnosis using logistic regression, comparing eight ethnicity groups to the White group. We compared annual receipt of HbA1c and eye screening during the entire follow‐up using generalised linear mixed effects. All analyses adjusted for confounders. Results: Receipt of diabetes care was lower in other ethnic groups compared to White people in the first‐year post‐diagnosis. Differences were most pronounced for people in the: African, Caribbean or Black; Indian; and other ethnicity groups for almost all processes of care. For example, compared to White people, odds of HbA1c monitoring were: 44% lower in African, Caribbean or Black people (OR 0.56 [95% CI 0.48, 0.66]); 47% lower in Indian people (OR 0.53 [95% CI 0.47, 0.61]); and 50% lower in people in the other ethnicity group (OR 0.50 [95% CI 0.46, 0.58]). Odds of receipt of eye screening were 30%–40% lower in most ethnic groups compared to the White group. During median 5 year follow‐up, differences in HbA1c monitoring and eye screening largely persisted, but attenuated slightly for the former. Conclusions: There are marked ethnic disparities in routine diabetes care in Scotland in the short‐ and medium‐term following diabetes diagnosis. Further investigation is needed to establish and effectively address the underlying reasons. [ABSTRACT FROM AUTHOR]

Aims Evaluation of left and right ventricular (RV) longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and RV longitudinal systolic function and RV–pulmonary artery (RV–PA) coupling from baseline to 30 days and 1 year after AVR. Methods and results Left ventricular (LV) longitudinal strain (LS), tricuspid annulus plane systolic excursion (TAPSE), and RV–PA coupling were evaluated in patients from the PARTNER 2A surgical AVR (SAVR) arm (n = 985) and from the PARTNER 2 SAPIEN 3 registry (n = 719). TAPSE and RV–PA coupling decreased significantly following SAVR, but remained stable following TAVR. Lower LV LS, TAPSE, or RV–PA coupling at baseline was associated with increased risk of the composite of death, hospitalization, and stroke at 5 years [adjusted hazard ratios (HRs) for LV LS < 15%: 1.24, 95% confidence interval (CI) 1.05–1.45, P = 0.001; TAPSE < 14 mm: 1.44, 95% CI 1.21–1.73, P < 0.001; RV–PA coupling < 0.55 mm/mmHg: 1.32, 95% CI 1.07–1.63, P = 0.011]. Reduced TAPSE at baseline was the most powerful predictor of the composite endpoint at 5 years. Patients with LV ejection fraction <50% at baseline had increased risk of the primary endpoint with SAVR (HR: 1.34, 95% CI 1.08–1.68, P = 0.009) but not with TAVR (HR: 1.12, 95% CI 0.88–1.42). Lower RV–PA coupling at 30 days showed the strongest association with cardiac mortality. Conclusion SAVR but not TAVR was associated with a marked deterioration in RV longitudinal systolic function and RV–PA coupling. Lower TAPSE and RV–PA coupling at 30 days were associated with inferior clinical outcomes at 5 years. In patients with LVEF < 50%, TAVR was associated with superior 5-year outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Primary total elbow replacement (TER) services in England are being restructured with the goal of centralising care to specialised centres. It is important to monitor the impact of this service redesign. This protocol outlines an intended analysis to provide detailed descriptions of the patients who are receiving primary TER, where and by whom TER is being performed, and what the current surgical practices for TER are in England before the reconfiguration. Methods: This analysis will use the National Joint Registry (NJR) elbow dataset and link it with NHS England Hospital Episode Statistics-Admitted Patient Care (HES-APC). It will include eligible patients from the start of the NJR elbow dataset in April 2012 to December 2022. The main objective is to determine the incidence of TER in England. Age-sex standardised rates will be calculated for groups including different ethnicities, and socioeconomic backgrounds, using the mid-year population data provided by the Office for National Statistics. This planned analysis will summarise patient characteristics such as age, sex, body mass index (BMI), hand dominance, American Society of Anaesthesiologists (ASA) grade, indication for TER, socioeconomic status, and patient co-morbidities. It will also examine implant fixation type, classification, brand/type, and changes over time in implant types used in England. Additionally, it will explore the characteristics and volume of the surgeons and hospitals providing primary TER services, including the grade of the primary surgeons, funding source for surgery, and admission type. The analysis will cover the number of procedures performed by surgeons and hospitals annually in England and in each region of England. Finally, the planned analysis will summarise the elective wait time, postoperative length of stay, and any serious adverse events or re-admissions within 30 and 90 days after the TER. Discussion: This protocol describes the first deep dive analysis into the NJR elbow dataset to describe the incidence of TER surgery in England and the characteristics of patients who are receiving it. This analysis will summarise current primary TER practices in England before service reconfigurations. The impact of reconfiguration can be monitored by comparing future practice to the outcomes from this study. Trial registration ClinicalTrials.gov, NCT06355011. Registered 02 April 2024, https://clinicaltrials.gov/ct2/show/NCT06355011. [ABSTRACT FROM AUTHOR]

