Many countries are launching large-scale, digitally enabled change programmes as part of efforts to improve the quality, safety and efficiency of care. We have been commissioned to conduct an independent evaluation of a major national change programme, the Global Digital Exemplar (GDE) Programme, which aims to develop exemplary digital health solutions and encourage their wider adoption by creating a learning ecosystem across English National Health Service (NHS) provider organisations.
This theoretically informed, qualitative, longitudinal formative evaluation comprises five inter-related work packages. We will conduct a combination of 12 in-depth and 24 broader qualitative case studies in GDE sites exploring digital transformation, local learning and mechanisms of spread of knowledge within the Programme and across the wider NHS. Data will be collected through a combination of semistructured interviews with managers, implementation staff (clinical and non-clinical), vendors and policymakers, plus non-participant observations of meetings, site visits, workshops and documentary analysis of strategic local and national plans. Data will be analysed through inductive and deductive methods, beginning with in-depth case study sites and testing the findings against data from the wider sample and national stakeholders.
This work is commissioned as part of a national change programme and is therefore a service evaluation. We have ethical approval from the University of Edinburgh. Results will be disseminated at six monthly intervals to national policymakers, and made available via our publicly accessible website. We will also identify lessons for the management and evaluation of large-scale evolving digital health change programmes that are of international relevance.
We aimed to examine whether eHealth interventions can effectively improve anthropometric and biochemical indicators of patients with metabolic syndrome (MetS).
Systematic review and meta-analysis.
PubMed, the Web of Science, Embase, Medline, CINAHL, PsycINFO, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang and Weipu databases were comprehensively searched for papers that were published from database inception to May 2019. Articles were included if the participants were metabolic syndrome (MetS) patients, the participants received eHealth interventions, the participants in the control group received usual care or were wait listed, the outcomes included anthropometric and biochemical indicators of MetS, and the study was a randomised controlled trial (RCT) or a controlled clinical trial (CCT). The Quality Assessment Tool for Quantitative Studies was used to assess the methodological quality of the included articles. The meta-analysis was conducted using Review Manager V.5.3 software.
In our review, seven RCTs and two CCTs comprising 935 MetS participants met the inclusion criteria. The results of the meta-analysis revealed that eHealth interventions resulted in significant improvements in body mass index (standardised mean difference (SMD)=–0.36, 95% CI (–0.61 to –0.10), p
The results indicated that eHealth interventions were beneficial for improving specific anthropometric outcomes, but did not affect biochemical indicators of MetS. Therefore, whether researchers adopt eHealth interventions should be based on the purpose of the study. More rigorous studies are needed to confirm these findings.
To investigate psychological and behavioural responses to COVID-19 among the Chinese general population.
We conducted a population-based mobile phone survey between 1 February and 10 February 2020 via random digit dialling. A total of 1011 adult residents in Wuhan (n=510), the epicentre and quarantined city, and Shanghai (n=501) were interviewed. Proportional quota sampling and poststratification weighting were used. Multivariable logistic regression models were used to investigate perception factors associated with the public responses.
We measured anxiety levels using the 7-item Generalised Anxiety Disorder Scale (GAD-7) and asked respondents to report their precautionary behaviours before and during the outbreak.
The prevalence of moderate or severe anxiety was significantly higher (p
Prevalence of moderate or severe anxiety and strict personal precautionary behaviours was generally high, regardless of the quarantine status. Our results support efforts for handwashing education programmes with a focus on hygiene procedures in China and timely dissemination of reliable information.
Graft versus host disease (GVHD) is a major cause of morbidity and mortality following allogenic haematopoietic stem cell transplantation. It is an immunological reaction, involving many organs, leading to a wide range of clinical manifestations. Cutaneous manifestations are the most common sign of GVHD, as well as pain, vulnerability to infection and impaired quality of life.
Despite the burdens that cutaneous GVHD presents for patients, their carers and the healthcare system, limited evidence is available to guide day to day supportive skin care and wound management. Our objective is to conduct a scoping review to map the evidence for skin and wound management and identify evidence-practice gaps for individuals with acute or chronic cutaneous GVHD.
