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Hyperuricemia, gout and the associated comorbidities in China: findings from a prospective study of 0.5 million adults.
BACKGROUND: Despite the growing prevalence of hyperuricemia and gout, their epidemiology and associated comorbidity burden remains poorly studied in many populations, including China. We aimed to examine the patterns of plasma urate level, prevalence of hyperuricemia, and incidence of gout, and investigate the associations of gout with a range of comorbidities and all-cause mortality in Chinese adults. METHODS: The prospective China Kadoorie Biobank recruited 512,724 adults aged 30-79 years from ten diverse areas in 2004-2008 and measured plasma urate level among 16,817 participants. The incidence of gout and other diseases and deaths were monitored by electronic linkages with registries and hospital records. Cox and logistic regression yielded adjusted HRs and ORs for risks of mortality and comorbidities associated with gout, hyperuricemia, and urate level. FINDINGS: The gout incidence rate was 23.4 per 100,000 person-years, and was higher in men and older participants, and varied substantially by region. Gout was associated with higher risks of all-cause mortality (HR = 1.58, 95% CI 1.37-1.82), CVD (1.87, 1.64-2.14), CKD (5.61, 4.45-7.07), urolithiasis (2.50, 1.85-3.38), diabetes (1.99, 1.51-2.62), diseases of the oesophagus, stomach, and duodenum (2.14, 1.72-2.66), infectious and parasitic diseases (1.91, 1.47-2.48), arthropathies (6.06, 4.98-7.38), and other musculoskeletal disorders (2.10, 1.77-2.51). Most of these associations were bi-directional, sustained over time and little affected by adjustment for cardiometabolic risk factors. Moreover, participants who developed gout were more likely to have multiple major diseases and more hospitalisations. Among the subset with plasma urate measured, 15% had hyperuricemia, which was more common in men, older women, and urban residents, and was associated with increased risks of gout, all-cause mortality, and several cardiometabolic, renal, digestive, and musculoskeletal diseases. INTERPRETATION: In Chinese adults, gout was associated with several comorbidities and a poor health trajectory. Our findings reinforce the need for prevention and management of gout and associated comorbidities. FUNDING: Kadoorie Charitable Foundation, National Natural Science Foundation of China, Noncommunicable Chronic Diseases-National Science and Technology Major Project, British Heart Foundation, Cancer Research UK, Wellcome Trust, UK Medical Research Council, Nuffield Department of Population Health at the University of Oxford.
Iron deficiency causes aspartate-sensitive dysfunction in CD8+ T cells.
Iron is an irreplaceable co-factor for metabolism. Iron deficiency affects >1 billion people and decreased iron availability impairs immunity. Nevertheless, how iron deprivation impacts immune cell function remains poorly characterised. We interrogate how physiologically low iron availability affects CD8+ T cell metabolism and function, using multi-omic and metabolic labelling approaches. Iron limitation does not substantially alter initial post-activation increases in cell size and CD25 upregulation. However, low iron profoundly stalls proliferation (without influencing cell viability), alters histone methylation status, gene expression, and disrupts mitochondrial membrane potential. Glucose and glutamine metabolism in the TCA cycle is limited and partially reverses to a reductive trajectory. Previous studies identified mitochondria-derived aspartate as crucial for proliferation of transformed cells. Despite aberrant TCA cycling, aspartate is increased in stalled iron deficient CD8+ T cells but is not utilised for nucleotide synthesis, likely due to trapping within depolarised mitochondria. Exogenous aspartate markedly rescues expansion and some functions of severely iron-deficient CD8+ T cells. Overall, iron scarcity creates a mitochondrial-located metabolic bottleneck, which is bypassed by supplying inhibited biochemical processes with aspartate. These findings reveal molecular consequences of iron deficiency for CD8+ T cell function, providing mechanistic insight into the basis for immune impairment during iron deficiency.
Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis.