Introduction: The use of stereotactic ablative radiotherapy (SABR) over conventional fractionated radiotherapy (CFRT) for early‐stage non‐small‐cell lung cancer (NSCLC) has been advocated, but is also debated in the literature. Methods: In this retrospective cohort study, we adopted a target trial emulation framework to identify eligible patients diagnosed between 2011 and 2021 using the Taiwan Cancer Registry. In the primary analysis, the overall survival (OS) was the primary endpoint, whereas incidences of lung cancer mortality and radiation pulmonary toxicity were the secondary endpoints. Extensive supplementary analyses were also conducted. Results: We included 351 patients in the primary analysis and found that the OS was not significantly different between the SABR (n = 290) and CFRT (n = 61) groups. The propensity score weighting adjusted hazard ratio of death was 0.75 (95% confidence interval 0.53–1.07, p = 0.118). The secondary endpoints and supplementary analyses showed no significant differences. Conclusions: The OS of patients with early‐stage NSCLC treated with SABR was not significantly different from that of patients treated with CFRT alone. The results of the relevant ongoing clinical trials are eagerly awaited. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the surgical, oncological and quality of life outcomes in the setting of radical resection of colorectal carcinoma involving major nerve resection. Methods: A systematic review of the literature was registered with the International Prospective Register for Systematic Reviews (PROSPERO) and performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify papers relating to outcomes in radical resection of colorectal cancer where major nerve resection was undertaken. Papers were identified from OVID Medline, EMBASE Classic and Web of Science encompassing all publications in English from January 2010 to June 2023. A total of 1357 nonduplicate studies were identified and screened for relevance, with six studies included in the final review. Results: A total of 354 major nerve resections were undertaken across the six included studies. Overall postoperative morbidity was reported at rates of up to 82%. Two studies considered nerve-resection-specific oncological outcomes, with complete pathological resection achieved at rates comparable to the wider pelvic exenteration cohort (65–68%) and without any overall survival disadvantage being conveyed by major nerve resection (p = 0.78). Two studies considered functional outcomes and noted a transient decrease in physical quality of life over the first 6 months postoperatively (p = 0.041) with significant loss to follow-up. One study considered postoperative pain in nerve resection and noted no significant increase in patient-reported pain scores associated with nerve resection (p = 0.184–0.618). Conclusions: Major nerve resections in locally advanced and recurrent colorectal cancer remain understudied but with encouraging initial oncological and functional outcomes. Multicentre collaborative prospective reviews are needed to better elucidate contributors to postoperative morbidity and functional deficits and further establish interventions to ameliorate them. [ABSTRACT FROM AUTHOR]

