A Comparison of Sodium-Glucose Co-Transporter 2 Inhibitor Kidney Outcome Trial Participants with a Real-World Chronic Kidney Disease Primary Care Population.

BACKGROUND/HYPOTHESIS: Observational studies suggest sodium-glucose co-transporter-2 (SGLT2) inhibitor kidney outcome trials are not representative of the broader population of people with chronic kidney disease (CKD). However, there are limited data on the generalisability to those without co-existing type 2 diabetes (T2D), and the representativeness of the EMPA-KIDNEY trial has not been adequately explored. We hypothesised that SGLT2 inhibitor kidney outcome trials are more representative of people with co-existing T2D than those without, and that EMPA-KIDNEY is more representative than previous trials. METHODS: A cross-sectional analysis of adults with CKD in English primary care was conducted using the Oxford-Royal College of General Practitioners Clinical Information Digital Hub. The proportions that met the eligibility criteria of SGLT2 inhibitor kidney outcome trials were determined, and their characteristics described. Logistic regression analyses were performed to identify factors associated with trial eligibility. RESULTS: Of 6,670,829 adults, 516,491 (7.7%) with CKD were identified. In the real-world CKD population, 0.9%, 2.2%, and 8.0% met the CREDENCE, DAPA-CKD, and EMPA-KIDNEY eligibility criteria, respectively. All trials were more representative of people with co-existing T2D than those without T2D. Trial participants were 9-14 years younger than the real-world CKD population, and had more advanced CKD, including higher levels of albuminuria. A higher proportion of the CREDENCE (100%), DAPA-CKD (67.6%) and EMPA-KIDNEY (44.5%) trial participants had T2D compared to the real-world CKD population (32.8%). Renin-angiotensin system inhibitors were prescribed in almost all trial participants, compared to less than half of the real-world CKD population. Females were under-represented and less likely to be eligible for the trials. CONCLUSION: SGLT2 inhibitor kidney outcome trials represent a sub-group of people with CKD at high risk of adverse kidney events. Out study highlights the importance of complementing trials with real-world studies, exploring the effectiveness of SGLT2 inhibitors in the broader population of people with CKD.

Counting the lifetime cost of obesity: Analysis based on national England data.

