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First clinical evaluation of the safety and efficacy of tarumase for the debridement of venous leg ulcers

Abstract

We report the first clinical evaluation of a new enzymatic wound debridement product containing tarumase in venous leg ulcer patients. As a first-in-human study, this was a prospective, open-label, multi-centre, dose escalation study across five dose cohorts and involving a total of 43 patients treated three times weekly for up to 4 weeks (12 applications). The primary and secondary endpoints of the study were to assess the systemic safety, local tolerability, and early proof of concept both for wound debridement and healing. Results indicated that the tarumase enzyme was well tolerated when applied topically to wounds, with no indications of systemic absorption, no evidence of antibody generation, and no systemic effects on coagulation pathways. Locally, there was no evidence of pain on application, no local itching, no increases in erythema, oedema, exudate or bleeding and only a few treatment emergent adverse events were reported. As the concentration of tarumase was escalated, trends towards faster and improved effectiveness of wound debridement were observed, especially in patients with significant slough at baseline. Trends towards faster rates of healing were also noted based on observations of increased granulation tissue, increased linear healing and reduction in surface area over the 4-week treatment period.

Silhouette showcards confirm altered obesity-associated body image perception in international cohort study of African-origin populations

Por: Choo-Kang · C. · Reese · T. O. · Micklesfield · L. K. · Bovet · P. · Bedu-Addo · K. · Forrester · T. · Gilbert · J. A. · Goedecke · J. H. · Plange-Rhule · J. · Lambert · E. V. · Layden · B. T. · Rae · D. E. · Viswanathan · B. · Luke · A. · Dugas · L.
Objectives

Given the increasing prevalence of obesity and need for effective interventions, there is a growing interest in understanding how an individual’s body image can inform obesity prevention and management. This study’s objective was to examine the use of silhouette showcards to measure body size perception compared with measured body mass index, and assess body size dissatisfaction, in three different African-origin populations spanning the epidemiological transition. An ancillary objective was to investigate associations between body size perception and dissatisfaction with diabetes and hypertension.

Setting

Research visits were completed in local research clinics in respective countries.

Participants

Seven hundred and fifty-one African-origin participants from the USA and the Republic of Seychelles (both high-income countries), and Ghana (low/middle-income country).

Primary and secondary outcome measures

Silhouette showcards were used to measure perceived body size and body size dissatisfaction. Objectively measured body size was measured using a scale and stadiometer. Diabetes was defined as fasting blood glucose ≥126 mg/dL and hypertension was defined as ≥130 mm Hg/80 mm Hg.

Results

Most women and men from the USA and Seychelles had ‘Perceived minus Actual weight status Discrepancy’ scores less than 0, meaning they underestimated their actual body size. Similarly, most overweight or obese men and women also underestimated their body size, while normal weight men and women were accurately able to estimate their body size. Finally, participants with diabetes were able to accurately estimate their body size and similarly desired a smaller body size.

Conclusions

This study highlights that overweight and obese women and men from countries spanning the epidemiological transition were unable to accurately perceive their actual body size. Understanding people’s perception of their body size is critical to implementing successful obesity prevention programmes across the epidemiological transition.

Integrated health system intervention aimed at reducing type 2 diabetes risk in women after gestational diabetes in South Africa (IINDIAGO): a randomised controlled trial protocol

Por: Norris · S. A. · Zarowsky · C. · Murphy · K. · Ware · L. J. · Lombard · C. · Matjila · M. · Chivese · T. · Muhwava · L. S. · Mutabazi · J. C. · Harbron · J. · Fairall · L. R. · Lambert · E. · Levitt · N.
Introduction

South Africa has a high prevalence of gestational diabetes mellitus (GDM; 15%) and many of these women (48%) progress to type 2 diabetes mellitus (T2DM) within 5 years post partum. A significant proportion (47%) of the women are not aware of their diabetes status after the index pregnancy, which may be in part to low postnatal diabetes screening rates. Therefore, we aim to evaluate a intervention that reduces the subsequent risk of developing T2DM among women with recent GDM. Our objectives are fourfold: (1) compare the completion of the nationally recommended 6-week postpartum oral glucose tolerance test (OGTT) between intervention and control groups; (2) compare the diabetes risk reduction between control and intervention groups at 12 months’ post partum; (3) assess the process of implementation; and (4) assess the cost-effectiveness of the proposed intervention package.

