bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of multicomponent interventions in type 2 diabetes mellitus in a cluster randomised controlled trial: the INDICA study
Authors: García-Pérez Lidia , Ramallo-Fariña Yolanda , Vallejo-Torres Laura , Rodríguez-Rodríguez Leticia , González-Pacheco Himar , Santos-Hernández Beatriz , García-Bello Miguel Angel , Wägner Ana María , Carmona Montserrat , Serrano-Aguilar Pedro G 
Published: April 2022

ObjectiveTo analyse the cost-effectiveness of multicomponent interventions designed to improve outcomes in type 2 diabetes mellitus (T2DM) in primary care in the Canary Islands, Spain, within the INDICA randomised clinical trial, from the public health system perspective.DesignAn economic evaluation was conducted for the within-trial period (2 years) comparing the four arms of the INDICA study.SettingPrimary care in the Canary Islands, Spain.Participants2334 patients with T2DM without complications were included.InterventionsInterventions for patients (PTI), for primary care professionals (PFI), for both (combined intervention arm for patients and professionals, CBI) and usual care (UC) as a control group.OutcomesThe main outcome was the incremental cost per quality-adjusted life-years (QALY). Only the intervention and the healthcare costs were included.AnalysisMultilevel models were used to estimate results, and to measure the size and significance of incremental changes. Missed values were treated by means of multiple imputations procedure.ResultsThere were no differences between arms in terms of costs (p=0.093), while some differences were observed in terms of QALYs after 2 years of follow-up (p=0.028). PFI and CBI arms were dominated by the other two arms, PTI and UC. The differences between the PTI and the UC arms were very small in terms of QALYs, but significant in terms of healthcare costs (p=0.045). The total cost of the PTI arm (€2571, 95% CI €2317 to €2826) was lower than the cost in the UC arm (€2750, 95% CI €2506 to €2995), but this difference did not reach statistical significance. Base case estimates of the incremental cost per QALY indicate that the PTI strategy was the cost-effective option.ConclusionsThe INDICA intervention designed for patients with T2DM and families is likely to be cost-effective from the public healthcare perspective. A cost-effectiveness model should explore this in the long term.Trial registration numberNCT01657227.
Incremental benefits of novel pharmaceuticals in the UK: a cross-sectional analysis of NICE technology appraisals from 2010 to 2020
Authors: Polak Tobias B , Cucchi David GJ , Darrow Jonathan J , Versteegh Matthijs M 
Published: April 2022

ObjectivesTo evaluate the incremental value of new drugs across disease areas receiving favourable coverage decisions by the UK’s National Institute for Health and Care Excellence (NICE) over the past decade.Design, setting, and participantsThis cross-sectional study assessed favourable appraisal decisions of drugs between 1 January 2010 and 31 December 2020. Estimates of incremental benefit were extracted from NICE’s evidence review groups reports.Primary outcome measureIncremental benefit of novel drugs relative to the best alternative therapeutic option, expressed in quality-adjusted life-years (QALYs).Results184 appraisals of 129 drugs provided QALYs. The median incremental value was 0.27 QALY (IQR: 0.07–0.73). Benefits varied across drug-indication pairs (range: −0.49 to 5.22 QALY). The highest median benefits were found in haematology (0.70, IQR: 0.55–1.22) and oncology (0.46, IQR: 0.20–0.88), the lowest in ophthalmology (0.09, IQR: 0.04–0.22) and endocrinology (0.02, IQR: 0.01–0.06). Eight appraisals (4.3%) found contributions of more than two QALYs, but one in four (50/184) drug-indication pairs provided less than the equivalent of 1 month in perfect health compared to existing treatments.ConclusionsIn our review period, the median incremental value of novel drugs approved for use within the English National Health System, relative to the best alternative therapeutic option, was equivalent to 3–4 months of life in perfect health, but data were heterogeneous. Objective evaluations of therapeutic value helps patients and physicians to develop reasonable expectations of drugs and delivers insights into disease areas where medicinal therapeutic progress has had the most and least impact.
Low-dose naltrexone for the induction of remission in patients with mild to moderate Crohn’s disease: protocol for the randomised, double-blinded, placebo-controlled, multicentre LDN Crohn study
Authors: Paulides Emma , Lie Mitchell R K L , van der Woude Christien Janneke 
Published: April 2022

