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

User-centred design using Gamestorming

© 2016 IMIA and IOS Press. User-centered design (UX) is becoming a standard in software engineering and has tremendous potential in healthcare. The purpose of this tutorial will be to demonstrate and provide participants with practice in usercentred design methods that involve 'Gamestorming', a form of brainstorming where 'the rules of life are temporarily suspended'. Participants will learn and apply gamestorming methods including persona development via empathy mapping and methods to translate artefacts derived from participatory design sessions into functional and design requirements

Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin

Introduction Insulin analogues have become increasingly popular despite their greater cost compared with human insulin. The aim of this study was to calculate the incremental cost to the National Health Service (NHS) of prescribing analogue insulin preparations instead of their human insulin alternatives. Methods Open-source data from the four UK prescription pricing agencies from 2000 to 2009 were analysed. Cost was adjusted for inflation and reported in UK pounds at 2010 prices. Results Over the 10-year period, the NHS spent a total of £2732 million on insulin. The total annual cost increased from £156 million to £359 million, an increase of 130%. The annual cost of analogue insulin increased from £18.2 million (12% of total insulin cost) to £305 million (85% of total insulin cost), whereas the cost of human insulin decreased from £131 million (84% of total insulin cost) to £51 million (14% of total insulin cost). If it is assumed that all patients using insulin analogues could have received human insulin instead, the overall incremental cost of analogue insulin was £625 million. Conclusion Given the high marginal cost of analogue insulin, adherence to prescribing guidelines recommending the preferential use of human insulin would have resulted in considerable financial savings over the period

Deriving health state utilities for the numerical pain rating scale

Background The use of patient reported outcome measures within cost-effectiveness analysis has become commonplace. However, specific measures are required that produce values, referred to as 'utilities', that are capable of generating quality adjusted life years. One such measure - the EQ-5D - has come under criticism due to the inherent limitations of its three-level response scales. In evaluations of chronic pain, the numerical pain rating scale (NPRS) which has eleven levels is routinely used which has a greater measurement range, but which can not be used in cost-effetiveness analyses. This study derived utility values for a series of EQ-5D health states that replace the pain dimensions with the NPRS, thereby allowing a potentially greater range of pain intensities to be captured and included in economic analyses. Methods Interviews were undertaken with 100 member of the general population. Health state valuations were elicited using the time trade-off approach with a ten year time horizon. Additionally, respondents were asked where the EQ-5D response scale descriptors of moderate and extreme pain lay on the 11-point NPRS scale. Results 625 valuations were undertaken across the study sample with the crude mean health state utilities showing a negative non-linear relationship with respect to increasing pain intensity. Relative to a NPRS of zero (NPRS0), the successive pain levels (NPRS1-10) had mean decrements in utility of 0.034, 0.043, 0.061, 0.121, 0.144, 0.252, 0.404, 0.575, 0.771 and 0.793, respectively. When respondents were asked to mark on the NPRS scale the EQ-5D pain descriptors of moderate and extreme pain, the median responses were '4' and '8', respectively. Conclusions These results demonstrate the potential floor effect of the EQ-5D with respect to pain and provide estimates of health reduction associated with pain intensity described by the NPRS. These estimates are in excess of the decrements produced by an application of the EQ-5D scoring tariff for both the United States and the United Kingdom

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

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

The model of mortality with incident cirrhosis (MoMIC) and the model of long-term outlook of mortality in dcirrhosis (LOMiC)

The purpose of this study was to produce two statistical survival models in those with cirrhosis utilising only routine parameters, including non-liver-related clinical factors that influence survival. The first model identified and utilised factors impacting short-term survival to 90-days post incident diagnosis, and a further model characterised factors that impacted survival following this acute phase. Data were from the Clinical Practice Research Datalink linked with Hospital Episode Statistics. Incident cases in patients ≥18 years were identified between 1998 and 2014. Patients that had prior history of cancer or had received liver transplants prior were excluded. Model-1 used a logistic regression model to predict mortality. Model-2 used data from those patients who survived 90 days, and used an extension of the Cox regression model, adjusting for time-dependent covariables. At 90 days, 23% of patients had died. Overall median survival was 3.7 years. Model-1: numerous predictors, prior comorbidities and decompensating events were incorporated. All comorbidities contributed to increased odds of death, with renal disease having the largest adjusted odds ratio (OR = 3.35, 95%CI 2.97–3.77). Model-2: covariables included cumulative admissions for liver disease-related events and admissions for infections. Significant covariates were renal disease (adjusted hazard ratio (HR = 2.89, 2.47–3.38)), elevated bilirubin levels (aHR = 1.38, 1.26–1.51) and low sodium levels (aHR = 2.26, 1.84–2.78). An internal validation demonstrated reliability of both models. In conclusion: two survival models that included parameters commonly recorded in routine clinical practice were generated that reliably forecast the risk of death in patients with cirrhosis: in the acute, post diagnosis phase, and following this critical, 90 day phase. This has implications for practice and helps better forecast the risk of mortality from cirrhosis using routinely recorded parameters without inputs from specialists

Using rapid prototyping to design a smoking cessation website with end-users

© 2016 IMIA and IOS Press. Rapid prototyping is an iterative approach to design involving cycles of prototype building, review by end-users and refinement, and can be a valuable tool in user-centered website design. Informed by various user-centered approaches, we used rapid prototyping as a tool to collaborate with users in building a peer-support focused smoking-cessation website for gay men living with HIV. Rapid prototyping was effective in eliciting feedback on the needs of this group of potential end-users from a smoking cessation website

Risk of cardiovascular events, arrhythmia and all-cause mortality associated with clarithromycin versus alternative antibiotics prescribed for respiratory tract infections: a retrospective cohort study

Objective: To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics. Design: Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication. Setting: Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES). Participants: Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998–2012 and eligible for data linkage to HES. Main outcome measures: The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and allcause mortality. Results: Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22. Conclusions: CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with clarithromycin was no different to other antibiotics

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