Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data.

OBJECTIVE: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice. DESIGN: Cohort study emulating a comparative effectiveness trial (target trial). SETTING: Linked primary care, hospital, and death data in England, 2015-21. PARTICIPANTS: 75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin. MAIN OUTCOME MEASURES: Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures. RESULTS: 75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43). CONCLUSIONS: This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.

Adapting Patient and Public Involvement processes in response to the Covid-19 pandemic.

BACKGROUND: The COVID-19 pandemic brought rapid and major changes to research, and those wishing to carry out Patient and Public Involvement (PPI) activities faced challenges, such as restrictions on movement and contact, illness, bereavement and risks to potential participants. Some researchers moved PPI to online settings during this time but remote consultations raise, as well as address, a number of challenges. It is important to learn from PPI undertaken in this period as face-to-face consultation may no longer be the dominant method for PPI. METHODS: UK stay-at-home measures announced in March 2020 necessitated immediate revisions to the intended face-to-face methods of PPI consultation for the ESORT Study, which evaluated emergency surgery for patients with common acute conditions. PPI plans and methods were modified to all components being online. We describe and reflect on: initial plans and adaptation; recruitment; training and preparation; implementation, contextualisation and interpretation. Through first-hand accounts we show how the PPI processes were developed, experienced and viewed by different partners in the process. DISCUSSION AND CONCLUSIONS: While concerns have been expressed about the possible limiting effects of forgoing face-to-face contact with PPI partners, we found important benefits from the altered dynamic of the online PPI environment. There were increased opportunities for participation which might encourage the involvement of a broader demographic, and unexpected benefits in that the online platform seemed to have a 'democratising' effect on the meetings, to the benefit of the PPI processes and outcomes. Other studies may however find that their particular research context raises particular challenges for the use of online methods, especially in relation to representation and inclusion, as new barriers to participation may be raised. It is important that methodological challenges are addressed, and researchers provide detailed examples of novel methods for discussion and empirical study. PATIENT AND PUBLIC CONTRIBUTION: We report a process which involved people with lived experience of emergency conditions and members of the public. A patient member was involved in the design and implementation, and two patients with lived experience contributed to the manuscript.

Ethnic and socioeconomic disparities in initiation of second-line antidiabetic treatment for people with type 2 diabetes in England: A cross-sectional study.

AIMS: To assess any disparities in the initiation of second-line antidiabetic treatments prescribed among people with type 2 diabetes mellitus (T2DM) in England according to ethnicity and social deprivation level. MATERIALS AND METHODS: This cross-sectional study used linked primary (Clinical Practice Research Datalink) and secondary care data (Hospital Episode Statistics), and the Index of Multiple Deprivation (IMD). We included people aged 18 years or older with T2DM who intensified to second-line oral antidiabetic medication between 2014 and 2020 to investigate disparities in second-line antidiabetic treatment prescribing (one of sulphonylureas [SUs], dipeptidyl peptidase-4 [DPP-4] inhibitors, or sodium-glucose cotransporter-2 [SGLT2] inhibitors, in combination with metformin) by ethnicity (White, South Asian, Black, mixed/other) and deprivation level (IMD quintiles). We report prescriptions of the alternative treatments by ethnicity and deprivation level according to predicted percentages derived from multivariable, multinomial logistic regression. RESULTS: Among 36 023 people, 85% were White, 10% South Asian, 4% Black and 1% mixed/other. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by ethnicity were 21% (95% confidence interval [CI] 19-23%), 20% (95% CI 18-22%), 19% (95% CI 16-22%) and 17% (95% CI 14-21%) among people with White, South Asian, Black, and mixed/other ethnicity, respectively. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by deprivation were 22% (95% CI 20-25%) and 19% (95% CI 17-21%) for the least deprived and the most deprived quintile, respectively. When stratifying by prevalent cardiovascular disease (CVD) status, we found lower predicted percentages of people with prevalent CVD prescribed SGLT2 inhibitors compared with people without prevalent CVD across all ethnicity groups and all levels of social deprivation. CONCLUSIONS: Among people with T2DM, there were no substantial differences by ethnicity or deprivation level in the percentage prescribed either SGLT2 inhibitors, DPP-4 inhibitors or SUs as second-line antidiabetic treatment.

