Oncology phase I trial design and conduct: time for a change - MDICT Guidelines 2022.

In 2021, the Food and Drug Administration Oncology Center of Excellence announced Project Optimus focusing on dose optimization for oncology drugs. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Taskforce met to review and discuss the optimization of dosage for oncology trials and to develop a practical guide for oncology phase I trials. Defining a single recommended phase II dose based on toxicity may define doses that are neither the most effective nor the best tolerated. MDICT recommendations address the need for robust non-clinical data which are needed to inform trial design, as well as an expert team including statisticians and pharmacologists. The protocol must be flexible and adaptive, with clear definition of all endpoints. Health authorities should be consulted early and regularly. Strategies such as randomization, intrapatient dose escalation, and real-world eligibility criteria are encouraged whereas serial tumor sampling is discouraged in the absence of a strong rationale and appropriately validated assay. Endpoints should include consideration of all longitudinal toxicity. The phase I dose escalation trial should define the recommended dose range for later testing in randomized phase II trials, rather than a single recommended phase II dose, and consider scenarios where different populations may require different dosages. The adoption of these recommendations will improve dosage selection in early clinical trials of new anticancer treatments and ultimately, outcomes for patients.

Pre-hospital prediction of adverse outcomes in patients with suspected COVID-19: Development, application and comparison of machine learning and deep learning methods.

BACKGROUND: COVID-19 infected millions of people and increased mortality worldwide. Patients with suspected COVID-19 utilised emergency medical services (EMS) and attended emergency departments, resulting in increased pressures and waiting times. Rapid and accurate decision-making is required to identify patients at high-risk of clinical deterioration following COVID-19 infection, whilst also avoiding unnecessary hospital admissions. Our study aimed to develop artificial intelligence models to predict adverse outcomes in suspected COVID-19 patients attended by EMS clinicians. METHOD: Linked ambulance service data were obtained for 7,549 adult patients with suspected COVID-19 infection attended by EMS clinicians in the Yorkshire and Humber region (England) from 18-03-2020 to 29-06-2020. We used support vector machines (SVM), extreme gradient boosting, artificial neural network (ANN) models, ensemble learning methods and logistic regression to predict the primary outcome (death or need for organ support within 30 days). Models were compared with two baselines: the decision made by EMS clinicians to convey patients to hospital, and the PRIEST clinical severity score. RESULTS: Of the 7,549 patients attended by EMS clinicians, 1,330 (17.6%) experienced the primary outcome. Machine Learning methods showed slight improvements in sensitivity over baseline results. Further improvements were obtained using stacking ensemble methods, the best geometric mean (GM) results were obtained using SVM and ANN as base learners when maximising sensitivity and specificity. CONCLUSIONS: These methods could potentially reduce the numbers of patients conveyed to hospital without a concomitant increase in adverse outcomes. Further work is required to test the models externally and develop an automated system for use in clinical settings.

How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with Type 1 diabetes?

In 2011, the James Lind Alliance published a 'top 10' list of priorities for Type 1 diabetes research based on a structured consultation process. Whether reducing fluctuations in blood glucose can prevent long-term microvascular and macrovascular complications was one of these. In this narrative review, 8 years on, we have assessed the updated evidence for the assertion that increased glucose variability plays an independent and clinically important role in the complications of Type 1 diabetes, over and above mean blood glucose and the effects of hypoglycaemia: the 'glucose variability hypothesis'. Although studies in cultured cells and ex vivo vessels have been suggestive, most studies in Type 1 diabetes have been small and/or cross-sectional, and based on 'finger-prick' glucose measurements that capture glucose variability only in waking hours and are affected by missing data. A recent analysis of the Diabetes Control and Complications Trial that formally imputed missing data found no independent effect of short-term glucose variability on long-term complications. Few other high-quality longitudinal studies have directly addressed the glucose variability hypothesis in Type 1 diabetes. We conclude that there is little substantial evidence to date to support this hypothesis in Type 1 diabetes, although increasing use of continuous glucose monitoring provides an opportunity to test it more definitively. In the meantime, we recommend that control of glycaemia in Type 1 diabetes should continue to focus on the sustained achievement of target HbA1c and avoidance of hypoglycaemia.

Severe morbidity among hospitalised adults with acute influenza and other respiratory infections: 2014-2015 and 2015-2016.

Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014-2015 and 2015-2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0-2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2-0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2-1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0-2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.

Fludrocortisone therapy for persistent hyperkalaemia.

BACKGROUND: Type 4 renal tubular acidosis causes hyperkalaemia, for which diabetes and medications commonly used in this patient group are aetiological factors. Here we describe the novel use of fludrocortisone in this difficult condition. CASE REPORT: A 55-year-old woman with complex co-morbidities, including Type 2 diabetes (HbA1c 37 mmol/mol 5.5%), was admitted with renal failure. Bloods on admission: eGFR 25 ml/min, creatinine 184 ?mol/L, urea 35.9 mmol/L, sodium 128 mmol/L, potassium 5.6 mmol/L, bicarbonate 15 mmol/L, and albumin 30 g/L. Her admission was prolonged, complicated by hospital-acquired sepsis (lower respiratory tract, urinary tract, and infected leg ulcers), poor venous access and severe depression. She had recurrent hyperkalaemia and deteriorating renal function, from presumed Type 4 renal tubular acidosis and excessive fluid losses from leg ulcers. Her renal function recurrently deteriorated, despite conventional treatment methods. After 69 days, she was commenced on fludrocortisone 50 mcg/day. Her renal function and serum potassium stabilized and she was discharged with potassium 4.3 mmol/L, eGFR 42 ml/min, and bicarbonate 23 mmol/L. She has remained stable on this treatment, without requiring further hospital admission for over 6 months, with eGFR 40 ml/min, and potassium 5.5 mmol/L, and albumin 26 g/L. CONCLUSION: This woman was presumed to have Type 4 renal tubular acidosis and recurrent hyperkalaemia due to renal insufficiency, in the context of underlying diabetes and chronic kidney disease, which was poorly responsive to conventional management. There is limited evidence for using fludrocortisone in this setting. Our case suggests that fludrocortisone might offer a novel therapeutic strategy when conventional management is not working.

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial.

BACKGROUND: Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. METHODS: LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). RESULTS: Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. CONCLUSIONS: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

Instability in total knee arthroplasty : assessment and solutions.

Instability is a common indication for early revision after both primary and revision total knee arthroplasty (TKA), accounting for up to 20% in the literature. The number of TKAs performed annually continues to climb exponentially, thus having an effective algorithm for treatment is essential. This relies on a thorough pre- and intra-operative assessment of the patient. The underlying cause of the instability must be identified initially and subsequently, the surgeon must be able to balance the flexion and extension gaps and be comfortable using a variety of constrained implants. This review describes the assessment of the unstable TKA, and the authors' preferred form of treatment for these difficult cases where the source of instability is often multifactorial.

Hospital costs of out-of-hospital cardiac arrest patients treated in intensive care; a single centre evaluation using the national tariff-based system.

OBJECTIVES: There is a scarcity of literature reporting hospital costs for treating out of hospital cardiac arrest (OOHCA) survivors, especially within the UK. This is essential for assessment of cost-effectiveness of interventions necessary to allow just allocation of resources within the National Health Service. We set out primarily to calculate costs stratified against hospital survival and neurological outcomes. Secondarily, we estimated cost effectiveness based on estimates of survival and utility from previous studies to calculate costs per quality adjusted life year (QALY). SETTING: We performed a single centre (London) retrospective review of in-hospital costs of patients admitted to the intensive care unit (ICU) following return of spontaneous circulation (ROSC) after OOHCA over 18 months from January 2011 (following widespread introduction of targeted temperature management and primary percutaneous intervention). PARTICIPANTS: Of 69 successive patients admitted over an 18-month period, survival and cerebral performance category (CPC) outcomes were obtained from review of databases and clinical notes. The Trust finance department supplied ICU and hospital costs using the Payment by Results UK system. RESULTS: Of those patients with ROSC admitted to ICU, survival to hospital discharge (any CPC) was 33/69 (48%) with 26/33 survivors in CPC 1-2 at hospital discharge. Cost per survivor to hospital discharge (including total cost of survivors and non-survivors) was £50,000, cost per CPC 1-2 survivor was £65,000. Cost and length of stay of CPC 1-2 patients was considerably lower than CPC 3-4 patients. The majority of the costs (69%) related to intensive care. Estimated cost per CPC 1-2 survivor per QALY was £16,000. CONCLUSIONS: The costs of in-hospital patient care for ICU admissions following ROSC after OOHCA are considerable but within a reasonable threshold when assessed from a QALY perspective.

