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Incidence and prevalence of Parkinson's disease and utilization of antiparkinson treatments: A population-based cohort study

Primary Care Resource Utilisation and Costs of Fragility Fractures in Postmenopausal Women in the UK Using CPRD Data Mapped to OMOP Common Data Model

Large Scale Propensity Score Matching With Time-Stratification in Older Women With or Without Fractures in the UK

Feasibility of a Federated Network Analysis Using Real-World Data Mapped to OMOP Common Data Model to Estimate Healthcare Resource Utilisation and Costs of Imminent Subsequent Fracture

The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study

Using Prescription Symmetry Sequence Analysis in the Context of Antiparkinsonian Treatments in the United Kingdom

Prescription Sequence Symmetry Analysis to Identify Prescription Cascades for Dementia Drug Treatments in the United Kingdom

Secular trends of incidence and prevalence of parkinsonism and subtypes: A cohort study in the United Kingdom

Challenges to fracture service availability and readiness provided by allopathic and traditional health providers: national surveys across The Gambia and Zimbabwe

A systematic review of the association between early comprehensive geriatric assessment and outcomes in hip fracture care for older people.

AIMS: Performance indicators are increasingly used to improve the quality of healthcare provided to hip fracture patients. Joint care, under orthopaedic surgeons and physicians with an interest in older patients, is one of the more common indicators of high-quality care. In this systematic review, we investigated the association between 'comprehensive geriatric assessment' and patient outcomes following hip fracture injury. METHODS: In total, 12 electronic databases and other sources were searched for evidence, and the methodological quality of studies meeting the inclusion criteria was assessed. The protocol for this suite of related systematic reviews was registered with PROSPERO (ID: CRD42023417515). RESULTS: A total of 24,591 articles were reviewed, and 39 studies met the inclusion criteria for the review, involving a total of 25,363 patients aged over 60 years with a hip fracture. There were five randomized clinical trials, three quasi-experimental studies, two non-randomized parallel group control trials, 22 pre-/post-intervention studies, and seven retrospective cohort studies, conducted between January 1992 and December 2021. The timing and content of a comprehensive geriatric assessment was ill-defined in many studies and care pathways were heterogeneous, which precluded meta-analysis of the data. Early comprehensive geriatric assessment was associated with improved outcomes in 31 of the 36 (86%) patient-reported outcomes, including improved mobility (acute/long-term), functional status, and better quality of life. In total, 155 out of 219 (70.78%) clinical outcomes derived from hospital records showed a positive association with early comprehensive geriatric review, including reduced preoperative time and length of hospital stay, reduced incidence of postoperative complications, fewer hospital readmissions, and lower mortality. CONCLUSION: Early comprehensive geriatric assessments after hip fracture in older people is associated with improved patient-reported outcomes and better clinical outcomes such as reduced incidence of complications, length of hospital stay, preoperative waiting time, and mortality. Standardization of the definitions of 'early' and 'comprehensive' geriatric assessments and consistent reporting of care pathway models would improve future evidence synthesis.

Changing life expectancy in European countries 1990-2021: a subanalysis of causes and risk factors from the Global Burden of Disease Study 2021.

