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BACKGROUND: Pressure pain threshold (PPT) measurements require standardised verbal instructional cues to ensure that the increasing pressure is stopped at the correct time consistently. This study aimed to compare how PPT values and their test-retest reliability were affected by different instructional cues. METHODS: At two separate sessions, two PPT measurements were taken at the anterior knee for each of four different instructional cues: the cue of the German Neuropathic Research Network instructions ('DFNS'), the point where pressure first feels uncomfortable ('Uncomfortable'), 3/10 on the numerical pain rating scale ('3NPRS'), and where pain relates to an image from the pictorial-enhanced NPRS scale ('Pictorial'). Linear mixed modeling was used to quantify differences between pairs of instructional cues. Test-retest reliability was estimated using intraclass correlation coefficients (ICC[2,1] and ICC[2,k]). RESULTS: Twenty participants were recruited. The cue resulting in greatest PPT value was DFNS (394.32 kPa, 95%CI [286.32 to 543.06]), followed by Pictorial (342.49 kPa, 95%CI [248.68 to 471.68]), then Uncomfortable (311.85 kPa, 95%CI [226.43 to 429.48]), and lastly 3NPRS (289.78 kPa, 95%CI [210.41 to 399.09]). Five of six pairwise contrasts were statistically significant. Regardless of the cues, the point estimates of ICC (2,1) ranged from 0.80 to 0.86, and the ICC (2,k) values ranged from 0.89 to 0.93. No statistically significant differences were found between any pairwise contrasts of reliability indices. CONCLUSION: Words matter when instructing people when to stop testing in pressure algometry. Clinicians should use the same instructional cue when assessing pain thresholds to ensure reliability.
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Background To address rural physician workforce shortages, the Health Resources and Services Administration funded multiple Rural Residency Planning and Development (RRPD) awards, beginning in 2019, to develop rural residency programs in needed specialties. Objective To describe early resident recruitment outcomes of the RRPD grants program. Methods A cross-sectional survey of program directors or administrators of these 25 new rural residency training programs across the United States was administered at RRPD award conclusion in 2022. We performed descriptive analyses of applicant and Match data, including applications and interviews per resident position, positions filled in the main Match vs the Supplemental Offer and Acceptance Program (SOAP), and recruitment of residents from the program's state. Results The 25 Cohort 1 RRPD programs ranged from 2 to 8 residents per year. Most programs (16 of 25, 64.0%) were rural expansion tracks of an urban program. Most programs were sufficiently developed to participate in the 2022 (N=17) or 2023 (N=20) Match; we report on 13 of 17 (76.5%) programs for 2022 and 14 of 20 (70.0%) programs for 2023. Programs completed a median of 14.8 interviews per position. Most positions were filled in the Match (43 of 58, 74.1% in 2022; 45 of 58, 77.6% in 2023); most others were filled in the SOAP. On average, 34.4% of enrolled residents were from the same state as the program (range 0-78.6%). Conclusions The early resident recruitment outcomes of the RRPD model for developing new physician training in rural communities had sufficient recruitment success to support program continuation.
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Internato e Residência , Seleção de Pessoal , Serviços de Saúde Rural , Humanos , Estudos Transversais , Estados Unidos , Educação de Pós-Graduação em Medicina , Inquéritos e Questionários , United States Health Resources and Services Administration , População RuralRESUMO
Background: Lumbar mobility is regarded as important for assessing and managing low back pain (LBP). Inertial Measurement Units (IMUs) are currently the most feasible technology for quantifying lumbar mobility in clinical and research settings. However, their gyroscopes are susceptible to drift errors, limiting their use for long-term remote monitoring. Research question: Can a single tri-axial accelerometer provide an accurate and feasible alternative to a multi-sensor IMU for quantifying lumbar flexion mobility and velocity? Methods: In this cross-sectional study, 18 healthy adults performed nine repetitions of full spinal flexion movements. Lumbar flexion mobility and velocity were quantified using a multi-sensor IMU and just the tri-axial accelerometer within the IMU. Correlations between the two methods were assessed for each percentile of the lumbar flexion movement cycle, and differences in measurements were modelled using a Generalised Additive Model (GAM). Results: Very high correlations (r > 0.90) in flexion angles and velocities were found between the two methods for most of the movement cycle. However, the accelerometer overestimated lumbar flexion angle at the start (-4.7° [95 % CI -7.6° to -1.8°]) and end (-4.8° [95 % CI -7.7° to -1.9°]) of movement cycles, but underestimated angles (maximal difference of 4.3° [95 % CI 1.4° to 7.2°]) between 7 % and 92 % of the movement cycle. For flexion velocity, the accelerometer underestimated at the start (16.6°/s [95%CI 16.0 to 17.2°/s]) and overestimated (-12.3°/s [95%CI -12.9 to -11.7°/s]) at the end of the movement, compared to the IMU. Significance: Despite the observed differences, the study suggests that a single tri-axial accelerometer could be a feasible tool for continuous remote monitoring of lumbar mobility and velocity. This finding has potential implications for the management of LBP, enabling more accessible and cost-effective monitoring of lumbar mobility in both clinical and research settings.
