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AIMS/HYPOTHESIS: Our aim was to characterise the in-depth metabolic response to aerobic exercise and the impact of residual pancreatic beta cell function in type 1 diabetes. We also aimed to use the metabolome to distinguish individuals with type 1 diabetes with reduced maximal aerobic capacity in exercise defined by V Ë O 2peak . METHODS: Thirty participants with type 1 diabetes (≥3 years duration) and 30 control participants were recruited. Groups did not differ in age or sex. After quantification of peak stimulated C-peptide, participants were categorised into those with undetectable (<3 pmol/l), low (3-200 pmol/l) or high (>200 pmol/l) residual beta cell function. Maximal aerobic capacity was assessed by V Ë O 2peak test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% V Ë O 2peak ) with venous blood taken prior to exercise, immediately post exercise and after 60 min recovery. Serum was analysed using targeted metabolomics. Metabolomic data were analysed by multivariate statistics to define the metabolic phenotype of exercise in type 1 diabetes. Receiver operating characteristic (ROC) curves were used to identify circulating metabolomic markers of maximal aerobic capacity ( V Ë O 2peak ) during exercise in health and type 1 diabetes. RESULTS: Maximal aerobic capacity ( V Ë O 2peak ) inversely correlated with HbA1c in the type 1 diabetes group (r2=0.17, p=0.024). Higher resting serum tricarboxylic acid cycle metabolites malic acid (fold change 1.4, p=0.001) and lactate (fold change 1.22, p=1.23×10-5) differentiated people with type 1 diabetes. Higher serum acylcarnitines (AC) (AC C14:1, F value=12.25, p=0.001345; AC C12, F value=11.055, p=0.0018) were unique to the metabolic response to exercise in people with type 1 diabetes. C-peptide status differentially affected metabolic responses in serum ACs during exercise (AC C18:1, leverage 0.066; squared prediction error 3.07). The malic acid/pyruvate ratio in rested serum was diagnostic for maximal aerobic capacity ( V Ë O 2peak ) in people with type 1 diabetes (ROC curve AUC 0.867 [95% CI 0.716, 0.956]). CONCLUSIONS/INTERPRETATION: The serum metabolome distinguishes high and low maximal aerobic capacity and has diagnostic potential for facilitating personalised medicine approaches to manage aerobic exercise and fitness in type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Exercício Físico , Metaboloma , Humanos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Masculino , Feminino , Adulto , Metaboloma/fisiologia , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologia , Teste de Esforço , Metabolômica/métodos , Adulto Jovem , Peptídeo C/sangue , Pessoa de Meia-Idade , Células Secretoras de Insulina/metabolismoRESUMO
AIMS/HYPOTHESIS: The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency. METHODS: In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity. RESULTS: Among 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001). CONCLUSIONS/INTERPRETATION: In individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance.
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AIMS: The HypoCOMPaSS multi-centre trial achieved improvement in hypoglycaemia awareness and 20-fold reduction in severe hypoglycaemia (SH) in a cohort with long-standing type 1 diabetes (T1D). All participants received 'my hypo compass' (MHC) brief structured psycho-educational intervention in addition to optimisation of insulin delivery/glucose monitoring. In this 24-week, prospective, single-centre feasibility RCT, we piloted MHC as a sole intervention in comparison to standard clinical care alone (CON). METHODS: Participants with T1D and impaired hypoglycaemia awareness (IAH) (Clarke score ≥4) were recruited. MHC comprised a group/individual 1-2 h face-to-face session followed by a telephone call and second face-to-face session at 4 weeks. Outcome measures at 24 weeks were compared with baseline. RESULTS: Fifty-two individuals provided consent for screening with 39 fulfilling eligibility criteria. Fifteen withdrew before any study intervention. Twenty-four adults with (mean ± SD) T1D duration 41.0 ± 15.1 years commenced/completed the study (100% visit attendance); 12 randomised to MHC and 12 to CON. All had IAH at baseline and at 24 weeks. Annualised SH rate following MHC was 3.8 ± 19.0 (24 weeks) versus 12.6 ± 3.5 (Baseline) and in CON group 2.0 ± 19.0 (24 weeks) versus 4.6 ± 11.5 (Baseline). 'Immediate Action' for and 'Worry' about hyperglycaemia measured by the Hyperglycaemia Avoidance Scale appeared lower following MHC. Participants attended all study visits and reflected positively on the MHC intervention. CONCLUSIONS: Feasibility of MHC implementation without additional intervention has been demonstrated. MHC education was associated with positive changes in attitudes and behaviours with the potential to reduce SH risk. MHC provides a validated, simple, well-received programme to fulfil the educational component within RCTs targeting problematic hypoglycaemia and as part of holistic clinical care.