Methods and analyses

Convergent parallel mixed-methods study with the main component being a pragmatic, 2-arm individually randomised controlled trial, which will be carried out at five major referral centres and up to 26 well-baby clinics in the Western Cape and Gauteng provinces of South Africa. Participants (n=370) with GDM (with no prior history of either type 1 or type 2 diabetes) will be recruited into the study at 24–36 weeks’ gestational age, at which stage first data collection will take place. Subsequent data collection will take place at 6–8 weeks after delivery and again at 12 months. The primary outcome for the trial is twofold: first, the completion of the recommended 2-hour OGTT at the well-baby clinics 6–8 weeks post partum, and second, a composite diabetes risk reduction indicator at 12 months. Process evaluation will assess fidelity, acceptability, and dose of the intervention.

Ethics and dissemination

Ethics approval has been granted from University of Cape Town (829/2016), University of the Witwatersrand, Johannesburg (M170228), University of Stellenbosch (N17/04/032) and the University of Montreal (2019-794). The results of the trial will be disseminated through publication in peer-reviewed journals and presentations to key South African Government stakeholders and health service providers.

Protocol version

1 December 2022 (version #2). Any protocol amendments will be communicated to investigators, Human Ethics Research Committees, trial participants, and trial registries.

Trial registration number

PAN African Clinical Trials Registry (https://pactr.samrc.ac.za) on 11 June 2018 (identifier PACTR201805003336174).

The other COVID‐19 survivors: Timing, duration, and health impact of post‐acute sequelae of SARS‐CoV‐2 infection

Abstract

Aims and Objectives

To determine the frequency, timing, and duration of post-acute sequelae of SARS-CoV-2 infection (PASC) and their impact on health and function.

Background

Post-acute sequelae of SARS-CoV-2 infection is an emerging major public health problem that is poorly understood and has no current treatment or cure. PASC is a new syndrome that has yet to be fully clinically characterised.

Design

Descriptive cross-sectional survey (n = 5163) was conducted from online COVID-19 survivor support groups who reported symptoms for more than 21 days following SARS-CoV-2 infection.

Methods

Participants reported background demographics and the date and method of their covid diagnosis, as well as all symptoms experienced since onset of covid in terms of the symptom start date, duration, and Likert scales measuring three symptom-specific health impacts: pain and discomfort, work impairment, and social impairment. Descriptive statistics and measures of central tendencies were computed for participant demographics and symptom data.

Results

Participants reported experiencing a mean of 21 symptoms (range 1–93); fatigue (79.0%), headache (55.3%), shortness of breath (55.3%) and difficulty concentrating (53.6%) were the most common. Symptoms often remitted and relapsed for extended periods of time (duration M = 112 days), longest lasting symptoms included the inability to exercise (M = 106.5 days), fatigue (M = 101.7 days) and difficulty concentrating, associated with memory impairment (M = 101.1 days). Participants reported extreme pressure at the base of the head, syncope, sharp or sudden chest pain, and “brain pressure” among the most distressing and impacting daily life.

Conclusions

Post-acute sequelae of SARS-CoV-2 infection can be characterised by a wide range of symptoms, many of which cause moderate-to-severe distress and can hinder survivors' overall well-being.

Relevance to Clinical Practice

This study advances our understanding of the symptoms of PASC and their health impacts.

Excess mortality during the COVID-19 pandemic in low-income and lower middle-income countries: protocol for a systematic review and meta-analysis

Por: Gmanyami · J. M. · Jarynowski · A. · Belik · V. · Lambert · O. · Amuasi · J. · Quentin · W.
Introduction

The COVID-19 pandemic has been marked by a massive death toll. However, the overall effect of the pandemic, including potential unintended negative impacts of some control measures, on mortality remains poorly understood in low-income and lower middle-income countries (LLMICs). This review aims to summarise the available literature on excess mortality in LLMICs, focusing on the methods and data sources used in estimating excess mortality and the drivers of excess mortality.

