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1.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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2.
  • Brownstein, Catherine A., et al. (författare)
  • An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
  • 2014
  • Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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3.
  • Pirkis, Jane, et al. (författare)
  • Suicide numbers during the first 9-15 months of the COVID-19 pandemic compared with pre-existing trends : An interrupted time series analysis in 33 countries
  • 2022
  • Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 51
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age-and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation. Findings We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries' COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries' income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well. Interpretation Although there are some countries/areas-within-countries where overall suicide numbers and numbers for certain sex- and age-based groups are greater-than-expected, these countries/areas-within-countries are in the minority. Any upward movement in suicide numbers in any place or group is concerning, and we need to remain alert to and respond to changes as the pandemic and its mental health and economic consequences continue. Copyright (C) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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4.
  • Baigent, Colin, et al. (författare)
  • The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection) : a randomised placebo-controlled trial
  • 2011
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9784, s. 2181-2192
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and I SRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0.85 mmol/L (SE 0.02; with about two-thirds compliance) during a median follow-up of 4.9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11.3%] simvastatin plus ezetimibe vs 619 [13.4%] placebo; rate ratio [RR] 0.83, 95% CI 0.74-0.94; log-rank p=0.0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4.6%] vs 230 [5.0%]; RR 0.92,95% CI 0.76-1.11; p=0.37) and there were significant reductions in non-haemorrhagic stroke (131 [2.8%] vs 174 [3.8%]; RR 0.75,95% CI 0.60-0.94; p=0.01) and arterial revascularisation procedures (284 [6.1%] vs 352 [7.6%]; RR 0.79, 95% CI 0.68-0.93; p=0.0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0.2%] vs 5 [0.1%]). There was no evidence of excess risks of hepatitis (21 [0.5%] vs 18 [0.4%]), gallstones (106 [2.3%] vs 106 [2.3%]), or cancer (438 [9.4%] vs 439 [9.5%], p=0.89) and there was no significant excess of death from any non-vascular cause (668 [14.4%] vs 612 [13.2%], p=0.13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.
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5.
  • Bray, Lucy, et al. (författare)
  • Developing rights-based standards for children having tests, treatments, examinations and interventions : using a collaborative, multi-phased, multi-method and multi-stakeholder approach to build consensus
  • 2023
  • Ingår i: European Journal of Pediatrics. - : Springer Nature. - 0340-6199 .- 1432-1076.
  • Tidskriftsartikel (refereegranskat)abstract
    • Children continue to experience harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. The international ISupport collaboration aimed to develop standards to outline and explain good procedural practice and the rights of children within the context of a clinical procedure. The rights-based standards for children undergoing tests, treatments, investigations, examinations and interventions were developed using an iterative, multi-phased, multi-method and multi-stakeholder consensus building approach. This consensus approach used a range of online and face to face methods across three phases to ensure ongoing engagement with multiple stakeholders. The views and perspectives of 203 children and young people, 78 parents and 418 multi-disciplinary professionals gathered over a two year period (2020–2022) informed the development of international rights-based standards for the care of children having tests, treatments, examinations and interventions. The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.Conclusion: This is the first study of its kind which outlines international rights-based procedural care standards from multi-stakeholder perspectives. The standards offer health professionals and educators clear evidence-based tools to support discussions and practice changes to challenge prevailing assumptions about holding or restraining children and instead encourage a focus on the interests and rights of the child.What is Known:• Children continue to experience short and long-term harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care.• Professionals report uncertainty and tensions in applying evidence-based practice to children’s procedural care. What is New:• This is the first study of its kind which has developed international rights-based procedural care standards from multi-stakeholder perspectives.• The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.
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6.
  • Bray, Molly S, et al. (författare)
  • NIH working group report-using genomic information to guide weight management: From universal to precision treatment.