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Automonitorização da Glicemia , Diabetes Mellitus Tipo 1 , Estudos de Viabilidade , Hipoglicemia , Educação de Pacientes como Assunto , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Hipoglicemia/prevenção & controle , Feminino , Masculino , Educação de Pacientes como Assunto/métodos , Adulto , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Conscientização , Estudos Prospectivos , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
AIMS: To determine the frequency, severity, burden, and utility of hypoglycaemia symptoms among adults with type 1 diabetes (T1D) and impaired awareness of hypoglycaemia (IAH) at baseline and week 24 following the HypoCOMPaSS awareness restoration intervention. METHODS: Adults (N = 96) with T1D (duration: 29 ± 12 years; 64% women) and IAH completed the Hypoglycaemia Burden Questionnaire (HypoB-Q), assessing experience of 20 pre-specified hypoglycaemia symptoms, at baseline and week 24. RESULTS: At baseline, 93 (97%) participants experienced at least one symptom (mean ± SD 10.6 ± 4.6 symptoms). The proportion recognising each specific symptom ranged from 15% to 83%. At 24 weeks, symptom severity and burden appear reduced, and utility increased. CONCLUSIONS: Adults with T1D and IAH experience a range of hypoglycaemia symptoms. Perceptions of symptom burden or utility are malleable. Although larger scale studies are needed to confirm, these findings suggest that changing the salience of the symptomatic response may be more important in recovering protection from hypoglycaemia through regained awareness than intensifying symptom frequency or severity.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 1/complicações , Conscientização , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemia/diagnóstico , Inquéritos e QuestionáriosRESUMO
AIMS: Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. METHODS: Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. RESULTS: Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001). CONCLUSIONS: IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.
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Diabetes Mellitus Tipo 1 , Neuropatias Diabéticas , Hipoglicemia , Humanos , Feminino , Masculino , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/fisiopatologia , Pessoa de Meia-Idade , Hipoglicemia/epidemiologia , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Conscientização , Hipoglicemiantes/uso terapêuticoRESUMO
BACKGROUND: There is variability in recommended viral monitoring protocols after kidney transplant. In response to increased demand for laboratory testing during the COVID-19 pandemic, the Transplant Manitoba Adult Kidney Program updated its monitoring protocols for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) to a reduced frequency. METHODS: This single-center nested case-control study evaluated 252 adult kidney transplant recipients transplanted from 2015 to 2021, with the updated protocols effective on March 19th 2020. Cases included recipients transplanted after the protocol update who developed CMV, EBV, and BKV DNAemia and were matched to controls with DNAemia transplanted prior to the protocol update. The primary outcome was the difference in maximum DNA load titers between cases and matched controls. Secondary outcomes included time to initial DNAemia detection and DNAemia clearance. Safety outcomes of tissue-invasive viral disease were described. RESULTS: There were 216 recipients transplanted preupdate and 36 recipients postupdate. There was no difference between cases and controls in maximum or first DNA load titers for EBV, CMV, or BKV. Cases experienced earlier EBV DNAemia detection (26 (IQR 8, 32) vs. 434 (IQR 96, 1184) days, p = .005). Median follow-up was significantly longer for recipients transplanted preupdate (4.3 vs. 1.3 years, p < .0001). After adjusting for follow-up time, there was no difference in DNAemia clearance or tissue-invasive viral disease. CONCLUSION: Our findings suggest that reduced frequency viral monitoring protocols may be safe and cost-effective. This quality assurance initiative should be extended to detect longer-term and tissue-invasive disease outcomes.