Sepsis is a common cause of neonatal mortality and morbidity. Though antibiotics are the mainstay of treatment in culture‐positive neonatal sepsis, the dilemma persists for the optimum duration of antimicrobial therapy. The present study aimed to evaluate the efficacy of short‐course antibiotics for uncomplicated culture‐positive neonatal sepsis. This systematic review and meta‐analysis (PROSPERO: CRD42023444899) identified, appraised, and synthesised the available evidence from randomised and quasi‐randomised controlled trials related to the efficacy of short‐course (7–10 days) versus standard‐course (14 days) antibiotics for uncomplicated culture‐positive neonatal sepsis on the rate of treatment failure, mortality, duration of hospitalisation, morbidities including antibiotics‐related adverse events, long‐term neurodevelopmental outcomes and cost analysis. Data were pooled using RevMan 5.4 software. Certainty of evidence (COE) for predefined outcomes was analysed by GRADE. Available evidence showed no significant difference in the rate of treatment failure between 7‐ to 10‐day versus 14‐day antibiotics courses [risk ratio (95% confidence interval, CI), 2.45 (0.93–6.47), I2 = 0%, six studies, n = 573, very low COE]. No incidence of death was reported in either treatment arm in the two included studies. Duration of hospitalisation was significantly shorter with the short‐course antibiotics arm compared to standard‐course [mean difference (95% CI), −3.88 (−4.22 to −3.54) days, I2 = 0%, five studies, n = 507, low COE]. Morbidities reported in the three studies were similar. Other outcomes were not reported. To conclude the evidence is very uncertain about the effect of short‐course antibiotic regimen, compared to a standard‐course, on the treatment failure rate in uncomplicated culture‐positive neonatal sepsis. Adequately powered trials with outcomes including death and long‐term neurodevelopmental impairment are needed. [ABSTRACT FROM AUTHOR]

Occupational exposures in the large industrial mining sector contributed significantly to South Africa's high excess death rate due to COVID-19. Historically poor work-protection oversight has perpetuated centuries of risky labor and living conditions within the industry, driving high levels of disease co-morbidities, and supporting enduring social vulnerabilities. In this paper, we offer a syndemic lens to consider the clustering of adversely interacting diseases among mineworkers in South Africa, drawing attention to the complex occupational health crisis and the need to move beyond simply reporting individual diseases or comorbidities among this population. The physically demanding and dangerous working conditions, the lack of adequate changes to crowded and unsanitary working and living situations, the failure to meet social and labor plan targets, the continued precarious nature of working contracts and mines, and the limited access to robust healthcare reflect the historically exploitative nature of industrial mining in South Africa that places miners at increased risk for various syndemics. This assessment of the adverse interactions of diseases and socioeconomic and political conditions highlights the need for focused research and more follow-through in comprehensive occupational reforms. [ABSTRACT FROM AUTHOR]

Objective To understand the status quo of infectious disease reports automatically exchanged by secondary and above medical institutions in Sichuan province based on regional platform, and provide basis for improving the work on automatic exchange of infectious disease information reports in the next step. Methods Check and calculate the success rates of exchange and rough exchange through the system, the use of the infectious disease reporting management related systems was investigated by questionnaire survey, T - test and chi - square test were used for comparison between groups, and spearman correlation analysis was used for correlation. Results From July to September 2023, the exchange success rate in 68 medical institutions was 92. 67%, and the success rate of crude exchange reached 95. 87%. Compared with other level medical institutions, municipal medical institutions had higher success rate of exchange and crude exchange, and longer time interval to realize automatic exchange. The exchange success rate was positively correlated with the time interval to realize automatic exchange (r = 0. 44, P < 0. 001) and the crude exchange success rate (r = 0. 51, P < 0. 001). More than 90% of the institutions had HIS, LIS, PACS. 77. 94% of the institutions could automatically generate the report card, more than 80% had the report card management and information statistics query functions. 73. 53% realized the automatic early warning of infectious disease report card, and 25% of the institutions reported the card forcibly after the early warning. 88. 24% felt that the workload of infectious disease report was reduced after automatic exchange. Conclusion The success rate of automatic exchange and the success rate of crude exchange in medical institutions were higher overall, municipal medical institutions were higher than other levels of medical institutions. The construction rate of basic information system in medical institutions was high, but the basic functions of automatic exchange were not perfect. Automatic exchange improves the efficiency of reporting to some extent, but it still could not completely replace manual reporting. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer and type 2 diabetes mellitus are highly prevalent and closely related diseases. Type 2 diabetes increases the risk of breast cancer. Our retrospective matched cohort study involving 318 women with type 2 diabetes assessed the evolution of cardiometabolic parameters and diabetic complications in women with (n = 106) and without subsequent breast cancer (n = 212). Over a 7-year follow-up period, women with breast cancer had worse glycemic control but not higher rates of diabetic complications compared to women without breast cancer. During breast cancer (BC), cardiometabolic disorders can worsen prognosis, particularly in women with type 2 diabetes mellitus (T2DM). This study aimed to determine the impact of BC diagnosis on cardiometabolic parameters and the incidence of complication in women over 50 years of age (90% aged ≥ 65 years) with pre-existing T2DM. Using primary care registries from Asturias (Spain), a total of 106 women diagnosed with T2DM followed by BC were selected and matched with women with T2DM (n = 212) in a cohort study. Indicators of cardiometabolic health and microvascular complications associated with T2DM were collected. Women were monitored from two years prior to five years after BC diagnosis. Conditional logistic regressions were used to compare the adjusted odds of staying below each indicator's threshold. During follow-up, women with T2DM+BC had a higher risk of fasting blood glucose ≥126 mg/dL (adjusted odds ratio [aOR] = 1.83; 95% confidence interval [CI95%]: 1.01–3.32) and glycosylated hemoglobin (Hb1Ac) ≥ 48 mmol/mol or 6.5% (aOR: 2.44; IC95%: 1.21–4.91). There was no difference between the groups regarding the incidence of microvascular complications. BC incidence negatively impacted the glycemic control of Spanish women with pre-existing T2DM measured by basal blood glucose and HbA1c, but not cardiometabolic health indicators or T2DM complications. [ABSTRACT FROM AUTHOR]