Red blood cell development from erythroid progenitors requires profound reshaping of metabolism and gene expression. How these transcriptional and metabolic alterations are coupled is unclear. Nprl3 (an inhibitor of mTORC1) has remained in synteny with the α-globin genes for >500 million years, and harbours most of the a-globin enhancers. However, whether Nprl3 serves an erythroid role is unknown. We found that while haematopoietic progenitors require basal Nprl3 expression, erythroid Nprl3 expression is further boosted by the α-globin enhancers. This lineage-specific upregulation is required for sufficient erythropoiesis. Loss of Nprl3 affects erythroblast metabolism via elevating mTORC1 signalling, suppressing autophagy and disrupting glycolysis. Broadly consistent with these murine findings, human NPRL3-knockout erythroid progenitors produce fewer enucleated cells and demonstrate dysregulated mTORC1 signalling in response to nutrient availability and erythropoietin. Therefore, we propose that the anciently conserved linkage of NprI3, α-globin and their associated enhancers has coupled metabolic and developmental control of erythropoiesis.
Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.
The emergence of Plasmodium falciparum parasites resistant to artemisinins compromises the efficacy of Artemisinin Combination Therapies (ACTs), the global first-line malaria treatment. Artemisinin resistance is a complex genetic trait in which nonsynonymous SNPs in PfK13 cooperate with other genetic variations. Here, we present population genomic/transcriptomic analyses of P. falciparum collected from patients with uncomplicated malaria in Cambodia and Vietnam between 2018 and 2020. Besides the PfK13 SNPs, several polymorphisms, including nonsynonymous SNPs (N1131I and N821K) in PfRad5 and an intronic SNP in PfWD11 (WD40 repeat-containing protein on chromosome 11), appear to be associated with artemisinin resistance, possibly as new markers. There is also a defined set of genes whose steady-state levels of mRNA and/or splice variants or antisense transcripts correlate with artemisinin resistance at the base level. In vivo transcriptional responses to artemisinins indicate the resistant parasite's capacity to decelerate its intraerythrocytic developmental cycle (IDC), which can contribute to the resistant phenotype. During this response, PfRAD5 and PfWD11 upregulate their respective alternatively/aberrantly spliced isoforms, suggesting their contribution to the protective response to artemisinins. PfRAD5 and PfWD11 appear under selective pressure in the Greater Mekong Sub-region over the last decade, suggesting their role in the genetic background of the artemisinin resistance.
The validity of test-negative design for assessment of typhoid conjugate vaccine protection: comparison of estimates by different study designs using data from a cluster-randomised controlled trial.
BACKGROUND: Typhoid fever remains a substantial public health challenge in low-income and middle-income countries. By 2023, typhoid conjugate vaccines (TCVs) had been introduced in six countries globally, with more than 50 million doses distributed. Now that TCVs are being deployed, there is a need for observational studies to assess vaccine effectiveness in the field. We aimed to evaluate the validity of different observational study designs in estimating vaccine protection. METHODS: We compared different observational and experimental study designs for assessing vaccine effectiveness by re-analysing data from the TyVAC Bangladesh trial, a participant-blinded and observer-blinded cluster-randomised controlled trial done in Mirpur, Dhaka, Bangladesh. 150 geographical clusters were randomly assigned (1:1) to receive either TCV or Japanese encephalitis vaccine. Eligible children aged 9 months to 15 years were offered a single dose of the vaccine randomly assigned to their cluster of residence, and baseline vaccination was done between April 15 and May 15, 2018. We compared estimates of vaccine effectiveness from the cluster-randomised controlled trial analysis-which assessed the risk of blood-culture-confirmed typhoid fever among recipients of TCV versus recipients of Japanese encephalitis vaccine-with estimates from cohort study and test-negative case-control study design (TND) analyses, which compared recipients of TCV with non-vaccinees in the 75 geographical clusters where TCV was administered. We further conducted negative-control exposure (NCE) and negative-control outcome (NCO) analyses as bias indicators. FINDINGS: 41 344 (67%) of 62 025 age-eligible children in the study area received the TCV or Japanese