IntroductionCrohn’s disease (CD) is an inflammatory bowel disease (IBD). Several drugs exist to induce and maintain remission, but a significant part of the patients is refractory to current IBD drugs or experiences side effects. Whether low-dose naltrexone (LDN) is a safe and easily accessible alternative treatment option for these patients needs to be investigated. The aim of this study is to assess the efficacy of LDN for the induction of remission in patients with mild to moderate CD.Methods and analysisThe LDN Crohn study is a randomised, double-blinded, placebo-controlled multicentre trial. Patients with CD are randomised 1:1 to receive treatment with either LDN 4.5 mg once daily or placebo for 12 weeks. The primary objective is endoscopic remission at week 12, defined as Simple Endoscopic Score-CD≤2 and ulcerated surface subscore ≤1 in all five segments. Secondary aims include clinical and endoscopic response, changes in laboratory measures of inflammation, adverse events and patient-reported outcomes. To have 85% power to detect a true difference in the primary outcome measure between placebo and LDN, 61 patients will be needed in both groups.Ethics and disseminationThe study is approved by the Medical Ethics Committee of the Erasmus MC, Rotterdam, the Netherlands (registration number NL69149.078.19, MEC-2019-0602). Results will be published in peer-reviewed journals and presented at international conferences.Trial registration numbersEudraCT2019-000852-32; NL9259.
Research on the influencing factors of fatigue and professional identity among CDC workers in China: an online cross-sectional study
Authors: Cui Qi , Liu Li , Hao Zejun , Li Mengyao , Liu Chunli , Chenxin Yang , Zhang Qiuling , Wu Hui 
Published: April 2022

ObjectiveThis study aimed to investigate the status quo and the influencing factors of fatigue and professional identity among the Centers for Disease Control and Prevention (CDC) workers in China during the pandemic.DesignA cross-sectional design.SettingCDC workers employed by the Liaoning CDC system were enrolled (administrative staffs were excluded).Participants1020 CDC workers.Primary outcome measuresFatigue scores and professional identity scores.Secondary outcome measuresPostcompetency scores, respect scores, occupational stress scores, resilience scores and self-efficacy scores.ResultsThe average scores of fatigue and professional identity were 8.23, 38.88, respectively. Factors including perceived public respect (β=−0.129, p<0.01), resilience (β=−0.104, p<0.05) and self-efficacy (β=−0.22, p<0.01) were negatively associated with fatigue. Educational background (bachelor vs junior college or below) (β=0.105, p<0.01), (master or above vs junior college or below) (β=0.092, p<0.05), workplace (county vs district) (β=0.067, p<0.05), (city vs district) (β=0.085, p<0.05), fighting the COVID-19 on the front line (β=0.059, p<0.05) and occupational stress (β=0.166, p<0.01) were positively correlated with fatigue. Educational background (bachelor vs junior college or below) (β=−0.097, p<0.01), (master or above vs junior college or below) (β=−0.114, p<0.01), workplace (city vs district) (β=−0.114, p<0.01), fighting the COVID-19 on the front line (β=−0.047, p<0.05) and occupational stress (β=−0.105, p<0.01) were negatively associated with professional identity. Factors including postcompetency (β=0.362, p<0.01), perceived public respect (general vs low) (β=0.219, p<0.01), (high vs low) (β=0.288, p<0.01), resilience (β=0.097, p<0.05) and self-efficacy (β=0.113, p<0.01) were positively connected with professional identity.ConclusionThe fatigue among the CDC workers was at a higher level. The level of professional identity was high, and administrators should take measures to alleviate fatigue and maintain professional identity. In addition, methods aiming to attenuate occupational stress, and improve resilience and self-efficacy should be immediately put into action.
Dexmedetomidine after Cardiac Surgery for Prevention of Delirium (EXACTUM) trial protocol: a multicentre randomised, double-blind, placebo-controlled trial
Authors: Gargadennec Thomas , Oilleau Jean-Ferréol , Rozec Bertrand , Nesseler Nicolas , Lasocki Sigismond , Futier Emmanuel , Amour Julien , Durand Michel , Bougle Adrien , Kerforne Thomas , Consigny Maëlys , Eddi Dauphou , Huet Olivier 
Published: April 2022

