Characterization and Associated Costs of Constipation Relating to Exposure to Strong Opioids in England: An Observational Study.

PURPOSE: Opioid use is associated with gastrointestinal adverse events, including nausea and constipation. We used a real-world dataset to characterize the health care burden associated with opioid-induced constipation (OIC) with particular emphasis on strong opioids. METHODS: This retrospective cohort study was conducted using the Clinical Practice Research Datalink, a large UK primary care dataset linked to hospital data. Patients prescribed opioids during 2016 were selected and episodes of opioid therapy constructed. Episodes with ≥84 days of exposure were classified as chronic, with date of first prescription as the index date. The main analysis focused on patients prescribed strong opioids who were laxative naive. Constipation was defined by ≥2 laxative prescriptions during the opioid episode. Patients for whom initial laxative therapy escalated by switch, augmentation, or dose were defined as OIC unstable, and the first 3 lines of OIC escalation were classified. Health care costs accrued in the first 12 months of the opioid episode were aggregated and compared. FINDINGS: A total of 27,629 opioid episodes were identified; 5916 (21.4%) involved a strong opioid for patients who were previously laxative naive. Of these patients, 2886 (48.8%) were defined as the OIC population; 941 (33.26%) were classified as stable. Of the 1945 (67.4%) episodes classified as unstable, 849 (43.7%), 360 (18.5%), and 736 (37.8%) had 1, 2, and ≥3 changes of laxative prescription, respectively. Patients without OIC had lower costs per patient year (£3822 [US$5160/€4242]) compared with OIC (£4786 [US$6461/€5312]). Costs increased as patients had multiple changes in therapy: £4696 (US$6340/€5213), £4749 (US$6411/€5271), and £4981 (US$6724/€5529) for 1, 2, and ≥3 changes, respectively. The adjusted cost ratio relative to non-OIC was 1.14 (95% CI, 1.09-1.32) for those classified as stable and 1.19 (95% CI, 1.09-1.32) for those with ≥3 laxative changes. Similar patterns were observed for patients taking anyopioid, with costs increased for those classified as having OIC (£3727 [US$5031/€4137] vs £2379 [US$3212 /€2641),and for those patients classified as unstable versus stable (£3931 [US$5307/€4363] vs £3432 [US$4633/€3810). Costs increased with each additional line of therapy from £3701 (US$4996/€4108), £3916 (US$5287/€4347), and £4318 (US$5829/€4793). IMPLICATIONS: OIC was a common adverse event of opioid treatment and was poorly controlled for a large number of patients. Poor control was associated with increased health care costs. The impact of OIC should be considered when prescribing opioids. These results should be interpreted with consideration of the caveats associated with the analysis of routine data.

Insulin-like growth factor-1, growth hormone and disease outcomes in acromegaly: A population study.

CONTEXT: A lack of consensus remains about the relative importance of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in predicting adverse outcomes in patients with acromegaly. OBJECTIVE: To describe the differing association between IGF-1 and GH and major disease outcomes in acromegaly. DESIGN: Retrospective cohort study. PATIENTS: United Kingdom National Health Service patients with acromegaly who had an IGF-1 and/or a GH measurement recorded following diagnosis, prior to December 2019. MEASUREMENTS: A composite endpoint including all-cause mortality (ACM), type 2 diabetes (DM), major adverse cardiovascular events (MACE) or cancer was the primary outcome. These outcomes were also analysed individually. Follow-up period was capped at 5 years. RESULTS: A maximum of 417 cases and 332 cases were eligible for the IGF-1 and GH analyses, respectively, comprising 1041.5 and 938.9 years of follow-up. There was a direct association between increased IGF-1 concentration and adjusted event risk for the composite endpoint (hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 1.02-1.5); in GH, the HR was 1.1 (1.0-1.2). For the individual endpoints in relation to IGF-1 level, the HRs were ACM (1.2; 0.93-1.5), MACE (1.2; 0.64-2.1), DM (1.53; 1.09-2.2) and cancer (1.3; 0.95-1.7). For GH, the HRs were ACM (1.1; 0.97-1.2), MACE (0.99; 0.73-1.3), DM (1.1; 0.99-1.2) and cancer (0.90; 0.66-1.2). CONCLUSIONS: In this contemporary data set with extended follow-up, IGF-1 and GH concentrations showed an association with major adverse outcomes from acromegaly.