Background: Stage III surgically resected melanoma is a disease at high risk of recurrence. Immune checkpoint inhibitors (ICIs) and the target therapy with BRAF and MEK inhibitors significantly changed the outcome of patients with metastatic melanoma and several studies have also shown their benefit in the adjuvant setting for the delay of recurrence in stage III melanoma patients. Hyperprogression disease was observed as a possible adverse response to immunotherapy in the metastatic setting, suggesting that some patients could face additional risk of progression with ICIs, although no consensus was found for the correct definition of this event. Case presentation: We describe here two cases of rapid multiorgan metastatization during adjuvant immunotherapy in patients with stage III resected melanoma. Even though it would be not accurate to define this syndrome as hyperprogression because of apparent absence of the initial disease in the adjuvant setting, we observed in these two cases the same very rapid progression after first administration of adjuvant ICIs that resulted in death of patients within two months from the starting of treatment. Both patients had NRAS mutated melanoma. Conclusion: There is an urgent need for a better understanding of the causes of these fatal outcomes and for the identification of biomarkers that would allow to select the patients before offering theman adjuvant treatment, reducing the risk of hyperprogression. Fromthese cases, we suggest that it could be useful a particular attention in proposing ICI adjuvant treatment based on the molecular profile. [ABSTRACT FROM AUTHOR]

The aim of this pilot study was to explore whether executive functioning (EF) problems of children with severe congenital heart disease (CHD) could be improved through a personalized EF-training program. Eleven preschool-aged children (mean age = 62 months, SD = 6) received a standardized test battery. Eight children were eligible for training and six children participated in the training and posttest. Due to the small sample size, only effect sizes were analyzed. Clinically relevant improvements were found with large effect sizes. Findings indicate that a personalized EF-training program could be effective in improving EF of children with severe CHD. Further research is needed. [ABSTRACT FROM AUTHOR]

In this report, we present an Asian male patient who was 30 years old and admitted to the hospital due to pancreatitis. While undergoing a CT scan, an isolated mass was unexpectedly discovered in the patient's abdomen. The patient's abdominal pain, which was caused by pancreatitis, had resolved before he underwent surgical resection to remove the mass. Subsequently, the patient was diagnosed with Castleman disease based on pathology. Castleman disease occurring in the mesentery is exceptionally rare. Therefore, we have reviewed the essential information regarding Castleman disease and have found that the crucial part lies in the diagnosis and the consideration of distinct treatment strategies based on different types. [ABSTRACT FROM AUTHOR]

Background: Device‐related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. Methods and Results: This sub‐analysis from the EUROC‐DRT‐registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0 ± 6.7 vs. 74.9 ± 9.1 years, p =.06) with lower rates of comorbidities. While DRT was detected significantly later in women (173 ± 267 vs. 127 ± 192 days, p =.01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p =.40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p =.24). Women were followed‐up for a similar time as men (779 ± 520 vs. 908 ± 687 days, p =.51). Kaplan–Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%‐Confidence interval [95%‐CI]:.68–4.37, p =.25) and no differences in stroke (HR:.83, 95%‐CI:.30–2.32, p =.72) within 2 years after LAAC. Conclusion: Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective. [ABSTRACT FROM AUTHOR]

