Early findings from the NHS Type 2 Diabetes Path to Remission Programme: a prospective evaluation of real-world implementation.

BACKGROUND: Randomised controlled trials have shown that total diet replacement (TDR) can lead to remission of type 2 diabetes. In 2019, the English National Health Service (NHS) committed to establishing a TDR-based interventional programme delivered at scale within real-world environments; development followed of the NHS Type 2 Diabetes Path to Remission (T2DR) programme, a 12-month behavioural intervention to support weight loss involving an initial 3-month period of TDR. We assessed remission of type 2 diabetes for programme participants. METHODS: In this national prospective service evaluation of programme implementation, people in England aged 18-65 years and diagnosed with type 2 diabetes in the last 6 years were referred to the programme between programme launch on Sept 1, 2020, and Dec 31, 2022. Programme data were linked to the National Diabetes Audit to ascertain HbA1c measurements and glucose-lowering medication prescriptions. The primary outcome was remission of type 2 diabetes at 1 year, defined as two HbA1c measurements of less than 48 mmol/mol recorded at least 3 months apart with no glucose-lowering medications prescribed from 3 months before the first HbA1c measurement, and the second HbA1c measurement recorded 11-15 months after the programme start date. Outcomes were assessed in two ways: for all participants who started TDR on the 12-month programme before January, 2022, for whom there were no missing data; and for all participants who started TDR on the 12-month programme before January, 2022, and had completed the programme (ie, had a valid weight recorded at month 12) by Dec 31, 2022, for whom there were no missing data. FINDINGS: Between Sept 1, 2020, and Dec 31, 2022, 7540 people were referred to the programme; of those, 1740 started TDR before January, 2022, and therefore had a full 12-month opportunity to undertake the programme by the time of data extraction at the end of December, 2022. Of those who started TDR before January, 2022, 960 (55%) completed the programme (defined as having a weight recorded at 12 months). The mean weight loss for the 1710 participants who started the programme before January, 2022 and had no missing data was 8·3% (95% CI 7·9-8·6) or 9·4 kg (8·9-9·8), and the mean weight loss for the 945 participants who completed the programme and had no missing data was 9·3% (8·8-9·8) or 10·3 kg (9·7-10·9). For the subgroup of 710 (42%) of 1710 participants who started the programme before January, 2022, and also had two HbA1c measurements recorded, 190 (27%) had remission, with mean weight loss of 13·4% (12·3-14·5) or 14·8 kg (13·4-16·3). Of the 945 participants who completed the programme, 450 (48%) had two HbA1c measurements recorded; of these, 145 (32%) had remission, with mean weight loss of 14·4% (13·2-15·5) or 15·9 kg (14·3-17·4). INTERPRETATION: Findings from the NHS T2DR programme show that remission of type 2 diabetes is possible outside of research settings, through at-scale service delivery. However, the rate of remission achieved is lower and the ascertainment of data is more limited with implementation in the real world than in randomised controlled trial settings. FUNDING: None.

Protocol update for a multi-centre randomised controlled trial of exercise rehabilitation for people with pulmonary hypertension: the SPHERe trial.

BACKGROUND: The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020. In response to the COVID-19 pandemic, the trial was stopped in March 2020. In person delivery of the SPHERe intervention to a vulnerable population was not possible during the COVID-19 pandemic. We describe here how trial procedures and intervention delivery were adapted in response to the COVID-19 pandemic. METHODS: Restrictions imposed by the COVID-19 pandemic on the clinically vulnerable PH population meant that trial delivery was changed from a centre-based rehabilitation programme to remotely delivered group online sessions. This led to minor alterations to the eligibility criteria. These changes followed a consultation process with stakeholders and people with PH and were approved by the funder and independent trial committees. CONCLUSIONS: We describe the modified SPHERe trial protocol in response to restrictions imposed by the COVID-19 pandemic. SPHERe is the first randomised controlled trial to assess the clinical and cost-effectiveness of an online group rehabilitation programme for people with PH compared to usual care. TRIAL REGISTRATION: ISRCTN no. 10608766. Prospectively registered on 18th March 2019, updated 16th August 2023.

Transparency and reproducibility in the Adolescent Brain Cognitive Development (ABCD) study.

