Recent Submissions

  • Ethnicity and outcomes for patients with gastrointestinal disorders attending an emergency department serving a multi-ethnic population

    Abeyratne, Ruw; Brunskill, Nigel; Coats, Tim; Martin, Christopher A; Pareek, Manish (2024-07-02)
    Background: Ethnic inequalities in acute health acute care are not well researched. We examined how attendee ethnicity influenced outcomes of emergency care in unselected patients presenting with a gastrointestinal (GI) disorder. Methods: A descriptive, retrospective cohort analysis of anonymised patient level data for University Hospitals of Leicester emergency department attendees, from 1 January 2018 to 31 December 2021, receiving a diagnosis of a GI disorder was performed. The primary exposure of interest was self-reported ethnicity, and the two outcomes studied were admission to hospital and whether patients underwent clinical investigations. Confounding variables including sex and age, deprivation index and illness acuity were adjusted for in the analysis. Chi-squared and Kruskal-Wallis tests were used to examine ethnic differences across outcome measures and covariates. Multivariable logistic regression was used to examine associations between ethnicity and outcome measures. Results: Of 34,337 individuals, median age 43 years, identified as attending the ED with a GI disorder, 68.6% were White. Minority ethnic patients were significantly younger than White patients. Multiple emergency department attendance rates were similar for all ethnicities (overall 18.3%). White patients had the highest median number of investigations (6, IQR 3-7), whereas those from mixed ethnic groups had the lowest (2, IQR 0-6). After adjustment for age, sex, year of attendance, index of multiple deprivation and illness acuity, all ethnic minority groups remained significantly less likely to be investigated for their presenting illness compared to White patients (Asian: aOR 0.80, 95% CI 0.74-0.87; Black: 0.67, 95% CI 0.58-0.79; mixed: 0.71, 95% CI 0.59-0.86; other: 0.79, 95% CI 0.67-0.93; p < 0.0001 for all). Similarly, after adjustment, minority ethnic attendees were also significantly less likely to be admitted to hospital (Asian: aOR 0.63, 95% CI 0.60-0.67; Black: 0.60, 95% CI 0.54-0.68; mixed: 0.60, 95% CI 0.51-0.71; other: 0.61, 95% CI 0.54-0.69; p < 0.0001 for all). Conclusions: Significant differences in usage patterns and disparities in acute care outcomes for patients of different ethnicities with GI disorders were observed in this study. These differences persisted after adjustment both for confounders and for measures of deprivation and illness acuity and indicate that minority ethnic individuals are less likely to be investigated or admitted to hospital than White patients.
  • Management of a giant adrenal schwannoma

    Dales, Jolyon; Levy, Miles; Shah, Vikas (2024-07-05)
    In this case report, we present a man in his 60s who presented with an incidentally discovered right adrenal mass, which turned out to be an adrenal schwannoma. This is a very rare tumour that originates from Schwann cells and involves the peripheral nerves. The tumour was removed by open adrenalectomy, and this 15-cm adrenal schwannoma is one of the largest reported in the literature, with none >16 cm having ever been reported. This case highlights the importance of keeping an open mind about the cause of an incidentally discovered adrenal mass, which is an increasingly common way for adrenal tumours to present given the increased access to cross-sectional imaging. As well as presenting the case and the pathological basis behind adrenal schwannomas, we include a review of the literature and a general discussion about incidentally discovered adrenal masses.
  • Quantifying the effect of vaccination on transmission in modelling studies

    Nazareth, Joshua; Pan, Daniel; Pareek, Manish (2024-06-06)
  • Diabetic foot disease carries an intrinsic high risk of mortality and other severe outcomes in type 2 diabetes: a propensity score-matched retrospective population-based study

    Zaccardi, Francesco (2024-06-19)
    Background: To evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings. Methods: We built a cohort of people with a first DFD episode during 2010-2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events. Results: Overall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7-22.6, HR: 15.1, 95% CI: 13.8-16.5, respectively) was found. Conclusions: Although DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis.
  • Management of adults with bacterial meningitis in the Emergency Department