Purpose: To study the association between meat intake (predominantly red and processed meats) and the risk of hip fracture, as well as the association between meat intake and biomarkers of inflammation, oxidative stress, bone turnover, body composition, and bone mineral density (BMD). Methods: Data from the Swedish Mammography Cohort and the Cohort of Swedish men (n = 83,603, 54% men) with repeated investigations and their respective clinical sub-cohorts was utilised. Incident hip fractures were ascertained through individual linkage to registers. Associations were investigated using multivariable Cox and linear regression analyses. Results: During up to 23 years of follow-up (mean 18.2 years) and 1,538,627 person-years at risk, 7345 participants (2840 men) experienced a hip fracture. Each daily serving of meat intake conferred a hazard ratio (HR) of 1.03 (95% confidence interval [CI] 1.00; 1.06) for hip fracture. In quintile 5, compared to quintile 2, the HR was 1.11 (95% CI 1.01; 1.21) among all participants. In the sub-cohorts, meat intake was directly associated with circulating levels of interleukin-6, C-reactive protein, leptin, ferritin, parathyroid hormone, and calcium. Conclusion: A modest linear association was found between a higher meat intake and the risk of hip fractures. Our results from the sub-cohorts further suggest that possible mechanisms linking meat intake and hip fracture risk may be related to the regulation of bone turnover, subclinical inflammation, and oxidative stress. Although estimates are modest, limiting red and processed meat intake in a healthy diet is advisable to prevent hip fractures. [ABSTRACT FROM AUTHOR]

Introduction: The impact of early recurrence of atrial tachyarrhythmia (ERAT) within the 90‐day blanking period on long‐term outcomes in atrial fibrillation (AF) patients undergoing cryoballoon ablation (CBA) is controversial. This study aimed to assess the relationship between ERAT and late recurrence of atrial tachyarrhythmia (LRAT) post‐CBA. Methods: Utilizing data from a multicenter registry in Korea (May 2018 to June 2022), we analyzed the presence and timing of ERAT (<30, 30–60, and 60–90 days) and its association with LRAT risk after CBA. LRAT was defined as any recurrence of AF, atrial flutter, or atrial tachycardia lasting more than 30 s beyond the 90 days. Results: Out of 2636 patients, 745 (28.2%) experienced ERAT post‐CBA. Over an average follow‐up period of 21.2 ± 10.3 months, LRAT was observed in 874 (33.1%) patients. Patients with ERAT had significantly lower 1‐year LRAT freedom compared to those without ERAT (42.6% vs. 85.5%, p <.001). Multivariate analysis identified ERAT as a potential predictor of LRAT, with a hazard ratio (HR) of 3.98 (95% confidence interval [CI], 3.47–4.57). Significant associations were noted across all examined time frames (HR, 3.84; 95% CI, 3.32–4.45 in <30 days, HR, 5.53; 95% CI, 4.13–7.42 in 30–60 days, and HR, 4.29; 95% CI, 3.12–5.89 in 60–90 days). This finding was consistently observed across all types of AF. Conclusion: ERAT during the 90‐day blanking period strongly predicts LRAT in AF patients undergoing CBA, indicating a need to reconsider the clinical significance of this period. [ABSTRACT FROM AUTHOR]