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Acute pancreatitis (AP) is a life-threatening inflammatory disease with no specific therapy. Excessive cytoplasmic Ca2+ elevation and intracellular ATP depletion are responsible for the initiation of AP. Inhibition of Ca2+ release-activated Ca2+ (CRAC) channels has been proposed as a potential treatment, and currently, a novel selective CRAC channel inhibitor CM4620 (Auxora, CalciMedica) is in Phase 2b human trials. While CM4620 is on track to become the first effective treatment for AP, it does not produce complete protection in animal models. Recently, an alternative approach has suggested reducing ATP depletion with a natural carbohydrate galactose. Here, we have investigated the possibility of using the smallest effective concentration of CM4620 in combination with galactose. Protective effects of CM4620, in the range of 1-100 n m, have been studied against necrosis induced by bile acids, palmitoleic acid, or l-asparaginase. CM4620 markedly protected against necrosis induced by bile acids or asparaginase starting from 50 n m and palmitoleic acid starting from 1 n m. Combining CM4620 and galactose (1 m m) significantly reduced the extent of necrosis to near-control levels. In the palmitoleic acid-alcohol-induced experimental mouse model of AP, CM4620 at a concentration of 0.1 mg/kg alone significantly reduced edema, necrosis, inflammation, and the total histopathological score. A combination of 0.1 mg/kg CM4620 with galactose (100 m m) significantly reduced further necrosis, inflammation, and histopathological score. Our data show that CM4620 can be used at much lower concentrations than reported previously, reducing potential side effects. The novel combination of CM4620 with galactose synergistically targets complementary pathological mechanisms of AP.
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Galactose , Pancreatite , Galactose/farmacologia , Animais , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Camundongos , Bloqueadores dos Canais de Cálcio/farmacologia , Cinacalcete/farmacologia , Cinacalcete/uso terapêutico , Humanos , Masculino , Ácidos e Sais Biliares/metabolismo , Modelos Animais de Doenças , Necrose/tratamento farmacológico , Doença Aguda , Ácidos Graxos MonoinsaturadosRESUMO
BACKGROUND: Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients' ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data. METHODS: We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census. RESULTS: 78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%). CONCLUSIONS: Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data.
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Etnicidade , Atenção Primária à Saúde , Medicina Estatal , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Inglaterra , Etnicidade/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
An alternative to lifelong antiretroviral therapy (ART) is needed to achieve durable control of HIV-1. Here we show that adeno-associated virus (AAV)-delivery of two rhesus macaque antibodies to the SIV envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected with barcoded SIVmac239M after discontinuing suppressive ART. Following AAV administration, sustained antibody expression with minimal anti-drug antibody responses was achieved in all but one animal. After ART withdrawal, SIV replication rebounded within two weeks in all of the control animals but remained below the threshold of detection in plasma (<15 copies/mL) for more than a year in four of the eight animals that received AAV vectors encoding Env-specific antibodies. Viral sequences from animals with delayed rebound exhibited restricted barcode diversity and antibody escape. Thus, sustained expression of antibodies with potent antiviral activity can afford durable, ART-free containment of pathogenic SIV infection.