IntroductionIncidence of delirium after cardiac surgery remains high and delirium has a significant burden on short-term and long-term outcomes. Multiple causes can trigger delirium occurence, and it has been hypothesised that sleep disturbances can be one of them. Preserving the circadian rhythm with overnight infusion of low-dose dexmedetomidine has been shown to lower the occurrence of delirium in older patients after non-cardiac surgery. However, these results remain controversial. The aim of this study was to demonstrate the usefulness of sleep induction by overnight infusion of dexmedetomidine to prevent delirium after cardiac surgery.Methods and analysisDexmedetomidine after Cardiac Surgery for Prevention of Delirium is an investigator-initiated, randomised, placebo-controlled, parallel, multicentre, double-blinded trial. Nine centres in France will participate in the study. Patients aged 65 years or older and undergoing cardiac surgery will be enrolled in the study. The intervention starts on day 0 (the day of surgery) until intensive care unit (ICU) discharge; the treatment is administered from 20:00 to 08:00 on the next day. Infusion rate is modified by the treating nurse or the clinician with an objective of Richmond Agitation and Sedation Scale score from −1 to +1. The primary outcome is delirium occurrence evaluated with confusion assessment method for the ICU two times per day during 7 days following surgery. Secondary outcomes include incidence of agitation related events, self-evaluated quality of sleep, cognitive evaluation 3 months after surgery and quality of life 3 months after surgery. The sample size is 348.Ethics and disseminationThe study was approved for all participating centers by the French Central Ethics Committee (Comité de Protection des Personnes Ile de France VI, registration number 2018-000850-22). The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03477344.
Experience of co-creation of a health plan and support for sustainable physical activity among people with chronic widespread pain: a qualitative interview study in Sweden
Authors: Feldthusen Caroline , Bergenheim Anna , Barenfeld Emmelie , Gjertsson Inger , Larsson Anette , Mannerkorpi Kaisa 
Published: April 2022

ObjectivesThe aim of this study was to gain deeper knowledge about how people with chronic widespread pain (CWP) experience the co-creation of a health plan for sustainable physical activity, working in partnership with a physiotherapist, supported by a digital platform.DesignQualitative semistructured in-depth individual interviews were analysed with qualitative content analysis.SettingFive primary healthcare centres in western Sweden.ParticipantsThe interviewees comprised 19 individuals with CWP who had previously participated in a person-centred intervention involving co-creation of a health plan and support via a digital platform. The interviews were carried out from late 2019 to spring 2020, 1–6 months after the respondents’ final follow-up.ResultsThe analysis resulted in an overarching theme; hope for physical activity that actually works, illustrating the experience of taking part in co-creating a reasonable health plan, based on the respondents’ own goals and interests with the potential to actually work. This theme was based on two categories: a plan tailored for me and a frame for participation and accessibility to help fulfil the plan. The digital platform provided a way to participate and an assurance that there was someone there for them if necessary.ConclusionsThe co-creation of a health plan nurtured hope of having developed a manageable plan for physical activity that could lead to improved future health and well-being. Digital support may serve as a valuable complement in order to sustain and adjust the planned physical activity.Trial registration numberClinicalTrials.gov Identifier: NCT03434899.
Durvalumab with or without tremelimumab combined with particle therapy for advanced hepatocellular carcinoma with macrovascular invasion: protocol for the DEPARTURE phase Ib trial
Authors: Ogasawara Sadahisa , Koroki Keisuke , Makishima Hirokazu , Wakatsuki Masaru , Takahashi Asahi , Yumita Sae , Nakagawa Miyuki , Ishino Takamasa , Ogawa Keita , Fujiwara Kisako , Iwanaga Terunao , Sakuma Takafumi , Fujita Naoto , Kojima Ryuta , Kanzaki Hiroaki , Kobayashi Kazufumi , Kiyono Soichiro , Nakamura Masato , Kanogawa Naoya , Saito Tomoko , Kondo Takayuki , Nakagawa Ryo , Nakamoto Shingo , Muroyama Ryosuke , Chiba Tetsuhiro , Ozawa Yoshihito , Kawasaki Yohei , Kurokawa Tomoya , Hanaoka Hideki , Tsuji Hiroshi , Kato Naoya 
Published: April 2022

