Real-world evidence from the first online healthcare analytics platform-Livingstone. Validation of its descriptive epidemiology module.

Incidence and prevalence are key epidemiological determinants characterizing the quantum of a disease. We compared incidence and prevalence estimates derived automatically from the first ever online, essentially real-time, healthcare analytics platform-Livingstone-against findings from comparable peer-reviewed studies in order to validate the descriptive epidemiology module. The source of routine NHS data for Livingstone was the Clinical Practice Research Datalink (CPRD). After applying a general search strategy looking for any disease or condition, 76 relevant studies were first retrieved, of which 10 met pre-specified inclusion and exclusion criteria. Findings reported in these studies were compared with estimates produced automatically by Livingstone. The published reports described elements of the epidemiology of 14 diseases or conditions. Lin's concordance correlation coefficient (CCC) was used to evaluate the concordance between findings from Livingstone and those detailed in the published studies. The concordance of incidence values in the final year reported by each study versus Livingstone was 0.96 (95% CI: 0.89-0.98), whilst for all annual incidence values the concordance was 0.93 (0.91-0.94). For prevalence, concordance for the final annual prevalence reported in each study versus Livingstone was 1.00 (0.99-1.00) and for all reported annual prevalence values, the concordance was 0.93 (0.90-0.95). The concordance between Livingstone and the latest published findings was near perfect for prevalence and substantial for incidence. For the first time, it is now possible to automatically generate reliable descriptive epidemiology from routine health records, and in near-real time. Livingstone provides the first mechanism to rapidly generate standardised, descriptive epidemiology for all clinical events from real world data.

The financial burden of treating patients presenting with acute and chronic cough.

OBJECTIVE: Coughing is a common symptom and responsible for a large number of healthcare visits. This study aimed to characterize healthcare resource use and associated financial costs in people with acute or chronic cough. METHODS: A retrospective cohort study using routine data from the UK National Health Service. Adults (≥18 years) were selected if they had a cough record between 1 March 2014 and 28 February 2015 and were classified by duration. RESULTS: A cohort of 150,231 patients was identified, of whom 12,513 (8.3%) had chronic cough, 38,599 (25.7%) had an acute cough with more than one cough event, and 99,119 (66.0%) had acute cough with one event in the study year. Resource use and combined costs of all healthcare contacts differed between cough groups. The healthcare cost per person-year in patients with a single record of acute cough was £739; for those with chronic cough, the cost was £3,663. CONCLUSIONS: Patients with cough represented a substantial financial burden to the NHS. It was difficult to discern the specific portion of treatment associated with cough itself. However, people with chronic cough were associated with substantially increased healthcare use and costs than were those with acute cough.

Retinal thickness fluctuations in patients receiving fluocinolone acetonide implant for diabetic macular edema.

Objectives: To evaluate central foveal thickness (CFT) variability and accompanying changes in visual acuity (VA) 12 months before and after treatment with the 190 mcg fluocinolone acetonide (FAc) intravitreal implant for diabetic macular edema (DME).Methods: The Iluvien Clinical Evidence cohort study in the United Kingdom (ICE-UK) investigated the effectiveness of the FAc implant in people treated at 13 hospitals from April 2013 to April 2015. The following parameters were calculated for CFT for each patient: mean, standard deviation (SD), retinal thickness amplitude (RTA, the difference between maximum and minimum values), and coefficient of variation (CV).Results: In 149 eyes with ≥2 CFT observations both before and after FAc implantation, the median VA was 50 ETDRS letters at implantation. Mean CFT was 487 µm at implantation and 135 µm at 12 months post-implant. Before implantation, the mean CV and mean SD for CFT were 24.6% and 112 µm, respectively; the mean RTA was 254 µm. A statistically significant (p < .001) decrease in all three parameters was observed after implantation (18.3%, 68.2 µm and 146 µm, respectively). There was an association between CFT change between extremes and the corresponding change in VA (Pearson's correlation coefficient, r = -0.292, p < .001, prior to the implant; r = -0.379, p < .001, post-implant).Conclusions: After accounting for the reduction in CFT, retinal thickness stabilized following FAc implantation. There might be VA benefits in reducing variability in CFT over time. This merits further exploration but would require more frequent CFT observations in order to properly determine patterns of retinal thickness variability.