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Vírus BK , Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Transplante de Rim , Adulto , Humanos , Herpesvirus Humano 4/genética , Citomegalovirus/genética , Transplante de Rim/efeitos adversos , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/etiologia , Vírus BK/genética , Estudos de Casos e Controles , Pandemias , Infecções por Citomegalovirus/diagnóstico , DNA , DNA Viral/genética , TransplantadosRESUMO
BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.
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Vírus BK , Rejeição de Enxerto , Sobrevivência de Enxerto , Testes de Função Renal , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Viremia , Humanos , Transplante de Rim/efeitos adversos , Vírus BK/imunologia , Vírus BK/isolamento & purificação , Feminino , Masculino , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/complicações , Pessoa de Meia-Idade , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Seguimentos , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Viremia/imunologia , Viremia/virologia , Prognóstico , Fatores de Risco , Taxa de Filtração Glomerular , Adulto , Complicações Pós-Operatórias , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Estudos Retrospectivos , Falência Renal Crônica/cirurgia , Falência Renal Crônica/imunologia , Nefropatias/virologia , Nefropatias/imunologia , Nefropatias/cirurgia , TransplantadosRESUMO
OBJECTIVES: This study assessed the content validity of generic and condition-specific preference-based measures (PBMs) with patients treated for cancer, evaluated against 10 Consensus-Based Standards for the Selection of Health Measurement Instruments criteria for good content validity, to best inform measurement strategies regarding the use of PBMs in oncology development programs and real-world applications. METHODS: Individual, semistructured interviews were conducted with patients who received drug treatment for cancer in the United Kingdom (n = 47) and the United States (n = 49). During the interview, patients completed 3 generic PBMs (EQ-5D-5L, EuroQol Health and Wellbeing measure-Short Form, Château Santé Base) and 2 condition-specific PBMs (Quality of Life Utility-Core 10 Dimension, Functional Assessment of Cancer Therapy Eight Dimension [FACT-8D]). Interviews were conducted via teleconference, audio recorded, and transcribed verbatim. Transcripts were coded using thematic and content analysis methods. RESULTS: Condition-specific measures were evaluated as having better relevancy than generic PBMs. Overall, the FACT-8D was evaluated as holding the best content validity in terms of relevancy, and the EuroQol Health and Wellbeing measure-Short Form received the most favorable evaluation of relevancy for generic PBMs. All measures demonstrated comparable comprehensiveness, with all suggested by patients to be missing concepts. The EQ-5D-5L was evaluated best in terms of comprehensibility. This was followed by the Quality of Life Utility-Core 10 Dimension and FACT-8D; both received similar evaluations. CONCLUSIONS: All measures were generally seen by patients as adequate in capturing appropriate aspects of health-related quality of life for measuring cancer outcomes, although together condition-specific measures were evaluated as having better relevancy than generic PBMs. Further health-related quality of life instrument development is encouraged, particularly with regard to the longer-term detrimental impacts of cancer and treatment side effects. Other developments could include new cancer-specific tools inclusive of conventional health items, treatment impacts, and psychological items.
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Neoplasias , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Inquéritos e Questionários , Neoplasias/tratamento farmacológico , Oncologia , Reino Unido , Psicometria/métodos , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: Time trade-off (TTO) and discrete choice experiment (DCE) preference-elicitation techniques can be administered using face-to-face interviews (F2F), unassisted online (UO) surveys, or remote-assisted (RA) interviews. The objective of this study was to explore how the mode of administration affects the quality and reliability of preference-elicitation data. METHODS: EQ-5D-5L health states were valued using composite TTO (cTTO) and DCE approaches by the UK general population. Participants were allocated to 1 of 2 study groups. Group A completed both F2F and UO surveys (n = 271), and group B completed both RA and UO surveys (n = 223). The feasibility of survey completion and the reliability and face-validity of data collected were compared across all modes of administration. RESULTS: Fewer participants reported receiving sufficient guidance on the cTTO tasks during the UO survey compared with the 2 assisted modes. Participants across all modes typically reported receiving sufficient guidance on the DCE tasks. cTTO data were less reliable from the UO survey compared with both assisted modes, but there were no differences in DCE data reliability. cTTO data from all modes demonstrated face-validity; however, the UO survey produced higher utilities for moderate and severe health states than both assisted modes. Both F2F and RA modes provided comparably reliable data. CONCLUSIONS: The reliability of DCE data is not affected by the mode of administration. Interviewer-assisted modes of administration (F2F or RA) yield more reliable cTTO data than unassisted surveys. Both F2F and RA surveys produced similar-quality data.