encephalitis vaccine during the baseline vaccination campaign. Among the 62 025 age-eligible children, 5582 blood-culture specimens were collected by passive surveillance, including 2546 (46%) specimens from the 75 TCV clusters. The estimated vaccine efficacy was 89% (95% CI 81-93) in the cluster-randomised controlled trial analysis, 79% (70-86) by the cohort design, 88% (79-93) by the TND when pan-negatives were used as test-negative controls, and 90% (75-96) by the TND when specimens positive for pathogens other than Salmonella enterica serotype Typhi were used as test-negative controls. Using NCE analysis, Japanese encephalitis vaccination was associated with an increased risk of typhoid fever compared with non-vaccinees in the 75 Japanese encephalitis clusters in the cohort design (incidence rate ratio 1·98 [95% CI 1·56-2·52]), but no significant association between Japanese encephalitis vaccination and typhoid fever was found with the TND. Similarly, an increased risk of non-typhoid infections was observed in the cohort NCO analyses when comparing vaccinees with non-vaccinees in both Japanese encephalitis vaccine clusters and TCV clusters, but not in the TND NCO analyses. INTERPRETATION: Our findings suggests that the TND provides reliable estimates of TCV effectiveness, whereas the cohort design can bias vaccine effectiveness estimates, possibly due to unmeasured confounding effects, such as health-care-seeking behaviours. NCE and NCO approaches are useful tools for identifying such biases. FUNDING: The Bill & Melinda Gates Foundation.
Commentary: Without Values, Complexity is Reduced to Mathematics.
This commentary on Sturmberg and Mercuri's paper 'Every Problem is Embedded in a Greater Whole' [1] argues that those authors have approached complexity from a largely mathematical perspective, drawing on the work of Sumpter. Whilst such an approach allows us to challenge the simple linear causality assumed in randomised controlled trials, it is itself limited. Mathematical complexity can explain nonlinearity and network effects but it cannot explain human values. It overlooks, for example, how science itself is historically and culturally shaped and how values-driven misunderstandings and conflicts are inevitable when people with different world views come together to try to solve a problem. This paper argues that the mathematical version of complexity thinking is necessary but not sufficient in medical research, and that we need to enhance such thinking further with attention to human values.
Technostress, technosuffering, and relational strain: a multi-method qualitative study of how remote and digital work affects staff in UK general practice.
BACKGROUND: The introduction of remote and digital forms of working in UK general practice has driven the development of new routines and working styles. AIM: To explore and theorise how new forms of work have affected general practice staff. DESIGN AND SETTING: Multi-sited, qualitative case study in UK general practice. METHOD: Using longitudinal ethnography by researchers in residence, we followed 12 practices for 28 months (September 2021 to December 2023). This core dataset was supplemented by workshops and stakeholder interviews. Data analysis applied theories from the sociology of work, organisation studies, and internet studies. RESULTS: Staff made significant efforts to adapt to and embed digital services into their work. When technologies work well they can offer improved convenience, efficiency, more comprehensive patient care, and workplace fulfilment for staff. However, for many clinical and administrative staff, compromises and frictions embedded in digitalised workplace routines and processes could also lead to job dissatisfaction, worsened wellbeing, and misalignments with professional values and identities. We found that this workplace suffering caused relational strain between team members and had an impact on team cohesiveness and coordination. CONCLUSION: The digitalisation of working routines in UK general practice poses a unique challenge to the workforce, risking technostress, workplace suffering, and increased relational strain within and between teams. To embed the benefits of digitalisation, we must first improve practice teams' readiness for change, which includes strengthening practices' relational structures that provide support during periods of adaptation. Practices must be empowered to determine a locally appropriate configuration of digital tools and given the resources and time to adapt working routines.
Ethnicity and breast cancer incidence in over 329,500 women in England in 2011-2019.