Incidence of type II diabetes in chronic obstructive pulmonary disease: a nested case-control study.

We investigated the incidence of type II diabetes mellitus (T2DM) among people with COPD and whether exposure to inhaled corticosteroid (ICS) and exacerbation status was associated with T2DM. This descriptive cohort study used primary care data from the Clinical Practice Research Datalink (CPRD). The patient cohort included people with a diagnosis of COPD and previous smoking history registered at a CPRD practice between January 2010 and December 2016. We determined incidence rates by age, gender and deprivation. Using a nested case-control design-where cases and controls are drawn from the cohort population-we matched 1:5 with patients by age, gender and GP practice and estimated odds of T2DM using logistic regression (adjusting for smoking status, deprivation, BMI, hypertension, coronary heart disease and heart failure). We identified 220,971 COPD patients; mean age at COPD diagnosis was 66 years (SD 12) and 54% were male. The incidence rate of T2DM in COPD patients was 1.26 per 100 patient years (95% CI: 1.24-1.28) and was higher among men (1.32 vs 1.18 among women). The adjusted odds ratio for T2DM was 1.47 (95% CI: 1.36-1.60) among frequent exacerbators (≥2 treated exacerbations per year) compared to infrequent exacerbators and the odds ratio for patients receiving high-dose ICS (>800 mcg budesonide equivalent dose) was 1.73 (95% CI 1.65-1.82) compared to patients receiving no ICS therapy. Incidence of T2DM among COPD patients is high and exposure to ICS and frequent exacerbations are associated with a higher risk of T2DM among patients with COPD.

What is the impact of GOLD 2017 recommendations in primary care? - a descriptive study of patient classifications, treatment burden and costs.

PURPOSE: The changes in grading of disease severity and treatment recommendations for patients with COPD in the 2017 GOLD strategy may present an opportunity for reducing treatment burden for the patients and costs to the health care system. The aim of this study was to assess the implications of the GOLD 2017 grading system in terms of change in distribution across GOLD groups A-D for existing patients in UK primary care and estimate the potential cost savings of implementing GOLD 2017 treatment recommendations in UK primary care. PATIENTS AND METHODS: Using electronic health record data from the Clinical Practice Research Datalink (CPRD), patients aged ≥35 years with spirometry-confirmed COPD, receiving care during 2016, were included. The cohort was graded according to the GOLD 2017 groups (A-D), and treatment costs were calculated, according to corresponding recommendations, to observe the difference in actual vs predicted costs. RESULTS: When applying GOLD 2013 criteria, less than half of the cohort (46%) was assigned to GOLD A or B, as compared to 86% when applying the GOLD 2017 grading. The actual mean annual maintenance treatment cost was £542 per patient vs a predicted £389 for treatment according to the 2017 GOLD strategy. CONCLUSION: There is a potential to make significant cost savings by implementing the grading and treatment recommendations from the 2017 GOLD strategy.

Evaluation of the cost-effectiveness of rifaximin-α for the management of patients with hepatic encephalopathy in the United Kingdom.