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Comportamento de Escolha , Preferência do Paciente , Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Reprodutibilidade dos Testes , Reino Unido , Inquéritos e Questionários , Idoso , Nível de Saúde , Adulto Jovem , Entrevistas como Assunto , AdolescenteRESUMO
OBJECTIVES: This literature review provides an overview of meaningful change thresholds for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and the Functional Assessment of Cancer Therapy - General (FACT-G) used across hematological cancers and solid tumors (melanoma, lung, bladder, and prostate). METHODS: Embase, MEDLINE, and PubMed were searched to identify relevant oncology publications from 2016 to 2021. Label claims from the US Food and Drug Administration and the European Medicines Agency for 7 recently approved drugs (pembrolizumab, atezolizumab, glasdegib, gilteritinib, tisagenlecleucel, axicabtagene ciloleucel, and daratumumab plus hyaluronidase-fihj) were reviewed. RESULTS: Publications providing guidance on meaningful change thresholds for the QLQ-C30 displayed a growing trend away from broad "legacy" thresholds of 10 points for all QLQ-C30 scales), toward deriving "contemporary" thresholds (eg, subscale specific, population specific). Contemporary publications generally provide guidance on selecting thresholds for specific scales that account for improved or worsening thresholds (eg, QLQ-C30 subscales). This trend was not clear for FACT-G, with less new guidance available. Most clinical trials used in regulatory label submissions have used thresholds of 10 points for the QLQ-C30 subscales and 3 to 7 points for the FACT-G total score. Despite the availability of more recent guidelines, contemporary meaningful change thresholds seem slow to emerge in the published literature and regulatory labels. CONCLUSIONS: Trialists should consider using contemporary thresholds, rather than legacy thresholds, for QLQ-C30 endpoints. Thresholds derived for a similar patient-population should be used where available. Further work is required to provide these across a broader range of cancer sites.
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Neoplasias Hematológicas , Melanoma , Humanos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Estimates of minimally important differences (MID) can assist interpretation of data collected using patient-reported outcomes (PRO), but variability exists in the emphasis placed on MIDs in health technology assessment (HTA) guidelines. This study aimed to identify to what extent information on the MID of a commonly used PRO, the EQ-5D, is required and utilised by selected HTA agencies. METHODS: Technology appraisal (TA) documents from HTA agencies in England, France, Germany, and the US between 2019 and 2021 were reviewed to identify documents which discussed MID of EQ-5D data as a clinical outcome assessment (COA) endpoint. RESULTS: Of 151 TAs utilising EQ-5D as a COA endpoint, 58 (38%) discussed MID of EQ-5D data. Discussion of MID was most frequent in Germany, in 75% (n = 12/16) of Gemeinsamer Bundesausschuss (G-BA) and 44% (n = 34/78) of Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, (IQWiG) TAs. MID was predominantly applied to the EQ-VAS (n = 50), most frequently using a threshold of > 7 or > 10 points (n = 13). G-BA and IQWiG frequently criticised MID analyses, particularly the sources of MID thresholds for the EQ-VAS, as they were perceived as being unsuitable for assessing the validity of MID. CONCLUSION: MID of the EQ-5D was not frequently discussed outside of Germany, and this did not appear to negatively impact decision-making of these HTA agencies. While MID thresholds were often applied to EQ-VAS data in German TAs, analyses were frequently rejected in benefit assessments due to concerns with their validity. Companies should pre-specify analyses of continuous data in statistical analysis plans to be considered for treatment benefit assessment in Germany.