INTRODUCTION: Previous studies have reported an overall lower breast cancer incidence in women from Asian and Black backgrounds compared with white women. Age standardised and age specific incidence rates in the largest specific ethnicities within Asian and Black groups are not reported. MATERIALS AND METHODS: Data on population size and the age distribution of women in five ethnic groups of interest (white British, Black African, Black Caribbean, Indian and Pakistani) were extracted from the Office for National Statistics 2001, 2011 and 2021 census data for England.Cancer registrations for invasive breast cancer (ICD-10 C50) in women in England aged ≥25 years during 2011-2019 with a recorded ethnicity were extracted from the National Cancer Registration and Analysis Service.Age standardised (ASIRs) and age specific (ASRs) incidence rates in five ethnic groups of interest were calculated. RESULTS: 329,655 women who were aged ≥25 years and in one of the five ethnic groups of interest had a record of an incident C50 cancer registration during 2011-2019. The ASIR was highest for white women (199.6 (95% CI 198.9-200.3)), and lowest for Black African women (118.2 (95% CI 111.6-125.1)). The ASRs for invasive breast cancer were generally lower in women from minority ethnic groups compared to white women in all age groups examined except for younger Black Caribbean women. CONCLUSIONS: There are significant differences in breast cancer incidence rates between women from specific ethnicities. This requires further investigation in large scale prospective studies considering potential differences by ethnicity in known risk factors for breast cancer.
Type and Timing of Menopausal Hormone Therapy and Breast Cancer Risk: Individual Participant Meta-Analysis of the Worldwide Epidemiological Evidence
The benefits and risks of the use of menopausal hormone therapy (MHT, also known as hormone replacement therapy [HRT]) comprise an area of considerable debate. The widespread use of MHT began in the 1960s with initial preparations containing only oestrogen. Subsequent observations that these preparations led to endometrial disorders in postmenopausal women with an intact uterus resulted in the addition of progestogens to MHT preparations to confer protection to the endometrial lining in these women. As the use of MHT became more widespread, concerns began to be raised about breast cancer risk related to the use of these preparations. Broadly, modern MHT preparations may include oestrogen and progestogen, in which the progestogen component is given continuously or intermittently (for women with an intact uterus), or they may be oestrogen-only preparations (for women without an intact uterus). The different types of MHT are usually administered orally or transdermally (as creams or patches). Topical vaginal preparations are used only to treat local vaginal symptoms and are minimally absorbed systemically.
How do study participants want to be informed about study results: Findings from a malaria trial in Cambodia, Ethiopia, Pakistan, and Indonesia.
BACKGROUND: Researchers acknowledge the need to share study results with the patients and their communities, but this is not done consistently due to a plethora of barriers, including a paucity of data to guide best practice approaches in different populations. METHODS: This study was nested within a large multi-center randomized controlled trial of antimalaria treatment. Data on dissemination preferences were collected at the third-month follow-up visit using a short questionnaire. Data were analyzed using descriptive statistics and subsequently fed into an iterative process with key stakeholders, to develop suitable strategies for result dissemination. RESULTS: A total of 960 patients were enrolled in the trial, of whom 84.0% participated in the nested survey. A total of 601 (74.6%) participants indicated interest in receiving trial results. There was significant heterogeneity by study country, with 33.3% (58/174) of patients indicating being interested in Cambodia, 100% (334/334) in Ethiopia, 97.7% (209/214) in Pakistan, but none (0/85) in Indonesia. The preferred method of dissemination varied by site, with community meetings, favored in Ethiopia (79.0%, 264/334) and individualized communication such as a letter (27.6%, 16/58) or phone calls (37.9%, 22/58) in Cambodia. Dissemination strategies were designed with key stakeholders and based on patient preferences but required adaptation to accommodate local logistical challenges. CONCLUSION: The varying preferences observed across different sites underscore that a one-size-fits-all approach is inadequate. Strategies can be tailored to patient preference but require adaptation to accommodate logistical challenges.
Molnupiravir or nirmatrelvir-ritonavir plus usual care versus usual care alone in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.