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BACKGROUND: Public involvement is important to the relevance and impact of health and care research, as well as supporting the democratisation of research. In 2020, the National Institute for Health Research (NIHR) reorganized and eliminated INVOLVE, an internationally recognised group that had played a central role in public involvement in the UK since 1996. Its remit was subsumed within a new center tasked with public involvement, participant recruitment, and evidence dissemination. A year later, in 2021, interested parties came together to discuss the evolution of INVOLVE and consider how to retain some of the important historical details and learn lessons from its long and important tenure. METHODS: We hosted a witness seminar in 2022 that was one of four work groups and brought together public involvement leaders that had been part of the conception, development, and evolution of INVOLVE between 1995 and 2020. Witness seminars are a method used to capture the complexity and nuance of historical events or initiatives. They support critical thinking and reflection rather than simple commemoration. We identified those who had played a role in INVOLVE history, ensuring diversity of perspective, and invited them to attend and speak at the seminar. This took place during two sessions where witnesses provided their recollections and participated in a facilitated discussion. RESULTS: Across the two online sessions, 29 witnesses attended and contributed thoughts and recollections. Two authors (SS, MP) identified six themes that were described in the witness seminar report and have been discussed, elaborated, and illustrated with witness quotations. These are: the importance of historical perspective; INVOLVE as a social movement; how INVOLVE worked (e.g. its hospitality, kindness, and inclusivity); INVOLVE as a quiet disruptor; public involvement evidence, knowledge, and learning; the infrastructure, processes, and systems developed by INVOLVE; and the demise and loss of INVOLVE as an internationally recognized center of excellence. DISCUSSION: The authors of this commentary reflected on the discussions that took place during the witness seminar and the themes that emerged, and share six broad learnings for future practice; (1) it is important to create and nurture public involvement communities of practice; (2) collaborative ways of working support open discussion amongst diverse groups; (3) be aware of the tensions between activism and being part of the establishment; (4) continued efforts should be made to build an evidence base for public involvement practice; (5) there are both benefits and drawbacks to having a centralized organization leading public involvement; and (6) support for public involvement in research requires a fit-for-purpose tendering process that embeds robust public involvement.
BACKGROUND: Involving members of the public in research can improve the way that research is planned, managed, and shared. Between 1996 and 2020 an organization in the UK called INVOLVE had an important role in public involvement in research. When INVOLVE lost this role, some people who had been part of the group got together to think about how to save some of the important information and learn lessons from the time it had existed. METHODS: A meeting was arranged where people who have been part of an event or topic get together to share what it was like for them. This was called a witness seminar and it took place online over two days in 2022. Twenty-nine people attended and spoke about their experiences. RESULTS: The people who attended the witness seminar had different ideas about why INVOLVE was important and agree that it is now missed. People talked about INVOLVE as part of a certain time in history and said it was a social movement. They felt that it was kind and caring, brought together lots of people with different ideas, and supported changes in thinking. INVOLVE had a focus on evidence and learning and created structure and systems to support public involvement in research. Losing INVOLVE was difficult because a lot of people within the UK and beyond looked to them as a leader in public involvement. We share quotes on all of these topics. DISCUSSION: In this article we looked at how people remembered INVOLVE and thought about what information could be saved. We share lessons that will support thinking about the future of public involvement. These include things like how important it is for there to be spaces for people to come together to learn, discuss, and share, and that we have more work to do to understand public involvement and fully include it in research.
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The Late Cretaceous of western North America supported diverse dinosaur assemblages, though understanding patterns of dinosaur diversity, evolution, and extinction has been historically limited by unequal geographic and temporal sampling. In particular, the existence and extent of faunal endemism along the eastern coastal plain of Laramidia continues to generate debate, and finer scale regional patterns remain elusive. Here, we report a new centrosaurine ceratopsid, Lokiceratops rangiformis, from the lower portion of the McClelland Ferry Member of the Judith River Formation in the Kennedy Coulee region along the Canada-USA border. Dinosaurs from the same small geographic region, and from nearby, stratigraphically equivalent horizons of the lower Oldman Formation in Canada, reveal unprecedented ceratopsid richness, with four sympatric centrosaurine taxa and one chasmosaurine taxon. Phylogenetic results show that Lokiceratops, together with Albertaceratops and Medusaceratops, was part of a clade restricted to a small portion of northern Laramidia approximately 78 million years ago. This group, Albertaceratopsini, was one of multiple centrosaurine clades to undergo geographically restricted radiations, with Nasutuceratopsini restricted to the south and Centrosaurini and Pachyrostra restricted to the north. High regional endemism in centrosaurs is associated with, and may have been driven by, high speciation rates and diversity, with competition between dinosaurs limiting their geographic range. High speciation rates may in turn have been driven in part by sexual selection or latitudinally uneven climatic and floral gradients. The high endemism seen in centrosaurines and other dinosaurs implies that dinosaur diversity is underestimated and contrasts with the large geographic ranges seen in most extant mammalian megafauna.