There is a significant variability in the prevalence of psychotropic medication use among young autistic persons worldwide and this is under-studied in Australia. Apart from risperidone, approved by the Therapeutic Goods Administration to manage challenging behaviour, the appropriateness of other psychotropic medications prescribed to young autistic persons warrants scrutiny. This retrospective study aims to gain initial insight into the magnitude, types and indications of psychotropic medication use in autistic children and adolescents in Western Australia. We analysed de-identified data from 239 autistic children and adolescents (⩽21 years) who participated in the Western Australian Autism Biological Registry between 2011 and 2015 and who completed a questionnaire regarding medication use. One-quarter (n = 66, 28%) of young autistic people reported using a total of 137 medications. Most (n = 46, 70%) of those medicated were under 12 years of age; half (n = 33) were 6–12 years and a fifth (n = 13) were under 6 years. The most used medications were stimulants (n = 35, 53.0%), followed by antidepressants (n = 24, 36.4%), antiepileptics (n = 21, 31.8%), sedatives (n = 15, 22.7%) and antipsychotics (n = 14, 21.2%). These medications were mainly to manage attention deficit hyperactivity disorder, challenging behaviours, seizures, insomnia, undefined anxiety, depression and mood instability. While most autistic young people in the Western Australian Autism Biological Registry did not report using psychotropic medication, over a quarter were prescribed medications, primarily stimulants, to manage symptoms of attention deficit hyperactivity disorder. Various medications, including risperidone, were used to help manage challenging behaviours. Medication use should be studied more comprehensively in a larger cohort of autistic persons to confirm our current preliminary observations. Further, future studies should monitor the effectiveness and safety outcomes of such medications due to a limited understanding of their effectiveness in managing the atypical presentation of co-occurring disorders in young autistic persons. Prescriptions and use of medications to treat mental health conditions in young autistic populations are inconsistent worldwide. This makes it hard to compare findings from international studies to the Australian autistic population, where there are limited relevant studies. Apart from risperidone, there are no other medications specified for direct use in autistic persons. This study aims to gain initial broad understanding of the use of medications, commonly prescribed for mental health conditions, specifically by autistics under the age of 21 years. We analysed data that were previously collected as part of the Western Australian Autism Biological Registry between 2011 and 2015 which amounted to 239 surveys completed on young persons with diagnosed autism. The questionnaires included information on co-occurring conditions, current or previous use of medications and reasons for use of the medications. Only one-quarter of the participants in this study reported using at least one mental health–related medication in their lifetime. The most reported medications were stimulants, antidepressants and antiepileptics. The reasons for using medication included managing attention deficit hyperactivity disorder, challenging behaviours, seizures, sleep difficulties and symptoms of anxiety and depression. The number of individuals reporting medication use in this study was lower compared to other developed countries. Nevertheless, these medications should be monitored due to limited understanding of their use to manage co-occurring symptoms in young autistic persons. The findings highlight the importance of ongoing research to better understand mental health–related medications and inform best practice. [ABSTRACT FROM AUTHOR]

Background: Older adults presenting with trauma have worse outcomes than younger adults. Starting in 2016, we provided geriatrics consultation (GC) to older adults admitted to the trauma service. We aimed to analyze the impact of GC on patient outcomes. Methods: We performed a retrospective pre–post study and year‐matched cohort study. We identified patients from the trauma registry at our level 1 trauma center. In the pre–post study, we compared patients who received GC (2016–2022) with controls (2011–2015). In the cohort study (2016–2022), we compared patients who received GC with controls. We matched for age, race, sex, and injury severity score (ISS) in both studies, as well as admission year in the cohort study. Outcome variables included mortality (in‐hospital, 30‐day, 90‐day), length of stay (LOS), discharge disposition, and hospital readmission rates (30‐day, 90‐day). Results: We analyzed 1968 patients in the pre–post study and 2544 patients in the cohort study. Patients were similar in age, race, and sex. GC patients had a slightly higher ISS score and a higher rate of ICU stay. Delirium occurrence was lower among GC patients. GC patients had lower in‐hospital mortality compared to controls (pre–post OR 0.27, p < 0.001; cohort OR 0.31, p < 0.001) and increased LOS (6 days vs 4 days, p < 0.001; both studies). GC patients in the cohort study also had lower 30‐ and 90‐day mortality (OR 0.52 and 0.65, p < 0.01) and were less likely to return home (OR 0.81, p < 0.01); similar trends, though not statistically significant, were noted in the pre–post study. Lower readmission rates (statistically non‐significant) were noted in the GC group across both studies. Conclusions: GC in older adults with trauma has proven benefit with reduced mortality and a trend toward lower readmission rates but was associated with increased LOS and higher rates of discharge to skilled facility. [ABSTRACT FROM AUTHOR]