BACKGROUND: Molnupiravir and nirmatrelvir-ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce. METHODS: The RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19. In this study we report the molnupiravir and nirmatrelvir-ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia; the nirmatrelvir-ritonavir comparison was conducted at 32 hospitals in the UK. Participants could take part in both comparisons. The primary outcome was 28-day mortality, and secondary outcomes were time to discharge alive from hospital and progression to invasive ventilation or death. Analysis was by intention to treat. Both comparisons were stopped because of low recruitment. This study is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. FINDINGS: From Jan 24, 2022, to May 24, 2023, 923 participants were recruited to the molnupiravir comparison (445 allocated to molnupiravir and 478 to usual care), and from March 31, 2022, to May 24, 2023, 137 participants were recruited to the nirmatrelvir-ritonavir comparison (68 allocated to nirmatrelvir-ritonavir and 69 to usual care). More than three-quarters of participants were vaccinated and had antispike antibodies at randomisation, and more than two-thirds were receiving other SARS-CoV-2 antivirals. In the molnupiravir comparison, 74 (17%) participants allocated to molnupiravir and 79 (17%) allocated to usual care died within 28 days (hazard ratio [HR] 0·93 [95% CI 0·68-1·28], p=0·66). In the nirmatrelvir-ritonavir comparison, 13 (19%) participants allocated to nirmatrelvir-ritonavir and 13 (19%) allocated to usual care died within 28 days (HR 1·02 [0·47-2·23], p=0·96). In neither comparison was there evidence of any difference in the duration of hospitalisation or the proportion of participants progressing to invasive ventilation or death. INTERPRETATION: Adding molnupiravir or nirmatrelvir-ritonavir to usual care was not associated with improvements in clinical outcomes. However, low recruitment meant a clinically meaningful benefit of treatment could not be ruled out, particularly for nirmatrelvir-ritonavir. FUNDING: UK Research and Innovation (UK Medical Research Council), the National Institute for Health and Care Research, and the Wellcome Trust.
Transforming health in Nepal: a historical and contemporary review on disease burden, health system challenges, and innovations
Introduction: Nepal witnessed a tumultuous journey over past two centuries, marked by significant political, social, and cultural shifts. From fighting British colonial encroachments in 1800s, the dynastic Rana regime (1846–1951), and democracy movements in the late 1950s, 1990s and 2000s, Nepal became a federal republic in 2008. The main objective of this review is to lay out an interpretative summary on Nepal’s epidemiological transition (includes general trends and disease specific topics) followed by discussion on health system development over key periods: historical period (–1950s), modern period (1950–1990), post-democracy (1991–2016), and post-federalization (2016–). Methods: We conducted a scoping review of available literature using the Arksey and O’Malley framework to synthesize the key insights. Searches were performed in PubMed (via NLM), Embase and Google Scholar using a combination of search terms related to Nepal’s health system, epidemiological transition, disease burden and emerging health issues. A total of 1204 records were identified, of which 123 documents – including peer-reviewed articles, government reports and grey literature – met the inclusion criteria. Results: Major advances in maternal and child health, nutritional health and reduction of infectious diseases have been observed in recent decades. The maternal mortality ratio (MMR) declined by 55% (1996–2016), and neonatal mortality halved (40 to 20 per 1000 live births) due to improved antenatal care, skilled birth attendance and family planning. Stunting rates fell from 66% (1996) to 25% (2022), yet rising non-communicable diseases (NCDs) pose new challenges. Communicable diseases, once dominant, have declined owing to expanded immunization and tuberculosis control. However, NCDs now account for over two thirds of deaths, driven by urbanization, ageing and lifestyle shifts. Health system gaps persist, with workforce shortages, rural–urban disparities and out-of-pocket health costs limiting access. Addressing rising health inequities, digital health innovations and service expansion is critical to achieving universal health coverage and sustaining Nepal’s health gains. Conclusions: Nepal’s health care landscape has continuously evolved over the past centuries, coinciding with key demographic and political changes. Advances through innovation are necessary for the country’s overstretched health system to reduce the cost of health services whilst increasing quality and access.
Acceptability and feasibility of glucose-6-phosphate dehydrogenase (G6PD) testing using SD Biosensor by village malaria workers in Cambodia: a qualitative study.
