e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.

BACKGROUND: During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent. METHODS: A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research. RESULTS: Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions. CONCLUSION: e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.

Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. TRIAL REGISTRATION: PROSPERO 2020 CRD42020175648.

The Case for Writing Critical Thinking Reports as a Teaching Strategy on Today's Hospital Wards.

I review some of the challenges in teaching medical students and housestaff on today's hospital medicine wards, including increasingly limited time for dedicated teaching. Tapping into the extensive literature of "writing to learn" or "writing-across-the curriculum" in non-medical educational settings ranging from elementary school to college classes, I urge consideration of writing concise critical thinking reports (CTRs) by medical students and housestaff in response to questions raised during patient rounds as a means of enhancing their ward-based learning experience. Several potential reasons for writing CTRs are offered: (1) Nurtures curiosity; (2) Demands self-directed search for and encoding of new knowledge; (3) Emphasizes metacognition and conceptualization crucial to meaningful learning; (4) Provides opportunity for learners to teach and share newly-assimilated material with a broader web-based audience; (5) Encourages the concept of narrow but more in-depth learning related to a specific clinically relevant subject matter; (6) Nudges learners toward clear and succinct writing as an important general skill to develop in their everyday professional activities, including electronic medical record documentation; and (7) Reduces work-related burnout. Barriers to writing CTRs, including lack of general appreciation for explanatory writing as a potential teaching strategy in medical education and allowing sufficient time for medical students and housestaff to engage in this activity among other competing demands, are discussed. Writing CTRs is a potentially powerful pedagogical tool in ward-based learning that deserves consideration and formal evaluation by properly designed studies.

Repurposing Existing Medications for Coronavirus Disease 2019: Protocol for a Rapid and Living Systematic Review.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020 CRD42020175648.

Management of primary skin cancer during a pandemic: Multidisciplinary recommendations.

During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID-19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID-19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID-19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early-stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID-19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is unlikely to worsen disease-specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.

Repurposing Existing Medications for Coronavirus Disease 2019: Protocol for a Rapid and Living Systematic Review

BackgroundCoronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. MethodsThis systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DiscussionThe challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. Systematic review registrationPROSPERO 2020 CRD42020175648

Coexisting Systemic Infections in Patients Hospitalized Because of a Fall: Prevalence and Risk Factors.

BACKGROUND: Infectious disease-related factors that may contribute to or complicate falls have received relatively little attention in the literature. OBJECTIVE: Our aim was to determine the prevalence of, and risk factors for, coexisting systemic infections (CSIs) in patients admitted to the hospital because of a fall or its complications. METHODS: We conducted a retrospective cohort study of adult patients seen at a tertiary care hospital emergency department and subsequently hospitalized because of a fall or its complications. RESULTS: Of 1,456 evaluable cases, 775 patients (53.2%) were female. Mean age was 71.6 years (range 18-104 years). CSI was diagnosed in 303 patients (20.8%), of which 166 (54.8%) were urinary tract infections and 108 (35.6%) were pneumonia cases; 14 patients (4.6%) were bacteremic. CSI was not initially suspected by providers in 98 (32.5%) subsequently diagnosed cases. Age ≥50 years (odds ratio [OR] 5.6; 95% confidence interval [CI] 1.2-24.9), inability to get up on own after the index fall (OR 2.1; 95% CI 1.2-3.6), preexisting symptom(s) (OR 3.0; 95% CI 1.8-5.2), and systemic inflammatory response syndrome (SIRS) (OR 2.9; 95% CI 1.5-5.4), or confusion at presentation (OR 3.0; 95% CI 1.5-6.0) were independently associated with CSI. In-hospital mortality rate was significantly higher among patients with CSI (6.9% vs. 3.8 %, OR 1.9; 95% CI 1.1-3.3). CONCLUSIONS: CSIs are common among patients admitted to the hospital after a fall or its complications. Age ≥ 50 years, inability to get up on own, preexisting symptom(s), and the presence of SIRS or confusion at presentation are potential predictors of CSI in this patient population.

Longer-term effectiveness of systemic family therapy compared with treatment as usual for young people after self-harm: An extended follow up of pragmatic randomised controlled trial.