  • 2016
  • Ingår i: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 24:1, s. 14-22
  • Forskningsöversikt (refereegranskat)abstract
    • Precision medicine utilizes genomic and other data to optimize and personalize treatment. Although more than 2,500 genetic tests are currently available, largely for extreme and/or rare phenotypes, the question remains whether this approach can be used for the treatment of common, complex conditions like obesity, inflammation, and insulin resistance, which underlie a host of metabolic diseases.
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7.
  • Fung, Victor S. C., et al. (författare)
  • Continuous subcutaneous foslevodopa/foscarbidopa infusion for the treatment of motor fluctuations in Parkinson's disease: Considerations for initiation and maintenance
  • 2024
  • Ingår i: CLINICAL PARKINSONISM & RELATED DISORDERS. - 2590-1125. ; 10
  • Forskningsöversikt (refereegranskat)abstract
    • Background: As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations by the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady dopaminergic stimulation that can reduce symptom fluctuation. Objective: Our aim is to review the initiation, optimization, and maintenance of LDp/CDp therapy, identify possible challenges, and share potential mitigations. Methods: Review available LDp/CDp clinical trial data for practical considerations regarding the management of patients during LDp/CDp therapy initiation, optimization, and maintenance based on investigator clinical trial experience. Results: LDp/CDp initiation, optimization, and maintenance can be done without hospitalization in the clinic setting. Continuous 24 h/day LDp/CDp infusion can offer more precise symptom control than oral medications, showing improvements in motor fluctuations during both daytime and nighttime hours. Challenges include infusion -site adverse events for which early detection and prompt management may be required, as well as systemic adverse events (eg, hallucinations) that may require adjustment of the infusion rate or other interventions. A learning curve should be anticipated with initiation of therapy, and expectation setting with patients and care partners is key to successful initiation and maintenance of therapy. Conclusion: Continuous subcutaneous infusion of LDp/CDp represents a promising therapeutic option for individuals with PD. Individualized dose optimization during both daytime and nighttime hours, coupled with patient education, and early recognition of certain adverse events (plus their appropriate management) are required for the success of this minimally invasive and highly efficacious therapy.
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8.
  • Kidayi, Paulo L, et al. (författare)
  • Cross-Cultural Adaptation and Psychometric Properties of the Swahili Version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR45 among Breast Cancer Patients in Tanzania
  • 2023
  • Ingår i: Healthcare. - : MDPI. - 2227-9032. ; 11:18
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer is the most frequent cancer in women in Africa and contributes to premature death and poor quality of life. This study aimed to determine the validity, reliability, and psychometric properties of the Swahili version of EORTC QLQ-BR45 among women with breast cancer in Tanzania. A cross-sectional study design with non-probability convenience sampling was employed. Data were collected in two tertiary hospitals and one national cancer institute; 414 participants completed the EORTC-QLQ-C-30 and EORTC-QLQ-BR45. The reliability of QLQ-BR45 was measured using Cronbach's alpha and McDonald's Omega coefficients. The factor structure of EORTC QLQ-BR45 was assessed using confirmatory factor analysis. The internal consistencies for the five dimensions were all above 0.7 indicating satisfaction, except for systemic therapy side effects with a marginal value of 0.594 and significant correlations between the dimensions of QLQ-C30 and BR45. The final model fit well to the data, with the comparative fit index = 0.953, Tucker-Lewis index = 0.947, root mean square error of approximation = 0.041 (90% CI: 0.035, 0.046), and standardized root mean square residual = 0.072. In conclusion, the QLQ BR45 Swahili version displayed good reliability, validity, and psychometric properties and can be used in Swahili-speaking Sub-Saharan countries.
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10.
  • Lightfoot, J. Timothy, et al. (författare)
  • Biological/Genetic Regulation of Physical Activity Level : Consensus From Genbiopac
  • 2018
  • Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 50:4, s. 863-873
  • Forskningsöversikt (refereegranskat)abstract
    • Purpose: Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity.Conclusions: Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.
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