Cough presentation in primary care and the identification of chronic cough: a need for diagnostic clarity?

Objective: To investigate patterns of presentation of cough in primary care and develop an algorithm to identify probable and possible chronic cough (CC).Methods: This retrospective observational study used routine English primary care data and linked hospital data. Patients with ≥1 cough event in the study period (March 2014-February 2015) were selected. Index date was that of the earliest cough event in this period. Adults (aged ≥18 years) were classified as having probable CC if they had an explicit CC diagnosis; as having possible CC if they had ≥3 cough events recorded over 8-26 weeks; or, otherwise, as having acute cough. Underlying conditions associated with CC were identified.Results: 198,151 people were identified. 56.5% were female; median age was 47.0 years. The prevalence of cough in the study year was 17.6%. Of the 150,213 identified adults, 1600 (1.1%), 10,913 (7.3%) and 137,718 (91.7%) were classified as having probable CC, possible CC or acute cough, respectively. Compared with probable CC and acute cough, a higher percentage of possible CC cases had a record on or prior to index date indicative of chronic obstructive pulmonary disease (30.6% versus 10.1% and 9.7%), gastro-esophageal reflux disease (32.6% versus 24.9% and 21.1%) or asthma (45.9% versus 27.6% and 27.9%). Prevalences of probable and possible CC were 0.18% and 1.2%, respectively.Conclusions: The prevalence of CC was lower than reported in previous studies. People with possible CC had higher rates of underlying conditions associated with CC. These observations may suggest poor recognition and/or under-recording of CC in primary care.

Comparison of data characterizing the clinical effectiveness of the fluocinolone intravitreal implant (ILUVIEN) in patients with diabetic macular edema from the real world, non-interventional ICE-UK study and the FAME randomized controlled trials.

Objective: To compare the effectiveness and safety of the fluocinolone acetonide (FAc) intravitreal implant between the observational Iluvien Clinical Evidence study in the United Kingdom (ICE-UK) and the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) randomized controlled trials (RCTs) in people with diabetic macular edema (DME). Clinical Trials Registration: NCT00344968. Methods: This study selected patients randomized to receive 0.2 µg/day FAc insert (FAc treated eyes) or sham injection (control eyes) from the FAME RCTs, and patients' first FAc treated eye and non-FAc treated fellow (control) eye from the ICE-UK study. Outcomes included change in visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP). Results: After 12 months follow-up, mean change in VA was 5.0 letters improvement (p < .001) and 1.6 letters improvement (p = .003) in FAME FAc treated and control eyes, and 3.8 letters (p = .012) and -2.1 letters (p = .056) in ICE-UK FAc treated and control eyes, respectively. Mean change in CFT was -144 µm (p < .001) vs -72 µm (p < .001) in FAME FAc treated and control eyes and -113 µm (p < .001) vs -13 µm (p < .001) in ICE-UK FAc treated and control eyes. For eyes with a follow-up of 12 months, 77 (22.3%) and 15 (8.6%) FAME FAc treated and control eyes and 25 (18.7%) and six (4.3%) ICE-UK FAc treated and control eyes required emergent IOP-lowering therapy. Conclusions: Statistically significant improvements in VA 12 months after FAc implantation were observed in both the real-world study and in the RCTs. The improvement in VA and CFT in the RCTs was marginally greater than in the real-world study; however, recruits in the real-world study had more severe visual morbidity at baseline. Whilst there were many changes in the care of people with DME over this time, these data all support the value of treatment with FAc intravitreal implant.

Poor compliance and increased mortality, depression and healthcare costs in patients with congenital adrenal hyperplasia.