INTRODUCTION: Plasmodium vivax is the predominant cause of malaria in the Greater Mekong Subregion. To ensure safe treatment with primaquine, point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing was rolled out in Cambodia at the health facility level, although most malaria patients are diagnosed in the community. The current study aims to explore the acceptability and feasibility of implementing community-level G6PD testing in Cambodia. METHODS: Semistructured interviews and focus group discussions (FGD) were conducted. Across eight study sites in three provinces, 142 respondents, including policymakers, programme officers, healthcare providers and patients, participated in 67 interviews and 19 FGDs in 2022 and 2023. Data were analysed thematically using an adapted framework derived from Bowen et al's feasibility framework and Sekhon et al's acceptability framework. RESULTS: All stakeholders attributed value to the intervention. Acknowledging an intervention's different values can help discern policy implications for an intervention's successful implementation. Building and maintaining confidence in the device, end users, infrastructure and health systems were found to be key elements of acceptability. In general, health centre workers and village malaria workers (VMWs) had confidence that VMWs could conduct the test and administer treatment given appropriate initial training, monthly refresher training and the test's repeated use. More is required to build policymakers' confidence, while some implementation challenges, including the test's regulatory approval, stability above 30°C and cost, need to be overcome. CONCLUSION: Implementation of G6PD testing at the community level in Cambodia is an acceptable and potentially feasible option but requires addressing implementation challenges and building and maintaining confidence among stakeholders.
Why should we be concerned by internalised racism in global health?
Internalised racism constitutes an adoption of beliefs about one's inferiority, weaknesses or shortcomings as a function of racial hierarchy affecting one's identity and self-worth, thoughts, emotions and behaviours. Internalised racism stems from widely known and discussed institutional racial discrimination, which perpetuates epistemic injustice, social injustice and health inequities in global health. In this article, reflecting on our experiential knowledge from working on global health, we engage with relevant literature to (1) highlight the concepts associated with internalised racism, (2) explore the potential impacts of internalised racism on individuals, organisations and global health and (3) propose strategies to redress and mitigate its impact on global health practice.
Piloting the options assessment toolkit with national malaria programme leaders from the Asia-Pacific countries: a meeting report.
Plasmodium vivax malaria remains a major challenge in the Asia-Pacific region, where National Malaria Programmes (NMPs) will need to determine optimal radical cure strategies given the availability of novel options, such as high-dose primaquine and tafenoquine. The Options Assessment Toolkit (OAT) was developed to assist NMPs to make decisions on the optimal combination of G6PD testing and radical cure drug regimen. This study reports on the piloting of OAT with NMP representatives during the APMEN Vivax Working Group Annual Meeting in December 2022. A total of 23 NMP representatives from 13 Asia-Pacific countries participated in facilitated discussions. Thematic analysis of qualitative data revealed that NMPs found the OAT useful and timely for structuring malaria policy discussions. However, concerns were raised regarding mismatches between OAT-generated scenarios and country-specific contexts, the inclusion of political and economic factors, and the feasibility of implementing expert-suggested options. Many NMPs expressed enthusiasm for single-dose tafenoquine, but preferred to await WHO recommendations before considering policy changes. Overall, the OAT was well received as a tool for initiating policy discussions on P. vivax radical cure. The OAT represents an important step toward accelerating evidence-based policy change in malaria-endemic countries, with further refinements enhancing its utility.
Co-design of a routine clinical review to improve the safety of high dose radical cure treatment for Plasmodium vivax malaria: findings from Cambodia and Ethiopia.
