Modeling Respiratory Syncytial Virus Adult Vaccination in the United States With a Dynamic Transmission Model.

BACKGROUND: Respiratory syncytial virus (RSV) is shown to cause substantial morbidity, hospitalization, and mortality in infants and older adults. Population-level modeling of RSV allows to estimate the full burden of disease and the potential epidemiological impact of novel prophylactics. METHODS: We modeled the RSV epidemiology in the United States across all ages using a deterministic compartmental transmission model. Population-level symptomatic RSV acute respiratory tract infection (ARI) cases were projected across different natural history scenarios with and without vaccination of adults aged ≥60 years. The impact of vaccine efficacy against ARIs, infectiousness and vaccine coverage on ARI incidence were assessed. The impact on medical attendance, hospitalization, complications, death, and other outcomes was also derived. RESULTS: Without a vaccine, we project 17.5-22.6 million symptomatic RSV ARI cases annually in adults aged ≥18 years in the US, with 3.6-4.8 million/year occurring in adults aged ≥60 years. Modeling indicates that up to 2.0 million symptomatic RSV-ARI cases could be prevented annually in ≥60-year-olds with a hypothetical vaccine (70% vaccine efficacy against symptomatic ARI and 60% vaccine coverage) and that up to 0.69 million/year could be prevented in the nonvaccinated population, assuming 50% vaccine impact on infectiousness. CONCLUSIONS: The model provides estimated burden of RSV in the US across all age groups, with substantial burden projected specifically in older adults. Vaccination of adults aged ≥60 years could significantly reduce the burden of disease in this population, with additional indirect effect in adults aged <60 years due to reduced transmissibility.

Adherence to rotavirus vaccination quality measures in a commercially insured population.

BACKGROUND: This retrospective study determined the level of compliance to rotavirus vaccination guidelines within a large, commercially insured US population, as well as compliance with PI, ACIP and HEDIS measures for rotavirus vaccination. METHODS: Medical and pharmacy claims were obtained from the HealthCore Integrated Research Database. Enrolled children were stratified into PI, ACIP and HEDIS cohorts. The PI cohort was subdivided into RV5 and RV1 cohorts due to the differences in dosing schedules and patients with mixed dosing were excluded from the these two cohorts. Patients identified in the HEDIS cohort were linked to the administering physicians. RESULTS: Of 162,614 patients in PI cohort, 27% did not receive rotavirus vaccinations, 24% (RV5) and 15% (RV1) had incomplete doses (p < 0.0001; RV1 vs. RV5). A total of 76% of patients completed RV5 series but not on schedule, 54% completed on schedule. A total of 85% of patients completed the RV1 series at any time, 69% completed on schedule. Among health plans, 53% of patients completed the series, 22% (RV5) and 15% (RV1) had incomplete doses (p < 0.0001). Of 2,086 physicians who treated ≥ 10 patients within the plan (regardless of vaccination status), 78% had > 50% of patients complete, 22% had > 90% of patients completed. CONCLUSION: Despite both two effective rotavirus vaccines and national immunization recommendations, rotavirus vaccination remains underutilized for infants.

Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature.

AIM: The objective of this review was to assess the published evidence for an association between glycaemic variability and the development of chronic micro- and macrovascular complications in patients with diabetes mellitus (DM). METHODS: A systematic review of English-language literature published from January 1990 through November 2008 was performed. Interventional and observational studies in patients with type 1 or type 2 DM reporting a measure of glycaemic variability and its impact on the development or progression of micro- and macrovascular diabetic complications were assessed. RESULTS: A total of 18 studies -8 on type 1 DM and 10 on type 2 DM patients-meeting the inclusion criteria were identified. Studies in patients with type 1 DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two of the eight type 1 DM studies did glucose variability have a significant association with microvascular complications, but not with macrovascular complications. Among type 2 DM studies, a significant positive association between glucose variability and the development or progression of diabetic retinopathy, cardiovascular events and mortality was reported in 9 of 10 studies. Only one type 2 DM study reported no association between glucose variability and progression of retinopathy. CONCLUSIONS: Based on this overview of the available evidence, there appears to be a signal suggesting that glucose variability, characterized by extreme glucose excursions, could be a predictor of diabetic complications, independent of HbA1c levels, in patients with type 2 DM. Better daily control of blood glucose excursions, especially in the postprandial period, may reduce the risk of these complications. Future prospective trials evaluating and comparing the effect of the control of glycaemic variability on the development of diabetic micro- and macrovascular complications are needed to further strengthen the evidence base.