OBJECTIVE: Rifaximin-α 550 mg twice daily plus lactulose has demonstrated efficacy in reducing recurrence of episodes of overt hepatic encephalopathy (OHE) and the risk of hepatic encephalopathy (HE)-related hospitalizations compared with lactulose alone. This analysis estimated the cost effectiveness of rifaximin-α 550 mg twice daily plus lactulose versus lactulose alone in United Kingdom (UK) cirrhotic patients with OHE. METHOD: A Markov model was built to estimate the incremental cost-effectiveness ratio (ICER). The perspective was that of the UK National Health Service (NHS). Clinical data was sourced from a randomized controlled trial (RCT) and an open-label maintenance study in cirrhotic patients in remission from recurrent episodes of OHE. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. Resource use data describing the impact of rifaximin-α on hospital admissions and length of stay for cirrhotic patients with OHE was from four single-center UK audits. Costs (2012) were derived from published sources; costs and benefits were discounted at 3.5%. The base-case time horizon was 5 years. RESULTS: The average cost per patient was £22,971 in the rifaximin-α plus lactulose arm and £23,545 in the lactulose arm, a saving of £573. The corresponding values for benefit were 2.35 quality adjusted life years (QALYs) and 1.83 QALYs per person, a difference of 0.52 QALYs. This translated into a dominant base-case ICER. Key parameters that impacted the ICER included number of hospital admissions and length of stay. CONCLUSION: Rifaximin-α 550 mg twice daily in patients with recurrent episodes of OHE was estimated to generate cost savings and improved clinical outcomes compared to standard care over 5 years.

Prescription of DPP-4 Inhibitors to Patients With Adult Type 2 Diabetes Mellitus and Creatinine Clearance >50 mL/min: The UK Primary Care Experience.

The aim of the study was to examine the extent to which patients with type 2 diabetes mellitus (T2DM) initiating a dipeptidyl peptidase 4 (DPP-4) inhibitor, who had no recorded objective evidence to justify dose adjustment, were initiated on the manufacturer-specified dose. Adopting a cross-sectional study design and using data from the UK General Practice, this study showed that at least 10% of patients with T2DM and a creatinine clearance level >50 mL/min initiating treatment with a DPP-4 inhibitor were prescribed a dose lower than specified in the Summary of Product Characteristics. This study provides further insights regarding DPP-4 inhibitor dose selection with respect to manufacturer specification in relation to renal function.

Assessing the healthcare resource use associated with inappropriate prescribing of inhaled corticosteroids for people with chronic obstructive pulmonary disease (COPD) in GOLD groups A or B: an observational study using the Clinical Practice Research Datalink (CPRD).

BACKGROUND: Recent recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations (≥ 2 or ≥ 1 requiring hospitalisation); i.e. GOLD groups C and D. However, it is known that ICS is frequently prescribed for patients with less severe COPD. Potential drivers of inappropriate ICS use may be historical clinical guidance or a belief among physicians that intervening early with ICS would improve outcomes and reduce resource use. The objective of this study was to compare healthcare resource use in the UK for COPD patients in GOLD groups A and B (0 or 1 exacerbation not resulting in hospitalisation) who have either been prescribed an ICS-containing regimen or a non-ICS-containing regimen. METHODS: Linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database were used. For the study period (1 July 2005 to 30 June 2015) a total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing therapy and 2264 receiving non-ICS therapy. Treatment groups were propensity score-matched to account for potential confounders in the decision to prescribe ICS, leaving 1739 patients in both treatment arms. Resource use was assessed in terms of frequency of healthcare practitioner (HCP) interactions and rescue therapy prescribing. Treatment acquisition costs were not assessed. RESULTS: Results showed no benefit associated with the addition of ICS, with numerically higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate: 1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163; adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared to the non-ICS group. Rate ratios favoured the non-ICS group for eight of nine outcomes assessed. Outcomes were similar for subgroup analyses surrounding potential influential parameters, including patients with poorer lung function (FEV1 <  50% predicted), one prior exacerbation or elevated blood eosinophils. CONCLUSIONS: These data suggest that ICS use in GOLD A and B COPD patients is not associated with a benefit in terms of healthcare resource use compared to non-ICS bronchodilator-based therapy; using ICS according to GOLD recommendations may offer an opportunity for improving patient care and reducing resource use.