BACKGROUND: Self-harm in adolescents is common and repetition frequent. Evidence for effective interventions to reduce self-harm is limited. Long term follow-up of existing studies is rare. METHODS: Extended follow up, from 18 to at least 36-months, of the SHIFT trial: a pragmatic, multi-centre, individually-randomised, controlled trial involving young people (11-17) who had self-harmed at least twice and presented to Child & Adolescent Mental Health Services (CAMHS). SHIFT evaluated manualised family therapy (FT) versus treatment as usual (TAU) in reducing repetition of self-harm leading to hospital attendance 18 months post-randomisation.We obtained ONS mortality data, adult mental health data, and further details of hospital attendance from routine Hospital Episode Statistics (HES) data plus researcher follow-up. We assessed longer-term differences in outcome using multivariable Cox Proportional Hazards regression analysis, and assessed all-cause mortality and morbidity relating to hospital attendances for reasons other than self-harm. STUDY REGISTRATION: ISRCTN 59793150. OUTCOMES: The original sample of 832 were randomised between April 2010 and December 2013. Extended follow-up continued until February 2017 for a median 55·4 months (range 0-82·5 months), providing post 18-month data for 804 (96·6%) participants, of whom 785 (94·4%) had a minimum of 36-months follow-up.There was no evidence of a between-group difference in the primary outcome during the extended follow-up period (Hazard Ratio (HR) 1·03; 95% CI: 0·83, 1·28; p-value=0·78), consistent with our findings in the original trial with 18 months follow-up (HR 1·14, 95% CI 0·87, 1·49; p-value 0·33). There was a reduced rate of self-harm in older participants aged 15-17 (HR 0·7, 95% CI 0·56, 0·88), as compared with those aged 11-14; and significantly increased rates of self-harm in participants whose index episode combined self-injury and poisoning (HR 1·8, 95% CI 1·2, 2·7). Two deaths were reported during the extended follow up period. INTERPRETATION: For adolescents referred to CAMHS after self-harm, having self-harmed at least once before, trial FT confers no benefits over TAU in reducing subsequent hospitalisation for self-harm over 18 months or 36 months. FUNDING: NIHR HTA Reference: 07/33/01.

Writing to learn on the wards: scholarly blog posts by medical students and housestaff at a teaching hospital.

BACKGROUND: Informative writing is a valuable tool for learning and fostering the scientific process. Pearls4Peers (P4P) is an educational open-access website dedicated to scholarly blog posts in hospital medicine based on questions raised during ward teaching rounds. A goal of P4P is to enhance the learning experience of medical students and housestaff (i.e., interns and upper-level residents) by inviting them to write blog posts for a worldwide audience. OBJECTIVE: To describe our experience with inviting medical students and housestaff to contribute blog posts to a clinically oriented educational website with the aim of promoting concise evidence-based informative medical writing. DESIGN: Medical students and housestaff assigned to the hospital ward team of an attending physician (FM) on the medical service were routinely invited to submit one or more posts or 'pearls' based on clinical questions raised during patient rounds. Selected features of submissions during the first 2 years of P4P (27 June 2015 through 26 June 2017) were then retrospectively reviewed and analyzed. RESULTS: Of 156 pearls posted during the study period, 25 (16%) were contributed by medical students and 16 (10.3%) by housestaff. Medical students were significantly more likely to contribute than housestaff (19[70.4%] vs. 11 (9.6%], p < 0.01). Superfluous information was noted in 12 (29.3%) submissions. Word count exceeded the suggested limit of 200 words in 12 (29.3%) cases. An inverted pyramid structure, a widely recognized web writing format with the most important information presented at the outset, was noted in only 17 (41.5%) of entries. Unsolicited comments by contributors suggested a positive learning experience in writing the posts. CONCLUSIONS: Writing clinically oriented concise blog posts appears feasible and may be an effective tool in enhancing the ward-based learning experience of medical students and housestaff. More formal instructions on the proper content and structure of blog posts seem warranted.

The feasibility of using the EQ-5D-3L with adults with mild to moderate learning disabilities within a randomized control trial: a qualitative evaluation.