BACKGROUND: Decades of steady improvements in life expectancy in Europe slowed down from around 2011, well before the COVID-19 pandemic, for reasons which remain disputed. We aimed to assess how changes in risk factors and cause-specific death rates in different European countries related to changes in life expectancy in those countries before and during the COVID-19 pandemic. METHODS: We used data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to compare changes in life expectancy at birth, causes of death, and population exposure to risk factors in 16 European Economic Area countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, and Sweden) and the four UK nations (England, Northern Ireland, Scotland, and Wales) for three time periods: 1990-2011, 2011-19, and 2019-21. Changes in life expectancy and causes of death were estimated with an established life expectancy cause-specific decomposition method, and compared with summary exposure values of risk factors for the major causes of death influencing life expectancy. FINDINGS: All countries showed mean annual improvements in life expectancy in both 1990-2011 (overall mean 0·23 years [95% uncertainty interval [UI] 0·23 to 0·24]) and 2011-19 (overall mean 0·15 years [0·13 to 0·16]). The rate of improvement was lower in 2011-19 than in 1990-2011 in all countries except for Norway, where the mean annual increase in life expectancy rose from 0·21 years (95% UI 0·20 to 0·22) in 1990-2011 to 0·23 years (0·21 to 0·26) in 2011-19 (difference of 0·03 years). In other countries, the difference in mean annual improvement between these periods ranged from -0·01 years in Iceland (0·19 years [95% UI 0·16 to 0·21] vs 0·18 years [0·09 to 0·26]), to -0·18 years in England (0·25 years [0·24 to 0·25] vs 0·07 years [0·06 to 0·08]). In 2019-21, there was an overall decrease in mean annual life expectancy across all countries (overall mean -0·18 years [95% UI -0·22 to -0·13]), with all countries having an absolute fall in life expectancy except for Ireland, Iceland, Sweden, Norway, and Denmark, which showed marginal improvement in life expectancy, and Belgium, which showed no change in life expectancy. Across countries, the causes of death responsible for the largest improvements in life expectancy from 1990 to 2011 were cardiovascular diseases and neoplasms. Deaths from cardiovascular diseases were the primary driver of reductions in life expectancy improvements during 2011-19, and deaths from respiratory infections and other COVID-19 pandemic-related outcomes were responsible for the decreases in life expectancy during 2019-21. Deaths from cardiovascular diseases and neoplasms in 2019 were attributable to high systolic blood pressure, dietary risks, tobacco smoke, high LDL cholesterol, high BMI, occupational risks, high alcohol use, and other risks including low physical activity. Exposure to these major risk factors differed by country, with trends of increasing exposure to high BMI and decreasing exposure to tobacco smoke observed in all countries during 1990-2021. INTERPRETATION: The countries that best maintained improvements in life expectancy after 2011 (Norway, Iceland, Belgium, Denmark, and Sweden) did so through better maintenance of reductions in mortality from cardiovascular diseases and neoplasms, underpinned by decreased exposures to major risks, possibly mitigated by government policies. The continued improvements in life expectancy in five countries during 2019-21 indicate that these countries were better prepared to withstand the COVID-19 pandemic. By contrast, countries with the greatest slowdown in life expectancy improvements after 2011 went on to have some of the largest decreases in life expectancy in 2019-21. These findings suggest that government policies that improve population health also build resilience to future shocks. Such policies include reducing population exposure to major upstream risks for cardiovascular diseases and neoplasms, such as harmful diets and low physical activity, tackling the commercial determinants of poor health, and ensuring access to affordable health services. FUNDING: Gates Foundation.

Routine sterile glove and instrument change at the time of abdominal wound closure to prevent surgical site infection (ChEETAh): a model-based cost-effectiveness analysis of a pragmatic, cluster-randomised trial in seven low-income and middle-income countries.

BACKGROUND: Surgical site infection (SSI) is a major burden on patients and health systems. This study assessed the cost-effectiveness of routine change of sterile gloves and instruments before abdominal wall closure to prevent SSI. METHODS: A decision-analytic model was built to estimate average costs and outcomes of changing gloves and instruments before abdominal wall closure compared with current practice. Clinical data were obtained from the ChEETAh trial, a multicentre, cluster-randomised trial in seven low-income and middle-income countries (LMICs), and costs were obtained from a study (KIWI) that assessed costs associated with SSIs in LMICs. Outcomes were measured as the percentage of surgeries resulting in SSIs. Costs were measured from a health-care provider perspective and were reported in 2021 US$. The economic analysis used a partially split single-country costing approach, with pooled outcomes data from all seven countries in the ChEETAh trial, and data for resource use and unit costs from India (KIWI); secondary analyses used resource use and costs from Mexico and Ghana (KIWI). FINDINGS: In the base case, the average cost of the intervention was $259∙92 compared with $261∙10 for current practice (cost difference -$1∙18, 95% CI -4∙08 to 1∙33). In the intervention group, an estimated 17∙6% of patients had an SSI compared with 19∙7% of patients in the current practice group (absolute risk reduction 2∙10%, 95% CI 2∙07-2∙84). At all cost-effectiveness thresholds assumed ($0 to $14 000), the intervention had a higher likelihood of being cost-effective compared with current practice, indicating that the intervention was cost-effective. Similar results were obtained when the analysis using data from India was repeated using resource use and unit cost data from Mexico and Ghana. INTERPRETATION: Routine sterile glove and instrument change before abdominal wall closure is effective and the costs are similar to those for current practice. Routine change of gloves and instruments before abdominal wall closure should be rolled out in LMICs. FUNDING: National Institute for Health and Care Research (NIHR) Clinician Scientist Award, NIHR Global Health Research Unit Grant, and Mölnlycke Healthcare.