Fatal Canine Intoxications Linked to the Presence of Saxitoxins in Stranded Marine Organisms Following Winter Storm Activity.

At the start of 2018, multiple incidents of dog illnesses were reported following consumption of marine species washed up onto the beaches of eastern England after winter storms. Over a two-week period, nine confirmed illnesses including two canine deaths were recorded. Symptoms in the affected dogs included sickness, loss of motor control, and muscle paralysis. Samples of flatfish, starfish, and crab from the beaches in the affected areas were analysed for a suite of naturally occurring marine neurotoxins of dinoflagellate origin. Toxins causing paralytic shellfish poisoning (PSP) were detected and quantified using two independent chemical testing methods in samples of all three marine types, with concentrations over 14,000 µg saxitoxin (STX) eq/kg found in one starfish sample. Further evidence for PSP intoxication of the dogs was obtained with the positive identification of PSP toxins in a vomited crab sample from one deceased dog and in gastrointestinal samples collected post mortem from a second affected dog. Together, this is the first report providing evidence of starfish being implicated in a PSP intoxication case and the first report of PSP in canines.

Prescription of DPP-4 Inhibitors to Type 2 Diabetes Mellitus Patients With Renal Impairment: A UK Primary Care Experience.

Members of the dipeptidyl peptidase-4 inhibitor drug class are indicated for glycemic control in patients with type 2 diabetes mellitus and all, except linagliptin, require dose adjustment in renal impairment. A cross-sectional analysis of a cohort of type 2 diabetes mellitus patients treated with dipeptidyl peptidase-4 inhibitors identified in the Clinical Practice Research Datalink was conducted to explore compliance with the renal adjustment requirements of the Summaries of Product Characteristics. Approximately one third of type 2 diabetes mellitus patients with creatinine clearance <50 mL/min who were at risk of inappropriate prescribing, were initiated on a DPP-4 inhibitor at a higher dose than the specified in their respective Summary of Product Characteristics.

Effectiveness of the capsaicin 8% patch in the management of peripheral neuropathic pain in European clinical practice: the ASCEND study.

BACKGROUND: In randomised studies, the capsaicin 8% patch has demonstrated effective pain relief in patients with peripheral neuropathic pain (PNP) arising from different aetiologies. METHODS: ASCEND was an open-label, non-interventional study of patients with non-diabetes-related PNP who received capsaicin 8% patch treatment, according to usual clinical practice, and were followed for ≤52 weeks. Co-primary endpoints were percentage change in the mean numeric pain rating scale (NPRS) 'average daily pain' score from baseline to the average of Weeks 2 and 8 following first treatment; and median time from first to second treatment. The primary analysis was intended to assess analgesic equivalence between post-herpetic neuralgia (PHN) and other PNP aetiologies. Health-related quality of life (HRQoL, using EQ-5D), Patient Global Impression of Change (PGIC) and tolerability were also assessed. RESULTS: Following first application, patients experienced a 26.6% (95% CI: 23.6, 29.62; n = 412) reduction in mean NPRS score from baseline to Weeks 2 and 8. Equivalence was demonstrated between PHN and the neuropathic back pain, post-operative and post-traumatic neuropathic pain and 'other' PNP aetiology subgroups. The median time from first to second treatment was 191 days (95% CI: 147, 235; n = 181). Forty-four percent of all patients were responders (≥30% reduction in NPRS score from baseline to Weeks 2 and 8) following first treatment, and 86.9% (n = 159/183) remained so at Week 12. A sustained pain response was observed until Week 52, with a 37.0% (95% CI: 31.3, 42.7; n = 176) reduction in mean NPRS score from baseline. Patients with the shortest duration of pain (0-0.72 years) experienced the highest pain response from baseline to Weeks 2 and 8. Mean EQ-5D index score improved by 0.199 utils (responders: 0.292 utils) from baseline to Week 2 and was maintained until Week 52. Most patients reported improvements in PGIC at Week 2 and at all follow-up assessments regardless of number of treatments received. Adverse events were primarily mild or moderate reversible application site reactions. CONCLUSION: In European clinical practice, the capsaicin 8% patch provided effective and sustained pain relief, substantially improved HRQoL, improved overall health status and was generally well tolerated in a heterogeneous PNP population. TRIAL REGISTRATION: NCT01737294 Date of registration - October 22, 2012.