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Avaliação da Tecnologia Biomédica , Humanos , Qualidade de Vida/psicologia , Inquéritos e Questionários/normas , Medidas de Resultados Relatados pelo Paciente , Alemanha , Diferença Mínima Clinicamente ImportanteRESUMO
Patient-reported outcome (PRO) questionnaires considered in this paper contain multiple subscales, although not all subscales are equally relevant for administration in all target patient populations. A group of measurement experts, developers, license holders, and other scientific-, regulatory-, payer-, and patient-focused stakeholders participated in a panel to discuss the benefits and challenges of a modular approach, defined here as administering a subset of subscales out of a multi-scaled PRO measure. This paper supports the position that it is acceptable, and sometimes preferable, to take a modular approach when administering PRO questionnaires, provided that certain conditions have been met and a rigorous selection process performed. Based on the experiences and perspectives of all stakeholders, using a modular approach can reduce patient burden and increase the relevancy of the items administered, and thereby improve measurement precision and eliminate wasted data without sacrificing the scientific validity and utility of the instrument. The panelists agreed that implementing a modular approach is not expected to have a meaningful impact on item responses, subscale scores, variability, reliability, validity, and effect size estimates; however, collecting additional evidence for the impact of context may be desirable. It is also important to recognize that adequate rationale and evidence (e.g., of fit-for-purpose status and relevance to patients) and a robust consensus process that includes patient perspectives are required to inform selection of subscales, as in any other measurement circumstance, is expected. We believe that the considerations discussed within (content validity, administration context, and psychometric factors) are relevant across multiple therapeutic areas.
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Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Reprodutibilidade dos Testes , Qualidade de Vida/psicologia , Inquéritos e Questionários , PsicometriaRESUMO
BACKGROUND: The ethical governance of Artificial Intelligence (AI) in health care and public health continues to be an urgent issue for attention in policy, research, and practice. In this paper we report on central themes related to challenges and strategies for promoting ethics in research involving AI in global health, arising from the Global Forum on Bioethics in Research (GFBR), held in Cape Town, South Africa in November 2022. METHODS: The GFBR is an annual meeting organized by the World Health Organization and supported by the Wellcome Trust, the US National Institutes of Health, the UK Medical Research Council (MRC) and the South African MRC. The forum aims to bring together ethicists, researchers, policymakers, research ethics committee members and other actors to engage with challenges and opportunities specifically related to research ethics. In 2022 the focus of the GFBR was "Ethics of AI in Global Health Research". The forum consisted of 6 case study presentations, 16 governance presentations, and a series of small group and large group discussions. A total of 87 participants attended the forum from 31 countries around the world, representing disciplines of bioethics, AI, health policy, health professional practice, research funding, and bioinformatics. In this paper, we highlight central insights arising from GFBR 2022. RESULTS: We describe the significance of four thematic insights arising from the forum: (1) Appropriateness of building AI, (2) Transferability of AI systems, (3) Accountability for AI decision-making and outcomes, and (4) Individual consent. We then describe eight recommendations for governance leaders to enhance the ethical governance of AI in global health research, addressing issues such as AI impact assessments, environmental values, and fair partnerships. CONCLUSIONS: The 2022 Global Forum on Bioethics in Research illustrated several innovations in ethical governance of AI for global health research, as well as several areas in need of urgent attention internationally. This summary is intended to inform international and domestic efforts to strengthen research ethics and support the evolution of governance leadership to meet the demands of AI in global health research.
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Inteligência Artificial , Bioética , Humanos , Saúde Global , África do Sul , Ética em PesquisaRESUMO
Digital technologies have produced many innovations in care delivery and enabled continuity of care for many people when in-person care was impossible. However, a growing body of research suggests that digital health can also exacerbate health inequities for those excluded from its benefits for reasons of cost, digital literacy, and structural discrimination related to characteristics such as age, race, ethnicity, and socioeconomic status. In this paper, we draw on a political economy perspective to examine structural barriers to progress in advancing digital health equity at the policy level. Considering the incentive structures and investments of powerful actors in the field, we outline how characteristics of neoliberal capitalism in Western contexts produce and sustain digital health inequities by describing 6 structural challenges to the effort to promote health equity through digital health, as follows: (1) the revenue-first incentives of technology corporations, (2) the influence of venture capital, (3) inequitable access to the internet and digital devices, (4) underinvestment in digital health literacy, (5) uncertainty about future reimbursement of digital health, and (6) justified mistrust of digital health. Building on these important challenges, we propose future immediate and long-term directions for work to support meaningful change for digital health equity.