Our review will follow the scoping review methodological framework developed by Arksey and O’Malley and further refined by the Joanna Briggs Institute Scoping Review Methods Manual. Databases to be searched include; PubMed, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Web of Science and MEDLINE from 1970 to February 2020. Database searches will be supplemented with searches from relevant reference lists and grey literature. Descriptive statistical analyses will be performed.
This scoping review does not require ethical approval. Findings will be disseminated through a peer-reviewed publication and conference presentation.
The incidence of bystander cardiopulmonary resuscitation (CPR) is low in China. CPR training could improve public attitudes and willingness, but at present, the attitudes of the public after online training are unclear. This study investigated individual attitudes towards CPR, the willingness to perform it in emergencies along with the main obstacles and the overall effects of online training.
Questionnaires were distributed to investigate the public attitudes and willingness towards performing bystander CPR.
Questionnaires were accessible after the online course ‘First Aid’.
1888 students who attended ‘First Aid’ from December 2019 to 1 January 2020 and then completed the questionnaire voluntarily.
The majority understood CPR (96.7%) and displayed a willingness to learn (98.4%) and to disseminate CPR knowledge (82.0%). Characteristics associated with more positive attitudes included women, the 26–35-year olds and those in medical-related occupations (p
The overwhelming majority of respondents showed positive attitudes and willingness towards CPR. In some cases, there is still reluctance, especially towards S-CPR. Obstacles arise mainly due to lack of confidence in administering CPR, while online CPR training can markedly improve it. Therefore, we should focus on disseminating CPR knowledge, targeting those who are less willing to perform CPR and helping overcome their obstacles by online training.
Both regional analgesia and intravenous analgesia are frequently used perioperatively for patients with critical limb ischaemia (CLI). Nevertheless, the comparison of perioperative effect of regional and intravenous analgesia has not yet been thoroughly illustrated. This study will comprehensively compare patient-controlled regional analgesia (PCRA) and patient-controlled intravenous analgesia (PCIA) as two different perioperative analgesia approaches for patients with CLI. It investigates their effects on analgesia, reperfusion and the quality of recovery perioperatively, also aims to provide clinical evidence to those non-surgical patients with non-reconstructable arteries.
This trial is a randomised, single-centre, open-label, parallel trial with target sample size of 52 in total. Eligible participants will be randomly allocated to the PCRA group (group R) or the PCIA group (group I) after admission. Participants in group R will receive ultrasound-guided subgluteal sciatic catheterisation, followed by continuous PCRA infusion (0.2% ropivacaine 15 mL as loading dose, 8 mL/hour as background with a patient-controlled bolus of 6 mL). Participants in group I will receive PCIA (morphine is given in boluses of 1 mg as needed, background infusion at 1 mg/hour). Data will be collected at baseline (T0), 2 hours before revascularisation treatment (T1) and 2 hours before discharge (T2). The primary outcomes include the Numerical Rating Scale pain score at T1 and T2. The secondary outcomes include the perioperative transcutaneous oxygen pressure, the Tissue Haemoglobin Index, Hospital Anxiety and Depression Scale at T1 and T2; the Patient Global Impression of Change and patient satisfaction at T1 and T2; the perioperative cumulative morphine consumption, the length of postoperative hospital stay and adverse events.
This study received authorisation from the Institutional Review Board of Peking Union Medical College Hospital on 21 March 2017 (approval no. ZS-1289X). Study findings will be disseminated through presentations at scientific conferences or publications in peer-reviewed journals.
Chinese Clinical Trial Registry (ChiCTR2000029298).
V.4CP.B2 (15 June 2020).
To assess the delirium severity (DS), its risk factors and association with adverse patient outcomes in chronically critically ill (CCI) patients.
A prospective cohort study.
A tertiary care hospital with postacute intensive care units (ICUs) in Germany.
