Search results

LISTEN: lived experiences of Long COVID: a social media analysis of mental health and supplement use

IntroductionLong COVID, or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), is a complex condition characterized by a wide range of persistent symptoms that can significantly impact an individual's quality of life and mental health. This study explores public perspectives on the mental health impact of Long COVID and the use of dietary supplements for recovery, drawing on social media content. It uniquely addresses how individuals with Long COVID discuss supplement use in the absence of public health recommendations.MethodsThe study employs the LISTEN method (“Collaborative and Digital Analysis of Big Qual Data in Time Sensitive Contexts”), an interdisciplinary approach that combines human insight and digital analysis software. Social media data related to Long COVID, mental health, and supplement use were collected using the Pulsar Platform. Data were analyzed using the free-text discourse analysis tool Infranodus and collaborative qualitative analysis methods.ResultsThe findings reveal key themes, including the impact of Long COVID on mental health, occupational health, and the use of food supplements. Analysis of attitudes toward supplement use highlights the prevalence of negative emotions and experiences among Long COVID patients. The study also identifies the need for evidence-based recommendations and patient education regarding supplement use.DiscussionThe findings contribute to a better understanding of the complex nature of Long COVID and inform the development of comprehensive, patient-centered care strategies addressing both physical and mental health needs.

The waning of maternal measles antibodies: a multi-country maternal-infant seroprevalence study.

OBJECTIVES: To assess geographical variation in maternal measles antibody levels from birth to nine months of age, to inform recommendations for the timing of first measles vaccine dose. METHODS: Stored infant serum samples from 11 countries taken at delivery and/or follow-up time points prior to measles vaccination (N=2,845) were tested for measles plaque reduction neutralisation (PRNT) and measles, mumps, and rubella immunoglobulin G at a central laboratory. Antibody decay in infants was modelled using linear mixed effects models with participant-level random intercepts and random slopes. Proportions of infants with antibody concentrations above the clinical protection threshold (0.12 IU/mL) were estimated at each age. RESULTS: At birth most (94%, 519/552) infants had PRNT ≥0.12 IU/mL, but geometric mean concentrations ranged 0.32 IU/mL (Guatemala) to 1.60 IU/mL (Pakistan). There was no geographical variation in decay rate of PRNT nor immunoglobulin G. Geometric mean PRNT fell below 0.12 IU/mL between ages 2.5 months (Guatemala) and 6.2 months (Pakistan). At age 6 months <50% of infants had PRNT ≥0.12 IU/mL in all countries except Pakistan. CONCLUSIONS: Reliance on maternal antibodies for protection until age 9 months or later leaves most infants with insufficient direct protection against measles infection between ages 6-9 months.

What is the current evidence base for measles vaccination earlier than 9 months of age?: Report from an informal technical consultation of the World Health Organization.

Measles is one of the most contagious vaccine preventable diseases, causing severe complications and deaths globally. While vaccination with a measles-containing vaccine (MCV) has prevented millions of measles deaths, recent trends, especially from low- and middle-income countries, are discouraging. Measles cases have increased since 2021 as MCV coverage has decreased; and an estimated 107,500 measles deaths, mostly in children under-five years, occurred in 2023. Thus, a renewed focus on proven and innovative strategies to control measles is needed. The World Health Organization (WHO) recommends a first MCV dose administered at 9-15 months of age (routine MCV1), however MCV1 below 9 months of age (early MCV1) may increase vaccination coverage because uptake of all vaccines tends to be higher the younger the child, and this might protect vulnerable infants earlier in life. However, due to concerns about possible reduced vaccine performance, early MCV1 is not routinely recommended by WHO. WHO hosted an informal technical consultation on December 6-7, 2023, in Geneva, Switzerland to evaluate recent evidence on early MCV1 and identify evidence gaps for policy making. The recent evidence suggests a robust humoral immune response shortly after early MCV1 at 5-8 months of age. Immune blunting of a routine second MCV dose (e.g., MCV2) after early MCV1 was not demonstrated in the presented data. However, 3-7 years after MCV1, children receiving early MCV1 had lower measles antibodies than children receiving routine MCV1, suggesting faster waning of immunity. The totality of evidence on immune blunting remains inconsistent. Meeting participants thought more data are needed before revisiting WHO's current recommendation for a potential revision. Evidence gaps include: understanding measles disease burden and severity in infants; early MCV1 effectiveness and duration; vaccine-induced cellular immunogenicity; whether measles in infants is acquired from other infants or older children or adults; and blunting of routine MCV2. Addressing evidence gaps through targeted studies and measles outbreak investigations, as well as evaluations of country-level introductions of early MCV1 are warranted. Ensuring high MCV1 and MCV2 coverage remains the priority in measles control.