AIM: Obesity has a significant impact on all-cause mortality rate and overall health care resource use (HCRU). These outcomes are also strongly linked to age, sex and local deprivation of the population. We aimed to establish the lifetime costs of obesity by demographic group/geographic area using published mortality rates and HCRU use for integrated care boards (ICB) in England in the context of costs of therapeutic intervention. METHODS: Population and expected mortality rates by age, sex and deprivation were obtained from national data. Obesity class prevalence was taken from the health of the nation study. The published impact of obesity by age, group, sex and deprivation on mortality and HCRU were applied to estimate life years lost and lifetime HCRU [by sex, age band and body mass index (BMI) class for each ICB]. The year 2019 was chosen as the study basis data to avoid influences of COVID-19 pandemic on obesity rates with application of 2022/23 HCRU values. Outcomes including prevalence, deaths, life years lost, HCRU and lifetime HCRU were compared by age and sex groups across four BMI classes normal/underweight (BMI <25 kg/m2 ), overweight (25-29.9 kg/m2 ), obese class I and II (30-39.9 kg/m2 ), and obese class III (≥40), with benchmarking being set against all population being BMI <25 kg/m2 overall and by each of the 42 ICBs. We also associated future life with deaths to provide an estimate of 'future life years lost' occurring each year. RESULTS: Total population aged >16 years was 45.4 million (51% female). PREVALENCE: 13.7 million (28% of the total adult population) had a BMI ≥30 mg/m2 and BMI ≥40 kg/m2 were 1.50 million (12%) of these 1.0 million (68%) were female and of these 0.6 million 40% were women aged 16-49 years. In addition, 35% of those with a BMI ≥40 kg/m2 were in the top deprivation quintile (i.e. overall 20%). Mortality was based on expected deaths of 518K/year, and modelling suggested that if a BMI <25 kg/m2 was achieved in all individuals, the death rate would fall by 63K to 455K/year for the English population (12% reduction). For those with a BMI ≥40 kg/m2 the predicted reduction was 12K deaths (54% lower); while in those aged 16-49 years with a BMI ≥40 kg/m2 72% of deaths were linked to obesity. For future life years lost, we estimated 2.5 years were lost in people with BMI 30-39.9 kg/m2 6.7 years when BMI ≥40 kg/m2 . However, for those aged 16-49 years with a BMI ≥40 kg/m2 , 8.3 years were lost. HCRU, for weight reduction, the annual HCRU decrease from BMI ≥40 kg/m2 to BMI 30-39.9 kg/m2 was £342 per person and from BMI 30-39.9 to 25-29.9 kg/m2 the reduction was £316/person. However, lifetime costs were similar because of reduced life expectancy for obese individuals. In quality adjusted life years (QALY), overall, 791 689 future life years were lost (13.1% of all) in people with BMI ≥25 kg/m2 and were related to excess weight. When the NICE £30 000 per QALY value was applied to the estimated total 791 689 future life years lost then the potential QALY value reduction lost was equivalent to £24 billion/year or £522/person in the obese population. For morbidly obese men and women the potential QALY value lost was £2864/person/year. Regarding geography, across the 42 ICBs, we observed significant variation in the prevalence of BMI ≥40 (1.8%-4.3%), excess mortality (11.6%-15.4%) and HCRU linked to higher BMI (7.2%-8.8%). The areas with the greatest impact on HCRU were in the north-west, north-east and Midlands of England, while the south shows less impact. CONCLUSION: The expected increases in annual HCRU because of obesity, when considered over a lifetime, are being mitigated by the increased mortality of obese individuals. Our data suggest that simple short-term HCRU reduction brought about through BMI reduction will be insufficient to fund additional specialist weight reduction interventions. The HRCUs associated with BMI are not in most cases related to short-term health conditions. They are a cumulative result over a number of years, so for age 16-49 years reducing BMI from ≥40 to 30-39.9 kg/m2 might show an annual decrease in HCRU/person by £325/year for women and £80/year for men but this might not have immediately occurred within that year. For those aged >70 years reducing BMI from ≥40 to 30-39.9 kg/m2 might show an annual decrease in HCRU/person by £777/year for women and £796/year for men but also may not be manifest within that year. However, for the morbidly obese men and women, the potential QALY value lost was £2864 per person per year with the potential for these funds to be applied to intensive weight management programmes, including pharmacotherapy.

Failure to control conventional cardiovascular risk factors in women with type 2 diabetes might explain worse mortality.

INTRODUCTION: The standardised mortality rate (SMR) for people with diabetes in England is 1.5-1.7, with differences in outcomes between sexes. There has been little work examining the factors that could have an impact on this or on what may determine sex differences in outcome. METHODS: Data were extracted for patients with type 2 diabetes (T2D) in Salford (England) in 2010 for the years up to 2020, including any deaths recorded. Expected deaths were calculated from annual Office of National Statistics mortality rate and life expectancy by age and gender, adjusted for the local Index of Multiple Deprivation (IMD). This provided the SMR deprivation (SMRd), and life expectancy years lost per death (LEYLD). The effects of treatment type, and clinical features on SMRd relative to sex were examined by univariable and multivariable analysis. RESULTS: Data from n = 11,806 (F = 5184; M = 6622) patients were included. Of these, n = 5540 were newly diagnosed and n = 3921 died (F = 1841; M = 2080). In total, n = 78,930 patient years. The expected deaths numbered n = 2596 (adjusted for age, sex, and IMD). Excess deaths were n = 1325 (F = 689; M = 636). Life expectancy years lost (LEYL) 18,989 (F = 9714; M = 9275). SMRd 1.51 (F = 1.60; M = 1.44) and LEYLD 4.84 years (F = 5.28; M = 4.46). The impact of risk factors was not different by sex. However, women had higher prevalence of % diagnosed >65 years of age; % last eGFR <60 mLs/min/1.73 m2 , and lower prevalence of % prescribed ACE-inhibitor/ARB, DPP4-inhibitor and SGLT2-inhibitor. Applying the male prevalence rate to the female population and expected mortality suggested n = 437 (55%) of excess T2D female deaths were attributed to sex difference in the prevalence of these risk and protective factors. CONCLUSIONS: Outcomes in women with T2DM are worse than in men, contributed to by greater prevalence of adverse factors and less prescribing of cardioprotective medication.

Sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: Are clinical trial benefits for heart failure reflected in real-world clinical practice? A systematic review and meta-analysis of observational studies.

AIM: To determine the absolute risk reduction (ARR) of heart failure events in people treated with sodium-glucose co-transporter-2 (SGLT2) inhibitors. MATERIALS AND METHODS: We searched PubMed, EMBASE, CINAHL and ISI Web of Science for observational studies published to 9 May 2022 that explored the association between SGLT2 inhibitors and any indication for heart failure (including new diagnosis or hospitalization for heart failure) in type 2 diabetes. Identified studies were independently screened by two reviewers and assessed for bias using the Newcastle-Ottawa scale. Eligible studies with comparable outcome data were pooled for meta-analysis using random-effects models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs). The ARR per 100 person-years was determined overall, and in subgroups with and without baseline cardiovascular disease (CVD). RESULTS: From 43 eligible studies, with a total of 4 818 242 participants from 17 countries, 21 were included for meta-analysis. SGLT2 inhibitors were associated with a reduced risk of hospitalization for heart failure (HR 0.65, 95% CI 0.59-0.72) overall and both in those with CVD (HR 0.78, 95% CI 0.68-0.89) and without CVD (HR 0.53, 95% CI 0.39-0.71). Risk reduction for hospitalization for heart failure in people with a history of CVD (ARR 1.17, 95% CI 0.78-1.55) was significantly greater than for those without CVD (ARR 0.39, 95% CI 0.32-0.47). The number-needed-to-treat to prevent one event of hospitalization for heart failure was 86 (95% CI 65-128) person-years of treatment for the CVD group and 256 (95% CI 215-316) person-years for those without CVD. CONCLUSIONS: Real-world SGLT2 inhibitor use supports randomized trial data for the size effect of reduced hospitalization for heart failure in type 2 diabetes, although with a much lower ARR in people without CVD.

Diabetes foot complications and standardized mortality rate in type 2 diabetes.

AIM: To quantify the impact of foot complications on mortality outcomes in people with type 2 diabetes (T2D), and how routinely measured factors might modulate that risk. MATERIALS AND METHODS: Data for individuals with T2D for 2010-2020, from the Salford Integrated Care Record (Salford, UK), were extracted for laboratory and clinical data, and deaths. Annual expected deaths were taken from Office of National Statistics mortality data. An index of multiple deprivation (IMD) adjusted the standardized mortality ratio (SMR_IMD). Life years lost per death (LYLD) was estimated from the difference between expected and actual deaths. RESULTS: A total of 11 806 T2D patients were included, with 5583 new diagnoses and 3921 deaths during 2010-2020. The number of expected deaths was 2135; after IMD adjustment, there were 2595 expected deaths. Therefore, excess deaths numbered 1326 (SMR_IMD 1.51). No foot complications were evident in n = 9857. This group had an SMR_IMD of 1.13 and 2.74 LYLD. In total, 2979 patients had any foot complication recorded. In this group, the SMD_IMR was 2.29; of these, 2555 (75%) had only one foot complication. Patients with a foot complication showed little difference in percentage HbA1c more than 58 mmol/mol. In multivariate analysis, for those with a foot complication and an albumin-to-creatinine ratio of more than 3 mg/mmol, the odds ratio (OR) for death was 1.93, and for an estimated glomerular filtration rate of less than 60 mL/min/1.73m2 , the OR for death was 1.92. CONCLUSIONS: Patients with T2D but without a foot complication have an SMR_IMD that is only slightly higher than that of the general population. Those diagnosed with a foot complication have a mortality risk that is double that of those without T2D.

Postdischarge venous thromboembolism following hospital admission with COVID-19.