The changing paradigm of research delivery during a pandemic - a reflective account.

BACKGROUND: As clinical pressures evolved amid the COVID-19 pandemic, the importance of research activity came to the forefront of health and care service requirements. AIM: To illustrate through reflection the experiences of clinical research teams based in the UK during the pandemic. DISCUSSION: The article describes operational experiences in different settings and reflects on important themes and implications for future practice. The authors use a reflective model to share perspectives of leading research delivery roles in geographically and organisationally different settings. A patient's perspective was included from the outset of the reflective process. Delegates at an interactive masterclass conference in April 2021 also contributed their experiences. Seven themes characterise the research teams' response to the pandemic: prioritising, team-building, protection, limitation of autonomy, reduced bureaucracy, collaboration and transformation of process. Balance through compassionate leadership underpinned by ethically grounded decision-making was a theme throughout. CONCLUSION: Implicitly held, tacit knowledge progressed to explicit knowledge, formalising the research teams' responses to the pandemic partly into codified learning. The authors characterise the experience as an 'operational balancing act', whereby significant innovations were integrated into working practices and research delivery. IMPLICATIONS FOR PRACTICE: The pandemic demonstrated what research progress is possible when all resources are diverted to one novel virus. The value of research teams was elevated through treatment and vaccine trials and the contribution of those involved to patient care. This reinforces an invigorated commitment to resources as well as new acceptance of and belief in research as a core care activity across and throughout systems and organisations at all levels.

Prescription practices for rigid ankle-foot orthoses among UK orthotists.

OBJECTIVE: The purpose of this study was to investigate rigid ankle-foot orthosis (AFO) prescription practices for adult men among UK orthotists. DESIGN: A cross-sectional study using a survey was distributed online to UK orthotists by the British Association of Prosthetists and Orthotists to its members and through social media and orthotic networks. The survey was completed between November 1, 2020, and November 29, 2020. MAIN OUTCOME MEASURES: Descriptive statistics of survey results include information related to the material used, the thickness of the material, positive cast rectification, AFO reinforcement, footplate design, padding, strapping system, and height of AFO. RESULTS: One hundred participants completed the survey, which equates to a response rate of 30.5% of the British Association of Prosthetists and Orthotists members targeted. A clear consensus emerged on the design of a bespoke rigid AFO for the hypothetical patient in this study, which is detailed as follows: 1) 4.5 mm copolymer polypropylene, 2) no additional reinforcement, 3) full-length footplate with mediolateral trimlines terminating behind the metatarsal heads, 4) 3-point correction with parallel sides, 5) padded VELCRO straps with D-rings at the calf and heel, 6) no forefoot or other additional strapping, 7) 3-mm PORON (international Ltd) padding at the malleoli, and 8) AFO height that finishes 2 cm below the fibular head. CONCLUSIONS: This study has highlighted a consensus on AFO prescription/design among UK orthotists surveyed, based on the hypothetical patient described in this study.

Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study.