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Saúde Digital , Promoção da Saúde , Humanos , Psicoterapia , Tecnologia Digital , EtnicidadeRESUMO
BACKGROUND: Telemedicine in the realm of rehabilitation includes the remote delivery of rehabilitation services using communication technologies (eg, telephone, emails, and video). The widespread application of virtual care grants a suitable time to explore the intersection of compassion and telemedicine, especially due to the impact of COVID-19 and how it greatly influenced the delivery of health care universally. OBJECTIVE: The purpose of this study was to explore how compassionate care is understood and experienced by physiatrists and patients engaged in telemedicine. METHODS: We used a qualitative descriptive approach to conduct interviews with patients and physiatrists between June 2021 and March 2022. Patients were recruited across Canada from social media and from a single hospital network in Toronto, Ontario. Physiatrists were recruited across Canada through social media and the Canadian Association for Physical Medicine and Rehabilitation (CAPM&R) email listserve. Interviews were recorded and transcribed. Data were analyzed thematically. RESULTS: A total of 19 participants were interviewed-8 physiatrists and 11 patients. Two themes capturing physiatrists' and patients' experiences with delivering and receiving compassionate care, especially in the context of virtual care were identified: (1) compassionate care is inherently rooted in health care providers' inner intentions and are, therefore, expressed as caring behaviors and (2) virtual elements impact the delivery and receipt of compassionate care. CONCLUSIONS: Compassionate care stemmed from physiatrists' caring attitudes which then manifest as caring behaviors. In turn, these caring attitudes and behaviors enable individualized care and the establishment of a safe space for patients. Moreover, the virtual care modality both positively and negatively influenced how compassion is enacted by physiatrists and received by patients. Notably, there was large ambiguity around the norms and etiquette surrounding virtual care. Nonetheless, the flexibility and person-centeredness of virtual care cause it to be useful in health care settings.
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COVID-19 , Empatia , Pesquisa Qualitativa , Telemedicina , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Fisiatras/psicologia , Ontário , Idoso , Atitude do Pessoal de Saúde , CanadáRESUMO
PURPOSE: To determine how COVID-19 lockdown impacted physical activity (PA) levels, wellbeing, and diabetes management in children (aged 0-17 years) with type 1 diabetes (T1D), from the perspectives of their parent/guardian. DESIGN AND METHODS: This qualitative descriptive study is part of a larger, parallel mixed-methods design study, which incorporated a cross-sectional survey and semi-structured one-to-one interviews. Interviewees were recruited from the survey, which was distributed to parents of children/adolescents with T1D in the UK. Interviews explored diabetes management, mental and physical wellbeing, changes in PA levels, sleep quality before/during lockdown, and the effects of lockdown on the individual and their family. The interviews were transcribed and the data were analysed thematically. RESULTS: 14 interviews were conducted with parents. Thematic analysis generated a central theme of routine disruption, with four further themes on diabetes management routines, harnessing the opportunities of lockdown, weighing up risk, and variable impact on wellbeing. CONCLUSIONS: Maintaining or increasing PA during COVID-19 lockdown was associated with better diabetes management, sleep, and wellbeing for children/adolescents with T1D, despite significant disruption to established routines. Use of technology during the pandemic contributed positively to wellbeing. PRACTICE IMPLICATIONS: It is crucial to emphasize the significance of maintaining a well-structured routine when treating patients with type 1 diabetes. A consistent routine, incorporating regular physical exercise and good sleep hygiene, will help with managing overall diabetes control.