Background: The incidence of thyroid cancer in the United States has risen dramatically since the 1970s, driven by an increase in the diagnosis of small tumors. There is a paucity of published New Mexico (NM) specific data regarding thyroid cancer. We hypothesized that due to New Mexico's unique geographic and cultural makeup, the incidence of thyroid cancer and tumor size at diagnosis in this state would differ from that demonstrated on a national level. Methods: The New Mexico Tumor Registry (NMTR) was queried to include all NM residents diagnosed with thyroid cancer between 1992 and 2019. For 2010 to 2019, age-adjusted incidence rates were calculated via direct method using the 2000 United States population as the adjustment standard. Differences in incidence rate and tumor size by race/ethnicity and residence (metropolitan vs non-metropolitan) were assessed with rate ratios between groups. For 1992 to 2019, temporal trends in age-adjusted incidence rates for major race/ethnic groups in NM [Non-Hispanic White (NHW), Hispanic, and American Indian (AI)] were assessed by joinpoint regression using National Cancer Institute software. Results: Our study included 3,161 patients for the time period 2010 to 2019, including NHW (1518), Hispanic (1425), and AI (218) cases. The overall incidence rates for NM AIs were lower than those for Hispanics and NHWs because of a decreased incidence of very small tumors (<1.1 cm). The incidence rates for large tumors (>5.1 cm) was equivalent among groups. In the early 2000s, Hispanics also had lower rates of small tumors when compared to NHWs but this trend disappeared over time. Conclusion: AIs in New Mexico have been left out of the nationwide increase in incidental diagnosis of small thyroid tumors. This same pattern was noted for Hispanics in the early 2000s but changed over time to mirror incidence rates for NHWs. These data are illustrative of the health care disparities that exist among New Mexico's population and how these disparities have changed over time. [ABSTRACT FROM AUTHOR]

Cat scratch disease (CSD) is an infection caused by Bartonella henselae, presents with non-specific symptoms like lymphadenopathy, fever, and fatigue. It can progress to disseminated disease, leading to complications such as liver and splenic micro abscesses, osteomyelitis, encephalitis, and uveitis. Diagnosis is challenging due to varied presentations and limited tests. Treatment involves supportive care, with severe cases requiring antimicrobial therapy. In this report, we present a case of Cat scratch disease characterized by an atypical clinical manifestation, hepatosplenic and paravertebral involvement. [ABSTRACT FROM AUTHOR]

Socio-economic status (SES) disparities exist in the uptake of COVID-19 vaccination; however, most studies were conducted during the initial pandemic wave when vaccination was less discretionary, limiting generalizability. We aimed to determine whether differences in vaccination uptake across SES strata widened after the removal of vaccination-differentiated measures prior to the rollout of the second boosters, in a nationwide cohort of older Singaporeans at higher risk of severe-COVID-19. Retrospective population-based cohort study. Retrospective population-based cohort study of all Singaporeans aged ≥60 years from 22nd February 2021–14th February 2023. Cox regression models controlling for demographics and comorbidities were used to estimate hazard-ratios (HRs) for the uptake of primary vaccination as well as first/second boosters, as recorded in the national vaccination registry, according to SES (housing type). 836,170 individuals were included for completion of a primary vaccine series; 784,938 individuals for completion of the first booster and 734,206 individuals for the completion of the second booster. Differences in vaccination uptake by SES strata were observed (e.g. vaccination uptake in lowest-SES [1–2 room public-housing] versus highest-SES [private housing]: second booster, 47.6% vs. 58.1%; first booster, 93.9% vs. 98.0%). However, relative differences did not markedly widen during second booster rollout when vaccination was more discretionary (e.g. amongst those aged 60–69 years: 0.75 [95% CI = 0.73–0.76] for the first booster; 0.81 [95% CI = 0.79–0.84] for the second booster). While differences in vaccination uptake across SES strata by housing type persisted during the rollout of primary vaccination and subsequent boosters in a nationwide cohort of older Singaporeans, differences did not widen substantially when vaccination was made more discretionary. [ABSTRACT FROM AUTHOR]

Simple Summary: Using the Proton Therapy Collaborative group registry, we describe the impact of pencil beam scanning (PBS) proton beam therapy (PBT) for Hodgkin lymphoma patients who require radiation to both mediastinal and axillary targets. We performed dosimetric comparisons between delivered PBS plans and photons with butterfly volumetric arc therapy (BVMAT). Compared to BVMAT, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving a lower dose to the lungs and heart. Nearly half of the BVMAT plans exceeded the lung V5 constraint (>55%). PBS was well tolerated without any pneumonitis or grade 3+ acute toxicity. We show here that patients requiring both mediastinal and axillary treatment may be another subgroup of lymphoma patients who may benefit from PBT. Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT. [ABSTRACT FROM AUTHOR]