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Dinossauros , Fósseis , Filogenia , Dinossauros/anatomia & histologia , Dinossauros/classificação , Animais , Montana , Evolução Biológica , Rios , BiodiversidadeRESUMO
Sexually and gender diverse staff in Higher Education Institutions may experience a sense of belonging and acceptance in inclusive environments, but may also face discrimination and bias, leading to feelings of isolation and exclusion. This paper reports on findings from 40 in-depth interviews and six focus group discussions with LGBTQIA+ self-identified staff members in a HEI and LGBTQIA+ allies who may identify as LGBTQIA+ themselves. Findings reveal that first impressions when joining a university as a staff member may have a long-lasting effect, while both positive and negative experiences are present. Further, a pattern is developed among gay men who may be placing more emphasis on their relationship with line managers, which can be supportive but at times toxic, unsupportive and inattentive. In addition to this, the findings highlight discrimination faced by staff, its impact on their wellbeing, and the significance of visibility and representation. This paper concludes that lived experiences of LGBTQIA+ staff members in Higher Education continue to be mixed with a high percentage of staff experiencing discrimination, primarily in the form of microaggressions, but institutions need to be more pro-active to foster safe spaces for all with more inclusive policies and practices.
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BACKGROUND: We have previously demonstrated that opioid prescribing increased by 127% between 1998 and 2016. New policies aimed at tackling this increasing trend have been recommended by public health bodies, and there is some evidence that progress is being made. OBJECTIVE: We sought to extend our previous work and develop a data-driven approach to identify general practices and clinical commissioning groups (CCGs) whose prescribing data suggest that interventions to reduce the prescribing of opioids may have been successfully implemented. METHODS: We analyzed 5 years of prescribing data (December 2014 to November 2019) for 3 opioid prescribing measures-total opioid prescribing as oral morphine equivalent per 1000 registered population, the number of high-dose opioids prescribed per 1000 registered population, and the number of high-dose opioids as a percentage of total opioids prescribed. Using a data-driven approach, we applied a modified version of our change detection Python library to identify reductions in these measures over time, which may be consistent with the successful implementation of an intervention to reduce opioid prescribing. This analysis was carried out for general practices and CCGs, and organizations were ranked according to the change in prescribing rate. RESULTS: We identified a reduction in total opioid prescribing in 94 (49.2%) out of 191 CCGs, with a median reduction of 15.1 (IQR 11.8-18.7; range 9.0-32.8) in total oral morphine equivalence per 1000 patients. We present data for the 3 CCGs and practices demonstrating the biggest reduction in opioid prescribing for each of the 3 opioid prescribing measures. We observed a 40% proportional drop (8.9% absolute reduction) in the regular prescribing of high-dose opioids (measured as a percentage of regular opioids) in the highest-ranked CCG (North Tyneside); a 99% drop in this same measure was found in several practices (44%-95% absolute reduction). Decile plots demonstrate that CCGs exhibiting large reductions in opioid prescribing do so via slow and gradual reductions over a long period of time (typically over a period of 2 years); in contrast, practices exhibiting large reductions do so rapidly over a much shorter period of time. CONCLUSIONS: By applying 1 of our existing analysis tools to a national data set, we were able to identify rapid and maintained changes in opioid prescribing within practices and CCGs and rank organizations by the magnitude of reduction. Highly ranked organizations are candidates for further qualitative research into intervention design and implementation.
