Search results
Found 30542 matches for
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.
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.
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.
Linear and Area Coverage With Closed Incision Negative Pressure Therapy Management: International Multidisciplinary Consensus Recommendations
Closed incision negative pressure therapy (ciNPT) with foam dressings has received broad recognition for its ability to support incision healing for a variety of surgical procedures. Over time, these dressings have evolved to include linear and ‘area’ shapes to better conform to different incision types and surface geometries. To address new studies on these configurations and provide guidance for dressing selection, an international, multidisciplinary panel of experts was convened. The panel reviewed recent publications on ciNPT with reticulated open cell foam (ROCF) dressings, shared their cases and experiences and engaged in roundtable discussions on benefits, drawbacks and technical challenges. Topics were ranked by importance and refined into potential consensus statements. These were shared for anonymous feedback, requiring 80% agreement for consensus. This manuscript establishes 12 consensus statements regarding risk factors supporting the use of ciNPT, conditions supporting preference of linear or area ciNPT dressings and tips for practical application of ciNPT with ROCF dressings. While this consensus panel expands on previous publications to aid clinicians' decision-making, further research is needed to refine recommendations and identify the strengths and limitations of ciNPT. Continued multidisciplinary collaboration will ensure ciNPT remains vital for improving surgical outcomes and patient care.
Characterisation of a pathogenic non-migratory fibroblast population in systemic sclerosis skin.
Fibroblasts are central to pathogenesis of systemic sclerosis (SSc). However, studies of conventional explant fibroblast cultures incompletely reflect disease biology and treatment response. We isolated a second non-migratory "resident" population of fibroblasts from skin biopsies after outgrowth of explant "migratory" cells. These non-motile resident fibroblasts were compared with migratory cells from the same biopsy, using functional studies, bulk and scRNAseq, and localised in situ by multichannel immunofluorescence. Migratory and resident fibroblast populations in SSc showed distinct pro-fibrotic characteristics and gene expression for pathogenic pathways differing by stage and autoantibody subgroup. TGFβ signalling was highly active in migratory fibroblasts in early stage dcSSc. Conversely, resident fibroblasts had less upregulated TGFβ signalling, especially in late dcSSc. Increased chemokine expression was a hallmark of resident fibroblasts at all stages. In vitro studies confirmed differential response to TGFβ1 and CCL2 between migratory and resident cells. We suggest that migratory fibroblasts are especially important in early skin disease whereas non-migratory fibroblasts may have a regulatory role and contribute more to fibrosis in later stage disease. Thus, we have identified a pathogenic fibroblast population in SSc, not isolated by conventional explant culture, that could play an important role in fibrosis and be targeted therapeutically.
Preoperative Anemia and Blood Management Strategies
The symptoms of anemia have been known since ancient times, and people have tried to cure its symptoms by various methods, including ferruginous water. The term “anemia” known to us today was introduced around 1843 by the French physician Gabriel Andral, one of the founders of scientific hematology. The word anemia comes from the ancient Greek ἄναιμος ánaimos “bloodless” and is composed of the prefix αν- an- “un-”, “without”, “not,” and the word αἷμα haíma “blood”.
A phase II open label, randomised study of ipilimumab with temozolomide versus temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma: the Ipi-Glio trial protocol.
BACKGROUND: Median survival for patients with glioblastoma is less than a year. Standard treatment consists of surgical debulking if feasible followed by temozolomide chemo-radiotherapy. The immune checkpoint inhibitor ipilimumab targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and has shown clinical efficacy in preclinical models of glioblastoma. The aim of this study is to explore the addition of ipilimumab to standard therapy in patients with glioblastoma. METHODS/DESIGN: Ipi-Glio is a phase II, open label, randomised study of ipilimumab with temozolomide (Arm A) versus temozolomide alone (Arm B) after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma. Planned accrual is 120 patients (Arm A: 80, Arm B: 40). Endpoints include overall survival, 18-month survival, 5-year survival, and adverse events. The trial is currently recruiting in seven centres in the United Kingdom. TRIAL REGISTRATION: ISRCTN84434175. Registered 12 November 2018.