The association of severe coronavirus disease 2019 (COVID-19) with an increased risk of venous thromboembolism (VTE) has resulted in specific guidelines for its prevention and management. The VTE risk appears highest in those with critical care admission. The need for postdischarge thromboprophylaxis remains controversial, which is reflected in conflicting expert guideline recommendations. Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only. We report postdischarge VTE data from an ongoing quality improvement program incorporating root-cause analysis of hospital-associated VTE (HA-VTE). Following 1877 hospital discharges associated with COVID-19, 9 episodes of HA-VTE were diagnosed within 42 days, giving a postdischarge rate of 4.8 per 1000 discharges. Over 2019, following 18 159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges). The odds ratio for postdischarge HA-VTE associated with COVID-19 compared with 2019 was 1.6 (95% confidence interval, 0.77-3.1). COVID-19 hospitalization does not appear to increase the risk of postdischarge HA-VTE compared with hospitalization with other acute medical illness. Given that the risk-benefit ratio of postdischarge thromboprophylaxis remains uncertain, randomized controlled trials to evaluate the role of continuing thromboprophylaxis in COVID-19 patients following hospital discharge are required.

What is the impact of microvascular complications of diabetes on severe COVID-19?

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.

GLP-1 receptor agonist use during hospitalisation: Better glycaemic control compared to premixed insulin.

INTRODUCTION: Glycaemic control associates with better outcomes for hospitalised patients. Whether GLP-1 receptor agonists (GLP-1 RA) are suitable and effective drugs for inpatients is unclear. METHODS: A retrospective, single centre, observational study using data from the electronic health record. Patients admitted using GLP-1 RA as outpatients, from 2016 to 2019, were identified. Outcomes were compared to those admitted using twice-daily (BD) mixed insulin. Capillary glucose, medication use, creatinine, and demographic data were collected. As drugs may be discontinued/not administered in hospital, days when GLP-1 RA was administered were 'GLP-1 RA active' and, for insulin, 'insulin active'. The primary comparison was rate of hypoglycaemia (<4 mmol/L) and severe hypoglycaemia (<3 mmol/L). A logistic regression model examined variables for hypoglycaemia. RESULTS: GLP-1 RA comprised n = 262 admissions and BD insulin n = 166. The 'insulin active' cohort (n = 957 patient days) had higher risk of hypoglycaemia than 'GLP-1 RA active' (n = 806 days); occurring on 14.7% of days; 95% confidence interval [CI] 12.6-17.1 versus 9.9% days; 95% CI 8.0-12.2; p = 0.002, and severe hypoglycaemia 4.0% of days (95% CI 2.8-5.4) versus 2.0% (95% CI 1.1%-3.2%; p = 0.005). Daily glucose (mean ± standard deviation) was 10.8 ± 5.2 mmol/L in insulin active versus 9.6 ± 4.7 mmol/L in GLP-1 RA active; p < 0.001. Insulin use, age, and acute admissions predicted hypoglycaemia. The odds ratio for hypoglycaemia was 2.15 times greater (95% CI, 1.14-4.08; p = 0.019) with insulin than with GLP-1 RA. CONCLUSIONS: GLP-1 RA provided better glycaemic control than BD mixed insulin and should be continued during hospitalisation unless there is a clear indication for cessation.

The change in glycaemic control immediately after COVID-19 vaccination in people with type 1 diabetes.

AIMS: Evidence suggests that some people with type 1 diabetes mellitus (T1DM) experience temporary instability of blood glucose (BG) levels after COVID-19 vaccination. We aimed to assess this objectively. METHODS: We examined the interstitial glucose profile of 97 consecutive adults (age ≥ 18 years) with T1DM using the FreeStyle Libre® flash glucose monitor in the periods immediately before and after their first COVID-19 vaccination. The primary outcome measure was percentage (%) interstitial glucose readings within the target range 3.9-10 mmol/L for 7 days prior to the vaccination and the 7 days after the vaccination. Data are mean ± standard error. RESULTS: There was a significant decrease in the % interstitial glucose on target (3.9-10.0) for the 7 days following vaccination (mean 52.2% ± 2.0%) versus pre-COVID-19 vaccination (mean 55.0% ± 2.0%) (p = 0.030). 58% of individuals with T1DM showed a reduction in the 'time in target range' in the week after vaccination. 30% showed a decrease of time within the target range of over 10%, and 10% showed a decrease in time within target range of over 20%. The change in interstitial glucose proportion on target in the week following vaccination was most pronounced for people taking metformin/dapagliflozin + basal bolus insulin (change -7.6%) and for people with HbA1c below the median (change -5.7%). CONCLUSION: In T1DM, we have shown that initial COVID-19 vaccination can cause temporary perturbation of interstitial glucose, with this effect more pronounced in people talking oral hypoglycaemic medication plus insulin, and when HbA1c is lower.