Accuracy of the Wound Healing Questionnaire in the diagnosis of surgical-site infection after abdominal surgery in low- and middle-income countries.

INTRODUCTION: Telemedicine is being adopted for postoperative surveillance but requires evaluation for efficacy. This study tested a telephone Wound Healing Questionnaire (WHQ) to diagnose surgical site infection (SSI) after abdominal surgery in low- and middle-income countries. METHOD: A multi-centre, international, prospective study was embedded in the FALCON trial; a factorial RCT testing measures to reduce SSI in seven low- and middle-income countries (NCT03700749). It was conducted according to a pre-registered protocol (SWAT126) and reported according to STARD guidelines. The reference test was in-person review by a trained clinician at 30 postoperative days according to US Centres for Disease Control criteria. The index test was telephone administration of an adapted WHQ at 27 to 30 postoperative days by a researcher blinded to the outcome of in-person review. The sum of item response scores generated an overall score between 0 and 29. The primary outcome was the diagnostic accuracy of the WHQ, defined as the proportion of SSI correctly identified by the telephone WHQ, and summarized using the area under the receiving operator characteristic curve (AUROC) and diagnostic test accuracy statistics. RESULTS: Patients were included from three upper-middle income (396 patients, 13 hospitals), three lower-middle income (746 patients, 19 hospitals), and one low-income country (54 patients, 4 hospitals). 90.3% (1088 of 1196) patients were successfully contacted. Those with non-midline incisions (adjusted odds ratio: 0.36, 95% c.i. 0.17 to 0.73, P=0.005) or a confirmed diagnosis of SSI on in-person assessment (odds ratio: 0.42, 95% c.i. 0.20 to 0.92, P=0.006) were harder to reach. The questionnaire correctly discriminated between most patients with and without SSI (AUROC 0.869, 95% c.i. 0.824 to 0.914), which was consistent across subgroups. A representative cut-off score of ≥4 displayed a sensitivity of 0.701 (0.610-0.792), specificity of 0.911 (0.878-0.943), positive predictive value of 0.723 (0.633-0.814) and negative predictive value of 0.901 (0.867-0.935). CONCLUSION: SSI can be diagnosed using a telephone questionnaire (obviating in-person assessment) in low resource settings.

Predictive genetic testing for Huntington's disease: Exploring participant experiences of uncertainty and ambivalence between clinic appointments.

Ambivalence and uncertainty are key themes throughout the psychology of healthcare literature. This is especially so for individuals at risk of Huntington's disease (HD) deliberating the decision to undergo genetic testing because there is currently no treatment that modifies disease progression. A better understanding of the experience of making a decision about genetic prediction will help practitioners support and guide individuals through this process. Our aim was to capture participants' experiences of uncertainty and ambivalence in between their genetic counseling appointments. We explored these issues through the experiences of nine participants who were referred for predictive HD testing at four regional genetics services in England and Wales. Data consisted of recordings of clinic consultations, diaries, and an in-depth interview conducted at the end of the testing process. Data were analyzed thematically. Four themes were identified representing four possible futures, each future dependent on the decision to undergo testing and the result of that test. Our results showed that participants, as well as attending more to a future that represents their current situation of not having undergone predictive testing, also attended more to a distant future where a positive predictive result is received and symptoms have started. Participants attended less to the two futures that were more immediate once testing was undertaken (a future where a positive result is received and symptoms have not started and a future where a negative result is received). The use of diaries gave us a unique insight into these participants' experiences of ambivalence and uncertainty, psychological distress, and the emotional burden experienced. These findings help inform discussions within the clinic appointment as well as encourage researchers to consider diary use as a method of exploring what happens for individuals outside of clinical encounters.