    Asemoto, Joshua; Marathe, Mandar (2024-06-20)
    Introduction: The Leicester Royal Infirmary Emergency Department is one of the largest single-site Emergency Departments in the UK. We evaluated the department's management of bacterial meningitis. The current national guideline recommends that all patients presenting with suspected bacterial meningitis receive antibiotics within one hour. Methods: A survey of 100 clinicians (Consultants, Registrars, House Officers, and Advanced Clinical Practitioners) working in the Emergency Department was performed to determine the awareness of the guidelines and a retrospective examination of case notes for patients who presented at the Leicester Royal Infirmary Emergency Department with suspected meningitis was carried out between May 1, 2022, and May 1, 2023. A random sample of 30 patients was drawn from the department's database of 190 patients, identified through discharge coding summaries. Results: Nine (25%) of the prescribers knew of the guidelines for managing meningitis, and six (16.7%) had utilised the hospital guidelines. Thirty-three (91.7%) prescribers acknowledged the importance of administering steroids to patients suspected of having bacterial meningitis (excluding those displaying signs of meningococcal sepsis, such as a rash). However, only seven (23%) of patients received this treatment. Additionally, only one (3.3%) patient was documented as having received a dose within the first hour of presentation. Conclusion: The timely diagnosis and administration of appropriate antibiotic therapy are pivotal elements in managing bacterial meningitis. As a result, we designed a checklist to facilitate the effective management of meningitis within the department by increasing awareness of the guidelines and making the critical principles of suspected meningitis management more accessible.
  • Inclusion of racial and ethnic groups in clinical trials for COVID-19 and post-acute COVID-19 syndrome: an analysis of studies registered on ClinicalTrials.gov

    Appleby, Ben E; Bird, Paul; Chaka, Aasiya; Divall, Pip; Nazareth, Joshua; Pan, Daniel; Pareek, Manish; Sze, Shirley (2024-06-20)
  • Epidemiology and management of pediatric group A streptococcal pneumonia with parapneumonic effusion: an observational study

    Bandi, Srini (2024-06-19)
    Background: During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. Methods: Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. Results: From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. Conclusions: Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.
  • Global analysis of RTS, S/AS01 malaria vaccine acceptance rates and influencing factors: A systematic review

    Rauf, Shiza (2024-05-20)
    Malaria remains a significant global health challenge, with Plasmodium parasites transmitted by Anopheles mosquitoes causing substantial morbidity and mortality. Despite historical efforts, malaria continues to affect millions worldwide, particularly in tropical regions. This systematic review aimed to assess the acceptability of the RTS, S/AS01 malaria vaccine among diverse populations. A comprehensive search strategy was employed across databases such as Cochrane Library, Embase, Google Scholar, and Medline. Studies were included based on specific criteria, including observational and cross-sectional designs involving adults. Data extraction and analysis were conducted meticulously, encompassing key variables related to vaccine acceptance rates and influencing factors. Analysis of 18 studies involving 18,561 participants revealed an overall malaria vaccine acceptance rate of 87.51%, ranging from 32.26% to 99.30%. Significant variations were observed based on demographics, with Ghana and Nigeria reporting high acceptance rates. Factors influencing acceptance included knowledge levels, past vaccination experiences, community preferences, and engagement in malaria prevention behaviors. Concerns about adverse reactions and regional disparities were noted as potential barriers to acceptance. This review highlights the importance of understanding public perceptions and concerns regarding malaria vaccines to enhance vaccine coverage and uptake. Tailored communication strategies, advocacy efforts, and targeted education interventions are crucial for addressing misconceptions and increasing vaccine acceptance. Policy recommendations should consider demographic and regional factors to ensure effective implementation of malaria vaccination programs, ultimately contributing to global malaria prevention efforts and public health initiatives.
  • Volume loss in the left anterior-superior subunit of the hypothalamus in amyotrophic lateral sclerosis

    Fatehi, Farzad
    Background and objective: Amyotrophic lateral sclerosis (ALS) causes motor neuron loss and progressive paralysis. While traditionally viewed as motor neuron disease (MND), ALS also affects non-motor regions, such as the hypothalamus. This study aimed to quantify the hypothalamic subregion volumes in patients with ALS versus healthy controls (HCs) and examine their associations with demographic and clinical features. Methods: Forty-eight participants (24 ALS patients and 24 HCs) underwent structural MRI. A deep convolutional neural network was used for the automated segmentation of the hypothalamic subunits, including the anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tuberal (supTub), inferior tuberal (infTub), and posterior (posHyp). The neural network was validated using FreeSurfer v7.4.1, with individual head size variations normalized using total intracranial volume (TIV) normalization. Statistical analyses were performed for comparisons using independent sample t-tests. Correlations were calculated using Pearson's and Spearman's tests (p < 0.05). The standard mean difference (SMD) was used to compare the mean differences between parametric variables. Results: The volume of the left a-sHyp hypothalamic subunit was significantly lower in ALS patients than in HCs (p = 0.023, SMD = -0.681). No significant correlation was found between the volume of the hypothalamic subunits, body mass index (BMI), and ALSFRS-R in patients with ALS. However, right a-sHyp (r = 0.420, p = 0.041) was correlated with disease duration, whereas right supTub (r = -0.471, p = 0.020) and left postHyp (r = -0.406, p = 0.049) were negatively correlated with age. There was no significant difference in the volume of hypothalamic subunits between males and females, and no significant difference was found between patients with revised ALS Functional Rating Scale (ALSFRS-R) scores ≤41 and >41 and those with a disease duration of 9 months or less. Discussion and conclusion: The main finding suggests atrophy of the left a-sHyp hypothalamic subunit in patients with ALS, which is supported by previous research as an extra-motor neuroimaging finding for ALS.
  • Determinants of the dynamic cerebral critical closing pressure response to changes in mean arterial pressure