Early and ongoing stable glycaemic control is associated with a reduction in major adverse cardiovascular events in people with type 2 diabetes: A primary care cohort study.

AIM: To determine whether achieving early glycaemic control, and any subsequent glycaemic variability, was associated with any change in the risk of major adverse cardiovascular events (MACE). MATERIALS AND METHODS: A retrospective cohort analysis from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database-a large, English primary care network-was conducted. We followed newly diagnosed patients with type 2 diabetes, on or after 1 January 2005, aged 25 years or older at diagnosis, with HbA1c measurements at both diagnosis and after 1 year, plus five or more measurements of HbA1c thereafter. Three glycaemic bands were created: groups A (HbA1c < 58 mmol/mol [<7.5%]), B (HbA1c ≥ 58 to 75 mmol/mol [7.5%-9.0%]) and C (HbA1c ≥ 75 mmol/mol [≥9.0%]). Movement between bands was determined from diagnosis to 1 year. Additionally, for data after the first 12 months, a glycaemic variability score was calculated from the number of successive HbA1c readings differing by 0.5% or higher (≥5.5 mmol/mol). Risk of MACE from 1 year postdiagnosis was assessed using time-varying Cox proportional hazards models, which included the first-year transition and the glycaemic variability score. RESULTS: From 26 180 patients, there were 2300 MACE. Compared with group A->A transition over 1 year, those with C->A transition had a reduced risk of MACE (HR 0.75; 95% CI 0.60-0.94; P = .014), whereas group C->C had HR 1.21 (0.81-1.81; P = .34). Compared with the lowest glycaemic variability score, the greatest variability increased the risk of MACE (HR 1.51; 1.11-2.06; P = .0096). CONCLUSION: Early control of HbA1c improved cardiovascular outcomes in type 2 diabetes, although subsequent glycaemic variability had a negative effect on an individual's risk.

Comparison of the QuikRead go® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide® laboratory analyser to diagnose colorectal cancer in symptomatic patients.

OBJECTIVES: Faecal immunochemical testing for haemoglobin (FIT) is used to triage patients for colonic investigations. Point-of-care (POC) FIT devices on the market have limited data for their diagnostic accuracy for colorectal cancer (CRC). Here, a POC FIT device is compared with a laboratory-based FIT system using patient collected samples from the urgent referral pathway for suspected CRC. METHODS: A prospective, observational cohort study. Patients collected two samples from the same stool. These were measured by POC QuikRead go® (Aidian Oy, Espoo, Finland) and laboratory-based FOB Gold Wide® (Sentinel Diagnostics, Italy). Faecal haemoglobin <10 µg haemoglobin/g of faeces was considered as negative. At this threshold, comparisons between the two systems were made by calculating percentage agreement and Cohen's kappa coefficient. Proportion of negative results were compared with Chi squared testing. Sensitivities for CRC were calculated. RESULTS: A total of 629 included patients provided paired samples for FIT to compare the QuikRead go® and FOB Gold Wide®. The agreement around the negative threshold was 83.0% and Cohen's kappa coefficient was 0.54. The QuikRead go® reported 440/629 (70.0% of samples) as negative compared to 523/629 (83.1%) for the FOB Gold Wide®, this difference was significant (p-value<0.001). Sensitivities for CRC detection by the QuikRead go® and FOB Gold Wide® were 92.9% (95% confidence interval (CI): 68.5-98.7%) and 100% (CI: 78.5-100%) respectively. CONCLUSIONS: Both systems were accurate in their ability to detect CRC. Whilst good agreement around the negative threshold was identified, more patients would be triaged to further colonic investigation if using the QuikRead go®.

Lessons learnt from the variation across 6741 family/general practices in England in the use of treatments for hypogonadism.