Informed consent for whole genome sequencing in mainstream clinics: logistical constraints and possible solutions.

U–Pb zircon–rutile dating of the Llangynog Inlier, Wales: constraints on an Ediacaran shallow-marine fossil assemblage from East Avalonia

The Llangynog Inlier of south Wales contains an assemblage of Ediacaran macrofossils from a shallow-marine environment, including discoidal morphs of Aspidella and rare examples of Hiemalora, Palaeopascichnus and Yelovichnus. These are taxa found at other sites in the Avalonian microcontinent (e.g. Charnwood Forest and eastern Newfoundland) and in the younger White Sea Ediacaran assemblages. As the Charnwood fossils reflect a deep-water environment, and no macrofossils have been found in the Ediacaran rocks of the Long Mynd, the fossils of the Llangynog Inlier represent a unique glimpse of shallow-marine life in southern Britain (East Avalonia). However, the lack of absolute age constraints has hampered direct comparison with other assemblages. Here, we report in situ zircon and rutile U–Pb dates from a rhyolitic ash-flow layer of the Coed Cochion Volcaniclastic Member, Llangynog Inlier, which constrains the age of the fossiliferous strata. A weighted mean single grain zircon isotope dilution thermal ionization mass spectrometry U–Pb age of 564.09 ± 0.70 Ma is interpreted as the rhyolite’s crystallization age. This age is consistent with in situ laser ablation inductively coupled plasma mass spectrometry zircon and rutile U–Pb dating. The Llangynog age temporally correlates these fossils to dated horizons within East Avalonia at the Beacon Hill Formation, Charnwood (565.22 ± 0.89 Ma) and the Stretton Shale Formation, Long Mynd (566.6 ± 2.9 Ma). Correlations to West Avalonia include the time-equivalent Fermeuse Formation, St John’s Group, eastern Newfoundland (564.13 ± 0.65 Ma). The data presented here establish the biota of the Llangynog Inlier as a lateral equivalent to the similarly shallow-marine, tidally influenced ecosystem of the upper Fermeuse Formation. Intra-terrane depositional environmental variability also affects what is preserved in Avalonian fossil sites. Further, time-constrained geochemical data reinforce the Llangynog Inlier’s classification within the Wrekin Terrane.

Somatic mutations in salivary duct carcinoma and potential therapeutic targets.

BACKGROUND: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. RESULTS: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p.H1047R: Everolimus), ERBB2 (p.V842I: Lapatinib), HRAS (p.Q61R: Selumetinib) and KIT (p.T670I: Sorafenib). Furthermore, alterations in PTEN, PIK3CA and HRAS that alter response to androgen deprivation therapy and HER2 inhibition were also seen. MATERIALS AND METHODS: Somatic mutation analysis was performed on DNA extracted from 15 archival cases of SDCa using the targeted Illumina TruSeq Amplicon Cancer Panel. Potential targetable genetic alterations were identified using extensive literature and international somatic mutation database (COSMIC, KEGG) search. Immunohistochemistry for androgen receptor and immunohistochemistry and fluorescent in situ hybridization for HER2 were also performed. CONCLUSIONS: SDCa show multiple somatic mutations, some that are amenable to pharmacologic manipulation and others that confer resistance to treatments currently under investigation. These findings emphasize the need to develop testing and treatment strategies for SDCa.