OBJECTIVES: To evaluate the risks of depression and all-cause mortality, healthcare utilisation costs and treatment adherence in congenital adrenal hyperplasia (CAH) in the United Kingdom. DESIGN AND METHODS: A retrospective, matched-cohort study using UK primary-care data from the Clinical Practice Research Datalink linked to hospital and death certification data. Patients diagnosed with CAH and having ≥1 corticosteroid prescription were matched 1:10 to reference subjects. Risk of death and lifetime prevalence of depression were compared using Cox regression models. Direct financial costs were estimated for healthcare contacts. Treatment adherence was measured by medical possession ratio (MPR). RESULTS: 605 patients with CAH were identified; 562 were matched. 270 CAH patients (2700 controls) were linkable to death-certificate data, with adjusted hazard ratio for all-cause mortality 5.17 (95% CI 2.81-9.50). Mean (s.d.) age at death in CAH patients was 54.8 (23.9) vs 72.8 (18.0) years in control patients. The prevalence ratio of depression in CAH vs control patients was 1.28 (95% CI 1.13-1.45). Mean (s.d.) annual healthcare costs were higher in CAH than controls: at age 0-6 years, £7038 (£14 846) vs £2879 (£13 972, P < 0.001); 7-17 years, £3766 (£7494) vs £1232 (£2451, P < 0.001); 18-40 years, £1539 (£872) vs £1344 (£1620, P = 0.007) and ≥41 years, £4204 (£4863) vs £1651 (£2303, P < 0.001). Treatment adherence was lowest in adults, with 141 (36%) of 396 eligible patients having an MPR <80%. CONCLUSIONS: This first analysis of CAH in routine UK healthcare suggests that patients with CAH have increased mortality, depression and healthcare utilisation and low treatment adherence.

Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival.

AIMS: To characterize survival in relation to achieved glycated haemoglobin (HbA1c) level within alternative glucose-lowering regimens with differing risks of hypoglycaemia. METHODS: Data were extracted from the UK Clinical Practice Research Datalink and the corresponding Hospital Episode Statistics. Patients with type 2 diabetes prescribed glucose-lowering therapy in monotherapy or dual therapy with metformin between 2004 and 2013 were identified. Risk of all-cause mortality within treatment cohorts was evaluated using the Cox proportional hazards model, introducing mean HbA1c as a quarterly updated, time-dependent covariable. RESULTS: There were 6646 deaths in a total follow-up period of 374 591 years. Survival for lower (<7%) vs moderate HbA1c levels (≥7%, <8.5%) differed by cohort: metformin, adjusted hazard ratio (aHR) 1.03 (95% confidence interval [CI] 0.95-1.12); sulphonylurea, aHR 1.11 (95% CI 0.99-1.25); insulin, aHR 1.47 (95% CI 1.25-1.72); combined regimens with low hypoglycaemia risk, aHR 1.02 (95% CI 0.94-1.10); and combined regimens with higher hypoglycaemia risk excluding insulin, aHR 1.24 (95% CI 1.13-1.35) and including insulin, aHR 1.28 (95% CI 1.18-1.37). Higher HbA1c levels were associated with increased mortality in regimens with low hypoglycaemia risk. Post hoc analysis by HbA1c deciles revealed an elevated risk of all-cause mortality for the lowest deciles across all cohorts, but particularly in those regimens associated with hypoglycaemia. High HbA1c was associated with no difference, or a small increase in mortality risk in regimens with increased risk of hypoglycaemia. CONCLUSIONS: The pattern of mortality risk across the range of HbA1c differed by glucose-lowering regimen. Lower HbA1c was associated with increased mortality risk compared with moderate control, especially in those regimens associated with hypoglycaemia. High levels of HbA1c were associated with the expected elevated mortality risk in regimens with low hypoglycaemia risk.

Evaluation of the clinical effectiveness of fluocinolone acetonide 190 µg intravitreal implant in diabetic macular edema: a comparison between study and fellow eyes.