INTRODUCTION: We have previously reported rates of diagnosis of male hypogonadism in United Kingdom (UK) general practices. We aimed to identify factors associated with testosterone prescribing in UK general practice. METHODS: We determined for 6741 general practices in England, the level of testosterone prescribing in men and the relation between volume of testosterone prescribing and (1) demographic characteristics of the practice, (2) % patients with specific comorbidities and (3) national GP patient survey results. RESULTS: The largest volume (by prescribing volume) agents were injectable preparations at a total cost in the 12-month period 2018/19 of £8,172,519 with gel preparations in second place: total cost £4,795,057. Transdermal patches, once the only alternative to testosterone injections or implants, were little prescribed: total cost £222,022. The analysis accounted for 0.27 of the variance in testosterone prescribing between general practices. Thus, most of this variance was not accounted for by the analysis. There was a strong univariant relation (r = .95, P < .001) between PDE5-I prescribing and testosterone prescribing. Other multivariant factors independently linked with more testosterone prescribing were as follows: HIGHER proportion of men with type 2 diabetes(T2DM) on target control (HbA1c ≤ 58 mmol/mol) and HIGHER overall practice rating on the National Patient Survey for good experience, while non-white ethnicity and socio-economic deprivation were associated with less testosterone prescribing. There were a number of comorbidity factors associated with less prescribing of testosterone (such as T2DM, hypertension and stroke/TIA). CONCLUSION: Our analysis has indicated that variation between general practices in testosterone prescribing in a well developed health economy is only related to small degree (r2  = 0.27) to factors that we can define. This suggests that variation in amount of testosterone prescribed is largely related to general practitioner choice/other factors not studied and may be amenable to measures to increase knowledge/awareness of male hypogonadism, with implications for men's health.

Effect of type 1 diabetes and type 2 diabetes on the risk of venous thromboembolism.

AIMS: Whether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2 diabetes for VTE risk. METHODS: Retrospective cohort study of the Royal College of General Practitioners Research and Surveillance Centre, comprising over 530 primary care practices. We determined whether type 1 diabetes and/or type 2 diabetes are independent risk factors for VTE. The index date was 1 January 2009, individuals were followed to 31 December 2018, or censoring. Cox proportional hazard regression analysis was used to investigate the risk of VTE in people with type 1 diabetes and type 2 diabetes relative to no diabetes. The primary outcome was occurrence of VTE. The model was adjusted for potential confounders for VTE. RESULTS: There were 7086 people with type 1 diabetes and 95,566 with type 2 diabetes, diagnosed before 1 January 2009. The non-diabetes group consisted of 1,407,699 people. In the unadjusted analysis, there was no increased risk of VTE with type 1 diabetes (HR 1.00, 95% CI 0.76-1.33) but there was for type 2 diabetes (HR 2.70, 95% CI 2.57-2.84). In the fully adjusted model, VTE risk was increased in type 1 diabetes (HR 1.46, 95% CI 1.11-1.92), but not with type 2 diabetes (HR 1.06, 95% CI 0.98-1.14). CONCLUSIONS: Type 1 diabetes was associated with a greater risk for VTE while type 2 diabetes was not. Further work is needed to determine the reason(s) for this.

Adoption of faecal immunochemical testing for 2-week-wait colorectal patients during the COVID-19 pandemic: an observational cohort study reporting a new service at a regional centre.

AIM: The COVID-19 pandemic has resulted in the near-complete loss of routine endoscopy services. We describe a major reorganization of service at a regional referral centre (Royal Surrey NHS Foundation Trust) to manage the crisis. Faecal immunochemical testing (FIT) was implemented for triage to make optimum use of limited diagnostic resources. Consultations were switched from face-to-face to telephone. Our aim was to evaluate the impact FIT had on resource allocation and patient diagnoses in the first 3 months of use. METHOD: All colorectal 2-week-wait patient referrals were posted a pack requesting FIT and notification of telephone consultation. A prepaid envelope was included for return of the samples. At consultation, FIT was incorporated with the presenting symptoms to guide the choice of investigation and triage urgency. FIT ≥10 µg/g was interpreted as positive. Outcome data were collected prospectively and compared with retrospective audit data from prepandemic levels across 3 months. RESULTS: From 26 March 2020 to 2 July 381 patients were referred who were invited to provide FIT samples and underwent telephone consultations. Three hundred and fifty eight FIT samples were returned (94%). Onward referral for colonoscopy reduced from 62% to 34% (P < 0.001). There were 14 colorectal cancers (CRC) (3.7%) diagnosed, which was not statistically different from the prepandemic level of 3.9% (P = 0.995). Twelve of the 14 patients with a CRC diagnosis had provided samples; all 12 had FIT ≥10 µg/g and were offered fast-track investigations. CONCLUSIONS: The incorporation of FIT optimized the allocation of limited resources to triage those who required urgent colonic investigation for detecting CRC.