Leveraging paired serology to estimate the incidence of typhoidal Salmonella infection in the STRATAA study

Seroprevalence of Cytomegalovirus Among Pregnant Women at Kawempe National Referral Hospital, Uganda: A Cross-sectional Study.

BACKGROUND: Maternal primary cytomegalovirus (CMV) infection is associated with abortion and congenital anomalies. In Uganda, the burden of maternal CMV infection is not well studied. This study thus assessed the seroprevalence and factors associated with CMV infection among pregnant women at Kawempe National Referral Hospital in Kampala. This work forms a part of the PROGRESS study, an observational cohort study undertaken in Kampala, Uganda, between November 2018 and April 2021. METHODS: We conducted a cross-sectional study between September 2020 and January 2021 among the 639 pregnant women admitted to the labor ward at a government hospital. Sociodemographic, medical, obstetric, and socioeconomic data were collected. Blood samples from study participants were drawn and analyzed for the presence of CMV immunoglobulin G (IgG) and IgM using enzyme-linked immunosorbent assay-based quantitative assays. Further analysis of all IgM-positive samples was conducted using CMV IgG avidity assays. All infants had a nasal polymerase chain reaction (PCR) on the first day of life to investigate CMV positivity. Logistic regression was performed to determine the factors associated with CMV infection. RESULTS: Seroprevalence of CMV IgG among the 637 women was universal (100%), and that of CMV (IgM) was 5.8% (37/637). CMV (IgM) was associated with being low socioeconomic status (odds ratio, 3.44; 95% CI, 1.05-11.32; P = .04). Transmission risk was low, and no infant had a positive PCR for CMV at birth. CONCLUSIONS: Universally, by the time women in Kampala conceive, they will have been exposed to CMV. Women of lower socioeconomic status were more likely to have recent CMV infection than their more affluent counterparts, highlighting the need for screening guidelines in this setting.

The validity of test-negative design for assessment of typhoid conjugate vaccine protection: comparison of estimates by different study designs using data from a cluster-randomised controlled trial.

BACKGROUND: Typhoid fever remains a substantial public health challenge in low-income and middle-income countries. By 2023, typhoid conjugate vaccines (TCVs) had been introduced in six countries globally, with more than 50 million doses distributed. Now that TCVs are being deployed, there is a need for observational studies to assess vaccine effectiveness in the field. We aimed to evaluate the validity of different observational study designs in estimating vaccine protection. METHODS: We compared different observational and experimental study designs for assessing vaccine effectiveness by re-analysing data from the TyVAC Bangladesh trial, a participant-blinded and observer-blinded cluster-randomised controlled trial done in Mirpur, Dhaka, Bangladesh. 150 geographical clusters were randomly assigned (1:1) to receive either TCV or Japanese encephalitis vaccine. Eligible children aged 9 months to 15 years were offered a single dose of the vaccine randomly assigned to their cluster of residence, and baseline vaccination was done between April 15 and May 15, 2018. We compared estimates of vaccine effectiveness from the cluster-randomised controlled trial analysis-which assessed the risk of blood-culture-confirmed typhoid fever among recipients of TCV versus recipients of Japanese encephalitis vaccine-with estimates from cohort study and test-negative case-control study design (TND) analyses, which compared recipients of TCV with non-vaccinees in the 75 geographical clusters where TCV was administered. We further conducted negative-control exposure (NCE) and negative-control outcome (NCO) analyses as bias indicators. FINDINGS: 41 344 (67%) of 62 025 age-eligible children in the study area received the TCV or Japanese encephalitis vaccine during the baseline vaccination campaign. Among the 62 025 age-eligible children, 5582 blood-culture specimens were collected by passive surveillance, including 2546 (46%) specimens from the 75 TCV clusters. The estimated vaccine efficacy was 89% (95% CI 81-93) in the cluster-randomised controlled trial analysis, 79% (70-86) by the cohort design, 88% (79-93) by the TND when pan-negatives were used as test-negative controls, and 90% (75-96) by the TND when specimens positive for pathogens other than Salmonella enterica serotype Typhi were used as test-negative controls. Using NCE analysis, Japanese encephalitis vaccination was associated with an increased risk of typhoid fever compared with non-vaccinees in the 75 Japanese encephalitis clusters in the cohort design (incidence rate ratio 1·98 [95% CI 1·56-2·52]), but no significant association between Japanese encephalitis vaccination and typhoid fever was found with the TND. Similarly, an increased risk of non-typhoid infections was observed in the cohort NCO analyses when comparing vaccinees with non-vaccinees in both Japanese encephalitis vaccine clusters and TCV clusters, but not in the TND NCO analyses. INTERPRETATION: Our findings suggests that the TND provides reliable estimates of TCV effectiveness, whereas the cohort design can bias vaccine effectiveness estimates, possibly due to unmeasured confounding effects, such as health-care-seeking behaviours. NCE and NCO approaches are useful tools for identifying such biases. FUNDING: The Bill & Melinda Gates Foundation.