N=267 CCI patients with critical illness polyneuropathy and/or critical illness myopathy, aged 18–75 years, who had undergone elective tracheotomy for weaning failure.
Primary outcomes: DS was assessed using the Confusion Assessment Method for the Intensive Care Unit-7 delirium severity score, within 4 weeks (t1) after the transfer to a tertiary care hospital. In post hoc analyses, univariate linear regressions were employed, examining the relationship of DS with clinical, sociodemographic and psychological variables. Secondary outcomes: additionally, correlations of DS with fatigue (using the Multidimensional Fatigue Inventory-20), quality of life (using the Euro-Quality of Life) and institutionalisation/mortality at 3 (t2) and 6 (t3) months follow-up were computed.
Of the N=267 patients analysed, 9.4% showed severe or most severe delirium symptoms. 4.1% had a full-syndromal delirium. DS was significantly associated with the severity of illness (p=0.016, 95% CI –0.1 to –0.3), number of medical comorbidities (p
Illness severity is positively associated with DS during postacute care in CCI patients. An adequate management of delirium is essential in order to mitigate functional and cognitive long-term sequelae following ICU.
To study the performance of the ‘van Loendersloot’ prognostic model for our clinic’s in vitro fertilisation (IVF) in its original version, the refitted version and in an adapted version replacing previous by current cycle IVF laboratory variables.
This retrospective cohort study in our academic tertiary fertility clinic analysed 1281 IVF cycles of 591 couples, who completed at least one 2nd–6th IVF cycle with own fresh gametes after a previous IVF cycle with the same partner in our clinic between 2010 and 2018. The outcome of interest was the chance on a live birth after one complete IVF cycle (including all fresh and frozen embryo transfers from the same episode of ovarian stimulation). Model performance was expressed in terms of discrimination (c-statistics) and calibration (calibration model, comparison of prognosis to observed ratios of five disjoint groups formed by the quintiles of the IVF prognoses and a calibration plot).
A total of 344 live births were obtained (26.9%). External validation of the original van Loendersloot model showed a poor c-statistic of 0.64 (95% CI: 0.61 to 0.68) and an underestimation of IVF success. The refitted and the adapted models showed c-statistics of respectively 0.68 (95% CI: 0.65 to 0.71) and 0.74 (95% CI: 0.70 to 0.77). Similar c-statistics were found with cross-validation. Both models showed a good calibration model; refitted model: intercept=0.00 (95% CI: –0.23 to 0.23) and slope=1.00 (95% CI: 0.79 to 1.21); adapted model: intercept=0.00 (95% CI: –0.18 to 0.18) and slope=1.00 (95% CI: 0.83 to 1.17). Prognoses and observed success rates of the disjoint groups matched well for the refitted model and even better for the adapted model.
External validation of the original van Loendersloot model indicated that model updating was recommended. The good performance of the refitted and adapted models allows informing couples about their IVF prognosis prior to an IVF cycle and at the time of embryo transfer. Whether this has an impact on couple’s expected success rates, distress and IVF discontinuation can now be studied.
The motivation and retention of community health workers (CHWs) is a challenge and inadequately addressed in research and policy. We sought to identify factors influencing the retention of CHWs in Ethiopia and ways to avert their exit.
A qualitative study was undertaken using in-depth interviews with the study participants. Interviews were audio-recorded, and then simultaneously translated into English and transcribed for analysis. Data were analysed in NVivo 12 using an iterative inductive-deductive approach.
The study was conducted in two districts each in the Tigray and Southern Nations, Nationalities and People’s Republic (SNNPR) regions in Ethiopia. Respondents were located in a mix of rural and urban settings.
Leavers of health extension worker (HEW) positions (n=20), active HEWs (n=16) and key informants (n=11) in the form of policymakers were interviewed.
We identified several extrinsic and intrinsic motivational factors affecting the retention and labour market choices of HEWs. While financial incentives in the form of salaries and material incentives in the form of improvements to health facility infrastructure, provision of childcare were reported to be important, non-material factors like HEWs’ self-image, acceptance and validation by the community and their supervisors were found to be critical. A reduction or loss of these non-material factors proved to be the catalyst for many HEWs to leave their jobs.