OBJECTIVES: To compare visual and anatomical outcomes between eyes treated with fluocinolone acetonide (FAc) 190 µg intravitreal implant for clinically significant chronic diabetic macular edema (DME) and fellow eyes not treated with FAc implant using data from the Iluvien Clinical Evidence study in the UK (ICE-UK) study. METHODS: In this retrospective cohort study, data on people attending hospital eye services and treated with the FAc implant between April 1, 2013 and April 15, 2015 were collected. Changes in visual acuity (VA), central foveal thickness (CFT) and intraocular pressure (IOP) were compared between study eyes (intervention) and fellow eyes. RESULTS: A total of 208 people were selected. Mean age was 68.1 years and 62% were male. Mean change in VA was -0.09 LogMAR units for study eyes and 0.04 LogMAR units for fellow eyes at 12 months post-implant (p < .001). Over the same period, ≥5 letter, ≥10 letter and ≥15 letter improvements in Early Treatment Diabetic Retinopathy Study (ETDRS) score were achieved by more FAc treated eyes than by fellow eyes (41% versus 23%, p < .001; 28% versus 11%, p < .001; and 18% versus 4%, p < .001 at 12 months, respectively). Differences in the mean change in CFT (-113 µm versus -13 µm, p < .001) and IOP (3.2 mmHg versus -0.2 mmHg, p < .001) were also observed between study and fellow eyes at 12 months. CONCLUSION: Visual acuity improved in study eyes over the 12 months following FAc implant and worsened in fellow eyes. Over the same period, study eyes showed a larger improvement in central foveal thickness. Intraocular pressure worsened in study eyes only. Change in visual acuity, central foveal thickness and intraocular pressure between FAc implant and the end of the 12-month follow-up period differed significantly between study and fellow eyes.

Health-economic evaluation of fluocinolone acetonide 190 µg implant in people with diabetic macular edema.

OBJECTIVES: To assess healthcare resource use and costs of treating people with clinically significant diabetic macular edema (DME) with fluocinolone acetonide (FAc) 190 µg intravitreal implant in routine clinical practice. METHODS: The retrospective Iluvien Clinical Evidence (ICE-UK) study collected data on people prescribed the FAc implant in any one of 13 ophthalmology centers between April 1, 2013 and April 15, 2015. Data were collected for 12 months before and after implantation. Standard UK costs were attributed to healthcare resource use. RESULTS: In total, 208 people contributing 233 FAc-treated eyes were selected. Mean age was 68.1 years and 62% were male. The mean (standard deviation, SD) number of anti-vascular endothelial growth factor (anti-VEGF) injections per FAc treated eye in the 12 months prior to implant was 2.8 (2.5), decreasing to 0.6 (1.4) for the same period after implant (p < .001). The corresponding figures for other steroid injections (dexamethasone and triamcinolone) were 0.14 (0.4) before and 0.08 (0.4) after implant (p = .016). There was no statistically significant difference in the number of laser therapies required in the 12 months before and after FAc implant (mean = 0.12 vs 0.11, respectively; p = .626). Overall, mean (SD) healthcare costs were £2,691 (£1,850) before and £1,239 (£1,203) after FAc implant (p < .001). The unit drug and administration cost per FAc implant was £5,680. CONCLUSIONS: Excluding the cost of the FAc implant, healthcare costs were significantly reduced in the 12 months post-implant. FAc implant has a duration of 3 years. This needs to be considered when interpreting the cost associated with the FAc implant.

Evaluation of the clinical effectiveness in routine practice of fluocinolone acetonide 190 µg intravitreal implant in people with diabetic macular edema.

