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Lupus Science & Medicine Feb 2024The paradigm of drug approval in SLE currently relies on successful large phase III randomised controlled trials and a set of primary, secondary and additional end... (Review)
Review
The paradigm of drug approval in SLE currently relies on successful large phase III randomised controlled trials and a set of primary, secondary and additional end points. Taken together, these outcomes offer a nuanced understanding of the efficacy and safety of the investigational agent. In this review, we thoroughly examine the main outcomes used in SLE trials and highlight unmet requirements as well as potential venues for future trial design in SLE. Disease activity indices can be broadly categorised into global-specific and organ-specific indices, in particular for skin, joints and kidneys, but there is no universal consensus about their use in clinical trials. Because each of these instruments has its own intrinsic strengths and weaknesses, the assessment of treatment response has progressed from relying solely on one individual disease activity index to using composite responder definitions. Those are typically measured from the trial baseline to the end point assessment date and may be combined with the need to taper and maintain glucocorticoids (GCs) within prespecified ranges. Remission and low disease activity are two critical states in the perspective of 'Treat-to-Target' trials, but are not fully recognised by regulators. While significant progress has been made in clinical trial outcomes for SLE, there is a clear need for continued innovation. Addressing these challenges will require collaboration between researchers, clinicians, patients as well as with regulatory agencies to refine existing outcome measures, incorporate meaningful and ethnically diverse patient perspectives, foster relevant digital opportunities and explore new therapeutic avenues, including early use of investigational agents. By doing so, we can advance our ability to manage SLE effectively and safely and improve the lives of those living with this complex and impactful autoimmune disease.
Topics: Humans; Treatment Outcome; Lupus Erythematosus, Systemic; Outcome Assessment, Health Care; Glucocorticoids
PubMed: 38360028
DOI: 10.1136/lupus-2023-001114 -
International Journal of Epidemiology Oct 2023Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health...
BACKGROUND
Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis.
METHODS
Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals.
RESULTS
Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect.
CONCLUSIONS
These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Educational Status; Academic Success; Polymorphism, Single Nucleotide; Outcome Assessment, Health Care
PubMed: 37295953
DOI: 10.1093/ije/dyad079 -
BMC Medicine Aug 2023Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a...
BACKGROUND
Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.
METHODS
We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.
RESULTS
Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.
CONCLUSIONS
Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.
Topics: Pregnancy; Infant, Newborn; Infant; Child; Humans; Female; Pregnant Women; Multimorbidity; Quality of Life; Mothers; Outcome Assessment, Health Care
PubMed: 37605204
DOI: 10.1186/s12916-023-03013-3 -
The Journal of Allergy and Clinical... Dec 2023Diet is increasingly recognized as a modifiable factor in lung health, predominantly due to the immunomodulatory effects of nutrients. The Dietary Inflammatory Index...
BACKGROUND
Diet is increasingly recognized as a modifiable factor in lung health, predominantly due to the immunomodulatory effects of nutrients. The Dietary Inflammatory Index (DII) is a score developed to express the inflammatory potential of a diet.
OBJECTIVE
We aimed to assess the association of the DII and food groups, with clinical, functional, and inflammatory asthma outcomes in adults with asthma.
METHODS
Patients with moderate-to-severe asthma were included in this cross-sectional study between June 2019 and October 2021, and completed a 3-day food diary, to calculate the DII and intake of food groups (ie, fruits, whole grains, processed meats, and sugar-sweetened beverages). Functional outcomes included pulmonary function tests and the 6-minute walking distance, whereas clinical outcomes were assessed using questionnaires on asthma control, quality of life, and health care utilization. Inflammatory markers were exhaled nitric oxide and blood leukocytes, eosinophils, and IL-6. Multivariable regression analyses were used to examine the association of DII and food groups with asthma outcomes.
RESULTS
A total of 109 patients participated (35% male, mean ± standard deviation age 51.8 ± 14.2 years, body mass index 27.4 ± 5.3 kg/m). Overall, 62% had a DII score >0, indicating a proinflammatory diet, which was not related to asthma severity. A more proinflammatory diet was consistently associated with lower forced vital capacity (%pred), but inconsistent results were observed with respect to airway obstruction. Neither the DII nor food groups were associated with clinical outcomes. Except for higher levels of exhaled nitric oxide in relation to an anti-inflammatory diet, we found no associations between inflammatory markers and the DII.
CONCLUSION
Results from this cross-sectional study among patients with moderate-to-severe asthma do not support the hypothesis that a proinflammatory diet is associated with worse asthma outcomes, although limitations in study design and dietary intake estimation should be considered. Future well-designed experimental studies are needed to assess whether targeting the inflammatory potential of diet could lead to better outcomes in adults with asthma.
