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Hepatopancreaticobiliary Resection Arginine Immunomodulation (PRIMe) trial: protocol for a randomised phase II trial of the impact of perioperative immunomodulation on immune function following resection for hepatopancreaticobiliary malignancy

Por: Behman · R. · Auer · R. C. · Bubis · L. · Xu · G. · Coburn · N. G. · Martel · G. · Hallet · J. · Balaa · F. · Law · C. · Bertens · K. A. · Abou Khalil · J. · Karanicolas · P. J.
Introduction

Surgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery.

Methods and analysis

This is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts.

Ethics and dissemination

This trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov.

Trial registration number

ClinicalTrials.gov identifier: NCT04549662.

Perioperative mental health intervention for depression and anxiety symptoms in older adults study protocol: design and methods for three linked randomised controlled trials

Por: Holzer · K. J. · Bartosiak · K. A. · Calfee · R. P. · Hammill · C. W. · Haroutounian · S. · Kozower · B. D. · Cordner · T. A. · Lenard · E. M. · Freedland · K. E. · Tellor Pennington · B. R. · Wolfe · R. C. · Miller · J. P. · Politi · M. C. · Zhang · Y. · Yingling · M. D. · Baumann
Introduction

Preoperative anxiety and depression symptoms among older surgical patients are associated with poor postoperative outcomes, yet evidence-based interventions for anxiety and depression have not been applied within this setting. We present a protocol for randomised controlled trials (RCTs) in three surgical cohorts: cardiac, oncological and orthopaedic, investigating whether a perioperative mental health intervention, with psychological and pharmacological components, reduces perioperative symptoms of depression and anxiety in older surgical patients.

Methods and analysis

Adults ≥60 years undergoing cardiac, orthopaedic or oncological surgery will be enrolled in one of three-linked type 1 hybrid effectiveness/implementation RCTs that will be conducted in tandem with similar methods. In each trial, 100 participants will be randomised to a remotely delivered perioperative behavioural treatment incorporating principles of behavioural activation, compassion and care coordination, and medication optimisation, or enhanced usual care with mental health-related resources for this population. The primary outcome is change in depression and anxiety symptoms assessed with the Patient Health Questionnaire-Anxiety Depression Scale from baseline to 3 months post surgery. Other outcomes include quality of life, delirium, length of stay, falls, rehospitalisation, pain and implementation outcomes, including study and intervention reach, acceptability, feasibility and appropriateness, and patient experience with the intervention.

Ethics and dissemination

The trials have received ethics approval from the Washington University School of Medicine Institutional Review Board. Informed consent is required for participation in the trials. The results will be submitted for publication in peer-reviewed journals, presented at clinical research conferences and disseminated via the Center for Perioperative Mental Health website.

Trial registration numbers

NCT05575128, NCT05685511, NCT05697835, pre-results.

Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling

Por: Wang · Y. · Kingwara · L. · Wagner · A. D. · Yongo · N. · Hassan · S. A. · Liu · S. · Oyaro · P. · Patel · R. C.
Background

HIV drug resistance (DR) is a growing threat to the durability of current and future HIV treatment success. DR testing (DRT) technologies are very expensive and specialised, relying on centralised laboratories in most low and middle-income countries. Modelling for laboratory network with point-of-care (POC) DRT assays to minimise turnaround time (TAT), is urgently needed to meet the growing demand.

Methods

We developed a model with user-friendly interface using integer programming and queueing theory to improve the DRT system in Kisumu County, Kenya. We estimated DRT demand based on both current and idealised scenarios and evaluated a centralised laboratory-only network and an optimised POC DRT network. A one-way sensitivity analysis of key user inputs was conducted.

Results

In a centralised laboratory-only network, the mean TAT ranged from 8.52 to 8.55 working days, and the system could not handle a demand proportion exceeding 1.6%. In contrast, the mean TAT for POC DRT network ranged from 1.13 to 2.11 working days, with demand proportion up to 4.8%. Sensitivity analyses showed that expanding DRT hubs reduces mean TAT substantially while increasing the processing rate at national labs had minimal effect. For instance, doubling the current service rate at national labs reduced the mean TAT by only 0.0%–1.9% in various tested scenarios, whereas doubling the current service rate at DRT hubs reduced the mean TAT by 37.5%–49.8%. In addition, faster batching modes and transportation were important factors influencing the mean TAT.

Conclusions

Our model offers decision-makers an informed framework for improving the DRT system using POC in Kenya. POC DRT networks substantially reduce mean TAT and can handle a higher demand proportion than a centralised laboratory-only network, especially for children and pregnant women living with HIV, where there is an immediate push to use DRT results for patient case management.