Our study contributes new empirical evidence to the global debate on factors influencing the motivation and retention of CHWs, by being the first to include job leavers in the analysis. Our findings suggest that policy interventions that appeal to the social needs of CHWs can prove to be more acceptable and potentially cost-effective in improving their retention in the long run. This is important for government policymakers in resource constrained settings like Ethiopia that rely heavily on lay workers for primary healthcare delivery.
We aimed to compare the incidence, subtypes and aetiology of stroke, and in-hospital death due to stroke, between Aboriginal and non-Aboriginal people in Central Australia, a remote region of Australia where a high proportion Aboriginal people reside (40% of the population). We hypothesised that the rates of stroke, particularly in younger adults, would be greater in the Aboriginal population, compared with the non-Aboriginal population; we aimed to elucidate causes for any identified disparities.
A retrospective population-based study of patients hospitalised with stroke within a defined region from 1 January 2011 to 31 December 2014.
Alice Springs Hospital, the only neuroimaging-capable acute hospital in Central Australia, serving a network of 50 healthcare facilities covering 672 000 km2.
161 residents (63.4% Aboriginal) of the catchment area admitted to hospital with stroke.
Rates of first-ever stroke, overall (all events) stroke and in-hospital death.
Of 121 residents with first-ever stroke, 61% identified as Aboriginal. Median onset-age (54 years) was 17 years younger in Aboriginal patients (p
Stroke incidence (both subtypes) and in-hospital deaths for remote Aboriginal Australians are dramatically greater than in non-Aboriginal people, especially in patients aged
To examine long-term trends in acute myocardial infarction (AMI) incidence and survival among Aboriginal and non-Aboriginal people.
Retrospective cohort study.
All first AMI hospital cases and deaths due to ischaemic heart disease in the Northern Territory of Australia (NT), 1992–2014.
Age standardised incidence, survival and mortality.
The upward trend in Aboriginal AMI incidence plateaued around 2007 for males and 2001 for females. AMI incidence decreased for non-Aboriginal population, consistent with the national trends. AMI incidence was higher and survival lower for males, for Aboriginal people and in older age groups. In 2014, the age standardised incidence was 881 and 579 per 100 000 for Aboriginal males and females, respectively, compared with 290 and 187 per 100 000 for non-Aboriginal counterparts. The incidence disparity between Aboriginal and non-Aboriginal population was much greater in younger than older age groups. Survival after an AMI improved over time, and more so for Aboriginal than non-Aboriginal patients, because of a decrease in prehospital deaths and improved survival of hospitalised cases.
There was an important breakpoint in increasing trends of Aboriginal AMI incidence between 2001 and 2007. The disparity in AMI survival between the NT Aboriginal and non-Aboriginal populations reduced over time as survival improved for both populations.
Contingency management (CM) is a treatment for substance misuse that involves the provision of incentives. This review examines the hypothesis that adding another formal psychotherapy, such as cognitive–behavioural therapy (CBT) or motivational enhancement therapy (MET), to CM improves substance use outcomes at both treatment end and at post-treatment follow-up compared with CM only.
Searches were performed in December 2017 and July 2019 of seven electronic bibliographic databases (MEDLINE, PsycINFO, EMBASE, Scopus, Web of Science, CINAHL, PsycEXTRA), as well as online trial registries and EThoS, and were followed by reference list screening.
Included studies were randomised controlled trials of adults (18–65) who were using illicit substances, alcohol or tobacco. Studies featured an experimental arm delivering CM combined with a structured evidence-based psychotherapeutic intervention and a CM-only arm. Studies published up to July 2019 were included.
The primary outcome was biometrically verified point prevalent abstinence (PPA) at treatment end. Secondary outcomes included biometrically verified PPA at post-treatment follow-up and self-reported days of use at treatment end and post-treatment follow-up. Pooled risk ratios for PPA outcomes and standardised mean differences for days of use were calculated using random effects models. Risk of bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation.