OBJECTIVE: The aim of the Iluvien Clinical Evidence study in the UK (ICE-UK) was to assess the real-world effectiveness of fluocinolone acetonide (FAc) 190 µg intravitreal implant for the treatment of clinically significant chronic diabetic macular edema (DME) in routine clinical practice. METHODS: This retrospective study collected data from patient medical records in 13 ophthalmology centers for people with DME prescribed FAc intravitreal implant between April 1, 2013 and April 15, 2015. Visual acuity (VA) and intraocular pressure (IOP) measurements were collected for 12 months prior to and after implant. RESULTS: Two hundred and eight people, contributing 233 eyes, treated with FAc implant were included. Mean age was 68.1 years and 62% were male. In the 12 months prior to FAc implant, VA declined. Median (interquartile range, IQR) VA was 0.66 (0.48-1.00) LogMAR units (equivalent to 52.0 ETDRS letters) at implant, improving to 0.60 (0.38-0.90) LogMAR units (55.0 letters) at 12 months post-implant (p < 0.001). In total, 44%, 30%, and 18% of people achieved an improvement in ETDRS score of ≥5, ≥10, and ≥15 letters, respectively, over the same period. A small but significant (p < .001) increase in median IOP was observed (median = 15.0, IQR = 13.0-18.0 mmHg at implant to 18.0, 15.0-21.0 mmHg at 12 months). In the 12 months following implant, additional IOP-lowering therapy was prescribed in 15% of subjects previously not requiring such therapy. CONCLUSION: Following FAc implant, an overall significant improvement in VA was observed over a period of 12 months, accompanied by a significant but small increase in IOP.

Patterns of retinal thickness prior to and following treatment with fluocinolone acetonide 190 µg intravitreal implant for diabetic macular edema.

OBJECTIVES: To compare retinal thickness before and after treatment with the fluocinolone acetonide (FAc) 190 µg intravitreal implant in people with diabetic macular edema (DME) using data from the Iluvien Clinical Evidence study in the UK (ICE-UK). METHODS: For this retrospective cohort study, data on people attending any one of 13 participating ophthalmology departments and treated with FAc intravitreal implant between April 1, 2013 and April 15, 2015 were collected for 12 months prior to and at least 12 months after implantation. Cross-sectional and longitudinal patterns of central foveal thickness (CFT) were compared before and after FAc implant. RESULTS: There were 208 people who contributed data from 233 individual eyes treated with the FAc implant. Mean age was 68.1 years and 62% were male. Median (interquartile range) CFT decreased from 462 µm (354-603 µm) at time of implant to 309 µm (222-433 µm) at 12 months post-implant (p < .001). Over the same period, a reduction of ≥10%, ≥25%, and ≥50% in CFT was observed in 113 (65%), 87 (50%), and 37 (21%) treated eyes, respectively. Eyes with a CFT of ≥400 µm at the time of implant were significantly more likely to achieve a reduction in CFT of ≥10%, ≥25%, and ≥50% at 12 months (all p < .001) compared with eyes with a CFT of <400 µm at implant. Both retinal thickness and changes in retinal thickness were loosely correlated with visual acuity. CONCLUSION: A marked reduction in retinal thickness was observed in people following FAc intravitreal implant for DME. The response was related to the degree of retinal thickness prior to treatment.

Direct medical costs of severe hypoglycaemic events in patients with type 2 diabetes in England: A retrospective database study.

AIMS: Hypoglycaemia in patients with diabetes can be induced by insulins and sulfonylureas. We assessed the real-world impact of specific monotherapy and combination regimens on hypoglycaemic events requiring hospitalisation and related secondary costs to the English healthcare system. METHODS: This retrospective observational study used the Clinical Practice Research Datalink with linked hospital admission data during 2008-2012. Patients with type 2 diabetes mellitus (T2DM) using antihyperglycaemic agents (AHAs) were assigned to mutually exclusive subgroups (insulin- and non-insulin-containing regimens; treatment groups of interest; age group) based on treatment at index date (date of first AHA prescription). Outcomes were number and cost of hospital admissions with hypoglycaemic event-related diagnosis codes. RESULTS: We identified 110 206 patients with T2DM (mean age 64.9 years, time since diagnosis 5.4 years, HbA1c at index 7.4%), with 439 hypoglycaemic events requiring inpatient hospitalisation (mean length of stay 6.3 days, mean cost/stay £1351). Event rates and cost of stay were highest in patients treated with sulfonylurea- or insulin-based regimens. Event rates, duration and cost of stay were higher in older patients. CONCLUSION: Rates of severe hypoglycaemic events varied substantially between T2DM regimens. In this study of patients treated in clinical practice in England, sulfonylurea- and insulin-based regimens were associated with the highest event rates and costs associated with hospitalisation for severe hypoglycaemic events; hospitalisation for severe hypoglycaemic events was not observed with dipeptidyl peptidase-4 inhibitor monotherapy or with metformin.