    Beishon, Lucy; Katsogridakis, Emmanuel; Minhas, Jatinder (2024-06-14)
    Objective. Cerebral critical closing pressure (CrCP) represents the value of arterial blood pressure (BP) where cerebral blood flow (CBF) becomes zero. Its dynamic response to a step change in mean BP (MAP) has been shown to reflect CBF autoregulation, but robust methods for its estimation are lacking. We aim to improve the quality of estimates of the CrCP dynamic response.Approach. Retrospective analysis of 437 healthy subjects (aged 18-87 years, 218 males) baseline recordings with measurements of cerebral blood velocity in the middle cerebral artery (MCAv, transcranial Doppler), non-invasive arterial BP (Finometer) and end-tidal CO2(EtCO2, capnography). For each cardiac cycle CrCP was estimated from the instantaneous MCAv-BP relationship. Transfer function analysis of the MAP and MCAv (MAP-MCAv) and CrCP (MAP-CrCP) allowed estimation of the corresponding step responses (SR) to changes in MAP, with the output in MCAv (SRVMCAv) representing the autoregulation index (ARI), ranging from 0 to 9. Four main parameters were considered as potential determinants of the SRVCrCPtemporal pattern, including the coherence function, MAP spectral power and the reconstruction error for SRVMAP, from the other three separate SRs.Main results. The reconstruction error for SRVMAPwas the main determinant of SRVCrCPsignal quality, by removing the largest number of outliers (Grubbs test) compared to the other three parameters. SRVCrCPshowed highly significant (p< 0.001) changes with time, but its amplitude or temporal pattern was not influenced by sex or age. The main physiological determinants of SRVCrCPwere the ARI and the mean CrCP for the entire 5 min baseline period. The early phase (2-3 s) of SRVCrCPresponse was influenced by heart rate whereas the late phase (10-14 s) was influenced by diastolic BP.Significance. These results should allow better planning and quality of future research and clinical trials of novel metrics of CBF regulation.
  • The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement

    Spear, J (2024-07)
    Objectives: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. Study design: This was a modified Delphi process. Methods: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. Results: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. Conclusions: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.
  • Differential associations of risk factors with severe and non-severe hypoglycaemia: the Hypoglycaemia Assessment Tool prospective observational study in people with insulin-treated type 1 diabetes and type 2 diabetes

    Choudhary, Pratik; Zaccardi, Francesco (2024-06-03)
    Aim: To assess the differential association of risk factors with severe and non-severe hypoglycaemia. Materials and methods: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia. Results: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen. Conclusions: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other.
  • Exercise as an anti-inflammatory Therapy in Axial Spondyloarthritis Therapeutic Intervention (EXTASI) study: a randomized controlled trial

    Moorthy, Arumugam (2024-05-11)
    Objectives: Axial SpA (axSpA) is a chronic inflammatory disease, yet despite known anti-inflammatory effects of exercise, the effect of exercise on inflammatory immune cell populations and associated inflammatory profiles in axSpA is unknown. This randomized controlled trial investigated the effect of 12 weeks of walking on symptom severity, cardiometabolic health, inflammatory biomarkers and immune cell populations. Methods: Twenty people (60% male) living with axSpA who were on a stable dose of NSAIDs participated. Participants were randomly assigned to control or exercise (30 min of walking five times per week). Participants were invited back every 4 weeks for assessment. Results: There was a 0% dropout rate and no adverse events in the exercise group, showing walking exercise was well tolerated. Home-based walking for 12 weeks lowered the proportion of pro-inflammatory monocytes, whereas they increased in the control group. Changes were associated with lower IL-6 and CRP concentrations, lower spinal pain and lower systolic blood pressure in the exercise group, whereas these markers increased in the control group. Reductions in IL-6 and pro-inflammatory monocytes with exercise were independent of lower body fat percentage. Conclusions: Supplementing NSAID therapy with walking exercise can improve inflammatory immune profiles in people with axSpA, coinciding with reductions in spinal pain. Importantly, the exercise was well tolerated, suggesting walking exercise can be used as an adjuvant anti-inflammatory therapy for NSAID treatments. This should now be explored in people living with axSpA who have had high enough disease activity to necessitate the prescription of biologic or synthetic DMARD treatments.
  • Depression of dynamic cerebral autoregulation during neural activation: The role of responders and non-responders