REKOVER study protocol: a pRospective patient treatment rEgistry of tramadol and dexKetoprofen trometamol oral fixed-dose combination (SKUDEXA) in mOderate to seVere acutE pain in Real-world setting in Asia

Por: Ho · K. Y. · Gyanwali · B. · Dimayuga · C. · Eufemio · E. M. · Bernardo · E. · Raju · G. · Chong · K. W. · Waithayayothin · K. · Ona · L. · Castro · M. A. L. · Sawaddiruk · P. · Salvador · R. C. · Roohi · S. A. · Tangwiwat · S. · Wilairatana · V. · Oon · Z. H. · Gupta · A. · Nagrale · D.
Introduction

Satisfactory management of acute pain remains a major medical challenge despite the availability of multiple therapeutic options including the fixed-dose combination (FDC) drugs. Tramadol and dexketoprofen trometamol (TRAM/DKP) 75/25 mg FDC was launched in 2018 in Asia and is widely used in the management of moderate to severe acute pain. There are limited data on its effectiveness and safety in Asian patients, and therefore, a need to better understand its usage patterns in clinical practice. We aim to understand the usage pattern of TRAM/DKP FDC, its effectiveness and tolerability in patients with moderate to severe acute pain in Asia.

Methods and analysis

REKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18–80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app.

Ethics and dissemination

The study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.

Strategies for research capacity building by family physicians in primary healthcare: a scoping review protocol

Por: Gil Conde · M. · Costa · I. · Silverio Serra · S. · Ramos · R. C. · Ribeiro · C. · Broeiro-Goncalves · P. · Penedo · C. R. · Parola · V. · Nicola · P.
Introduction

The qualities of primary healthcare (PHC) make it a very relevant environment for research; however, there is still work to be done to enhance the research capabilities of family physicians in healthcare units. Considering there is no ongoing review that specifically addresses this objective, the proposed goal of this scoping review is to determine the depth of the literature on the current strategies that support research capacity building among family physicians in the context of PHC.

Methods and analysis

The scoping review will include studies from PubMed, Scopus, Web of Science, Cochrane Library and grey literature, published from 2008 to 2023, that address strategies to promote research capacity building among family physicians in the context of PHC. Only studies published in English, Portuguese or Spanish will be considered. All study designs, including quantitative, qualitative and mixed-methods studies, will be eligible for inclusion. The literature search will be performed from January to March of 2024 and data charting will employ a descriptive-analytical method, systematically summarising study objectives, methodologies, findings and implications. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols and the review will employ the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews.

Ethics and dissemination

This review does not need ethical approval. Peer-reviewed publications, policy summaries, presentations at conferences and involvement with pertinent stakeholders are all part of our outreach approach.

IMPAACT: IMproving the PArticipAtion of older people in policy decision-making on common health CondiTions - a study protocol

Por: Ambagtsheer · R. C. · Hurley · C. J. · Lawless · M. · Braunack-Mayer · A. · Visvanathan · R. · Beilby · J. · Stewart · S. · Cornell · V. · Leach · M. J. · Taylor · D. · Thompson · M. · Dent · E. · Whiteway · L. · Archibald · M. · O'Rourke · H. M. · Williams · K. · Chudecka · A.
Introduction

Rapid population ageing is a demographic trend being experienced and documented worldwide. While increased health screening and assessment may help mitigate the burden of illness in older people, issues such as misdiagnosis may affect access to interventions. This study aims to elicit the values and preferences of evidence-informed older people living in the community on early screening for common health conditions (cardiovascular disease, diabetes, dementia and frailty). The study will proceed in three Phases: (1) generating recommendations of older people through a series of Citizens’ Juries; (2) obtaining feedback from a diverse range of stakeholder groups on the jury findings; and (3) co-designing a set of Knowledge Translation resources to facilitate implementation into research, policy and practice. Conditions were chosen to reflect common health conditions characterised by increasing prevalence with age, but which have been underexamined through a Citizens’ Jury methodology.

Methods and analysis

This study will be conducted in three Phases—(1) Citizens’ Juries, (2) Policy Roundtables and (3) Production of Knowledge Translation resources. First, older people aged 50+ (n=80), including those from traditionally hard-to-reach and diverse groups, will be purposively recruited to four Citizen Juries. Second, representatives from a range of key stakeholder groups, including consumers and carers, health and aged care policymakers, general practitioners, practice nurses, geriatricians, allied health practitioners, pharmaceutical companies, private health insurers and community and aged care providers (n=40) will be purposively recruited for two Policy Roundtables. Finally, two researchers and six purposively recruited consumers will co-design Knowledge Translation resources. Thematic analysis will be performed on documentation and transcripts.