Influence of context on engagement with COVID-19 testing: a scoping review of barriers and facilitators to testing for healthcare workers, care homes and schools in the UK.

OBJECTIVE: The UK government's response to the COVID-19 pandemic included a 'test, trace and isolate' strategy. Testing services for healthcare workers, care homes and schools accounted for the greatest spend and volume of tests. We reviewed relevant literature to identify common and unique barriers and facilitators to engaging with each of these testing services. DESIGN: Scoping review. SEARCH STRATEGY: PubMed, Scopus and the WHO COVID-19 Research Database were searched for evidence published between 1 January 2020 and 7 November 2022. This was supplemented by evidence identified via free-text searches on Google Scholar and provided by the UK Health Security Agency (UKHSA). DATA EXTRACTION AND SYNTHESIS: Data were extracted by a team of reviewers and synthesised thematically under the broad headings of perceptions, experiences, barriers and facilitators to engaging with the COVID-19 testing programme. RESULTS: This study included 40 sources, including 17 from projects that informed UKHSA's decisions during the pandemic. Eight themes emerged and were used to categorise barriers and facilitators to engaging with the testing services for healthcare workers, care homes and schools: (1) perceived value, (2) trust in the tests and public bodies, (3) importance of infrastructure, (4) impact of media and social networks, (5) physical burden of the test, (6) perceived capability to undertake testing, (7) importance of relevant information and 8) consequences of testing. CONCLUSIONS: Universal barriers and facilitators to engagement with the testing programme related to the core elements of each testing service, such as uncomfortable specimen collection and the influence of media and peers; these could be mitigated or leveraged to increase engagement across settings. However, the individuals involved, perceptions of value and available resources differed across services, leading to unique experiences between settings. Thus, consideration of context is crucial when designing and implementing a testing programme in response to a pandemic.

The TyphiNET data visualisation dashboard: unlocking Salmonella Typhi genomics data to support public health.

BACKGROUND: Salmonella enterica subspecies enterica serovar Typhi (abbreviated as 'Typhi') is the bacterial agent of typhoid fever. Effective antimicrobial therapy reduces complications and mortality; however, antimicrobial resistance (AMR) is a major problem in many endemic countries. Prevention through vaccination is possible through recently-licensed typhoid conjugate vaccines (TCVs). National immunisation programs are currently being considered or deployed in several countries where AMR prevalence is known to be high, and the Gavi vaccine alliance has provided financial support for their introduction. Pathogen whole genome sequence data are a rich source of information on Typhi variants (genotypes or lineages), AMR prevalence, and mechanisms. However, this information is currently not readily accessible to non-genomics experts, including those driving vaccine implementation or empirical therapy guidance. RESULTS: We developed TyphiNET ( https://www.typhi.net ), an interactive online dashboard for exploring Typhi genotype and AMR distributions derived from publicly available pathogen genome sequences. TyphiNET allows users to explore country-level summaries such as the frequency of pathogen lineages, temporal trends in resistance to clinically relevant antimicrobials, and the specific variants and mechanisms underlying emergent AMR trends. User-driven plots and session reports can be downloaded for ease of sharing. Importantly, TyphiNET is populated by high-quality genome data curated by the Global Typhoid Pathogen Genomics Consortium, analysed using the Pathogenwatch platform, and identified as coming from non-targeted sampling frames that are suitable for estimating AMR prevalence amongst Typhi infections (no personal data is included in the platform). As of February 2024, data from a total of n = 11,836 genomes from 101 countries are available in TyphiNET. We outline case studies illustrating how the dashboard can be used to explore these data and gain insights of relevance to both researchers and public health policy-makers. CONCLUSIONS: The TyphiNET dashboard provides an interactive platform for accessing genome-derived data on pathogen variant frequencies to inform typhoid control and intervention strategies. The platform is extensible in terms of both data and features, and provides a model for making complex bacterial genome-derived data accessible to a wide audience.

Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.

The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.

Apnoea suppresses brain activity in infants

Apnoea—the cessation of breathing—is commonly observed in premature infants. These events can reduce cerebral oxygenation and are associated with poorer neurodevelopmental outcomes. However, relatively little is known about how apnoea and shorter pauses in breathing impact brain function in infants, which will provide greater mechanistic understanding of how apnoea affects brain development. We analysed simultaneous recordings of respiration, electroencephalography (EEG), heart rate, and peripheral oxygen saturation in 124 recordings from 118 infants (post-menstrual age: 38.6 ± 2.7 weeks [mean ± standard deviation]) during apnoeas (pauses in breathing greater than 15 seconds) and shorter breathing pauses between 5 and 15 seconds. EEG amplitude significantly decreased during both apnoeas and short breathing pauses compared with normal breathing periods. Change in EEG amplitude was significantly associated with change in heart rate during apnoea and short breathing pauses and, during apnoeas only, with oxygen saturation change. No associations were found between EEG amplitude changes and apnoea/pause duration, post-menstrual age, or sleep state. As apnoeas often occur in premature infants, frequent disruption to brain activity may impact neural development and result in long-term neurodevelopmental consequences.

Hot, swollen or stiff joints in children and young people: British Society for Rheumatology guideline scope.

The objective of this guideline is to provide up-to-date, evidence-based recommendations for the management of children and young people (CYP) who present with one or more hot, swollen or stiff joints. It will incorporate assessment, diagnosis, monitoring, non-pharmacological and initial pharmacological management preceding definitive diagnosis. This is the first British Society for Rheumatology guideline for hot, swollen or stiff joints in CYP <18 years of age and will complement the hot, swollen joint guideline created for adults ≥18 years of age. The guideline will be developed using the methods and rigorous processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.4.

Real-world uptake of nirsevimab, RSV maternal vaccine, and RSV vaccines for older adults: a systematic review and meta-analysis

Background: In clinical trials, recently introduced respiratory syncytial virus (RSV) immunisation products have shown high efficacy in preventing severe RSV outcomes. Implementing successful immunisation programmes is however key to realising these benefits in real-world settings. We aimed to investigate uptake of the long-acting monoclonal antibody nirsevimab, the RSV maternal vaccine, and RSV vaccines for older adults in countries where immunisation programmes have been introduced, and to explore how uptake varies between countries and population subgroups. Methods: In this systematic review and meta-analysis, we carried out four monthly searches in Medline, Embase, and Global Health databases for studies reporting uptake of nirsevimab, the RSV maternal vaccine, and RSV vaccines for older adults. We included population-based studies published between December 1, 2022 and February 5, 2025. Two independent reviewers screened studies, extracted data, and completed a risk of bias assessment using the Joanna Briggs Institute (JBI) Critical Appraisal Tools. We assessed uptake stratified by country and socio-demographic and clinical subgroups. Meta-analyses were conducted using random-effects modelling. PROSPERO registration number: CRD42025643585. Findings: We screened a total of 1267 studies, 43 of which met the inclusion criteria reporting data on over 1.38 million individuals from six countries. Nirsevimab uptake data were reported in 34 studies: 16 from Spain, eight from the United States, seven from France, one with combined data from Andorra and Spain, and one from each of Italy and Luxembourg. Our pooled estimates showed that nirsevimab uptake on population level was 90.1% (95% confidence interval (CI): 86.4–92.9) in Spain and 51.2% (95% CI: 29.3–72.7) in the United States during the 2023/24 RSV season. Uptake data for the RSV maternal vaccine and RSV vaccines for older adults were reported in five and eight studies, respectively, all from the United States. Meta-analysis showed population-level uptake of 30.5% (95% CI: 20.6–42.6) and 18.2% (95% CI: 10.8–28.9), respectively. Uptake varied across subgroups. Interpretation: Uptake of nirsevimab varied substantially between the countries that have implemented infant RSV immunisation programmes. Despite the limited number of studies and the lack of more accurate data at national level the low uptake estimates for RSV maternal vaccine and RSV vaccines for older adults are concerning. National, clinical, and public health initiatives are needed to increase uptake of RSV immunisation products and ensure maximum benefit to people currently at risk of severe RSV outcomes. Funding: Health Data Research UK, Inflammation and Immunity Driver Programme.