Cardiovascular safety of the glucagon-like peptide-1 receptor agonist taspoglutide in people with type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.

AIMS: To study the short-term cardiovascular effects of the once-weekly glucagon-like peptide-1 receptor agonist taspoglutide. METHODS: We conducted a meta-analysis of individual-participant data from nine randomized controlled trials in the T-Emerge programme, which assessed the efficacy and safety of taspoglutide in type 2 diabetes. Our primary outcome was a composite of death from cardiovascular disease (CVD) and acute myocardial infarction, stroke and hospitalization for unstable angina. RESULTS: Overall, 7056 individuals were included in the analysis, and there were 67 primary endpoint events during 7478 person-years of follow-up (40 vs 27 events in the intervention vs control groups, respectively). The odds ratio for the composite endpoint among people randomized to taspoglutide was 0.94 (95% confidence interval 0.57-1.56), which was robust across multiple subgroups. Longer-term data were not available as the development of taspoglutide was stopped because of gastrointestinal intolerance and serious hypersensitivity reactions. CONCLUSIONS: The available data suggest that short-term, once-weekly administration of taspoglutide was not associated with an excess risk of CVD, and provide insights relevant to the development of other novel once-weekly incretin mimetics.

The multiply-operated total knee replacement patient: salvage options.

Although the vast majority of patients that undergo total knee replacement have satisfactory outcomes with a generally low complication rate, occasionally a patient will be encountered that has had multiple failed surgeries, and now reaches a crossroad as to whether limb salvage will be acceptable or not.

When femoral fracture fixation fails: salvage options.

Most hip fractures treated with modern internal fixation techniques will heal. However, failures occasionally occur and require revision procedures. Salvage strategies employed during revision are based on whether the fixation failure occurs in the femoral neck, or in the intertrochanteric region. Patient age and remaining bone stock also influence decision making. For fractures in young patients, efforts are generally focused on preserving the native femoral head via osteotomies and repeat internal fixation. For failures in older patients, some kind of hip replacement is usually selected. Disuse osteopenia, deformity, bone loss, and stress-risers from previous internal fixation devices all pose technical challenges to successful reconstruction. Attention to detail is important in order to minimise complications. In the majority of cases, good outcomes have been reported for the various salvage strategies.

Pelvic discontinuity: current solutions.

Pelvic discontinuity represents a rare but challenging problem for orthopaedic surgeons. It is most commonly encountered during revision total hip replacement, but can also result from an iatrogentic acetabular fracture during hip replacement. The general principles in management of pelvic discontinuity include restoration of the continuity between the ilium and the ischium, typically with some form of plating. Bone grafting is frequently required to restore pelvic bone stock. The acetabular component is then impacted, typically using an uncemented, trabecular metal component. Fixation with multiple supplemental screws is performed. For larger defects, a so-called 'cup-cage' reconstruction, or a custom triflange implant may be required. Pre-operative CT scanning can greatly assist in planning and evaluating the remaining bone stock available for bony ingrowth. Generally, good results have been reported for constructs that restore stability to the pelvis and allow some form of biologic ingrowth.

Insulin resistance in type 1 diabetes: what is 'double diabetes' and what are the risks?

In this review, we explore the concept of 'double diabetes', a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice.

Taking small steps towards targets - perspectives for clinical practice in diabetes, cardiometabolic disorders and beyond.

Big changes are hard. When trying to achieve guideline targets in diabetes and cardiometabolic disorders, patients can lack commitment or suffer despondency. It is much easier to make small changes in lifestyle or treatment, which are less noticeable and easier to manage long-term. Obesity is central to the cardiometabolic disorders, and even small weight losses of 2-5% can improve the cardiometabolic risk profile and substantially reduce the risk of developing type 2 diabetes. Likewise, small increases in physical activity, such as 15-30 min of brisk walking per day, can cut the risk of heart disease by 10%. Lifestyle or treatment changes that lead to small improvements in metabolic parameters also impact patient outcome - for example, a 5 mmHg decrease in blood pressure can translate into significant reductions in the rates of myocardial infarction and cardiovascular mortality. Benefits of small changes can also be seen in health economic outcome models. Implementing change at an individual versus a population level has different implications for overall benefit and patient motivation. Even very small steps taken in trying to reach guideline targets should represent a positive achievement for patients. Patient engagement is essential - only when patients commit themselves to change can benefits be maintained, and physicians should recognise their influence. Small changes in individual parameters can result in significant beneficial effects; however, a major impact can occur when small changes are made together in multiple parameters. More research is required to elucidate the full impact of small changes on patient outcome.

Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs.

AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p = 3 × 10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.

Area-based socioeconomic status, type 2 diabetes and cardiovascular mortality in Scotland.

AIMS/HYPOTHESIS: The aim of this study was to explore the relationships between type 2 diabetes mellitus, area-based socioeconomic status (SES) and cardiovascular disease mortality in Scotland. METHODS: We used an area-based measure of SES, Scottish national diabetes register data linked to mortality records, and general population cause-specific mortality data to investigate the relationships between SES, type 2 diabetes and mortality from ischaemic heart disease (IHD) and cerebrovascular disease (CbVD), for 2001-2007. We used negative binomial regression to obtain age-adjusted RRs of mortality (by sex), comparing people with type 2 diabetes with the non-diabetic population. RESULTS: Among 216,652 people aged 40 years or older with type 2 diabetes (980,687 person-years), there were 10,554 IHD deaths and 4,378 CbVD deaths. Age-standardised mortality increased with increasing deprivation, and was higher among men. IHD mortality RRs were highest among the least deprived quintile and lowest in the most deprived quintile (men: least deprived, RR 1.94 [95% CI 1.61, 2.33]; most deprived, RR 1.46 [95% CI 1.23, 1.74]) and were higher in women than men (women: least deprived, RR 2.84 [95% CI 2.12, 3.80]; most deprived, RR 2.04 [95% CI 1.55, 2.69]). A similar, weaker, pattern was observed for cerebrovascular mortality. CONCLUSIONS/INTERPRETATION: Absolute risk of cardiovascular mortality is higher in people with diabetes than in the non-diabetic population and increases with increasing deprivation. The relative impact of diabetes on cardiovascular mortality differs by SES, and further efforts to reduce cardiovascular risk both in deprived groups and people with diabetes are required. Prevention of diabetes may reduce socioeconomic health inequalities.

Setting research priorities for Type 1 diabetes.

AIMS: Research priorities are often set by academic researchers or the pharmaceutical industry. The interests of patients, carers and clinicians may therefore be overlooked and research questions that matter may be neglected. The aims of this study were to collect uncertainties about the treatment of Type 1 diabetes from patients, carers and health professionals, and to collate and prioritize these uncertainties to develop a top 10 list of research priorities, using a structured priority-setting partnership of patients, carers, health professionals and diabetes organizations, as described by the James Lind Alliance. METHODS: A partnership of interested organizations was set up, and from this a steering committee of 10 individuals was formed. An online and paper survey was used to identify uncertainties. These were collated, and the steering group carried out an interim priority-setting exercise with partner organizations. This group of uncertainties was then voted on to give a smaller list that went forward to the final priority-setting workshop. At this meeting, a final list of the top 10 research priorities was agreed. RESULTS: An initial 1141 uncertainties were described. These were reduced to 88 indicative questions, 47 of which went out for voting. Twenty-four were then taken forward to a final priority-setting workshop. This workshop resulted in a list of top 10 research priorities in Type 1 diabetes. CONCLUSION: We have shown that it is possible using the James Lind Alliance process to develop an agreed top 10 list of research priorities for Type 1 diabetes from health professionals, patients and carers.

Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population.