The first objective is to highlight the lack of tools to measure whether a given intervention affords neuroprotection in patients with Alzheimer's or Parkinson's diseases. A second aim is to present the primary outcome measures used in clinical trials in cohorts of patients with neurodegenerative diseases. The final aim is to discuss whether metabolomics using body fluids may lead to the discovery of biomarkers of neuroprotection. Information on the primary outcome measures in clinical trials related to Alzheimer's and Parkinson's disease registered since 2018 was collected. We analysed the type of measures selected to assess efficacy, not in terms of neuroprotection since, as stated in the aims, there is not yet any marker of neuroprotection. Proteomic approaches using plasma or CSF have been proposed. PET could estimate the extent of lesions, but disease progression does not necessarily correlate with a change in tracer uptake. We propose some alternatives based on considering the metabolome. A new opportunity opens with metabolomics because there have been impressive technological advances that allow the detection, among others, of metabolites related to mitochondrial function and mitochondrial structure in serum and/or cerebrospinal fluid; some of the differentially concentrated metabolites can become reliable biomarkers of neuroprotection. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Metastatic Crohn's disease is the rarest cutaneous manifestation of Crohn's disease, it presents as cutaneous lesions in areas that are anatomically non‐contiguous with the gastrointestinal tract. It requires a high index of suspicion for diagnosis which is confirmed on histopathology. Infliximab can be an effective treatment. [ABSTRACT FROM AUTHOR]

Background Type-2 diabetes (T2D) and hypertension (HTN) are two of the most prevalent non-communicable diseases (NCDs): they both cause a relevant number of premature deaths worldwide and heavily impact the national health systems. This study illustrates the impact of HTN and T2D in four European countries (Albania, Bulgaria, Greece and Spain) and compares their policies towards the monitoring and management of HTN and T2D and the prevention of NCDs as a whole. This analysis is conducted throughout the DigiCare4You Project (H2020)—which implements an innovative solution involving digital tools for the prevention and management of T2D and HTN. Methods The analysis is implemented through desk research, and it is enriched with additional information directly provided by the local coordinators in the four countries, by filling specific semi-structured forms. Results The countries exhibit significant differences in the prevalence of HTN and T2D and available policies and programs targeted to these two chronic conditions. Each country has implemented strategies for HTN and T2D, including prevention initiatives, therapeutic guidelines, educational programs and children's growth monitoring programs. However, patient education on proper disease management needs improvement in all countries, registries about patients affected by HTN and T2D are not always available, and not all countries promoted acts to contain the increasing rates of risk factors related to NCDs. Conclusions While political awareness of the risks associated with HTN, T2D and NCDs in general is growing, there is a collective need for countries to strengthen their policies for preventing and managing these chronic diseases. [ABSTRACT FROM AUTHOR]

Background To assess the amount of breast cancer overdiagnosis associated with the National Health Service Breast Screening Programme (NHSBSP) that started in 1988 in England. Methods First, numbers of breast cancers in women eligible for breast screening not attending screening were estimated for the period 1995–2019, which were extrapolated to all women. A second method was based on ratios of incidence rates of breast cancers in women aged 50–69 to women aged 70 years or more in 1971–1985. The ratio was used for estimating expected numbers of cancers in 1988–2019, and 1995–2019. Results From 1995 to 2019, 506,607 non-invasive and invasive breast cancers were diagnosed among women aged 50–64 years (1995–2001) and 50–70 years (2002–2019). A first method estimated that 95,297 cancers were in excess to the number of cancers that would be expected had the NHSBSP not existed. 42,567 screen-detected non-invasive and micro-invasive cancers represented 45.8% of the total excess cancer. 18.8% of all cancers diagnosed among women invited to screening, 25.1% of cancers found in women attending screening, and 35.1% of cancers detected by screening would represent overdiagnosis. A second method estimated that, 18.0% of all cancers diagnosed in 1988–2019, and 18.2% of all cancers diagnosed in 1995–2019 among women invited to screening would represent overdiagnosis. Conclusion The two independent methods obtained similar estimates of overdiagnosis. The NHS Breast Screening Programme in England is associated with substantial amount of overdiagnosis. [ABSTRACT FROM AUTHOR]