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Analgésicos Opioides , Padrões de Prática Médica , Humanos , Analgésicos Opioides/uso terapêutico , Estudos Retrospectivos , Padrões de Prática Médica/estatística & dados numéricos , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricosRESUMO
BACKGROUND: Disability is an important multifaceted construct. A brief, generic self-reported disability questionnaire that promises a broader and more comparable measure of disability than disease-specific instruments does not currently exist. The aim of this study was to develop and evaluate such a questionnaire: the Universal Disability Index (UDI). METHODS: An online survey was used to collect general population data. Data were randomly divided into training and validation subsets. The dimensionality and structure of eight UDI questionnaire items were evaluated using exploratory factor analysis (EFA, training subset) followed by confirmatory factor analysis (CFA, validation subset). To assess concurrent validity, the UDI summed score from the full dataset was compared to the Groningen Activity Restriction Scale (GARS) and the Graded Chronic Pain Scale (GCPS) disability scores. Internal consistency and discriminant validity were also assessed. Bootstrapping was used to evaluate model stability and generalisability. RESULTS: 403 participants enrolled; 364 completed at least one UDI item. Three single-factor versions of the UDI were assessed (8-item, 7-item, and 6-item). All versions performed well during EFA and CFA (182 cases assigned to each), but none met the RMSEA (Root Mean Square Error of Approximation) criterion (≤ 0.08). All versions of the UDI had high internal consistency (Cronbach's α > 0.90), were strongly correlated (Pearson's r > 0.7) with both GARS and GCPS disability scores, indicating concurrent validity, and could accurately discriminate between upper and lower quartiles of these comparators. Confidence intervals of estimates were narrow, suggesting model stability and generalisability. CONCLUSIONS: A brief, generic self-reported disability questionnaire was found to be valid and to possess good psychometric properties. The UDI has a single factor structure and either a 6-item, 7-item or 8-item version can be used to measure disability. For brevity and parsimony, the 6-item UDI is recommended, but further testing of all versions is warranted.
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Avaliação da Deficiência , Pessoas com Deficiência , Autorrelato , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários/normas , Análise Fatorial , Idoso , Psicometria/métodos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Detection of structural variants (SVs) is currently biased toward those that alter copy number. The relative contribution of inversions toward genetic disease is unclear. In this study, we analyzed genome sequencing data for 33,924 families with rare disease from the 100,000 Genomes Project. From a database hosting >500 million SVs, we focused on 351 genes where haploinsufficiency is a confirmed disease mechanism and identified 47 ultra-rare rearrangements that included an inversion (24 bp to 36.4 Mb, 20/47 de novo). Validation utilized a number of orthogonal approaches, including retrospective exome analysis. RNA-seq data supported the respective diagnoses for six participants. Phenotypic blending was apparent in four probands. Diagnostic odysseys were a common theme (>50 years for one individual), and targeted analysis for the specific gene had already been performed for 30% of these individuals but with no findings. We provide formal confirmation of a European founder origin for an intragenic MSH2 inversion. For two individuals with complex SVs involving the MECP2 mutational hotspot, ambiguous SV structures were resolved using long-read sequencing, influencing clinical interpretation. A de novo inversion of HOXD11-13 was uncovered in a family with Kantaputra-type mesomelic dysplasia. Lastly, a complex translocation disrupting APC and involving nine rearranged segments confirmed a clinical diagnosis for three family members and resolved a conundrum for a sibling with a single polyp. Overall, inversions play a small but notable role in rare disease, likely explaining the etiology in around 1/750 families across heterogeneous clinical cohorts.
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Inversão Cromossômica , Doenças Raras , Humanos , Doenças Raras/genética , Masculino , Feminino , Inversão Cromossômica/genética , Linhagem , Genoma Humano , Sequenciamento Completo do Genoma , Proteína 2 de Ligação a Metil-CpG/genética , Mutação , Proteínas de Homeodomínio/genética , Pessoa de Meia-IdadeRESUMO
The phenotypic impact of genetic variation of repetitive features in the human genome is currently understudied. One such feature is the multi-copy 47S ribosomal DNA (rDNA) that codes for rRNA components of the ribosome. Here, we present an analysis of rDNA copy number (CN) variation in the UK Biobank (UKB). From the first release of UKB whole-genome sequencing (WGS) data, a discovery analysis in White British individuals reveals that rDNA CN associates with altered counts of specific blood cell subtypes, such as neutrophils, and with the estimated glomerular filtration rate, a marker of kidney function. Similar trends are observed in other ancestries. A range of analyses argue against reverse causality or common confounder effects, and all core results replicate in the second UKB WGS release. Our work demonstrates that rDNA CN is a genetic influence on trait variance in humans.