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COVID-19 , Diabetes Mellitus Tipo 1 , Exercício Físico , Pais , Pesquisa Qualitativa , Humanos , Diabetes Mellitus Tipo 1/psicologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Criança , Masculino , Adolescente , Feminino , Reino Unido , Pais/psicologia , Estudos Transversais , Pré-Escolar , Adaptação Psicológica , SARS-CoV-2 , Quarentena/psicologia , LactenteRESUMO
ABSTRACT: Shaw, J, Gould, ZI, Oliver, JL, and Lloyd, RS. Twelve weeks of progressive resistance training positively improves physical fitness and golf swing performance in talented youth golfers. J Strength Cond Res 38(6): 1103-1110, 2024-This aim of this study was to investigate the effects of a 12-week resistance training program in talented junior golfers. Eighteen talented youth golfers were pair matched by maturity status and handicap, and subsequently allocated to an experimental (EXP) or control group. During the 12-week intervention, both groups continued with their normal golf practice while the EXP group also completed a progressive twice-weekly resistance training program. At baseline, subjects performed multiple trials of an isometric midthigh pull (IMTP), countermovement jump (CMJ), standing long jump, golf movement screen (GMS), and isometric plank hold. Club head speed (CHS) and carry distance for a 6-iron and driver were also measured using a commercial launch monitor. When controlled for maturity offset, there were significant ( p < 0.05) interaction effects in favor of the EXP group for absolute ( g = 1.29) and relative ( g = 2.06) peak force for the IMTP, CMJ absolute ( g = 0.73) and relative ( g = 0.66) peak power, jump height ( g = 1.05), modified reactive strength index ( g = 1.30), lateral ( g = 0.48-0.88) and horizontal jump distance ( g = 1.20), and GMS total score ( g = 1.07). Significant interaction effects were also reported in 6-iron and driver CHS and carry distance in favor of the EXP group ( p < 0.05; g = 0.41-1.64). These findings indicate that twice-weekly resistance training in combination with regular golf practice can stimulate increases in measures of strength, power, and movement competency in youth golfers, which should contribute to enhanced golf swing performance.
Assuntos
Desempenho Atlético , Golfe , Aptidão Física , Treinamento Resistido , Humanos , Golfe/fisiologia , Treinamento Resistido/métodos , Desempenho Atlético/fisiologia , Adolescente , Masculino , Aptidão Física/fisiologia , Força Muscular/fisiologia , FemininoRESUMO
BACKGROUND: Clinical outcomes of patients with renal transplant (RT) undergoing percutaneous coronary intervention (PCI) remain poorly elucidated. METHOD: Between 2014 and 2021, data were analysed for the following three groups of patients undergoing PCI enrolled in a multicentre Australian registry: (1) RT recipients (n=226), (2) patients on dialysis (n=992), and (3) chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR], 30â60 mL/min per 1.73 m2) without previous RT (n=15,534). Primary outcome was 30-day major adverse cardiac and cerebrovascular events (MACCEs)-composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, and stroke. RESULTS: RT recipients were younger than dialysis and patients with CKD (61±10 vs 68±12 vs 78±8.2 years, p<0.001). Patients with RT less frequently had severe left ventricular dysfunction compared with dialysis and CKD groups (6.7% vs 14% and 8.5%); however more, often presented with acute coronary syndrome (58% vs 52% and 48%), especially STEMI (all p<0.001). Patients with RT and CKD had lower rates of 30-day MACCE (4.4% and 6.8% vs 11.6%, p<0.001) than the dialysis group. Three-year survival was similar between RT and CKD groups, however was lower in the dialysis group (80% and 83% vs 60%, p<0.001). After adjustment, dialysis was an independent predictor of 30-day MACCE (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.44â2.50, p<0.001), however RT was not (OR 0.91, CI 0.42â1.96, p=0.802). Both RT (hazard ratio [HR] 2.07, CI 1.46â2.95, p<0.001) and dialysis (HR 1.35, CI 1.02â1.80, p=0.036) heightened the hazard of long-term mortality. CONCLUSIONS: RT recipients have more favourable clinical outcomes following PCI compared with patients on dialysis. However, despite having similar short-term outcomes to patients with CKD, the hazard of long-term mortality is significantly greater for RT recipients.