An estimate of the economic burden of vitamin D deficiency in pregnant women in the United Kingdom.

Pregnancy is associated with an increased risk of vitamin D deficiency beyond that of the general population. The aim of the current analysis was to synthesize the current evidence on the dose-outcome relationship of vitamin D/serum 25 hydroxyvitamin D (25-OHD) and complications during pregnancy. An additional aim was to estimate the economic burden attributable to inadequate levels of serum 25-OHD. Published literature on the effects of vitamin D supplementation/serum 25-OHD on pregnancy complications, including randomized control trials and non-interventional studies, was searched in bibliographic databases including Pubmed, Google Scholar, Scopus and EMBASE. A positive and significant treatment effect was obtained for pre-eclampsia (OR = 0.75 95% CI 0.662-0.843), but not for preterm birth (OR = 0.783, 95% CI 0.49-1.251) or small for gestational age (OR = 0.76 95% CI 0.38-1.28). Inadequate vitamin D accounted for 14.04% of risk for pre-eclampsia. It is estimated that addressing vitamin D inadequacy in pregnant women in England and Wales would reduce the number of cases of pre-eclampsia by 4126; and would result in a net saving of £18.6 million for the NHS in England and Wales. The current results suggest that based on current evidence a public health policy preventing vitamin D inadequacy in pregnant women is likely to have a positive impact on the NHS budget in England and Wales. This is contingent upon further evidence regarding the vitamin D dose-pregnancy outcome relationship becoming available.

Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland.

We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, -£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the probability of capsaicin 8% patch being cost-effective versus pregabalin was 97%. Capsaicin 8% patch is a cost-effective treatment option compared with dose-optimized pregabalin in patients with PNP who have failed one or more previous systemic treatments.

Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo.

BACKGROUND: In this analysis we report patients with advanced gastrointestinal stromal tumors (GIST) refractory to imatinib and sunitinib therapy as derived from the EuroQol-5D (EQ-5D) for progression-free (PF) and progressive disease health status. METHODS: Data were analyzed from a phase III trial conducted at 57 hospitals in 17 countries (trial registration number, NCT01271712). Patients with advanced GIST were randomized (2:1) to receive blinded treatment using oral regorafenib 160 mg daily or placebo, plus best supportive care (BSC) in both groups, for the first 3 weeks of each 4-week cycle. EQ-5D-3L was administered on day 1 of each cycle before contact with their physician and before any study-related procedures. The effect of disease progression on the utility of EQ-5D was tested with paired-samples comparison and general linear mixed modeling (GLMM). RESULTS: One hundred and eighty five patients [93 % of the intention-to-treat (ITT) population] completed 803 EQ-5D questionnaires: 77.7 % in progression-free (PF) state, 6.5 % at progression, 13.9 % following first progression, and 1.9 % after second progression. Mean baseline utility was 0.767 (SD 0.221) with no significant between-group differences for active treatment and BSC. The first post-progression health state was 0.647 (SD 0.343), suggesting significantly impaired health-related quality of life after confirmed disease progression showed a decrease of -0.120 (paired samples t test, p = 0.001). GLMM showed no effect of study treatment or cycle number on utility. CONCLUSIONS: We demonstrate a significant and clinically meaningful difference in health state utility values between PF and progression. Utility values remained stable over successive regorafenib cycles after controlling for disease status and treatment type.

Antibiotic treatment failure in four common infections in UK primary care 1991-2012: longitudinal analysis.