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Bancos de Espécimes Biológicos , Variações do Número de Cópias de DNA , Humanos , Variações do Número de Cópias de DNA/genética , Reino Unido , Taxa de Filtração Glomerular/genética , DNA Ribossômico/genética , Rim/metabolismo , Masculino , Feminino , Sequenciamento Completo do Genoma , Genoma Humano , Biobanco do Reino UnidoRESUMO
Structural equation models (SEMs) involving feedback loops may offer advantages over standard instrumental variables estimators in terms of modelling causal effects in the presence of bidirectional relationships. In the following note, we show that in the case of a single "exposure" and "outcome" variable, modelling relationships using a SEM with a simple bidirectional linear feedback loop offers no advantage over traditional instrumental variables estimators in terms of consistency (i.e. both approaches yield consistent estimates of the causal effect, provided that causal estimates are obtained in both directions). In the case of finite samples, traditional IV estimators and SEM exhibited similar power across many of the conditions we examined, although which method performed best depended on the residual correlation between variables and the strength of the instruments. In particular, the power of SEM was insensitive to the residual correlation between variables, whereas the power of the Wald estimator/2SLS improved (deteriorated) relative to SEM as the magnitude of the residual correlation increased (decreased) assuming a positive causal effect of the exposure on the outcome. The power of SEM improved relative to the Wald estimator/2SLS as the instruments explained more residual variance in the "outcome" variable.
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Análise da Randomização Mendeliana , Humanos , Análise da Randomização Mendeliana/métodos , Modelos Genéticos , Modelos Estatísticos , Causalidade , RetroalimentaçãoRESUMO
Objective: To investigate the effect of the covid-19 pandemic on the number of patients with group A streptococcal infections and related antibiotic prescriptions. Design: Retrospective cohort study in England using OpenSAFELY-TPP. Setting: Primary care practices in England that used TPP SystmOne software, 1 January 2018 to 31 March 2023, with the approval of NHS England. Participants: Patients registered at a TPP practice at the start of each month of the study period. Patients with missing data for sex or age were excluded, resulting in a population of 23 816 470 in January 2018, increasing to 25 541 940 by March 2023. Main outcome measures: Monthly counts and crude rates of patients with group A streptococcal infections (sore throat or tonsillitis, scarlet fever, and invasive group A streptococcal infections), and recommended firstline, alternative, and reserved antibiotic prescriptions linked with a group A streptococcal infection before (pre-April 2020), during, and after (post-April 2021) covid-19 restrictions. Maximum and minimum count and rate for each infectious season (time from September to August), as well as the rate ratio of the 2022-23 season compared with the last comparably high season (2017-18). Results: The number of patients with group A streptococcal infections, and antibiotic prescriptions linked to an indication of group A streptococcal infection, peaked in December 2022, higher than the peak in 2017-18. The rate ratios for monthly sore throat or tonsillitis (possible group A streptococcal throat infection), scarlet fever, and invasive group A streptococcal infection in 2022-23 relative to 2017-18 were 1.39 (95% confidence interval (CI) 1.38 to 1.40), 2.68 (2.59 to 2.77), and 4.37 (2.94 to 6.48), respectively. The rate ratio for prescriptions of first line, alternative, and reserved antibiotics to patients with group A streptococcal infections in 2022-23 relative to 2017-18 were 1.37 (95% CI 1.35 to 1.38), 2.30 (2.26 to 2.34), and 2.42 (2.24 to 2.61), respectively. For individual antibiotic prescriptions in 2022-23, azithromycin showed the greatest relative increase versus 2017-18, with a rate ratio of 7.37 (6.22 to 8.74). This finding followed a marked decrease in the recording of patients with group A streptococcal infections and associated prescriptions during the period of covid-19 restrictions where the maximum count and rates were lower than any minimum rates before the covid-19 pandemic. Conclusions: Recording of rates of scarlet fever, sore throat or tonsillitis, and invasive group A streptococcal infections, and associated antibiotic prescribing, peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed analysis of clinical and demographic subgroups.