MODELING THE PATHOGENESIS OF RUNX1 DEFICIENCY IN INHERITED AML PREDISPOSITION SYNDROMES IN PRIMARY CELLS

Simulated kangaroo care in very preterm infants does not reduce physiological instability: the COSYBABY randomised controlled cross-over trial.

INTRODUCTION: Infants who are born very preterm experience frequent episodes of physiological instability including apnoea, oxygen desaturation and bradycardia due to immaturity of the pulmonary and nervous systems. Parental contact, such as kangaroo care, may reduce physiological instability. However, there may be long periods when parents cannot be with their baby. The BABYBE SYSTEM® is a medical device designed to simulate kangaroo care. METHODS: We conducted a randomised cross-over trial to determine whether episodes of apnoea and other episodes of physiological instability were reduced when infants were on an active BABYBE mattress. Each infant was included in the study for five consecutive days, with successive 12-h periods of the BABYBE® mattress being switched on or off. Episodes of physiological instability were identified from recordings of the vital signs monitors and compared with clinical notes. Generalised estimating equations models were used to compare physiological instability when the BABYBE mattress was switched on vs. off. RESULTS: A total of 23 infants born before 32 weeks' gestation were included in the main analysis. There was no significant difference between the number of apnoeic episodes infants experienced in the 12-h period when the BABYBE mattress was on compared with when the mattress was switched off (difference between conditions = 1.5 apnoeas, 95% CI: -0.2-3.2, p = 0.09). The number of episodes of apnoea identified from vital signs recordings were much higher than those documented in the clinical records (a total of 1,157 apnoeic episodes were identified across all infants from vital signs recordings compared with a total of 27 documented in clinical/nursing notes of the same infants). DISCUSSION: This trial does not provide evidence of a benefit of the BABYBE mattress for improving physiological stability in preterm infants. This study provides confirmation of the under-recognition of apnoeic episodes in clinical notes and the benefit of assessing electronic recordings of vital signs to gain a more complete picture of physiological stability.

Early mucosal responses following a randomised controlled human inhaled infection with attenuated Mycobacterium bovis BCG.

The development of an effective vaccine against Mycobacterium tuberculosis is hampered by an incomplete understanding of immunoprotective mechanisms. We utilise an aerosol human challenge model using attenuated Mycobacterium bovis BCG, in BCG-naïve UK adults. The primary endpoint of this study (NCT03912207) was to characterise the early immune responses induced by aerosol BCG infection, the secondary endpoint was to identify immune markers associated with in-vitro protection. Blinded volunteers were randomised to inhale 1 × 107 CFU aerosolised BCG or 0.9% saline (20:6); and sequentially allocated to bronchoscopy at day 2 or 7 post-inhalation (10 BCG, 3 saline each timepoint). In the bronchoalveolar lavage post-aerosol BCG infection, there was an increase in frequency of eosinophils, neutrophils, NK cells and Donor-Unrestricted T cells at day 7, and the frequency of antigen presenting cells decreased at day 7 compared with day 2. The frequency of interferon-gamma+ BCG-specific CD4+ T cells increased in the BAL and peaked in the blood at day 7 post-BCG infection compared to day 2. BAL cells at day 2 and day 7 upregulated gene pathways related to phagocytosis, MHC-II antigen loading, T cell activation and proliferation. BCG's lack of key virulence factors and its failure to induce granulomas, may mean the observed immune responses do not fully recapitulate Mycobacterium tuberculosis infection. However, human infection models can provide unique insights into early immune mechanisms, informing vaccine design for complex pathogens.

Bi-specific CAR-iNKT cell immunotherapy for high-risk KMT2A-rearranged leukemia outperforms CAR-T in an NKG2D-dependent manner and eradicates leptomeningeal disease

Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast-phase MPN through targetable overexpression of DYRK1A

Abstract Chromothripsis, the chaotic shattering and repair of chromosomes, is common in cancer. Whether chromothripsis generates actionable therapeutic targets remains an open question. In a cohort of 64 patients in blast phase of a myeloproliferative neoplasm (BP-MPN), we describe recurrent amplification of a region of chromosome 21q (‘chr. 21amp’) in 25%, driven by chromothripsis in a third of these cases. We report that chr. 21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. DYRK1A, a serine threonine kinase, is the only gene in the 2.7-megabase minimally amplified region that showed both increased expression and chromatin accessibility compared with non-chr. 21amp BP-MPN controls. DYRK1A is a central node at the nexus of multiple cellular functions critical for BP-MPN development and is essential for BP-MPN cell proliferation in vitro and in vivo, and represents a druggable axis. Collectively, these findings define chr. 21amp as a prognostic biomarker in BP-MPN, and link chromothripsis to a therapeutic target.