OBJECTIVES: Insulin resistance is associated with increased CD36 expression in a number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic lesions. The aim of this study was to determine whether plasma soluble CD36 (sCD36) was associated with insulin resistance, fatty liver and carotid atherosclerosis in nondiabetic subjects. METHODS: In 1296 healthy subjects without diabetes or hypertension recruited from 19 centres in 14 European countries (RISC study), we determined the levels of sCD36, adiponectin, lipids and liver enzymes, insulin sensitivity (M/I) by euglycaemic-hyperinsulinaemic clamp, carotid atherosclerosis as intima-media thickness (IMT) and two estimates of fatty liver, the fatty liver index (FLI) and liver fat percentage (LF%). RESULTS: IMT, FLI, LF%, presence of the metabolic syndrome, impaired glucose regulation, insulin and triglycerides increased across sCD36 quartiles (Q2-Q4), whereas adiponectin and M/I decreased (P ≤ 0.01). sCD36 was lower in women than in men (P = 0.045). Log sCD36 showed a bimodal distribution, and amongst subjects with sCD36 within the log-normal distribution (log-normal population, n = 1029), sCD36 was increased in subjects with impaired glucose regulation (P = 0.045), metabolic syndrome (P = 0.006) or increased likelihood of fatty liver (P < 0.001). sCD36 correlated significantly with insulin, triglycerides, M/I and FLI (P < 0.05) after adjustment for study centre, gender, age, glucose tolerance status, smoking habits and alcohol consumption. In the log-normal population, these relationships were stronger than in the total study population and, additionally, sCD36 was significantly associated with LF% and IMT (P < 0.05). CONCLUSIONS: In this cross-sectional study of nondiabetic subjects, sCD36 was significantly associated with indices of insulin resistance, carotid atherosclerosis and fatty liver. Prospective studies are needed to further evaluate the role of sCD36 in the inter-relationship between atherosclerosis, fatty liver and insulin resistance.

Do men develop type 2 diabetes at lower body mass indices than women?

AIMS/HYPOTHESIS: To describe the associations between age, sex and BMI at diagnosis of type 2 diabetes, and test the hypothesis that men are diagnosed with diabetes at lower average BMI than women of similar age. METHODS: Linear regression was used to estimate and compare the relationship between age and BMI at diagnosis among 51,920 men and 43,137 women included in a population-based diabetes register in Scotland for whom an index BMI measurement was taken within 1 year of diabetes diagnosis. We also examined HbA(1c) values by sex within the same timescale. RESULTS: Mean BMI closest to date of diagnosis of type 2 diabetes mellitus was 31.83 kg/m(2) (SD 5.13) in men and 33.69 kg/m(2) (SD 6.43) in women. The inverse relationship between age and BMI at diagnosis of type 2 diabetes mellitus was significantly steeper in women than in men (slope estimate in men -0.12 kg/m(2) per year [95% CI -0.13, -0.12] women -0.18 kg/m(2) per year [95% CI -0.18, -0.17], p < 0.0001 for formal test of interaction). Mean BMI difference was most marked at younger ages and narrowed with advancing age. However, HbA(1c) levels within 1 year of diagnoses were broadly similar in men and women. CONCLUSIONS/INTERPRETATION: Men are diagnosed with type 2 diabetes at lower BMI than women across the age range. This observation may help explain why type 2 diabetes is more common among middle-aged men in populations of European extraction. Whether the same pattern is also observed in other ethnic groups requires confirmation.

Inpatient costs for people with type 1 and type 2 diabetes in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group.

AIMS/HYPOTHESIS: The rising prevalence of diabetes worldwide has increased interest in the cost of diabetes. Inpatient costs for all people with diabetes in Scotland were investigated. METHODS: The Scottish Care Information-Diabetes Collaboration (SCI-DC), a real-time clinical information system of almost all diagnosed cases of diabetes in Scotland, UK, was linked to data on all hospital admissions for people with diabetes. Inpatient stay costs were estimated using the 2007-2008 Scottish National Tariff. The probability of hospital admission and total annual cost of admissions were estimated in relation to age, sex, type of diabetes, history of vascular admission, HbA(1c), creatinine, body mass index and diabetes duration. RESULTS: In Scotland during 2005-2007, 24,750 people with type 1 and 195,433 people with type 2 diabetes were identified, accounting for approximately 4.3% of the total Scottish population (5.1 million). The estimated total annual cost of admissions for all people diagnosed with type 1 and type 2 diabetes was £26 million and £275 million, respectively, approximately 12% of the total Scottish inpatient expenditure (£2.4 billion). Sex, increasing age, serum creatinine, previous vascular history and HbA(1c) (the latter differentially in type 1 and type 2) were all associated with likelihood and total annual cost of admission. CONCLUSIONS/INTERPRETATION: Diabetes inpatient expenditure accounted for 12% of the total Scottish inpatient expenditure, whilst people with diabetes account for 4.3% of the population. Of the modifiable risk factors, HbA(1c) was the most important driver of cost in type 1 diabetes.