Ethics and dissemination

Ethical approval has been obtained through the Torrens University Human Research Ethics Committee. Participants will give written informed consent. Findings will be disseminated through development of a policy brief and lay summary, peer-reviewed publications, conference presentations and seminars.

Avoidance of healthcare service use and correlates among HIV-positive patients in Vietnam: a cross-sectional study

Por: Nguyen · H. L. T. · Bui · T. M. · Dam · V. A. T. · Nguyen · T. T. · Nguyen · H. T. · Zeng · G. M. · Bradley · D. · Nguyen · Q. N. · Ngo · T. V. · Latkin · C. A. · Ho · R. C. · Ho · C. S.
Objective

The prevention of HIV/AIDS is not making sufficient progress. The slow reduction of HIV/AIDS infections needs to prioritise hesitancy towards service utilisation, including treatment duration, social support and social stigma. This study investigates HIV-positive patients’ avoidance of healthcare services and its correlates.

Design

A cross-sectional study.

Setting

The secondary data analysis used cross-sectional data from a randomised controlled intervention, examining the effectiveness of HIV-assisted smartphone applications in the treatment of HIV/AIDS patients in the Bach Mai and Ha Dong clinics in Hanoi.

Methods

Simple random sampling was used to identify 495 eligible patients. Two-tailed 2, Mann-Whitney, multivariate logistic and ordered logistic regression models were performed.

Primary and secondary outcome measures

The main study outcome was the patients’ healthcare avoidance and frequency of healthcare avoidance. The association of individual characteristics, social and behavioural determinants of HIV patients’ usage of health services was also determined based on the collected data using structured questionnaires.

Results

Nearly half of the participants avoid health service use (47.3%), while 30.7% rarely avoid health service use. Duration of antiretroviral therapy and initial CD4 cell count were negatively associated with avoidance of health services and frequency of health service avoidance. Similarly, those with the middle and highest income were more likely to avoid health services compared with those with the lowest income. People having health problems avoided health service use more frequently (OR 1.47, 95% CI 1.35 to 1.61).

Conclusions

Our study’s findings identify characteristics of significance in relation to health service avoidance and utilisation among HIV-positive patients. The results highlighted the need to improve satisfaction, adherence and utilisation of treatment. Moreover, identifying ways to address or incorporate those social determinants in new policy may also help the treatment of HIV/AIDS and strategically allocate funding in the changing financial and political climate of Vietnam.

Trial registration number

Thai Clinical Trials Registry TCTR20220928003.

Qualitative interview study exploring the perspectives of pregnant women on participating in controlled human infection research in the UK

Por: Dorey · R. B. · Theodosiou · A. A. · Read · R. C. · Vandrevala · T. · Jones · C. E.
Introduction

Pregnant women have been historically excluded from interventional research. While recent efforts have been made to improve their involvement, there remains a disparity in the evidence base for treatments available to pregnant women compared with the non-pregnant population. A significant barrier to the enrolment of pregnant women within research is risk perception and a poor understanding of decision-making in this population.

Objective

Assess the risk perception and influences on decision-making in pregnant women, when considering whether to enrol in a hypothetical interventional research study.

Design

Semistructured interviews were undertaken, and thematic analysis was undertaken of participant responses.

Participants

Twelve pregnant women were enrolled from an antenatal outpatient clinic.

Results

Participants were unanimously positive about enrolling in the proposed hypothetical interventional study. Risk perception was influenced by potential risks to their fetus and their previous experiences of healthcare and research. Participants found the uncertainty in quantifying risk for new research interventions challenging. They were motivated to enrol in research by altruism and found less invasive research interventions more tolerable.

Conclusion

It is vital to understand how pregnant women balance the perceived risks and benefits of interventional research. This may help clinicians and scientists better communicate risk to pregnant women and address the ongoing under-representation of pregnant women in interventional research.

Lived experience of recurrent miscarriage: women and their partners experience of subsequent pregnancy and support within an NHS specialist clinic - a qualitative study

Por: Hawkes · A. · Shields · R. C. · Quenby · S. · Bick · D. · Parsons · J. · Harris · B.
Objective

This study aims to describe the lived experiences of couples with a history of recurrent miscarriage in subsequent pregnancies and their perception of clinic support and cytogenetic investigations.

Design

A qualitative interview study with a phenomenological approach. Semistructured interviews were conducted using video conferencing software. Two researchers coded the transcripts and developed themes.

Setting

A National Health Service (NHS) hospital in central England between May 2021 and July 2021, during the COVID-19 pandemic.

Participants

Patients attending a specialist recurrent miscarriage clinic and their partners. This clinic accepts referrals from all over the UK for couples who have suffered two or more miscarriages.