Diagnostic accuracy of point of care faecal immunochemical testing using a portable high-speed quantitative analyser for diagnosis in 2-week wait patients.

AIM: Laboratory-based faecal immunochemical testing (FIT) is the gold standard for detecting the presence of blood in the stool. The aim was to perform a diagnostic accuracy study to confirm if a point of care (POC) analyser for FIT could be safely used as an adjunct in the triage and management of 2-week wait (TWW) colorectal patients. METHODS: The Point of Care Faecal Immunochemical Testing (POC FIT) prospective observational cohort study was designed for TWW patients at a regional referral centre. Between July 2019 and March 2020, patients were invited to perform and bring a FIT sample to clinic. FIT was completed within the clinic appointment using a POC quantitative analyser that has a 2-min processing time (QuikRead go®). Patients and clinicians were blinded to results within the clinic appointment. The results were compared with subsequent diagnostic outcomes. Faecal haemoglobin of <10 µg haemoglobin/g of faeces was considered a negative result. Sensitivities for colorectal cancer (CRC) and combined serious bowel disease (SBD) were calculated using this pre-determined cut-off. RESULTS: A total of 553 patients were included for analytical comparison with diagnostic outcomes. There were 14 (2.5%) patients with CRC and 52 (9.4%) with SBD. The sensitivities for CRC and SBD were 92.9% (95% CI 68.5%-98.7%) and 76.9% (95% CI 63.9%-86.3%) respectively. 379 (68.5%) patients had a negative FIT result (negative predictive value for CRC was 99.7%). CONCLUSIONS: This POC FIT device is a useful adjunct to better manage TWW patients. The high observed sensitivity for CRC offers opportunities, within a single consultation, for improved triage and rationalization of investigation for those with bowel symptoms.

Analysis of continuous glucose tracking data in people with type 1 diabetes after COVID-19 vaccination reveals unexpected link between immune and metabolic response, augmented by adjunctive oral medication.

INTRODUCTION: The COVID-19 vaccination programme is under way worldwide. Anecdotal evidence is increasing that some people with type 1 diabetes mellitus (T1DM) experience temporary instability of blood glucose (BG) levels post-vaccination which normally settles within 2-3 days. We report an analysis of BG profiles of 20 individuals before/after vaccination. METHODS: We examined the BG profile of 20 consecutive adults (18 years of age or more) with T1DM using the FreeStyle Libre flash glucose monitor in the period immediately before and after COVID-19 vaccination. The primary outcome measure was percentage (%) BG readings in the designated target range 3.9-10 mmmol/L as reported on the LibreView portal for 7 days prior to the vaccination (week -1) and the 7 days after the vaccination (week +1). RESULTS: There was a significant decrease in the %BG on target following the COVID-vaccination for the 7 days following vaccination (mean 45.2% ± SE 4.2%) vs pre-COVID-19 vaccination (mean 52.6% ± SE 4.5%). This was mirrored by an increase in the proportion of readings in other BG categories 10.1%-13.9%/≥14%. There was no significant change in BG variability in the 7days post-COVID-19 vaccination. This change in BG proportion on target in the week following vaccination was most pronounced for people taking Metformin/Dapagliflozin+basal-bolus insulin (-23%) vs no oral hypoglycaemic agents (-4%), and median age <53 vs ≥53 years (greater reduction in %BG in target for older individuals (-18% vs -9%)). CONCLUSION: In T1DM, we have shown that COVID-19 vaccination can cause temporary perturbation of BG, with this effect more pronounced in patients talking oral hypoglycaemic medication plus insulin, and in older individuals. This may also have consequences for patients with T2DM who are currently not supported by flash glucose monitoring.