Healthcare resource utilization and related financial costs associated with glucose lowering with either exenatide or basal insulin: A retrospective cohort study.

AIMS: Type 2 diabetes is a major health problem placing increasing demands on healthcare systems. Our objective was to estimate healthcare resource use and related financial costs following treatment with exenatide-based regimens prescribed as once-weekly (EQW) or twice-daily (EBID) formulations, compared with regimens based on basal insulin (BI). MATERIALS AND METHODS: This retrospective cohort study used data from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES). Patients with type 2 diabetes who received exenatide or BI between 2009 and 2014 as their first recorded exposure to injectable therapy were selected. Costs were attributed to primary care contacts, diabetes-related prescriptions and inpatient admissions using standard UK healthcare costing methods (2014 prices). Frequency and costs were compared between cohorts before and after matching by propensity score using Poisson regression. RESULTS: Groups of 8723, 218 and 2180 patients receiving BI, EQW and EBID, respectively, were identified; 188 and 1486 patients receiving EQW and EBID, respectively, were matched 1:1 to patients receiving BI by propensity score. Among unmatched cohorts, total crude mean costs per patient-year were £2765 for EQW, £2549 for EBID and £4080 for BI. Compared with BI, the adjusted annual cost ratio (aACR) was 0.92 (95% CI, 0.91-0.92) for EQW and 0.82 (95% CI, 0.82-0.82) for EBID. Corresponding costs for the propensity-matched subgroups were £2646 vs £3283 (aACR, 0.80, 0.80-0.81) for EQW vs BI and £2532 vs £3070 (aACR, 0.84, 0.84-0.84) for EBID vs BI. CONCLUSION: Overall, exenatide once-weekly and twice-daily-based regimens were associated with reduced healthcare resource use and costs compared with basal-insulin-based regimens.

Cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor inhibitors across Europe.

OBJECTIVES: The aim of this study was to calculate the marginal cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor (TNF) inhibitors across Europe. METHODS: The proportion of people who escalate their dose of TNF inhibitor and the average percentage increase in TNF inhibitor cost associated with escalators versus non-escalators was calculated from previously published estimates, weighted by the sample size for each study. The number of people with rheumatoid arthritis treated with TNF inhibitors and the corresponding total drug sales were obtained for five European countries from Decision Resources' Pharmacor Market Forecast. Method 1 assumed that total sales of a TNF inhibitor represented the cost of an escalator multiplied by the number of escalators plus the cost of a non-escalator multiplied by the number of non-escalators. Method 2 assumed that the drug cost per day used to forecast total sales was calculated using the dose of TNF inhibitor used by non-escalators. The marginal cost of TNF inhibitor dose escalation was estimated by multiplying the difference in cost between escalators and non-escalators by the number of escalators. RESULTS: The estimated increase in TNF inhibitor costs associated with dose escalation in people with rheumatoid arthritis across five European countries (Germany, France, UK, Spain and Italy) was €51.5-54.4 million for adalimumab, €44.8-52.8 million for infliximab and €5.8-5.9 million for etanercept. CONCLUSIONS: Dose escalation of the TNF inhibitors adalimumab, etanercept and infliximab in people with rheumatoid arthritis has resulted in an increase in TNF inhibitor costs across five European countries.

Association between Insulin Monotherapy versus Insulin plus Metformin and the Risk of All-Cause Mortality and Other Serious Outcomes: A Retrospective Cohort Study.