12 studies (n=1654) were included. The primary analysis found no evidence of a synergistic effect in PPA at treatment end (relative risk (RR) 0.97, 95% CI 0.85 to 1.09; p=0.57). Sensitivity analysis of studies featuring CBT/MET also found no evidence of an effect (RR 0.92; 95% CI 0.79 to 1.08; p=0.32). None of the secondary outcomes showed any evidence of benefit.
The results of the meta-analyses found no evidence that combining CM with another intervention improves the short-term or long-term effects of CM treatment.
Fast diagnostic algorithms using high-sensitivity troponin (hsTn) in suspected acute coronary syndrome (ACS) are regarded as beneficial to expedite diagnosis and safe discharge of patients in crowded emergency departments (ED). This study investigates the effects of crowding on process times related to the diagnostic protocol itself or other time delays, and outcomes.
Prospective single-centre observational study.
Final study population of 2525 consecutive patients with suspected ACS within 12 months, after exclusion of patients with ST-elevation myocardial infarction, missing blood samples, referral from other hospitals or repeated visits.
Use of fast algorithms as per 2015 European Society of Cardiology guidelines.
Crowding was defined as mismatch between patient numbers and monitoring capacities, or mean physician time per case, categorised as normal, high and very high crowding. Outcome measures were length of ED stay, direct discharge from ED, laboratory turn around times (TAT), utilisation of fast algorithms, absolute and relative non-laboratory time, as well as mortality.
Crowding was associated with increased length of ED stay (3.75–4.89 hours, p
Process times, and particularly non-laboratory times, are prolonged in a crowded ED diminishing some positive effects of fast diagnostic algorithms in suspected ACS. Higher crowding levels were not significantly associated with higher all-cause mortality rates.
Automated haematology analysers measure various parameters of relevance to clinical research along with routine complete blood count (CBC)-related components. We aimed to establish ethnicity-specific and sex-specific reference intervals for 26 research-specific parameters as well as 18 routinely reported components using a large cohort of healthy Korean adults. The necessity of requiring separate sex-specific reference intervals for each parameter was also examined.
A retrospective database review.
Single tertiary-care hospital of approximately 375 physicians and 530 nurses.
This study included 1383 reference individuals (840 men and 543 women).
Following the Clinical and Laboratory Standards Institute guidelines for establishing reference intervals, routine CBCs as well as research parameters were measured using an ADVIA 2120i instrument.
All the routine components except for mean platelet volume and per cent lymphocytes differed significantly between men and women. Most research parameters also differed between the sexes; the exceptions were large platelets, platelet dry mass distribution width, per cent basophil saturation, per cent peroxidase saturation and per cent abnormal peroxidase absorption. Despite these differences, separate reference intervals for men and women were required only for two research-specific parameters: ‘percentage high cellular haemoglobin’ and ‘percentage of hyperchromic red blood cells (RBCs)’.
Even though most parameters showed significant differences between men and women, none of the evaluated parameters except two RBC-related factors required separate reference intervals for each sex.
Large disparities in colorectal cancer (CRC) management and survival have been observed across Europe. Despite recent increases, the survival deficit of Estonian patients with CRC persists, particularly for rectal cancer. The aim of this study was to examine diagnostic, staging and treatment patterns of CRC in Estonia, comparing clinical data from 1997 and 2011.
Nationwide population-based retrospective study.
All incident cases of colon and rectal cancer diagnosed in 1997 and 2011 identified from the Estonian Cancer Registry. Clinical data gathered from medical records.
Differences in diagnostic, staging and treatment patterns; 5-year relative survival ratios.