HDL-apoA-I kinetics in response to 16 wk of exercise training in men with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise (n = 15), or conventional lifestyle advice (n = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8-32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; P < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6-36.1% to 8.9% (4.4-17.8%); P = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.

Diabetes, obesity and COVID-19: A complex interplay.

With the accumulation of observational data showing an association of metabolic co-morbidities with adverse outcomes from COVID-19, there is a need to disentangle the contributions of pre-existing macro- and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID-19, the clinical and research questions which arise from this relationship, and the types of studies needed to answer those questions. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience of or interest in the management of COVID-19.

Is 3D faster and safer than 4K laparoscopic cholecystectomy? A randomised-controlled trial.

BACKGROUND: Laparoscopic surgery has well-established benefits for patients; however, laparoscopic procedures have a long and difficult learning curve, in large part due to the lack of stereoscopic depth perception. Developments in high-definition and stereoscopic imaging have attempted to overcome this. Three-dimensional high-definition (3D HD) systems are thought to improve operating times compared to two-dimensional high-definition systems. However their performance against new, ultra-high-definition ('4K') systems is not known. METHODS: Patients undergoing laparoscopic cholecystectomy were randomised to 3D HD or 4K laparoscopy. Operative videos were recorded, and the time from gallbladder exposure to separation from the liver (minus on table cholangiogram) was calculated. Blinded video assessment was performed to calculate intraoperative error scores. RESULTS: One hundred and twenty patients were randomised, of which 109 were analysed (3D HD n = 54; 4K n = 55). No reduction in operative time was detected with 3D HD compared to 4K laparoscopy (median [IQR]; 23.41 min [17.00-37.98] vs 20.90 min [17.67-33.03]; p = 0.91); nor was there any decrease observed in error scores (60 [56-62] vs 58 [56-60]; p = 0.27), complications or reattendance. Stone spillage occurred more frequently with 3D HD, but there were no other differences in individual error rates. Gallbladder grade and operating surgeon had significant effects on time to complete the operation. Gallbladder grade also had a significant effect on the error score. CONCLUSIONS: A 3D HD laparoscopic system did not reduce operative time or error scores during laparoscopic cholecystectomy compared with a new 4K imaging system.

3D laparoscopy does not reduce operative duration or errors in day-case laparoscopic cholecystectomy: a randomised controlled trial.

BACKGROUND: Contemporary 3D platforms have overcome past deficiencies. Available trainee and laboratory studies suggest stereoscopic imaging improves performance but there is little clinical data or studies assessing specialists. We aimed to determine whether stereoscopic (3D) laparoscopic systems reduce operative time and number of intraoperative errors during specialist-performed laparoscopic cholecystectomy (LC). METHODS: A parallel arm (1:1) randomised controlled trial comparing 2D and 3D passive-polarised laparoscopic systems in day-case LC using was performed. Eleven consultant surgeons that had each performed > 200 LC (including > 10 3D LC) participated. Cases were video recorded and a four-point difficulty grade applied. The primary outcome was overall operative time. Subtask time and the number of intraoperative consequential errors as identified by two blinded assessors using a hierarchical task analysis and the observational clinical human reliability analysis technique formed secondary endpoints. RESULTS: 112 patients were randomised. There was no difference in operative time between 2D and 3D LC (23:14 min (± 10:52) vs. 20:17 (± 9:10), absolute difference - 14.6%, p = 0.148) although 3D surgery was significantly quicker in difficulty grade 3 and 4 cases (30:23 min (± 9:24), vs. 18:02 (± 7:56), p < 0.001). No differences in overall error count was seen (total 47, median 1, range 0-4 vs. 45, 1, 0-3, p = 0.62) although there were significantly fewer 3D gallbladder perforations (15 vs. 6, p = 0.034). CONCLUSION: 3D laparoscopy did not reduce overall operative time or error frequency in laparoscopic cholecystectomies performed by specialist surgeons. 3D reduced Calot's dissection time and operative time in complex cases as well as the incidence of iatrogenic gallbladder perforation (NCT01930344).