Methods and analysis

We will review the available literature and report results in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis. Searches will be conducted in PubMed, Embase, Web of Science, Cochrane Library, Google Scholar and Scopus. All published studies that report on the estimates of excess mortality in populations of LLMICs will be included. This will include those with a publication date from 2019 onwards and those with at least a 1-year non-COVID-19 period as the comparator in the estimation of excess mortality during the pandemic. There will be no language restrictions on the search. The meta-analysis will include studies with extractable data on excess mortality, methods, population size, and observed and expected deaths. We will use the Mantel-Haenszel method to estimate the pooled risk ratio with 95% CIs.

Ethics and dissemination

As there is no primary data collection, there is no requirement for ethical review. The results will be disseminated through peer-reviewed journal publication and conference presentations.

PROSPERO registration number

CRD42022378267.

Intended changes in smoking behaviour of Dutch young adults after an increase in excise tax: a cross-sectional survey

Por: Visscher · K. · Everaars · B. · Suijkerbuijk · A. W. · Lambooij · M. · de Wit · G. A.
Objectives

Increasing the price of tobacco is one of the most effective measures to reduce the prevalence of smoking. In the Netherlands, the excise tax on tobacco increased by 1.14 in 2020, raising the price of a standard package of cigarettes to 8.00. This study investigates how young adults intend to change their smoking behaviour in the case of hypothetical price increases of a pack of cigarettes, and which background characteristics are associated with intended behaviour change.

Design

A cross-sectional online survey was carried out between September and November 2020. Smokers indicated how they would react to several hypothetical increases in price. Four behavioural options were investigated: smoking less, quitting smoking, switching to another/cheaper product and buying cheaper cigarettes cross-border.

Participants

Data were obtained from 776 Dutch smokers between 15 and 25 years.

Results

At a hypothetical price of 10 per package, most respondents reported an intention to smoke less (67%), followed by switching to another/cheaper product (61%), quitting smoking (49%) and shopping for cigarettes cross-border (47%). Prior quit attempts, agreeing with the increase in excise tax and the intention to quit smoking in the future increased the odds of changing behaviour. Higher self-efficacy decreased the odds of behavioural change.

Conclusion

Many young adults intend to change their smoking behaviour in the event of increased prices. Although intended behaviour can deviate significantly from actual behaviour, an increase in excise tax may result in a significant amount of quit attempts and reduced smoking among young adults.

Can phone surveys be representative in low- and middle-income countries? An application to Myanmar

by Isabel Lambrecht, Joanna van Asselt, Derek Headey, Bart Minten, Patrick Meza, Moe Sabai, Thet Su Sun, Hnin Ei Win

For decades, in-person data collection has been the standard modality for nationally and sub-nationally representative socio-economic survey data in low- and middle-income countries. As the COVID-19 pandemic rendered in-person surveys impossible and unethical, the urgent need for rapid monitoring necessitated researchers and statistical agencies to turn to phone surveys. However, apart from pandemic-related factors, a variety of other reasons can render large segments of a population inaccessible for in-person surveys, including political instability, climatic shocks, and remoteness. Such circumstances currently prevail in Myanmar, a country facing civil conflict and political instability since the February 2021 military takeover. Moreover, Myanmar routinely experiences extreme weather events and is characterized by numerous inaccessible and remote regions due to its mountainous geography. We describe a novel approach to sample design and statistical weighting that has been successfully applied in Myanmar to obtain nationally and sub-nationally representative phone survey data. We use quota sampling and entropy weighting to obtain a better geographical distribution compared to recent in-person survey efforts, including reaching respondents in areas of active conflict. Moreover, we minimize biases towards certain household and respondent characteristics that are usually present in phone surveys, for example towards well-educated or wealthy households, or towards men or household heads as respondents. Finally, due to the rapidly changing political and economic situation in Myanmar in 2022, the need for frequent and swift monitoring was critical. We carried out our phone survey over four quarters in 2022, interviewing more than 12,000 respondents in less than three months each survey. A survey of this scale and pace, though generally of much shorter duration than in-person interviews, could only be possible on the phone. Our study proves the feasibility of collecting nationally and sub nationally representative phone survey data using a non-representative sample frame, which is critical for rapid monitoring in any volatile economy.