The number of colon cancer cases was 337 in 1997 and 498 in 2011; for rectal cancer, the respective numbers were 209 and 349. From 1997 to 2011, large increases were seen in the use of colonoscopy and lung and liver imaging. Radical resection rate increased from 48% to 59%, but emergency surgeries showed a rise from 18% to 26% in colon and from 7% to 14% in rectal cancer. The proportion of radically operated patients with ≥12 lymph nodes examined pathologically increased from 2% to 58% in colon cancer and from 2% to 50% in rectal cancer. The use of neoadjuvant radiotherapy increased from 6% to 39% among stage II and from 20% to 50% among patients with stage III rectal cancer. The use of adjuvant chemotherapy in stage III colon cancer increased from 42% to 63%. The 5-year RSR increased from 50% to 58% in colon cancer and from 37% to 64% in patients with rectal cancer.
Major improvements were seen in the diagnostics, staging and treatment of CRC in Estonia contributing to better outcomes. Increase in emergency surgeries highlights possible shortcomings in timely diagnosis and treatment.
To evaluate the impact of new National Drug Pricing Policy (NDPP) 2018 on access to medicines in terms of prices, availability and affordability.
Two cross-sectional surveys were undertaken before and after the launch of NDPP 2018, using a modified WHO/Health Action International (WHO/HAI) methodology.
Four districts of Lahore division, Pakistan.
16 public sector hospitals and 16 private sector retail pharmacies.
The pre and post survey data on prices and availability of lowest price generics (LPGs) and originator brands (OBs) of 50 medicines were obtained by visiting the same public and private sector health facilities (n=32). Out of 50, 46 surveyed medicines were from the National Essential Medicines List. Inflation-adjusted median unit prices (MUPs) and median price ratios (MPRs) from 2019 were used for price comparison. Affordability was calculated in terms of number of days’ wages required to get a standard treatment by the lowest paid unskilled government worker.
The overall mean percent availabilities remained poor in both years, that is, far less than 80%. In the public sector, the mean percent availability of OBs improved from 6.8% to 33.1%, whereas, in the case of LPGs, it was reduced from 35.1% to 9%. In the private sector, the mean percent availability of both OBs and LPGs demonstrated slight improvements in 2019, that is, 55.0%–58.3% and 20.3%–32.3%. The adjusted MUPs and MPRs of OBs significantly increased by a median of 4.29% (Wilcoxon test p=0.001, p=0.0001), whereas the adjusted MUPs and MPRs of LPGs increased by a median of 15.7% (p=0.002, p=0.0002). Overall, the affordability of many medicines for common ailments was reduced significantly in 2019.
The availability of medicines slightly improved, except in the case of LPGs, which was reduced in the public sector. The implementation of NDPP 2018 led to increase in drug prices, making the standard treatment for some of the most prevalent ailments unaffordable. So verily, the drug pricing policy must be reviewed to ensure access to essential medicines.
To explore the association of patient or family reported functional deterioration (defined by a single question) in the preceding year, with mortality outcome for those admitted to the intensive care unit (ICU).
Retrospective observational analysis of a routinely collected data source.
Patients that were admitted to the ICU at Northwick Park and St Marks Hospitals, London North West University Healthcare NHS Trust between 01 October 2017 to 15 June 2019 were included. Patients were excluded if they had a prior ICU admission during the existing hospital episode or if information on functional deterioration could not be retrieved from either the patient or their advocate.
Mortality at the point of hospital discharge and 1 year following admission to the ICU.
Of the 1006 patients who were admitted to the ICU during the study period, information on functional deterioration was available for 621 patients who were included in the analysis. From these, 251 (40.4%) patients had patient or family reported functional deterioration in the preceding year, while 370 (59.6%) patients had a perceived stable functional baseline. Comparing the two groups, mortality was significantly higher in those who had functionally deteriorated compared with those with stable baseline function, at the point of hospital discharge (45.4% vs 25.9%; p
Patient or family reported functional deterioration was significantly associated with higher mortality at the point of hospital discharge and at 1 year. The concept of functional deterioration in the lead up to ICU admission warrants further exploration.
To assess the effectiveness of social support on treatment success promotion or lost to follow-up (LTFU) reduction for patients with drug-resistant tuberculosis (DR-TB).