    Beishon, Lucy; Robinson, Thompson G (2024-07)
    Neurovascular coupling (NVC) interaction with dynamic cerebral autoregulation (dCA) remains unclear. We investigated the effect of task complexity and duration on the interaction with dCA. Sixteen healthy participants (31.6 ± 11.6 years) performed verbal fluency (naming-words (NW)) and serial subtraction (SS) paradigms, of varying complexity, at durations of 05, 30 and 60 s. The autoregulation index (ARI), was estimated from the bilateral middle cerebral artery blood velocity (MCAv) step response, calculated by transfer function analysis (TFA), for each paradigm during unstimulated (2 min) and neuroactivated (1 min) segments. Intraclass correlation (ICC) and coefficient of variation (CV) determined reproducibility for two visits and objective criteria were applied to classify responders (R) and non-responders (NoR) to task-induced MCAv increase. ICC values demonstrated fair reproducibility in all tasks. ARI decreased in right (RH) and left (LH) hemispheres, irrespective of paradigm complexity and duration (p < 0.0001). Bilateral ARI estimates were significantly decreased during NW for the R group only (p < 0.0001) but were reduced in both R (p < 0.0001) and NoR (p = 0.03) groups for SS tasks compared with baseline. The reproducible attenuation of dCA efficiency due to paradigm-induced NVC response, its interaction, and different behaviour in R and NoR, warrant further research in different physiological and clinical conditions.
  • Uptake of self-management education programmes for people with type 2 diabetes in primary care through the embedding package: a cluster randomised control trial and ethnographic study

    Davies, Melanie J; Glab, Agnieszka; Northern, Alison; Schreder, Sally (2024-04-25)
    Background: Self-management education programmes are cost-effective in helping people with type 2 diabetes manage their diabetes, but referral and attendance rates are low. This study reports on the effectiveness of the Embedding Package, a programme designed to increase type 2 diabetes self-management programme attendance in primary care. Methods: Using a cluster randomised design, 66 practices were randomised to: (1) a wait-list group that provided usual care for nine months before receiving the Embedding Package for nine months, or (2) an immediate group that received the Embedding Package for 18 months. 'Embedders' supported practices and self-management programme providers to embed programme referral into routine practice, and an online 'toolkit' contained embedding support resources. Patient-level HbA1c (primary outcome), programme referral and attendance data, and clinical data from 92,977 patients with type 2 diabetes were collected at baseline (months - 3-0), step one (months 1-9), step 2 (months 10-18), and 12 months post-intervention. An integrated ethnographic study including observations, interviews, and document analysis was conducted using interpretive thematic analysis and Normalisation Process Theory. Results: No significant difference was found in HbA1c between intervention and control conditions (adjusted mean difference [95% confidence interval]: -0.10 [-0.38, 0.18] mmol/mol; -0.01 [-0.03, 0.02] %). Statistically but not clinically significantly lower levels of HbA1c were found in people of ethnic minority groups compared with non-ethnic minority groups during the intervention condition (-0.64 [-1.08, -0.20] mmol/mol; -0.06% [-0.10, -0.02], p = 0.004), but not greater self-management programme attendance. Twelve months post-intervention data showed statistically but not clinically significantly lower HbA1c (-0.56 [95% confidence interval: -0.71, -0.42] mmol/mol; -0.05 [-0.06, -0.04] %; p < 0.001), and higher self-management programme attendance (adjusted odds ratio: 1.13; 95% confidence interval: 1.02, 1.25; p = 0.017) during intervention conditions. Themes identified through the ethnographic study included challenges for Embedders in making and sustaining contact with practices and providers, and around practices' interactions with the toolkit. Conclusions: Barriers to implementing the Embedding Package may have compromised its effectiveness. Statistically but not clinically significantly improved HbA1c among ethnic minority groups and in longer-term follow-up suggest that future research exploring methods of embedding diabetes self-management programmes into routine care is warranted. Trial registration: ISRCTN23474120, registered 05/04/2018.
  • Quality metrics for same day emergency care-Consensus of a multi-professional panel of experts using a modified Delphi process