IntroductionAdvanced hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) has the worst prognosis among all phenotypes. This trial aims to evaluate whether treatment with durvalumab, alone or in combination with tremelimumab, plus particle therapy is a safe and synergistically effective treatment in patients with advanced HCC and MVI.Methods and analysisThis phase Ib, multicentre (two sites in Japan), open-label, single-arm, investigator-initiated clinical trial will assess durvalumab monotherapy in combination with particle therapy (cohort A) and that of durvalumab plus tremelimumab in combination with particle therapy (cohort B) for patients with advanced HCC with MVI. Cohort A will receive 1500 mg durvalumab every 4 weeks. Cohort B will receive 1500 mg durvalumab every 4 weeks in principle and 300 mg tremelimumab only on day 1 of the first cycle. Carbon-ion radiotherapy will be administered after day 8 of the first cycle. The primary endpoints are rates of any and severe adverse events, including dose-limiting toxicities (DLTs); secondary endpoints are overall survival, 6-month survival, objective response, 6-month progression-free survival and time to progression. Patients are initially enrolled into cohort A. If cohort A treatment is confirmed to be tolerated (ie, no DLT in three patients or one DLT in six patients), the trial proceeds to enrol more patients into cohort B. Similarly, if cohort B treatment is confirmed to be tolerated (ie, no DLT in three patients or one DLT in six patients), a total of 15 patients will be enrolled into cohort B.Ethics and disseminationThis study was approved by the ethics committees of the two participating institutions (Chiba University Hospital and National Institutes for Quantum (approval number: 2020040) and Radiological Science and Technology, QST Hospital (approval number: C20-001)). Participants will be required to provide written informed consent. Trial results will be reported in a peer-reviewed journal publication.Trial registration numberjRCT2031210046.
Histo-MRI map study protocol: a prospective cohort study mapping MRI to histology for biomarker validation and prediction of prostate cancer
Authors: Singh Saurabh , Mathew Manju , Mertzanidou Thomy , Suman Shipra , Clemente Joey , Retter Adam , Papoutsaki Marianthi-Vasiliki , Smith Lorna , Grussu Francesco , Kasivisvanathan Veeru , Grey Alistair , Dinneen Eoin , Shaw Greg , Carter Martyn , Patel Dominic , Moore Caroline M , Atkinson David , Panagiotaki Eleftheria , Haider Aiman , Freeman Alex , Alexander Daniel , Punwani Shonit 
Published: April 2022