INTRODUCTION: For people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of long-term complications compared with sulfonylureas (SU). There is widespread variation across National Health Service Clinical Commissioning Groups (CCGs) in drug choice for second-line treatment in part because National Institute for Health and Care Excellence guidelines do not specify a single preferred drug class, either overall or within specific patient subgroups. This study will evaluate the relative effectiveness of the three most common second-line treatments in the UK (SU, DPP4i and SGLT2i as add-ons to metformin) and help target treatments according to individual risk profiles. METHODS AND ANALYSIS: The study includes people with T2DM prescribed one of the second-line treatments-of-interest between 2014 and 2020 within the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics and Office of National Statistics. We will use an instrumental variable (IV) method to estimate short-term and long-term relative effectiveness of second-line treatments according to individuals' risk profiles. This method minimises bias from unmeasured confounders by exploiting the natural variation in second-line prescribing across CCGs as an IV for the choice of prescribed treatment. The primary outcome to assess short-term effectiveness will be change in haemoglobin A1c (%) 12 months after treatment initiation. Outcome measures to assess longer-term effectiveness (maximum ~6 years) will include microvascular and macrovascular complications, all-cause mortality and hospital admissions during follow-up. ETHICS AND DISSEMINATION: This study was approved by the Independent Scientific Advisory Committee (20-064) and the London School of Hygiene & Tropical Medicine Research Ethics Committee (21395). Results, codelists and other analysis code will be made available to patients, clinicians, policy-makers and researchers.

Clinical Implications of Climate Change on US Emergency Medicine: Challenges and Opportunities.

The adverse influences of climate change are manifesting as health burdens relevant to clinical practice, affecting the very underpinnings of health and stressing the health care system. Emergency medicine is likely to bear a large burden, with its focus on urgent and emergency care, through its role as a safety-net provider for vulnerable populations and as a leader in disaster medicine. Clinically, climate change is affecting emergency medicine practice through the amplification of climate-related disease patterns and epidemiologic shifts for conditions diagnosed and treated in emergency departments (EDs), especially for vulnerable populations. In addition, climate-driven intensification of extreme weather is disrupting health care delivery in EDs and health care systems. Thus, there are significant opportunities for emergency medicine to lead the medical response to climate change through 7 key areas: clinical practice improvements, building resilient EDs and health care systems, adaptation and public health engagement, disaster preparedness, mitigation, research, and education. In the face of this growing health threat, systemwide preparation rooted in local leadership and responsiveness is necessary to efficiently and effectively care for our vulnerable communities.

The design of a medical school social justice curriculum.

The acquisition of skills to recognize and redress adverse social determinants of disease is an important component of undergraduate medical education. In this article, the authors justify and define "social justice curriculum" and then describe the medical school social justice curriculum designed by the multidisciplinary Social Justice Vertical Integration Group (SJVIG) at the Geisel School of Medicine at Dartmouth. The SJVIG addressed five goals: (1) to define core competencies in social justice education, (2) to identify key topics that a social justice curriculum should cover, (3) to assess social justice curricula at other institutions, (4) to catalog institutionally affiliated community outreach sites at which teaching could be paired with hands-on service work, and (5) to provide examples of the integration of social justice teaching into the core (i.e., basic science) curriculum. The SJVIG felt a social justice curriculum should cover the scope of health disparities, reasons to address health disparities, and means of addressing these disparities. The group recommended competency-based student evaluations and advocated assessing the impact of medical students' social justice work on communities. The group identified the use of class discussion of physicians' obligation to participate in social justice work as an educational tool, and they emphasized the importance of a mandatory, longitudinal, immersive, mentored community outreach practicum. Faculty and administrators are implementing these changes as part of an overall curriculum redesign (2012-2015). A well-designed medical school social justice curriculum should improve student recognition and rectification of adverse social determinants of disease.

Neurology and orthopaedics.

Neurology encompasses all aspects of medicine and surgery, but is closer to orthopaedic surgery than many other specialities. Both neurological deficits and bone disorders lead to locomotor system abnormalities, joint complications and limb problems. The main neurological conditions that require the attention of an orthopaedic surgeon are disorders that affect the lower motor neurones. The most common disorders in this group include neuromuscular disorders and traumatic peripheral nerve lesions. Upper motor neurone disorders such as cerebral palsy and stroke are also frequently seen and discussed, as are chronic conditions such as poliomyelitis. The management of these neurological problems is often coordinated in the neurology clinic, and this group, probably more than any other, requires a multidisciplinary team approach.