OBJECTIVE: To characterise failure of antibiotic treatment in primary care in the United Kingdom in four common infection classes from 1991 to 2012. DESIGN: Longitudinal analysis of failure rates for first line antibiotic monotherapies associated with diagnoses for upper and lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. SETTING: Routine primary care data from the UK Clinical Practice Research Datalink (CPRD). MAIN OUTCOME MEASURES: Adjusted rates of treatment failure defined by standardised criteria and indexed to year 1 (1991=100). RESULTS: From 58 million antibiotic prescriptions in CPRD, we analysed 10,967,607 monotherapy episodes for the four indications: 4,236,574 (38.6%) for upper respiratory tract infections; 3,148,947 (28.7%) for lower respiratory tract infections; 2,568,230 (23.4%) for skin and soft tissue infections; and 1,013,856 (9.2%) for acute otitis media. In 1991, the overall failure rate was 13.9% (12.0% for upper respiratory tract infections; 16.9% for lower respiratory tract infections; 12.8% for skin and soft tissue infections; and 13.9% for acute otitis media). By 2012, the overall failure rate was 15.4%, representing an increase of 12% compared with 1991 (adjusted value indexed to first year (1991) 112, 95% confidence interval 112 to 113). The highest rate was seen in lower respiratory tract infections (135, 134 to 136). While failure rates were below 20% for most commonly prescribed antibiotics (amoxicillin, phenoxymethylpenicillin (penicillin-V), and flucloxacillin), notable increases were seen for trimethoprim in the treatment of upper respiratory tract infections (from 29.2% in 1991-95 to 70.1% in 2008-12) and for ciprofloxacin (from 22.3% in 1991-95 to 30.8% in 2008-12) and cefalexin (from 22.0% in 1991-95 to 30.8% in 2008-12) in the treatment of lower respiratory tract infections. Failure rates for broad spectrum penicillins, macrolides, and flucloxacillin remained largely stable. CONCLUSIONS: From 1991 to 2012, more than one in 10 first line antibiotic monotherapies for the selected infections were associated with treatment failure. Overall failure rates increased by 12% over this period, with most of the increase occurring in more recent years, when antibiotic prescribing in primary care plateaued and then increased.

The medico-legal aspects of prescribing vitamin D.

Vitamin D is a particularly important sterol hormone and its effects beyond bone are increasingly recognized. Over the last decade clinical interest has grown in vitamin D, with increased recognition of deficiency and hence increased prescribing of vitamin D products. However, the increased prescription of vitamin D has generally been met with unlicensed vitamin D products which potentially expose the patient to clinical risk. This review discusses the issues relating to the clinical use of unlicensed vitamin D products, safety concerns that may arise from this, as well as discussing the medico-legal responsibilities of the prescriber and dispenser.

The short-term impact of vitamin D-based hip fracture prevention in older adults in the United Kingdom.

PURPOSE: Vitamin D is a relatively inexpensive drug yet an important hormone in terms of calcium and bone homeostasis. Treatment with vitamin D is associated with reduced fracture risk particularly in an elderly population. Therefore, we assessed the budgetary impact of routine prescription of 800 IU daily colecalciferol on hip fracture among older adults in the United Kingdom. METHODS: Using meta-analysis findings for treatment effect and UK-estimates of incidence, we performed a health economic evaluation of treating the UK population aged 65 and over with 800 IU of vitamin D daily, assessing the impact upon hip fracture costs using incremental attributable costs and excess mortality for a range of age- gender-based treatment strategies. RESULTS: Using only a 1-year horizon, considering only reduction in hip fracture, prescribing colecalciferol 800 IU daily to all adults aged 65 and over, could reduce the number of incident hip fractures from 65,400 to 45,700, saving almost 1,700 associated deaths, whilst saving the UK taxpayer £22 million. CONCLUSIONS: As the UK government seeks to reduce public expenditure in all sectors, investment in prescribed prophylactic colecalciferol 800 IU therapy for adults aged 65 and over is likely to yield cost savings through reduction hip fracture alone in the first year.