AIMS: To determine if concomitant metformin reduced the risk of death, major adverse cardiac events (MACE), and cancer in people with type 2 diabetes treated with insulin. METHODS: For this retrospective cohort study, people with type 2 diabetes who progressed to insulin with or without metformin from 2000 onwards were identified from the UK Clinical Practice Research Datalink (≈7% sample of the UK population). The risks of all-cause mortality, MACE and incident cancer were evaluated using multivariable Cox models comparing insulin monotherapy with insulin plus metformin. We accounted for insulin dose. RESULTS: 12,020 subjects treated with insulin were identified, including 6,484 treated with monotherapy. There were 1,486 deaths, 579 MACE (excluding those with a history of large vessel disease), and 680 cancer events (excluding those in patients with a history of cancer). Corresponding event rates were 41.5 (95% CI 39.4-43.6) deaths, 20.8 (19.2-22.5) MACE, and 21.6 (20.0-23.3) cancer events per 1,000 person-years. The adjusted hazard ratios (aHRs) for people prescribed insulin plus metformin versus insulin monotherapy were 0.60 (95% CI 0.52-0.68) for all-cause mortality, 0.75 (0.62-0.91) for MACE, and 0.96 (0.80-1.15) for cancer. For patients who were propensity-score matched, the corresponding aHRs for all-cause mortality and cancer were 0.62 (0.52-0.75) and 0.99 (0.78-1.26), respectively. For MACE, the aHR was 1.06 (0.75-1.49) prior to 1,275 days and 1.87 (1.22-2.86) after 1,275 days post-index. CONCLUSIONS: People with type 2 diabetes treated with insulin plus concomitant metformin had a reduced risk of death and MACE compared with people treated with insulin monotherapy. There was no statistically significant difference in the risk of cancer between people treated with insulin as monotherapy or in combination with metformin.

Diabetes and Cancer.

Diabetes and cancer are common conditions, affecting 384 million and 33 million people worldwide, respectively. Therefore, there is great potential for overlap, with people with diabetes also developing cancer and vice versa. However, people with diabetes may be at increased risk of developing cancer when compared with the general population. This is due to both shared risk factors associated with the two diseases and the metabolic derangements associated with diabetes, such as hyperglycaemia, insulin resistance, hyperinsulinaemia and oxidative stress. Glucose-lowering therapies may influence the risk of cancer in people with type 2 diabetes due to these therapies' effects on risk factors that are common to both conditions, including hyperglycaemia and obesity, as well as effects that are specific to the class of drug or drugs. Drugs that reduce circulating insulin levels, such as metformin, may reduce cancer risk, and drugs that increase circulating insulin levels, including exogenous insulin and insulin secretagogues, may increase cancer risk. The influence of glucose-lowering therapies on cancer risk may become an important consideration when selecting glucose-lowering therapies to treat people with type 2 diabetes and a high risk of cancer occurrence or recurrence.

The prevalence and incidence, resource use and financial costs of treating people with attention deficit/hyperactivity disorder (ADHD) in the United Kingdom (1998 to 2010).

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common disorder that often presents in childhood and is associated with increased healthcare resource use. The aims of this study were to characterise the epidemiology of diagnosed ADHD in the UK and determine the resource use and financial costs of care. METHODS: For this retrospective, observational cohort study, patients newly diagnosed with ADHD between 1998 and 2010 were identified from the UK Clinical Practice Research Datalink (CPRD) and matched to a randomly drawn control group without a diagnosis of ADHD. The prevalence and incidence of diagnosed ADHD were calculated. Resource utilisation and corresponding financial costs post-diagnosis were estimated for general practice contacts, investigations, prescriptions, outpatient appointments, and inpatient admissions. RESULTS: Incidence of diagnosed ADHD (and percentage change using 1998 as a reference) increased from 6.9 per 100,000 population in 1998 to 12.2 per 100,000 (78%) in 2007 and then fell to 9.9 per 100,000 (44%) by 2009. The corresponding prevalence figures were 30.5, 88.9 (192%) and 81.5 (167%) per 100,000. Incidence and prevalence were higher in males than females. Mean annual total healthcare costs were higher for ADHD cases than controls (£1,327 versus £328 for year 1, £1,196 vs. £337 for year 2, £1,148 vs. £316 for year 3, £1,126 vs. £325 for year 4, and £1,112 vs. £361 for year 5). CONCLUSIONS: The prevalence of diagnosed ADHD in routine practice in the UK was notably lower than in previous reports, and both prevalence and incidence of diagnosed ADHD in primary care have fallen since 2007. Financial costs were more than four times higher in those with ADHD than in those without ADHD.