BACKGROUND: Low dose primaquine regimens are widely used to treat Plasmodium vivax malaria, but they have limited efficacy and effectiveness. Short courses with higher daily doses as well as single dose tafenoquine have the potential to improve effectiveness but can increase the risk of adverse events. A clinical review visit on day 3 post-treatment initiation could facilitate adherence and improve safety, but it is unclear how it could be integrated into routine malaria care. METHODS: Between March and September 2023, focus group discussions (FGDs) with P. vivax malaria patients and healthcare providers were conducted in Cambodia and Ethiopia. In the FGDs participants co-designed a day 3 review suitable for their setting based on material infrastructure 'building blocks' (location, implementer, procedures, and support mechanisms). Nine FGDs were completed in three health facility catchment areas in Cambodia and six FGDs in four facilities in Ethiopia. Data were analysed using an inductive-deductive analytical process allowing the development of themes. RESULTS: Participants in Cambodia and Ethiopia had different preferences for the material infrastructure of the day 3 review, from which a model for each country was developed. In Cambodia, proximity to patients was prioritized, maintaining the existing referral mechanism in which the initial day 3 review is conducted in the community, focusing on an enhanced symptom assessment. In Ethiopia, continuity of care was prioritized, resulting in the day 3 review occurring at the location of initial diagnosis, with a tiered approach to procedures conducted during the visit. In addition, the dynamics and relationships between people (relational infrastructure), specifically collaboration, were identified as key facilitators for the review's implementation in both study countries. Collaboration across levels of the health system and among healthcare providers was found to be a process influenced and necessitated by the environment (e.g., the infrastructural and epidemiological contexts), contributing to quality of care, continuity of care, safety, and effective treatment. CONCLUSION: Identifying how clinical review visits could be adapted to local settings is important and can be achieved through co-creation. Collaboration has the potential to enable quality of care and patient safety. Suitable ways of reinforcing this relational infrastructure are required to optimize case management of patients.
After the disruptive innovation: How remote and digital services were embedded, blended and abandoned in UK general practice - longitudinal study.
BACKGROUND: United Kingdom general practices transitioned rapidly to remote-by-default services in 2020 and subsequently considered whether and how to continue these practices. Their diverse responses provided a unique opportunity to study the longer-term embedding, adaptation and abandonment of digital innovations. Research questions: What was the range of responses to the expansion of remote and digital triage and consultations among United Kingdom general practices in the period following the acute phase of the coronavirus disease discovered in 2019 (COVID-19) pandemic? What can we learn from this example about the long-term impacts of crisis-driven sociotechnical change in healthcare settings? METHODS: We collected longitudinal data from 12 general practices from 2021 to 2023, comprising 500 hours of ethnographic observation, 163 interviews in participating practices and linked organisations (132 staff, 31 patients), 39 stakeholder interviews and 4 multi-stakeholder workshops (210 participants), with additional patient and public involvement input. Data were de-identified, uploaded to NVivo (QSR International, Warrington, UK) and synthesised into case studies, drawing on theories of organisational innovation. RESULTS: General practices' longitudinal progress varied, from a near-total return to traditional in-person services to extensive continuing use of novel digital technologies and pathways. Their efforts to find the right balance were shaped and constrained by numerous contextual factors. Large size, slack resources, high absorptive capacity, strong leadership and good intrapractice relationships favoured innovation. Readiness for remote and digital modalities varied depending on local tension for change, practice values and patient characteristics. Technologies' uptake and use were influenced by their material properties and functionality. Embedding and sustaining technologies required ongoing work to adapt and refine tasks and processes and adjust (or, where appropriate, selectively abandon) technologies. Adoption and embedding of technologies were affected by various staff and patient factors. When technologies fitted poorly with tasks and routines or when embedding efforts were unsuccessful, inefficiencies and 'techno-stress' resulted, with compromises to patient access and quality of care. LIMITATIONS: Sampling frame was limited to United Kingdom and patient interviews were relatively sparse. CONCLUSION: There is wide variation in digital maturity among United Kingdom general practices. Low use of remote and digital technologies and processes may be warranted and reflect local strategic choices, but it may also indicate lack of awareness and a reactive rather than strategic approach to digital innovation. We offer an updated typology of digital maturity in general practice with suggestions for tailored support. FUTURE WORK: The typology of digital maturity could be applied further to identify in more detail the kind of support needed for practices that are at different stages of maturity and are serving different populations. The need for strategically traditional practices in deprived settings should also be explored. FUNDING: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132807.