Patient and caregiver spinal muscular atrophy treatment attribute preferences in Latin America.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease associated with a significant burden of illness to both patients and caregivers; however, there is little evidence available regarding how patients and caregivers evaluate potential treatment benefit-risk profiles. As access to SMA disease-modifying therapies increases, it is imperative to understand which treatment attributes drive treatment choices. OBJECTIVE: To identify which treatment attributes drive treatment choices in adults with SMA and caregivers of children with SMA across nine countries in Latin America. METHODS: A discrete choice experiment (DCE) survey was developed for market research using data collected via qualitative interviews and consultations with medical experts. Adults with Type 2/3 SMA and caregivers of children with Types 1-3 SMA were recruited by patient advisory groups and physician referrals. Respondents completed a 30-min, online survey that collected patient demographics, disease-specific information, and quality of life data (via the EQ-5D-5L), and included the DCE, in which respondents were asked to choose between 14 sets of hypothetical treatment profiles. Data were pooled for analysis, as the country-level sample sizes were small. Raw data were aggregated in Microsoft Excel. Statistical testing was performed using data tables and SPSS (as appropriate). Demographic data were summarized descriptively. RESULTS: A total of 143 respondents (45 adults with SMA and 98 caregivers) completed the online survey. Most respondents were from Argentina (35.0%) or Brazil (19.6%). Breathing function outcome was the most important treatment attribute for caregivers, while adults with SMA placed greater importance on motor function outcome. Both adults with SMA and caregivers placed the greatest importance on improvements in function compared with worse or stable outcomes. CONCLUSIONS: Understanding treatment attribute preferences at a regional level will improve shared medical decision-making for individuals with SMA.

A systematic review on motor outcome measures in congenital myopathy.

Congenital myopathies (CMYOs) encompass a group of genetically heterogeneous rare muscle disorders with clinical features including hypotonia, muscle weakness leading to delayed or absent motor milestones, feeding and respiratory difficulties, and a myopathic facial appearance. CMYO categorisation includes: Nemaline Myopathy, Core Myopathy, Central Core Disease, Multi-Mini Core Disease, Congenital Fiber-type Disproportion Myopathy, Myosin Storage Myopathy, Centronuclear Myopathy, Myotubular Myopathy, X-linked Myotubular Myopathy, and Autosomal Centronuclear Myopathy. The aim of this systematic review is to evaluate the current evidence base of motor outcome measures used in the assessment of CMYO. Methodology was in accordance with the PRISMA 2020 guidelines and registered (PROSPERO CRD42024569701). Databases searched include PubMed, EMBASE, and Cochrane library. Peer reviewed, full-text, English language publications were included. The 31 articles included motor outcome measures of motor function, gross motor, muscle strength, and endurance. Twenty-six motor outcome measures were identified and all were found to have limited disease-specific metrics. This systematic review discussed motor outcome measure suitably in relation to disease characteristics and identified the lack of disease-specificity as the largest gap for future research.

Data-driven consideration of genetic disorders for global genomic newborn screening programs.

PURPOSE: Over 30 international studies are exploring newborn sequencing (NBSeq) to expand the range of genetic disorders included in newborn screening. Substantial variability in gene selection across programs exists, highlighting the need for a systematic approach to prioritize genes. METHODS: We assembled a data set comprising 25 characteristics about each of the 4390 genes included in 27 NBSeq programs. We used regression analysis to identify several predictors of inclusion and developed a machine learning model to rank genes for public health consideration. RESULTS: Among 27 NBSeq programs, the number of genes analyzed ranged from 134 to 4299, with only 74 (1.7%) genes included by over 80% of programs. The most significant associations with gene inclusion across programs were presence on the US Recommended Uniform Screening Panel (inclusion increase of 74.7%, CI: 71.0%-78.4%), robust evidence on the natural history (29.5%, CI: 24.6%-34.4%), and treatment efficacy (17.0%, CI: 12.3%-21.7%) of the associated genetic disease. A boosted trees machine learning model using 13 predictors achieved high accuracy in predicting gene inclusion across programs (area under the curve = 0.915, R2 = 84%). CONCLUSION: The machine learning model developed here provides a ranked list of genes that can adapt to emerging evidence and regional needs, enabling more consistent and informed gene selection in NBSeq initiatives.