BACKGROUND: Transparency can build trust in the scientific process, but scientific findings can be undermined by poor and obscure data use and reporting practices. The purpose of this work is to report how data from the Adolescent Brain Cognitive Development (ABCD) Study has been used to date, and to provide practical recommendations on how to improve the transparency and reproducibility of findings. METHODS: Articles published from 2017 to 2023 that used ABCD Study data were reviewed using more than 30 data extraction items to gather information on data use practices. Total frequencies were reported for each extraction item, along with computation of a Level of Completeness (LOC) score that represented overall endorsement of extraction items. Univariate linear regression models were used to examine the correlation between LOC scores and individual extraction items. Post hoc analysis included examination of whether LOC scores were correlated with the logged 2-year journal impact factor. RESULTS: There were 549 full-length articles included in the main analysis. Analytic scripts were shared in 30 % of full-length articles. The number of participants excluded due to missing data was reported in 60 % of articles, and information on missing data for individual variables (e.g., household income) was provided in 38 % of articles. A table describing the analytic sample was included in 83 % of articles. A race and/or ethnicity variable was included in 78 % of reviewed articles, while its inclusion was justified in only 41 % of these articles. LOC scores were highly correlated with extraction items related to examination of missing data. A bottom 10 % of LOC score was significantly correlated with a lower logged journal impact factor when compared to the top 10 % of LOC scores (ß=-0.77, 95 % -1.02, -0.51; p-value < 0.0001). CONCLUSION: These findings highlight opportunities for improvement in future papers using ABCD Study data to readily adapt analytic practices for better transparency and reproducibility efforts. A list of recommendations is provided to facilitate adherence in future research.

Transparency and Reproducibility in the Adolescent Brain Cognitive Development (ABCD) Study.

Background: Transparency can build trust in the scientific process, but scientific findings can be undermined by poor and obscure data use and reporting practices. The purpose of this work is to report how data from the Adolescent Brain Cognitive Development (ABCD) Study has been used to date, and to provide practical recommendations on how to improve the transparency and reproducibility of findings. Methods: Articles published from 2017 to 2023 that used ABCD Study data were reviewed using more than 30 data extraction items to gather information on data use practices. Total frequencies were reported for each extraction item, along with computation of a Level of Completeness (LOC) score that represented overall endorsement of extraction items. Univariate linear regression models were used to examine the correlation between LOC scores and individual extraction items. Post hoc analysis included examination of whether LOC scores were correlated with the logged 2-year journal impact factor. Results: There were 549 full-length articles included in the main analysis. Analytic scripts were shared in 30% of full-length articles. The number of participants excluded due to missing data was reported in 60% of articles, and information on missing data for individual variables (e.g., household income) was provided in 38% of articles. A table describing the analytic sample was included in 83% of articles. A race and/or ethnicity variable was included in 78% of reviewed articles, while its inclusion was justified in only 41% of these articles. LOC scores were highly correlated with extraction items related to examination of missing data. A bottom 10% of LOC score was significantly correlated with a lower logged journal impact factor when compared to the top 10% of LOC scores (ß=-0.77, 95% -1.02, -0.51; p-value < 0.0001). Conclusion: These findings highlight opportunities for improvement in future papers using ABCD Study data to readily adapt analytic practices for better transparency and reproducibility efforts. A list of recommendations is provided to facilitate adherence in future research.

Implementation of a primary-tertiary shared care model to improve the detection of familial hypercholesterolaemia (FH): a mixed methods pre-post implementation study protocol.

INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disorder of lipid metabolism and a preventable cause of premature cardiovascular disease. Current detection rates for this highly treatable condition are low. Early detection and management of FH can significantly reduce cardiac morbidity and mortality. This study aims to implement a primary-tertiary shared care model to improve detection rates for FH. The primary objective is to evaluate the implementation of a shared care model and support package for genetic testing of FH. This protocol describes the design and methods used to evaluate the implementation of the shared care model and support package to improve the detection of FH. METHODS AND ANALYSIS: This mixed methods pre-post implementation study design will be used to evaluate increased detection rates for FH in the tertiary and primary care setting. The primary-tertiary shared care model will be implemented at NSW Health Pathology and Sydney Local Health District in NSW, Australia, over a 12-month period. Implementation of the shared care model will be evaluated using a modification of the implementation outcome taxonomy and will focus on the acceptability, evidence of delivery, appropriateness, feasibility, fidelity, implementation cost and timely initiation of the intervention. Quantitative pre-post and qualitative semistructured interview data will be collected. It is anticipated that data relating to at least 62 index patients will be collected over this period and a similar number obtained for the historical group for the quantitative data. We anticipate conducting approximately 20 interviews for the qualitative data. ETHICS AND DISSEMINATION: Ethical approval has been granted by the ethics review committee (Royal Prince Alfred Hospital Zone) of the Sydney Local Health District (Protocol ID: X23-0239). Findings will be disseminated through peer-reviewed publications, conference presentations and an end-of-study research report to stakeholders.

Genetic testing in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally and is responsible for an estimated one-third of deaths as well as significant morbidity and health care utilisation. Technological and bioinformatic advances have facilitated the discovery of pathogenic germline variants for some specific CVDs, including familial hypercholesterolaemia, cardiomyopathies and arrhythmic syndromes. Use of these genetic tests for earlier disease identification is increasing due, in part, to decreasing costs, Medicare rebates, and consumer comfort with genetic testing. However, CVDs that occur more commonly, including coronary artery disease and atrial fibrillation, do not display monogenic inheritance patterns. Genetically, these diseases have generally been associated with many genetic variants each with a small effect size. This complexity can be expressed mathematically as a polygenic risk score. Genetic testing kits that provide polygenic risk scoring are becoming increasingly available directly to private-paying consumers outside the traditional clinical setting. An improved understanding of the evidence of genetics in CVD will offer clinicians new opportunities for individualised risk prediction and preventive therapy.

Resting cells of Skeletonema marinoi assimilate organic compounds and respire by dissimilatory nitrate reduction to ammonium in dark, anoxic conditions.

Diatoms can survive long periods in dark, anoxic sediments by forming resting spores or resting cells. These have been considered dormant until recently when resting cells of Skeletonema marinoi were shown to assimilate nitrate and ammonium from the ambient environment in dark, anoxic conditions. Here, we show that resting cells of S. marinoi can also perform dissimilatory nitrate reduction to ammonium (DNRA), in dark, anoxic conditions. Transmission electron microscope analyses showed that chloroplasts were compacted, and few large mitochondria had visible cristae within resting cells. Using secondary ion mass spectrometry and isotope ratio mass spectrometry combined with stable isotopic tracers, we measured assimilatory and dissimilatory processes carried out by resting cells of S. marinoi under dark, anoxic conditions. Nitrate was both respired by DNRA and assimilated into biomass by resting cells. Cells assimilated nitrogen from urea and carbon from acetate, both of which are sources of dissolved organic matter produced in sediments. Carbon and nitrogen assimilation rates corresponded to turnover rates of cellular carbon and nitrogen content ranging between 469 and 10,000 years. Hence, diatom resting cells can sustain their cells in dark, anoxic sediments by slowly assimilating and respiring substrates from the ambient environment.

Introduction to the Special Issue: International Responses to Prevention Intervention Research During Human Ecosystem Disruptions.

For decades, human ecosystem disruptions (HEDs), including pandemics, natural disasters, and socio-economic crises, have shaped national and international responses affecting everyday life. These disruptions present challenges and opportunities for prevention science to address emerging behavioral and mental health research questions, intervention strategies, methodologies, analyses, and research collaboration. This paper introduces a special issue that aims to document examples of how prevention science research teams had (1) globally improved health and well-being through swift, scientifically based responses during HED events and (2) advanced our understanding of the conduct and outcomes of prevention intervention research during crises such as pandemics, natural disasters, and socio-economic crises. The issue presents six research studies conducted in over ten different countries (e.g., Australia, Mexico, China). This issue includes original empirical and descriptive work that addressed HED implications for preventive interventions at within-country and cross-national levels. The findings hold potential applications for responses during current and future pandemics and natural disasters. Participants reflected on methodological and contextual considerations during HEDs, such as navigating travel restrictions, adapting ongoing research efforts to accommodate scientific learning during disruptions, and assessing the impact of policies redistributing preventive resources during and after a HED.