Test negative case-control study of COVID-19 vaccine effectiveness for symptomatic SARS-CoV-2 infection among healthcare workers: Zambia, 2021-2022

Por: Mweso · O. · Simwanza · J. · Malambo · W. · Banda · D. · Fwoloshi · S. · Sinyange · N. · Yoo · Y. M. · Feldstein · L. R. · Kapina · M. · Mulenga · L. B. · Liwewe · M. M. · Musonda · K. · Kapata · N. · Mwansa · F. D. · Agolory · S. · Bobo · P. · Hines · J. · Chilengi · R.
Objectives

The study aim was to evaluate vaccine effectiveness (VE) of COVID-19 vaccines in preventing symptomatic COVID-19 among healthcare workers (HCWs) in Zambia. We sought to answer the question, ‘What is the vaccine effectiveness of a complete schedule of the SARS-CoV-2 vaccine in preventing symptomatic COVID-19 among HCWs in Zambia?’

Design/setting

We conducted a test-negative case–control study among HCWs across different levels of health facilities in Zambia offering point of care testing for COVID-19 from May 2021 to March 2022.

Participants

1767 participants entered the study and completed it. Cases were HCWs with laboratory-confirmed SARS-CoV-2 and controls were HCWs who tested SARS-CoV-2 negative. Consented HCWs with documented history of vaccination for COVID-19 (vaccinated HCWs only) were included in the study. HCWs with unknown test results and unknown vaccination status, were excluded.

Primary and secondary outcome measures

The primary outcome was VE among symptomatic HCWs. Secondary outcomes were VE by: SARS-CoV-2 variant strains based on the predominant variant circulating in Zambia (Delta during May 2021 to November 2021 and Omicron during December 2021 to March 2022), duration since vaccination and vaccine product.

Results

We recruited 1145 symptomatic HCWs. The median age was 30 years (IQR: 26–38) and 789 (68.9%) were women. Two hundred and eighty-two (24.6%) were fully vaccinated. The median time to full vaccination was 102 days (IQR: 56–144). VE against symptomatic SARS-CoV-2 infection was 72.7% (95% CI: 61.9% to 80.7%) for fully vaccinated participants. VE was 79.4% (95% CI: 58.2% to 90.7%) during the Delta period and 37.5% (95% CI: –7.0% to 63.3%) during the Omicron period.

Conclusions

COVID-19 vaccines were effective in reducing symptomatic SARS-CoV-2 among Zambian HCWs when the Delta variant was circulating but not when Omicron was circulating. This could be related to immune evasive characteristics and/or waning immunity. These findings support accelerating COVID-19 booster dosing with bivalent vaccines as part of the vaccination programme to reduce COVID-19 in Zambia.

Hospital-based caregiver intervention for people following hip fracture surgery (HIP HELPER): multicentre randomised controlled feasibility trial with embedded qualitative study in England

Por: Smith · T. O. · Khoury · R. · Hanson · S. · Welsh · A. · Grant · K. · Clark · A. B. · Ashford · P.-A. · Hopewell · S. · Pfeiffer · K. · Logan · P. · Crotty · M. · Costa · M. L. · Lamb · S. · The HIP HELPER Study Collaborators · Clifford · Freeman · Gray · Cunningham · Langford · Baxter
Objectives

To assess the feasibility of conducting a pragmatic, multicentre randomised controlled trial (RCT) to test the clinical and cost-effectiveness of an informal caregiver training programme to support the recovery of people following hip fracture surgery.

Design

Two-arm, multicentre, pragmatic, open, feasibility RCT with embedded qualitative study.

Setting

National Health Service (NHS) providers in five English hospitals.

Participants

Community-dwelling adults, aged 60 years and over, who undergo hip fracture surgery and their informal caregivers.

Intervention

Usual care: usual NHS care. Experimental: usual NHS care plus a caregiver–patient dyad training programme (HIP HELPER). This programme comprised three, 1 hour, one-to-one training sessions for a patient and caregiver, delivered by a nurse, physiotherapist or occupational therapist in the hospital setting predischarge. After discharge, patients and caregivers were supported through three telephone coaching sessions.

Randomisation and blinding

Central randomisation was computer generated (1:1), stratified by hospital and level of patient cognitive impairment. There was no blinding.