Muscle Impairments in Osteogenesis Imperfecta: A Narrative Review

Abstract The aim of this review is to provide an overview of the available evidence on the effects of osteogenesis imperfecta (OI) on skeletal muscle. This encompasses multiple components of muscle function, underlying biological and environmental factors, clinical and functional consequences, and relevant epidemiology and therapeutic options. OI is a rare connective tissue disorder causing bone fragility and skeletal deformity, and extraskeletal features including cardiac and dental abnormalities, and hearing loss. The condition is also characterised by pronounced deficits in multiple aspects of skeletal muscle function, including lower muscle strength and power, impaired balance, and greater fatigability, resulting from lower muscle mass and poor muscle quality. These deficits have important implications for multiple aspects of health and general function including mobility, fall and fracture risk, and the ability to carry out activities of daily living. The muscle weakness and impaired function in OI appear multi-factorial in origin, and factors including deficits in sensory, ventilatory, and metabolic function may compound those observed in muscle mass and quality. Little is known about the epidemiology of muscle in OI, with the exception that more severe OI types are associated with greater impairments in function and mass. Consideration should be given to which aspects of muscle health and function are most relevant for individuals with different OI types. There is a limited evidence base for interventions to improve muscle in OI, and current findings from physical activity and pharmacological therapies are mixed. Muscle represents an important and under-researched area of health and function in OI.

A systematic review of outcomes reported in randomised controlled trials involving people with patellar dislocations

Risk factors associated with the development of complications after hip fracture

Aims: Mortality after hip fracture has declined in recent years but the risk of complications remains high. This study aims to identify non-modifiable and specifically, modifiable factors associated with the development of complications after hip fracture. Methods: A multi-centre, prospective cohort study of adults aged 60 years and older with a hip fracture across 77 representative hospitals in England, Wales and Northern Ireland between 2015 to 2022. Cox-proportional hazards regression models was used to assess associations between pre-specified (a priori) co-variates and the development of surgeryspecific and general complications at 120-days. Results: There were 24,523 patients with a hip fracture enrolled into the study. For surgeryspecific complications, male sex was associated with re-operation (HR: 1.23, 95% CI: 1.01 to 1.51) and surgical site infection (SSI) (HR: 1.20, 95% CI: 1.00 to 1.43); ASA grade ≥3 with prosthesis dislocation (HR: 2.19, 95% CI: 1.40 to 3.41), re-operation (HR: 1.35, 95% CI: 1.06 to 1.72) and SSI (HR: 1.26, 95% CI: 1.02 to 1.56); treatment with cephalomedullary nail with peri-prosthetic or peri-implant fracture (HR: 4.09, 95% CI: 1.62 to 10.32) and re-operation (HR: 1.94, 95% CI: 1.29 to 2.92); and treatment with total hip arthroplasty with prosthesis dislocation (HR: 2.43, 95% CI: 1.54 to 3.82). For general complications, age was associated with acute kidney injury (AKI) (HR: 1.04, 95% CI: 1.03 to 1.05), blood transfusion (HR: 1.02, 95% CI: 1.01 to 1.02), lower respiratory tract infection (LRTI) (HR: 1.02, 95% CI: 1.01 to 1.03) and urinary tract infection (UTI) (HR: 1.02, 95% CI 1.01 to 1.02); ASA grade ≥3 with AKI (HR: 1.52, 95% CI: 1.18 to 1.95), blood transfusion (HR: 1.35, 95% CI: 1.16 to 1.58), LRTI (HR: 2.02, 95% CI: 1.72 to 2.37) and UTI (HR: 1.33, 95% CI: 1.13 to 1.56); male sex with AKI (HR: 1.30, 95% CI: 1.09 to 1.55), and LRTI (HR: 1.33, 95% CI: 1.20 to 1.48); delayed mobilisation with AKI (HR: 1.68, 95% CI: 1.13 to 2.44), LRTI (HR: 1.96, 95% CI: 1.75 to 2.19), UTI (HR: 1.52, 95% CI: 1.32 to 1.74), myocardial infarction (MI) (HR: 2.05, 95% CI: 1.35 to 3.10) and pulmonary embolism (HR: 1.70, 95% CI: 1.05 to 2.74); and delayed surgery with MI (HR: 1.66, 95% CI: 1.13 to 2.44). Conclusions: Patient-related factors such as increasing age, male sex and higher comorbidity were associated with a number of complications, which may explain the higher mortality and worse recovery observed in these groups. We also identified a number of potentially modifiable treatment-related factors that may influence the development of complications that warrant further investigation.