    Rahman, Latif (2024-04-21)
    Same Day Emergency Care (SDEC) services are at the heart of recovery plans for Emergency Care in the National Health Service. There are no validated metrics for the quality of care in SDEC. The Society for Acute Medicine's Quality Improvement Committee invited to a three-stage modified Delphi process to gather metrics used by clinicians. Proposed metrics were ranked and further explored by 33 participating experts from a broad range of backgrounds including clinicians, data scientists and operational managers. Experts ranked five system-based metrics highest. These focus on optimisation of the proportion of patients receiving same day care in and out of SDEC units. Patient and staff experience metrics were ranked low, possibly due to present lack of viable examples. The paper adds a glossary with the rationale for ranking of metrics and their use for the improvement of quality and safety of clinical care.
  • Early-onset type 2 diabetes and Tirzepatide treatment: A post hoc analysis from the SURPASS clinical trial program

    Davies, Melanie J (2024-06)
    Objective: We evaluated baseline characteristics of participants with early-onset type 2 diabetes (T2D) from the SURPASS program and tirzepatide's effects on glycemic control, body weight (BW), and cardiometabolic markers. Research design and methods: This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in 3,792 participants with early-onset versus later-onset T2D at week 40 (A Study of Tirzepatide [LY3298176] in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone [SURPASS-1] and A Study of Tirzepatide [LY3298176] Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes [SURPASS-2]) or week 52 (A Study of Tirzepatide [LY3298176] Versus Insulin Degludec in Participants With Type 2 Diabetes [SURPASS-3]). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. Results: At baseline in SURPASS-2, participants with early-onset versus later-onset T2D were younger with longer diabetes duration (9 vs. 7 years, P < 0.001) higher glycemic levels (8.5% vs. 8.2%, P < 0.001), higher BW (97 vs. 93 kg, P < 0.001) and BMI (35 vs. 34 kg/m2, P < 0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs. 156 mg/dL). At week 40, similar improvements in HbA1c (-2.6% vs. -2.4%), BW (-14 vs. -13 kg), WC (-10 vs. -10 cm), triglycerides (-26% vs. -24%), HDL (7% vs. 7%), and systolic BP (-6 vs. -7 mmHg) were observed in both subgroups with tirzepatide. Conclusions: Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline versus those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW, and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D.
  • The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope

    Khan, Fasihul (2024-04-18)
    Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1.
  • Putamen iron quantification in diseases with neurodegeneration: a meta-analysis of the quantitative susceptibility mapping technique

    Fatehi, Farzad (2024-05-17)
    Quantitative susceptibility mapping (QSM) is an MRI technique that accurately measures iron concentration in brain tissues. This meta-analysis synthesized evidence from 30 studies that used QSM to quantify the iron levels in the putamen. The PRISMA statement was adhered to when conducting the systematic reviews and meta-analyses. We conducted a meta-analysis using a random-effects model, as well as subgroup analyses (disease type, geographic region, field strength, coil, disease type, age, and sex) and sensitivity analysis. A total of 1247 patients and 1035 controls were included in the study. Pooled results showed a standardized mean difference (SMD) of 0.41 (95% CI 0.19 to 0.64), with the strongest effect seen in Alzheimer's disease (AD) at 1.01 (95% CI 0.50 to 1.52). Relapsing-remitting multiple sclerosis (RRMS) also showed increased putaminal iron at 0.37 (95% CI 0.177 to 0.58). No significant differences were observed in Parkinson's disease (PD). No significant differences were found between subgroups based on geographic region, field strength, coil, disease type, age, and sex. The studies revealed significant heterogeneity, with field strength as the primary source, while other factors, such as disease type, location, age, sex, and coil type, may have contributed. The sensitivity analysis showed that these factors did not have a significant influence on the overall results. In summary, this meta-analysis supports abnormalities in putaminal iron content across different diseases with neurodegeneration, especially AD and RRMS, as measured by QSM. This highlights the potential of QSM as an imaging biomarker to better understand disease mechanisms involving disturbances in brain iron homeostasis.
  • Expert panel recommendations for a standardized ambulatory glucose profile report for connected insulin pens

    Choudhary, Pratik (2024-05-17)
    Background: Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. Methods: An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single, clinically useful report. An extensive literature review and identification of examples of current connected insulin pen reports was performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. Results: The AGP Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the ambulatory glucose profile (AGP) curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio (ICR), average bolus insulin dose and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. Conclusion: The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

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