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Wearable sensors like inertial measurement units (IMUs), and those available as smartphone or smartwatch applications, are increasingly used to quantify lumbar mobility. Currently, wearable sensors have to be placed on the back to measure lumbar mobility, meaning it cannot be used in unsupervised environments. This study aims to compare lumbar sagittal plane angles quantified from a wrist-worn against that of a lumbar-worn sensor. Twenty healthy participants were recruited. An IMU was placed on the right wrist and the L3 spinal level. Participants had to position their right forearm on their abdomen, parallel to the floor. Three sets of three consecutive repetitions of flexion, and extension were formed. Linear mixed models were performed to quantify the effect of region (lumbar vs. wrist) on six outcomes [minimum, maximum, range of motion (ROM) of flexion and extension]. Only flexion ROM was significantly different between the wrist and lumbar sensors, with a mean of 4.54° (95% CI = 1.82°-7.27°). Across all outcomes, the maximal difference between a wrist-worn and lumbar-worn sensor was <8°. A wrist-worn IMU sensor could be used to measure gross lumbar sagittal plane mobility in place of a lumbar-worn IMU. This may be useful for remote monitoring during rehabilitation.
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BACKGROUND: Musculoskeletal conditions are the leading contributor to global disability and health burden. Manual therapy (MT) interventions are commonly recommended in clinical guidelines and used in the management of musculoskeletal conditions. Traditional systems of manual therapy (TMT), including physiotherapy, osteopathy, chiropractic, and soft tissue therapy have been built on principles such as clinician-centred assessment, patho-anatomical reasoning, and technique specificity. These historical principles are not supported by current evidence. However, data from clinical trials support the clinical and cost effectiveness of manual therapy as an intervention for musculoskeletal conditions, when used as part of a package of care. PURPOSE: The purpose of this paper is to propose a modern evidence-guided framework for the teaching and practice of MT which avoids reference to and reliance on the outdated principles of TMT. This framework is based on three fundamental humanistic dimensions common in all aspects of healthcare: safety, comfort, and efficiency. These practical elements are contextualised by positive communication, a collaborative context, and person-centred care. The framework facilitates best-practice, reasoning, and communication and is exemplified here with two case studies. METHODS: A literature review stimulated by a new method of teaching manual therapy, reflecting contemporary evidence, being trialled at a United Kingdom education institute. A group of experienced, internationally-based academics, clinicians, and researchers from across the spectrum of manual therapy was convened. Perspectives were elicited through reviews of contemporary literature and discussions in an iterative process. Public presentations were made to multidisciplinary groups and feedback was incorporated. Consensus was achieved through repeated discussion of relevant elements. CONCLUSIONS: Manual therapy interventions should include both passive and active, person-empowering interventions such as exercise, education, and lifestyle adaptations. These should be delivered in a contextualised healing environment with a well-developed person-practitioner therapeutic alliance. Teaching manual therapy should follow this model.
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Manipulações Musculoesqueléticas , Humanos , Manipulações Musculoesqueléticas/educação , Manipulações Musculoesqueléticas/métodos , Doenças Musculoesqueléticas/terapiaRESUMO
The introduction of AlphaFold 21 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design2-6. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.2.37,8. Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework.
Assuntos
Aprendizado Profundo , Ligantes , Modelos Moleculares , Proteínas , Software , Humanos , Anticorpos/química , Anticorpos/metabolismo , Antígenos/metabolismo , Antígenos/química , Aprendizado Profundo/normas , Íons/química , Íons/metabolismo , Simulação de Acoplamento Molecular , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , Ligação Proteica , Conformação Proteica , Proteínas/química , Proteínas/metabolismo , Reprodutibilidade dos Testes , Software/normasRESUMO
Sub-Saharan Africa has fewer medical workers per capita than any region of the world, and that shortage has been highlighted consistently as a critical constraint to improving health outcomes in the region. This paper draws on newly available, systematic, comparable data from 10 countries in the region to explore the dimensions of this shortage. We find wide variation in human resources performance metrics, both within and across countries. Many facilities are barely staffed, and effective staffing levels fall further when adjusted for health worker absences. However, caseloads-while also varying widely within and across countries-are also low in many settings, suggesting that even within countries, deployment rather than shortages, together with barriers to demand, may be the principal challenges. Beyond raw numbers, we observe significant proportions of health workers with very low levels of clinical knowledge on standard maternal and child health conditions. This study highlights that countries may need to invest broadly in health workforce deployment, improvements in capacity and performance of the health workforce, and on addressing demand constraints, rather than focusing narrowly on increases in staffing numbers.