Main outcome measures

Data collected at baseline and 4 months post randomisation included: screening logs, intervention logs, fidelity checklists, acceptability data and clinical outcomes. Interviews were conducted with a subset of participants and health professionals.

Results

102 participants were enrolled (51 patients; 51 caregivers). Thirty-nine per cent (515/1311) of patients screened were eligible. Eleven per cent (56/515) of eligible patients consented to be randomised. Forty-eight per cent (12/25) of the intervention group reached compliance to their allocated intervention. There was no evidence of treatment contamination. Qualitative data demonstrated the trial and HIP HELPER programme was acceptable.

Conclusions

The HIP HELPER programme was acceptable to patient–caregiver dyads and health professionals. The COVID-19 pandemic impacting on site’s ability to deliver the research. Modifications are necessary to the design for a viable definitive RCT.

Trial registration number

ISRCTN13270387.

Perspectives of informal caregivers who support people following hip fracture surgery: a qualitative study embedded within the HIP HELPER feasibility trial

Por: Welsh · A. · Hanson · S. · Pfeiffer · K. · Khoury · R. · Clark · A. · Ashford · P.-A. · Hopewell · S. · Logan · P. · Crotty · M. · Costa · M. · Lamb · S. · Smith · T. · HIP HELPER Study · C.
Objectives

This study aims to illuminate the perspectives of informal caregivers who support people following hip fracture surgery.

Design

A qualitative study embedded within a now completed multicentre, feasibility randomised controlled trial (HIP HELPER).

Setting

Five English National Health Service hospitals.

Participants

We interviewed 20 participants (10 informal caregivers and 10 people with hip fracture), following hip fracture surgery. This included one male and nine females who experienced a hip fracture; and seven male and three female informal caregivers. The median age was 72.5 years (range: 65–96 years), 71.0 years (range: 43–81 years) for people with hip fracture and informal caregivers, respectively.

Methods

Semistructured, virtual interviews were undertaken between November 2021 and March 2022, with caregiver dyads (person with hip fracture and their informal caregiver). Data were analysed thematically.

Findings

We identified two main themes: expectations of the informal caregiver role and reality of being an informal caregiver; and subthemes: expectations of care and services; responsibility and advocacy; profile of people with hip fracture; decision to be a caregiver; transition from hospital to home.

Conclusion

Findings suggest informal caregivers do not feel empowered to advocate for a person’s recovery or navigate the care system, leading to increased and unnecessary stress, anxiety and frustration when supporting the person with hip fracture. We suggest that a tailored information giving on the recovery pathway, which is responsive to the caregiving population (ie, considering the needs of male, younger and more active informal caregivers and people with hip fracture) would smooth the transition from hospital to home.

Trial registration number

ISRCTN13270387.Cite Now

Comparing proficiency of obstetrics and gynaecology trainees with general surgery trainees using simulated laparoscopic tasks in Health Education England, North-West: a prospective observational study

Por: Khan · Z. N. · Shrestha · D. · Shugaba · A. · Lambert · J. E. · Clark · J. · Haslett · E. · Afors · K. · Bampouras · T. M. · Gaffney · C. J. · Subar · D. A.
Background

Training programmes for obstetrics and gynaecology (O&G) and general surgery (GS) vary significantly, but both require proficiency in laparoscopic skills. We sought to determine performance in each specialty.

Design

Prospective, observational study.

Setting

Health Education England North-West, UK.

Participants

47 surgical trainees (24 O&G and 23 GS) were subdivided into four groups: 11 junior O&G, 13 senior O&G, 11 junior GS and 12 senior GS trainees.

Objectives

Trainees were tested on four simulated laparoscopic tasks: laparoscopic camera navigation (LCN), hand–eye coordination (HEC), bimanual coordination (BMC) and suturing with intracorporeal knot tying (suturing).

Results

O&G trainees completed LCN (p

Discussion

GS trainees performed better than O&G trainees in core laparoscopic skills, and the structure of O&G training may require modification.

Trial registration number

ClinicalTrials.gov Registry (NCT05116332).