We searched Pubmed, Web of Science, Embase, Scopus and Medline databases until 18 June 2020 for interventional or mixed-method studies which reported social support and treatment outcomes of DR-TB patients. Two independent reviewers extracted data and disagreements were resolved by consensus with a third reviewer. Random-effects meta-analysis was performed to calculate the OR and 95% CI for the effects of social support on the improvement of treatment outcomes and the heterogeneity and risk of bias were assessed.
Low-income and middle-income countries.
Treatment success is defined as the combination of the cured and treatment completion, and LTFU is measured as treatment being interrupted for two consecutive months or more.
Among 173 articles selected for full-text review, 162 were excluded through independent review (kappa=0.87) and 10 studies enrolling 1621 DR-TB patients in eight countries were included for qualitative analysis. In these studies, the most frequently introduced social support was material support (10 studies), followed by informational (eight studies), emotional (seven studies) and companionship support (four studies). Seven studies that reported treatment outcomes in both intervention arm and control arm are qualified for meta-analysis. An encouraging improvement on treatment success rate (OR: 2.58; 95% CI: 1.80 to 3.69) was found when material support was integrated into social support packages and no heterogeneity was observed (I
Material support appeared feasible and effective to improve treatment success for DR-TB patients combined with other social support interventions.
Continuous antiretroviral therapy (ART) suppresses HIV plasma viral load (pVL) to very low levels, which allows for some immune recovery. Discontinuation of ART leads to pVL rebound from reservoirs of persistence and latency, and progressive immunodeficiency. One promising but controversial strategy targeting CD4+ T lymphocytes with a monoclonal antibody (mAb) against α4β7 integrin has shown promise through sustained virological remission of pVL (SVR) in SIV239-infected rhesus macaques. We propose to assess the safety and tolerability of vedolizumab, a licensed humanised mAb against human α4β7 integrin, in healthy HIV-infected adults on ART. This study will also assess, by analytical treatment interruption (ATI), whether vedolizumab treatment can induce SVR beyond ART and vedolizumab treatment.
The HIV-ART-vedolizumab-ATI (HAVARTI) trial is a single-arm, dose-ranging pilot trial in healthy HIV-positive adult volunteers receiving ART. Twelve consenting persons will be enrolled in sequential groups of 4 to each serial dosing vedolizumab regimen (300 mg, 150 mg, 75 mg). The primary outcomes are: (1) to assess the safety and tolerability of seven serial infusions of vedolizumab at each of three doses; (2) to identify the immunovirological measures, including pVL and T-cell kinetics, that characterise HIV/ART cases before, during, after vedolizumab treatment and ATI; and (3) to seek SVR of pVL after ATI. Secondary outcomes will include immune reconstitution and pVL suppression as well as immune reconstitution and long-term safety following re-initiation of ART in the absence of SVR.
The study protocol was approved by the Ottawa Health Science Network-REB and by the Health Canada Therapeutic Products Directorate. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open access journal within a year of study completion.
The study aimed to understand through qualitative research what patients considered material in their decision to consent to an acute surgical intervention.
The patients selected aged between 18 and 90, having been admitted to a major trauma centre to undergo an acute surgical intervention within 14 days of injury, where English was their first language. Data saturation point was reached after 21 patients had been recruited. Data collection and analysis were conducted simultaneously, through interviews undertaken immediately prior to surgery. The data were coded using NVIVO V.12 software.
The key theme that originated from the data analysis was patients were unable to identify any individual risk that would modify their decision-making process around giving consent. The patient’s previous experience and the experience of others around them were a further theme. Patients sensed that there were no non-operative options for their injuries.
This is the first study investigating what patient considered a material risk in the consent process. Patients in this study did attribute significance to past experiences of friends and family as material, prompting us to suggest that the surgeon asks about these experiences as part of the consent process. Concern about functional recovery was important to patients but insufficient to stop them from consenting to surgery, thus could not be classified as material risk.