IntroductionMultiparametric MRI (mpMRI) is now widely used to risk stratify men with a suspicion of prostate cancer and identify suspicious regions for biopsy. However, the technique has modest specificity and a high false-positive rate, especially in men with mpMRI scored as indeterminate (3/5) or likely (4/5) to have clinically significant cancer (csPCa) (Gleason ≥3+4). Advanced MRI techniques have emerged which seek to improve this characterisation and could predict biopsy results non-invasively. Before these techniques are translated clinically, robust histological and clinical validation is required.Methods and analysisThis study aims to clinically validate two advanced MRI techniques in a prospectively recruited cohort of men suspected of prostate cancer. Histological analysis of men undergoing biopsy or prostatectomy will be used for biological validation of biomarkers derived from Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours and Luminal Water imaging. In particular, prostatectomy specimens will be processed using three-dimension printed patient-specific moulds to allow for accurate MRI and histology mapping. The index tests will be compared with the histological reference standard to derive false positive rate and true positive rate for men with mpMRI scores which are indeterminate (3/5) or likely (4/5) to have clinically significant prostate cancer (csPCa). Histopathological validation from both biopsy and prostatectomy samples will provide the best ground truth in validating promising MRI techniques which could predict biopsy results and help avoid unnecessary biopsies in men suspected of prostate cancer.Ethics and disseminationEthical approval was granted by the London—Queen Square Research Ethics Committee (19/LO/1803) on 23 January 2020. Results from the study will be presented at conferences and submitted to peer-reviewed journals for publication. Results will also be available on ClinicalTrials.gov.Trial registration numberNCT04792138.
Models of integrated care for older people with frailty: a horizon scanning review
Authors: A Kjelsnes Ashwanee , Feiring Eli 
Published: April 2022

ObjectivesFrailty, a multifaceted geriatric condition, is an emerging global health problem. Integrated care models designed to meet the complex needs of the older people with frailty are required. Early identification of innovative models may inform policymakers and other stakeholders of service delivery alternatives they can introduce and locally adapt so as to tackle system fragmentation and lack of coordination. This study used horizon scanning methodologies to systematically search for, prioritise and assess new integrated care models for older people with frailty and investigated experts’ views on barriers and facilitators to the adoption of horizon scanning in health services research.MethodsA four-step horizon scanning review was performed. Frailty-specific integrated care models and interventions were identified through a review of published literature supplemented with grey literature searches. Results were filtered and prioritised according to preset criteria. An expert panel focus group session assessed the prioritised models and interventions on innovativeness, impact and potential for implementation. The experts further evaluated horizon scanning for its perceived fruitfulness in aiding decision-making.ResultsNine integrated care models and interventions at system level (n=5) and community level (n=4) were summarised and assessed by the expert panel (n=7). Test scores were highest for the Walcheren integrated care model (system-based model) and EuFrailSafe (community-based intervention). The participants stated that horizon scanning as a decision-making tool could aid in assessing knowledge gaps, criticising the status quo and developing new insights. Barriers to adoption of horizon scanning on individual, organisational and wider institutional level were also identified.ConclusionStudy findings demonstrated that horizon scanning is a potentially valuable tool in the search for innovative service delivery models. Further studies should evaluate how horizon scanning can be institutionalised and effectively used for serving this purpose.
Physician perspectives of abortion advocacy: findings from a mixed-methods study
Authors: Manze Meredith , Romero Diana , Kwan Amy , Ellsworth Taylor Rose , Jones Heidi 
Published: April 2022

ObjectiveOur aim was to assess physicians’ perspectives of what constitutes abortion advocacy and the skills needed to be effective in their efforts to safeguard legal abortion.MethodsAlumni from a physician training programme for sexual and reproductive health advocacy completed a cross-sectional survey including questions on perceived skills needed for effective advocacy. The research team conducted in-depth interviews (IDIs) with alumni, based on their level of engagement in advocacy. We present descriptive statistics for survey data and themes identified in the interview data using techniques informed by grounded theory.ResultsOf the survey respondents (n=231), almost a third (28.6%; n=66) felt the most important media skill they learnt was the ability to stay on message. The most important policy skill was communicating effectively with policymakers (47.0%; n=108), followed by distilling evidence for policymakers and laypeople (13.0%; n=30). In the IDIs (n=36), participants reported activities such as media interviews as clear examples of advocacy, but also considered implementing institutional policies and abortion provision to be advocacy. They discussed how individual comfort and capacity for advocacy activities may change over time, given personal and professional considerations. Regardless of the type of activity, physicians valued strategic communication and relationship-building skills.ConclusionsBased on our findings, training programmes that seek to mobilise physician advocates to advance sexual and reproductive health and rights should work with trainees to create a tailored advocacy plan that fits their personal and professional lives and goals. Regardless of the types of advocacy activities physicians focus on, strategic communication may be central in skills-based training.