Results

Seventeen participants were interviewed: 14 women and 3 male partners. Six main themes were identified from the data. Three related to the women’s lived experience of recurrent miscarriage (emotions in pregnancy, confidence in their bodies, expectations and coping strategies) and three related to the clinical support offered by the NHS service (impact of early pregnancy scanning, effect of the COVID-19 pandemic and cytogenetic investigations).

Conclusions

Pregnancy following recurrent miscarriage is extremely difficult. Recurrent miscarriage specialist services can provide couples with support and access to early pregnancy scanning, which can make the first trimester of pregnancy manageable. Partners should not be excluded from the clinic as it can result in a feeling of disconnect. Cytogenetic testing of pregnancy tissue can offer couples with recurrent miscarriage closure after pregnancy loss and is a desired investigation.

The Oxford Needle Experience (ONE) scale: a UK-based and US-based online mixed-methods psychometric development and validation study of an instrument to assess needle fear, attitudes and expectations in the general public

Por: Kantor · J. · Vanderslott · S. · Morrison · M. · Pollard · A. J. · Carlisle · R. C.
Objectives

To develop and validate the Oxford Needle Experience (ONE) scale, an instrument to assess needle fear, attitudes and expectations in the general population.

Design

Cross-sectional validation study.

Setting

Internet-based with participants in the UK and USA.

Participants

UK and US representative samples stratified by age, sex, and ethnicity using the Prolific Academic platform.

Main outcome measures

Exploratory factor analysis with categorical variables and a polychoric correlation matrix followed by promax oblique rotation on the UK sample for the ONE scale. Confirmatory factor analysis (CFA) with a Satorra-Bentler scaled test statistic evaluating the root mean squared error of approximation (RMSEA), standardised root mean squared residual (SRMR) and comparative fit index (CFI) on the US sample. Reliability as internal consistency using McDonald’s omega. Convergent validity using the Pearson correlation coefficient. Predictive and discriminant validity using logistic regression ORs of association (OR).

Results

The population included 1000 respondents, 500 in the UK and 500 in the USA. Minimum average partial correlation and a scree plot suggested four factors should be retained: injection hesitancy, blood-related hesitancy, recalled negative experiences and perceived benefits, yielding a 19-question scale. On CFA, the RMSEA was 0.070 (90% CI, 0.064 to 0.077), SRMR 0.053 and CFI 0.925. McDonald’s omega was 0.92 and 0.93 in the UK and US samples, respectively. Convergent validity with the four-item Oxford Coronavirus Explanations, Attitudes and Narratives Survey (OCEANS) needle fear scale demonstrated a strong correlation (r=0.83). Predictive validity with a single-question COVID-19 vaccination status question demonstrated a strong association, OR (95% CI) 0.97 (0.96 to 0.98), p

Conclusions

The ONE scale is a reliable and valid multidimensional scale that may be useful in predicting vaccine hesitancy, designing public health interventions to improve vaccine uptake and exploring alternatives to needles for medical procedures.

The long-term impact of the Covid-19 pandemic on financial insecurity in vulnerable families: Findings from the Born in Bradford Covid-19 longitudinal study

by Sian Reece, Josie Dickerson, Brian Kelly, Rosemary R. C. McEachan, Kate E. Pickett

There is growing recognition that the public health measures employed to control the spread of the COVID-19 pandemic had unintended consequences on socioeconomic security and health inequalities, having the greatest impact on the most vulnerable groups. This longitudinal study aims to explore the medium to long-term impacts of the COVID-19 pandemic and subsequent public health measures on financial security for families living in the deprived and ethnically diverse city of Bradford. We collected data at four time points before and during the pandemic from mothers who participated in one of two prospective birth cohort studies in Bradford. The findings demonstrate that the risk of experiencing financial insecurity rose sharply during the pandemic and has not returned to pre-COVID-19 baseline levels. Several individual characteristics were found to be possible predictors of financial insecurity, including homeowner status, free school meal eligibility and not working. Protective factors against financial insecurity include: living in more affluent areas; greater levels of educational attainment; and families with two or more adults in the household. Notably, families of Pakistani Heritage were found to have the greatest risk of experiencing financial insecurity throughout the pandemic. Furthermore, this study demonstrated that there were strong associations between financial insecurity and maternal health and wellbeing outcomes, with mothers experiencing financial insecurity being more likely to report unsatisfactory general health and clinically important symptoms of depression and anxiety. The findings of this study highlight that the impact of financial insecurity experienced by mothers and their families throughout the pandemic was severe, wide ranging and affected the most vulnerable. In the wake of the pandemic, the emerging cost of living and energy crisis emphasises the urgent need for policy makers to act to support vulnerable families to prevent further widening of existing health and social inequalities.
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