Estimation of health-related utility (EQ-5D index) in subjects with seasonal allergic rhinoconjunctivitis to evaluate health gain associated with sublingual grass allergen immunotherapy.

BACKGROUND: Grass allergen immunotherapy (AIT) reduces symptom severity in seasonal allergic rhinoconjunctivitis (ARC) but its impact on general health-related utility has not been characterised for the purposes of economic evaluation. The aim of this study was to model the preferred measure of utility, EQ-5D index, from symptom severity and estimate incremental quality adjusted life years (QALYs) associated with SQ-standardised grass immunotherapy tablet (GRAZAX®, 75,000 SQ-T/2,800 BAU, ALK, Denmark). METHODS: Data were analysed from five consecutive pollen seasons in a randomised placebo controlled trial of GRAZAX®. Binomial and Gaussian mixed effects modelling related weekly EQ-5D index score to daily symptom and medication scores (DSS & DMS respectively). In turn, daily EQ-5D index was estimated from ARC symptoms and medication use. RESULTS: DSS and DMS were the principal predictors of 'perfect' health (EQ-5D = 1.000; binomial) and 'imperfect' health (EQ-5D < 1.000; Gaussian). Each unit increase in DSS and DMS reduced the odds of 'perfect' health (EQ-5D = 1.000) by 27% and 16% respectively, and reduced 'imperfect' health by 0.17 and 0.13, respectively. Gender remained the only other significant main fixed effect (Male odds ratio [OR] = 1.82). Incremental estimated EQ-5D index utility for GRAZAX® was observed from day -30 to day +70 of the pooled pollen season; mean daily utility for GRAZAX® = 0.938 units (95%CI 0.932-0.943) vs. 0.914 (0.907-0.921) for placebo, an incremental difference of 0.0238 (p < 0.001). This translates into an incremental 0.0324 Quality Adjusted Life Years over the five year study period. CONCLUSIONS: ARC symptoms and medication use are the main predictors of EQ-5D index. The incremental QALYs observed for GRAZAX® may not fully describe the health benefits of this treatment, suggesting that economic modelling may be conservative.

The effect of withdrawal of rosiglitazone on treatment pathways, diabetes control and patient outcomes: a retrospective cohort study.

AIMS: To describe the withdrawal of rosiglitazone and the impact upon glycaemic control; intensification of therapy; and progression to major adverse cardiovascular events (MACE), cancer and mortality. METHODS: Data were from the Clinical Practice Research Datalink (CPRD), a longitudinal U.K. database. Rosiglitazone use was profiled from launch (2000) until withdrawal (2010). Patients discontinuing from July 2010 were included in the analysis to ascertain the impact on glycaemic control; therapy intensification; and progression to MACE, death and cancer. For comparison, patients were matched to those maintained on pioglitazone as a control group. RESULTS: Rosiglitazone use peaked in May 2007. Of patients prescribed rosiglitazone at discontinuation 54.1% patients used a dual-therapy regimen; most commonly with metformin (46.7%). 65.1% patients remained at the same stage of the diabetes pathway following discontinuation. 51.7% of patients replaced rosiglitazone with pioglitazone. Patients discontinuing were more likely (HR=2.29), to subsequently intensify therapy than controls. After discontinuation of rosiglitazone there was a significant increase in HbA1c, from a median of 6.9% to 7.3%. In matched analysis, there was a significantly greater increase in HbA1c for rosiglitazone patients (0.33% versus 0.10%). Following discontinuation, crude rates for MACE, cancer and mortality were 8.4, 17.9 and 15.8 pkpy, respectively. None was significantly different in the matched analysis. CONCLUSION: Withdrawal of rosiglitazone was associated with worsening glucose control and subsequent intensification of treatment regimen.