Assuntos
Transplante de Rim , Intervenção Coronária Percutânea , Sistema de Registros , Humanos , Intervenção Coronária Percutânea/métodos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Austrália/epidemiologia , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Taxa de Filtração Glomerular , Seguimentos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/mortalidade , Resultado do Tratamento , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , TransplantadosRESUMO
AIMS/HYPOTHESIS: The aims of this study were to assess cognitions relating to hypoglycaemia in adults with type 1 diabetes and impaired awareness of hypoglycaemia before and after the multimodal HypoCOMPaSS intervention, and to determine cognitive predictors of incomplete response (one or more severe hypoglycaemic episodes over 24 months). METHODS: This analysis included 91 adults with type 1 diabetes and impaired awareness of hypoglycaemia who completed the Attitudes to Awareness of Hypoglycaemia (A2A) questionnaire before, 24 weeks and 24 months after the intervention, which comprised a short psycho-educational programme with optimisation of insulin therapy and glucose monitoring. RESULTS: The age and diabetes duration of the participants were 48±12 and 29±12 years, respectively (mean±SD). At baseline, 91% reported one or more severe hypoglycaemic episodes over the preceding 12 months; this decreased to <20% at 24 weeks and after 24 months (p=0.001). The attitudinal barrier 'hyperglycaemia avoidance prioritised' (η2p=0.250, p=0.001) decreased from baseline to 24 weeks, and this decrease was maintained at 24 months (mean±SD=5.3±0.3 vs 4.3±0.3 vs 4.0±0.3). The decrease in 'asymptomatic hypoglycaemia normalised' from baseline (η2p=0.113, p=0.045) was significant at 24 weeks (1.5±0.3 vs 0.8±0.2). Predictors of incomplete hypoglycaemia response (one or more further episodes of severe hypoglycaemia) were higher baseline rates of severe hypoglycaemia, higher baseline scores for 'asymptomatic hypoglycaemia normalised', reduced change in 'asymptomatic hypoglycaemia normalised' scores at 24 weeks, and lower baseline 'hypoglycaemia concern minimised' scores (all p<0.05). CONCLUSIONS/INTERPRETATION: Participation in the HypoCOMPaSS RCT was associated with improvements in hypoglycaemia-associated cognitions, with 'hyperglycaemia avoidance prioritised' most prevalent. Incomplete prevention of subsequent severe hypoglycaemia episodes was associated with persistence of the cognition 'asymptomatic hypoglycaemia normalised'. Understanding and addressing cognitive barriers to hypoglycaemia avoidance is important in individuals prone to severe hypoglycaemia episodes. CLINICAL TRIALS REGISTRATION: www.isrctn.org : ISRCTN52164803 and https://eudract.ema.europa.eu : EudraCT2009-015396-27.
Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Hipoglicemia , Adulto , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicemia , Automonitorização da Glicemia , Hipoglicemia/tratamento farmacológico , Insulina/uso terapêutico , Conscientização , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , AtitudeRESUMO
BACKGROUND: Donor hyperglycaemia following brain death has been attributed to reversible insulin resistance. However, our islet and pancreas transplant data suggest that other mechanisms may be predominant. We aimed to determine the relationships between donor insulin use and markers of beta-cell death and beta-cell function in pancreas donors after brain death. METHODS: In pancreas donors after brain death, we compared clinical and biochemical data in 'insulin-treated' and 'not insulin-treated donors' (IT vs. not-IT). We measured plasma glucose, C-peptide and levels of circulating unmethylated insulin gene promoter cell-free DNA (INS-cfDNA) and microRNA-375 (miR-375), as measures of beta-cell death. Relationships between markers of beta-cell death and islet isolation outcomes and post-transplant function were also evaluated. RESULTS: Of 92 pancreas donors, 40 (43%) required insulin. Glycaemic control and beta-cell function were significantly poorer in IT donors versus not-IT donors [median (IQR) peak glucose: 8 (7-11) vs. 6 (6-8) mmol/L, p = .016; C-peptide: 3280 (3159-3386) vs. 3195 (2868-3386) pmol/L, p = .046]. IT donors had significantly higher levels of INS-cfDNA [35 (18-52) vs. 30 (8-51) copies/ml, p = .035] and miR-375 [1.050 (0.19-1.95) vs. 0.73 (0.32-1.10) copies/nl, p = .05]. Circulating donor miR-375 was highly predictive of recipient islet graft failure at 3 months [adjusted receiver operator curve (SE) = 0.813 (0.149)]. CONCLUSIONS: In pancreas donors, hyperglycaemia requiring IT is strongly associated with beta-cell death. This provides an explanation for the relationship of donor IT with post-transplant beta-cell dysfunction in transplant recipients.