BACKGROUND: In trials incorporating a health economic evaluation component, reliable validated measures for health-related quality of life (HRQOL) are essential. The EQ-5D is the preferred measure for cost-effectiveness analysis in UK trials. This paper presents a qualitative evaluation of the use of the EQ-5D-3L in a feasibility randomised control trial with participants who had a mild- to  moderate learning disability and type 2 diabetes. METHODS: Researchers administered the EQ-5D-3L to 82 participants at baseline and 77 at follow-up. After each interview, researchers rated the ease of administering the EQ-5D-3L and made free-text entries on the administration experience. For a subset of 16 interviews, researchers audio-recorded more detailed journal entries. Ease of administration data were analysed using descriptive statistics. Free-text responses were subject to a basic content analysis. The EQ-5D-3L-related journal entries were transcribed, coded and analysed thematically. RESULTS: Over half of participants were perceived to experience difficulty answering some or all of the items in the EQ-5D-3L (60% at baseline; 54% at follow-up). Analysis of the free-text entries and audio journals identified four themes that question the use of the EQ-5D-3L in this population. The first theme is related to observations of participant intellectual ability and difficulties, for example, in understanding the wording of the measure. Theme 2 is related to the normalisation of adjustments for impairments, which rendered the measure less sensitive in this population. Theme 3 is related to researcher adaptation and non-standard administration. An overarching fourth theme was identified in that people with learning disabilities were viewed as 'unreliable witnesses' by both researchers and supporters. CONCLUSIONS: It is recommended that the EQ-5D-3L should not be used in isolation to assess health-related quality of life outcomes in trials research in adults with a learning disability. Further research is required to develop and evaluate a version of the EQ-5D appropriate for this population in trials research. It is unrealistic to expect that adjustments to the wording alone will deliver an appropriate measure: supporter or researcher involvement will almost always be required. This requirement needs to be factored into the development and administration guidelines of any new version of the EQ-5D for adults with a learning disability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41897033 [registered 21 January 2013].

Randomized controlled feasibility trial of supported self-management in adults with Type 2 diabetes mellitus and an intellectual disability: OK Diabetes.

AIMS: To undertake a feasibility randomized controlled trial of supported self-management vs treatment as usual in a population of adults with obesity, Type 2 diabetes and an intellectual disability. METHODS: We conducted an individually randomized feasibility trial. Participants were adults aged >18 years with a mild or moderate intellectual disability, living in the community with Type 2 diabetes, on any therapy other than insulin. Participants had mental capacity to consent to research and the intervention. Inclusion criteria included HbA1c > 48 mmol/mol (6.5%), BMI >25 kg/m2 , or self-reported physical activity below national guideline levels. The experimental intervention was standardized supported self-management delivered by diabetes specialist nurses plus treatment as usual, compared with treatment as usual alone. Feasibility outcomes included: recruitment and retention; intervention acceptability and feasibility; data collection and completeness for physiological state and values for candidate primary outcomes (HbA1c and BMI). RESULTS: A total of 82 participants (89% of those contacted and eligible) were randomized. All supported self-management sessions were completed by 35/41 participants (85%); only four completed no sessions. Data on the follow-up candidate primary outcomes HbA1c and BMI were obtained for 75/82 (91%) and 77/82 participants (94%), respectively. The mean baseline HbA1c was 56±16.5 mmol/mol (7.3±1.5%) and the mean BMI was 34±7.6 kg/m2 . CONCLUSIONS: Adherence to supported self-management and willingness to have blood taken for outcome measurement was good. A definitive randomized controlled trial is feasible in this population. (Trial registration: Current Controlled Trials ISRCTN41897033).

Characterizing adults with Type 2 diabetes mellitus and intellectual disability: outcomes of a case-finding study.

AIMS: To report the results of a case-finding study conducted during a feasibility trial of a supported self-management intervention for adults with mild to moderate intellectual disability and Type 2 diabetes mellitus, and to characterize the study sample in terms of diabetes control, health, and access to diabetes management services and support. METHODS: We conducted a cross-sectional case-finding study in the UK (March 2013 to June 2015), which recruited participants mainly through primary care settings. Data were obtained from medical records and during home visits. RESULTS: Of the 325 referrals, 147 eligible individuals participated. The participants' mean (sd) HbA1c concentration was 55 (15) mmol/mol [7.1 (1.4)%] and the mean (sd) BMI was 32.9 (7.9) kg/m2 , with 20% of participants having a BMI >40 kg/m2 . Self-reported frequency of physical activity was low and 79% of participants reported comorbidity, for example, cardiovascular disease, in addition to Type 2 diabetes. The majority of participants (88%) had a formal or informal supporter involved in their diabetes care, but level and consistency of support varied greatly. Post hoc exploratory analyses showed a significant association between BMI and self-reported mood, satisfaction with diet and weight. CONCLUSIONS: We found high obesity and low physical activity levels in people with intellectual disability and Type 2 diabetes. Glycaemic control was no worse than in the general Type 2 diabetes population. Increased risk of morbidity in this population is less likely to be attributable to poor glycaemic control and is probably related, at least in part, to greater prevalence of obesity and inactivity. More research, focused on weight management and increasing activity in this population, is warranted.