Topics: Adult; Humans; Male; Middle Aged; Aged; Female; Inflammation; Cross-Sectional Studies; Nitric Oxide; Quality of Life; Diet; Asthma; Outcome Assessment, Health Care
PubMed: 37652347
DOI: 10.1016/j.jaip.2023.08.032 -
Genes Sep 2023Hereditary spastic paraplegia (HSP) is characterized by progressive lower limb spasticity. There is no disease-modifying treatment currently available. Therefore,... (Review)
Review
Hereditary spastic paraplegia (HSP) is characterized by progressive lower limb spasticity. There is no disease-modifying treatment currently available. Therefore, standardized, validated outcome measures to facilitate clinical trials are urgently needed. We performed a scoping review of outcome measures and biomarkers for HSP to provide recommendations for future studies and identify areas for further research. We searched Embase, Medline, Scopus, Web of Science, and the Central Cochrane database. Seventy studies met the inclusion criteria, and eighty-three outcome measures were identified. The Spastic Paraplegia Rating Scale (SPRS) was the most widely used (27 studies), followed by the modified Ashworth Scale (18 studies) and magnetic resonance imaging (17 studies). Patient-reported outcome measures (PROMs) were infrequently used to assess treatment outcomes (28% of interventional studies). Diffusion tensor imaging, gait analysis and neurofilament light chain levels were the most promising biomarkers in terms of being able to differentiate patients from controls and correlate with clinical disease severity. Overall, we found variability and inconsistencies in use of outcome measures with a paucity of longitudinal data. We highlight the need for (1) a standardized set of core outcome measures, (2) validation of existing biomarkers, and (3) inclusion of PROMs in HSP clinical trials.
Topics: Humans; Spastic Paraplegia, Hereditary; Diffusion Tensor Imaging; Paraplegia; Biomarkers; Outcome Assessment, Health Care
PubMed: 37761896
DOI: 10.3390/genes14091756 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Improving diet quality while simultaneously maintaining planetary health is of critical interest globally. Despite the shared motivation, advancement remains slow, and... (Review)
Review
Improving diet quality while simultaneously maintaining planetary health is of critical interest globally. Despite the shared motivation, advancement remains slow, and the research community continues to operate in silos, focusing on certain pairings (diet-climate), or with a discipline-specific lens of a sustainable diet, rather than examining their totality. This review aimed to summarize the literature on adherence to a priori defined dietary patterns in consideration of diet quality, metabolic risk factors for noncommunicable diseases (NCDs), environmental impacts, and affordability. A methodology using PRISMA guidelines was followed, and searches were performed in 7 databases as of October 2022. The Appraisal tool for Cross-Sectional Studies (AXIS) and the National Institutes of Health (NIH) quality assessment tool for observational cohort studies were employed for quality appraisal. The evidence was narratively synthesized according to the characteristics of the diet quality metrics. The review includes 24 studies published between 2017-2023. Thirteen distinct diet quality scores were identified, with those measuring adherence to national dietary guidelines the most reported. Thirteen distinct environmental impact indicators were identified, with greenhouse gas emissions (n=23) reported most. All studies reported on body mass index, and 7 studies assessed the cost of adherence. Our results are consistent with previous findings that healthier diets can reduce environmental impacts; however, incongruities between population and planetary health can occur. Hence, the "sustainability" of dietary patterns is dependent on the choice of indicators selected. Further, healthy, lower impact diets can increase financial cost, but may also provide a protective role against the risk of obesity. Given the Global Syndemic, strategies to reduce obesity prevalence should emphasize the win-win opportunities for population and planetary health through dietary change. Research should identify diets that address multiple environmental concerns to curtail burdens potentially transferring, and harmonize this with sociocultural and equity dimensions. This review was registered at PROSPERO as CRD42021238055.
Topics: United States; Humans; Cross-Sectional Studies; Diet; Obesity; Costs and Cost Analysis; Outcome Assessment, Health Care
PubMed: 37532100
DOI: 10.1016/j.advnut.2023.07.007 -
PloS One 2023Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the...
Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for studies evaluating the effectiveness of treatments for neonatal sepsis. Since a systematic review of key outcomes from randomised trials of therapeutic interventions in neonatal sepsis was published recently, we will complement this with a qualitative systematic review of the key outcomes of neonatal sepsis identified by parents, other family members, parent representatives, healthcare providers, policymakers, and researchers. We will interpret the outcomes of both studies using a previously established framework. Stakeholders across three different groups i.e., (1) researchers, (2) healthcare providers, and (3) patients' parents/family members and parent representatives will rate the importance of the outcomes in an online Real-Time Delphi Survey. Afterwards, consensus meetings will be held to agree on the final COS through online discussions with key stakeholders. This COS is expected to minimize outcome heterogeneity in measurements and publications, improve comparability and synthesis, and decrease research waste.
Topics: Infant, Newborn; Humans; Neonatal Sepsis; Research Design; Delphi Technique; Consensus; Outcome Assessment, Health Care; Treatment Outcome; Systematic Reviews as Topic
PubMed: 38051733
DOI: 10.1371/journal.pone.0295325 -
Yearbook of Medical Informatics Aug 2023To give an overview of recent research and propose a selection of best papers published in 2022 in Informatics for One Health. (Review)
Review
OBJECTIVE
To give an overview of recent research and propose a selection of best papers published in 2022 in Informatics for One Health.