What health inequalities exist in access to, outcomes from and experience of treatment for lung cancer? A scoping review

Por: Lennox · L. · Lambe · K. · Hindocha · C. N. · Coronini-Cronberg · S.
Objectives

Lung cancer (LC) continues to be the leading cause of cancer-related deaths and while there have been significant improvements in overall survival, this gain is not equally distributed. To address health inequalities (HIs), it is vital to identify whether and where they exist. This paper reviews existing literature on what HIs impact LC care and where these manifest on the care pathway.

Design

A systematic scoping review based on Arksey and O’Malley’s five-stage framework.

Data sources

Multiple databases (EMBASE, HMIC, Medline, PsycINFO, PubMed) were used to retrieve articles.

Eligibility criteria

Search limits were set to retrieve articles published between January 2012 and April 2022. Papers examining LC along with domains of HI were included. Two authors screened papers and independently assessed full texts.

Data extraction and synthesis

HIs were categorised according to: (a) HI domains: Protected Characteristics (PC); Socioeconomic and Deprivation Factors (SDF); Geographical Region (GR); Vulnerable or Socially Excluded Groups (VSG); and (b) where on the LC pathway (access to, outcomes from, experience of care) inequalities manifest. Data were extracted by two authors and collated in a spreadsheet for structured analysis and interpretation.

Results

41 papers were included. The most studied domain was PC (32/41), followed by SDF (19/41), GR (18/41) and VSG (13/41). Most studies investigated differences in access (31/41) or outcomes (27/41), with few (4/41) exploring experience inequalities. Evidence showed race, rural residence and being part of a VSG impacted the access to LC diagnosis, treatment and supportive care. Additionally, rural residence, older age or male sex negatively impacted survival and mortality. The relationship between outcomes and other factors (eg, race, deprivation) showed mixed results.

Conclusions

Findings offer an opportunity to reflect on the understanding of HIs in LC care and provide a platform to consider targeted efforts to improve equity of access, outcomes and experience for patients.

Nurse practitioner led telehealth services: A scoping review

Abstract

Aim

To explore the educational preparation of nurse practitioners to deliver telehealth services and their impact on access to care.

Design

Scoping review.

Methods

A search was undertaken 4 April 2022. Primary studies that focused on nurse practitioners and their patients/clients engaging in telehealth services in any healthcare setting or clinical area within Australia, New Zealand, United States, Canada, United Kingdom, and Ireland, published between 2010 to 2022, were included. Study findings were analysed using the Levesque et al. (2013) access to care framework and the Patterns, Advances, Gaps, Evidence for Practice and Research Recommendations framework (Bradbury-Jones et al., 2021). The PRISMA-ScR checklist was used to guide reporting.

Data Sources

CINAHL, Medline, Scopus, and Embase databases.

Results

Forty-two studies were included. Studies (n = 28) relating to access to care focused on appropriateness/ability to engage (n = 14), affordability/ability to pay (n = 1), and availability/ability to reach (n = 13). High levels of telehealth satisfaction were reported, including reduced travel time and costs, and appointment flexibility. Telehealth satisfaction was reduced when a perceived need for physical assessment, or privacy concerns were present. Service providers reported decreased emergency presentations, fewer missed appointments and improved consumer engagement. Fourteen studies related to nurse practitioner education, using a range of approaches such as didactic education modules, simulations and clinical experiences, all published within the past 3 years.

Conclusion

Findings suggest that nurse practitioner-led telehealth has improved access to care. High levels of satisfaction indicate patients accept nurse practitioner-led telehealth. Impacts to healthcare service use and patient engagement further support the viability of nurse practitioner-led telehealth. The recent increase in telehealth education studies reflects the rapid uptake of telehealth care in the mainstream.

Implications for the profession and/or patient care

Patients perceive telehealth as acceptable and appropriate to meet their healthcare needs and improve access to care. Telehealth is likely to be a mainstay in ongoing healthcare delivery, therefore, nurse practitioners must have educational preparation to provide telehealth.

Impact

This scoping review provides insight into the ways nurse practitioners deliver telehealth services, how they are educated to provide telehealth services, and their impact on access to care. Nurse practitioner-led telehealth improves access to care across service provision and consumer perspective domains. Nurse practitioner telehealth education is an emerging topic. This research is valuable for nurse practitioners using telehealth, nurse practitioner educators and telehealth policy decision makers.

Reporting Method

Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).

Patient or Public Contribution

No Patient or Public Contribution.

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