METHODS
An extensive search using PubMed and Web of Science was conducted to identify peer-reviewed articles published between December 2021 and December 2022, in order to find relevant publications in the 'Informatics for One Health' field. The selection process comprised three steps: (i) eight candidate best papers were first selected by the two section editors; (ii) external reviewers from internationally renowned research teams reviewed each candidate best paper; and (iii) the editorial committee of the Yearbook conducted the final best paper selection.
RESULTS
The candidate best papers represent studies that characterized significant challenges facing Informatics for One Health. Other trends of interest related to the deployment of medical artificial intelligence tools and the implementation of the FAIR principles within the One Health broad scenario. In general, papers identified in the search fell into one of the following categories: 1) Health improvement via digital technology; 2) Climate change/Environment/Biodiversity; and 3) Maturity of healthcare services.
CONCLUSION
The topic turns extremely important in the next future for what concerns the need to understand complex interactions in order to safeguard the health of populations and ecosystems.
Topics: Artificial Intelligence; Digital Technology; Ecosystem; Medical Informatics; Outcome Assessment, Health Care
PubMed: 38147852
DOI: 10.1055/s-0043-1768753 -
Autoimmunity Reviews Jul 2023To assess the long-term outcome in patients with Idiopathic Inflammatory Myopathies (IIM), focusing on damage and activity disease indexes using artificial intelligence... (Review)
Review
OBJECTIVE
To assess the long-term outcome in patients with Idiopathic Inflammatory Myopathies (IIM), focusing on damage and activity disease indexes using artificial intelligence (AI).
BACKGROUND
IIM are a group of rare diseases characterized by involvement of different organs in addition to the musculoskeletal. Machine Learning analyses large amounts of information, using different algorithms, decision-making processes and self-learning neural networks.
METHODS
We evaluate the long-term outcome of 103 patients with IIM, diagnosed on 2017 EULAR/ACR criteria. We considered different parameters, including clinical manifestations and organ involvement, number and type of treatments, serum creatine kinase levels, muscle strength (MMT8 score), disease activity (MITAX score), disability (HAQ-DI score), disease damage (MDI score), and physician and patient global assessment (PGA). The data collected were analysed, applying, with R, supervised ML algorithms such as lasso, ridge, elastic net, classification, and regression trees (CART), random forest and support vector machines (SVM) to find the factors that best predict disease outcome.
RESULTS AND CONCLUSION
Using artificial intelligence algorithms we identified the parameters that best correlate with the disease outcome in IIM. The best result was on MMT8 at follow-up, predicted by a CART regression tree algorithm. MITAX was predicted based on clinical features such as the presence of RP-ILD and skin involvement. A good predictive capacity was also demonstrated on damage scores: MDI and HAQ-DI. In the future Machine Learning will allow us to identify the strengths or weaknesses of the composite disease activity and damage scores, to validate new criteria or to implement classification criteria.
Topics: Humans; Artificial Intelligence; Myositis; Outcome Assessment, Health Care; Machine Learning
PubMed: 37142194
DOI: 10.1016/j.autrev.2023.103353 -
Investigacion Y Educacion En Enfermeria Nov 2023The aim of this review was to identify reported nursing-sensitive outcomes in the Emergency Department to date. (Review)
Review
OBJECTIVE
The aim of this review was to identify reported nursing-sensitive outcomes in the Emergency Department to date.
METHODS
An Umbrella review was conducted. Four databases, CINAHL, Pubmed, Web of Science and Scopus, were searched from inception until October 2022. MeSH terms were: "nursing", "sensitivity and specificity", "emergency service, hospital", "nursing care". Two reviewers independently screened studies against the inclusion criteria for eligibility, extracted data and assessed study quality with the SIGN tool. Results of the included studies were summarized and described in themes for narrative analysis. The study was enrolled in the PROSPERO registry (CRD42022376941) and PRISMA guidelines were followed.
RESULTS
The search strategy yielded 2289 records. After duplicate removal, title, abstract and full-text eligibility screening, nine systematic reviews were included in the review. A total of 35 nursing-sensitive outcomes were reported. The most described outcomes were waiting times, patient satisfaction and time to treatment. The less measured were mortality, left without being seen and physical function. Synthesizing nursing-sensitive outcomes in themes for reporting, the most measured outcomes were within the safety domain (n=20), followed by the clinical (n=9), perceptual (n=5) and the least explored functional domain (n=1).
CONCLUSION
Nursing sensitive outcomes research in emergency nursing practice is a conceptual challenge still in its early stage. Several nursing-sensitive outcomes were identified in this review that can evaluate the contribution of emergency department nursing care to patient outcomes. Further research is required to explore patient outcomes sensitive to emergency nursing care.
Topics: Humans; Emergency Service, Hospital; Emergency Medical Services; Outcome Assessment, Health Care; Hospitals; Patient Satisfaction
PubMed: 38589303
DOI: 10.17533/udea.iee.v41n3e03