Drug titration patterns and HbA 1c levels in type 2 diabetes.

OBJECTIVE: To evaluate oral antidiabetes drug (OAD) use, haemoglobin A(1c) (HbA(1c)) testing and glycaemic control in type 2 diabetes patients. STUDY DESIGN: Retrospective analysis based on claims data from the Integrated Healthcare Information Services (IHCIS) National Managed Care Benchmark Database. METHODS: OAD use and HbA(1c) testing were analysed for patients with >or= 2 claims indicating diagnosis of type 2 diabetes and >or= 1 90-day OAD treatment period between 1 January, 2000 and 30 June, 2006. Likelihood of HbA(1c) testing was examined using multivariable logistic regression analyses, adjusting for OAD regimen and patients' sociodemographical characteristics. RESULTS: Patients were classified based on initial OAD regimen: metformin (MET) (n = 22,203; 41.3%), sulphonylurea (SFU) (n = 18,439; 34.3%), thiazolidinedione (TZD) (n = 7663; 14.3%), SFU + MET (n = 5467; 10.2%) and TZD + MET (n = 2355; 4.2%). A total of 51.5% of patients had HbA(1c) testing during 90 days preceding OAD initiation through regimen completion. Approximately, 65% of MET and 58% of SFU patients had no titration of initial regimen. Patients demonstrating inadequate glucose control decreased from 68.5% at baseline to 46.9% within 90 days of regimen initiation. Multivariable logistic regression indicated several negative predictors of HbA(1c) testing, including SFU use, age 65+ years, moderate insurance copayment and preindex inpatient utilisation. Multivariable logistic regression of variables associated with reduced likelihood of up-titration included TZD, SFU + MET, or TZD + MET treatment, age 18-34 years, Medicare insurance and any preindex healthcare utilisation. CONCLUSIONS: Patients are not being transitioned to additional OADs in a stepwise fashion and/or are receiving inadequate titration on current OAD regimens. The low rate of HbA(1c) testing and rates of control are contributing factors.

Glycaemic control and adverse events in patients with type 2 diabetes treated with metformin + sulphonylurea: a meta-analysis.

AIM: The aim of this study was to quantify the effect of a sulphonylurea on glycaemic control and the risk adverse events when incorporated into the treatment regimen of patients with type 2 diabetes inadequately controlled on metformin. METHODS: A systematic review was carried out to identify randomized controlled trials of sulphonylurea therapy in patients with type 2 diabetes whose glycaemic control was inadequate after maximal treatment with metformin. Data on reductions in haemoglobin A(1C) (HbA(1C)), fasting plasma glucose (FPG) and risk of hypoglycaemic events were extracted from each study and pooled in meta-analyses. Data on weight change were also extracted and tabulated. RESULTS: Six studies including 1364 patients were identified. Based on random effects meta-analysis, the pooled estimate of change in HbA(1C) from baseline was 0.9% (95% CI 0.7-1.1, p = 0.00011 vs. baseline) and for change in FPG from baseline was 1.8 mmol/l (95% CI 1.1-2.5, p = 0.0026 vs. baseline). The odds of experiencing a hypoglycaemic event was significantly higher in sulphonylurea-treated patients than in those on comparator treatments (OR = 5.3, 95% CI 1.7-16.3, p = 0.03). Mean weight change ranged from +2.5 to -0.1 kg, depending on the comparator treatment. CONCLUSIONS: This analysis has demonstrated that, in patients with type 2 diabetes whose control is inadequate on metformin monotherapy, the magnitude of incremental HbA(1C) reduction achieved by the addition of a sulphonylurea is unlikely to exceed 1%, even after titration to maximum tolerated doses. Additionally, clinically relevant side-effects such as symptomatic hypoglycaemia and weight gain may be experienced.

Hypoglycaemia in patients with type 2 diabetes treated with a combination of metformin and sulphonylurea therapy in France.

CONTEXT: Hypoglycaemia from antihyperglycaemic drugs may have a significant impact on patients' health-related quality of life. Combination use of metformin and a sulphonylurea has become increasingly common; yet, the impact of hypoglycaemia on quality of life in these patients is not well documented. OBJECTIVE: To examine patient-reported experience of hypoglycaemia, worry about hypoglycaemic symptoms and the impact of hypoglycaemia on patients' quality of life associated with use of sulphonylurea co-administered with metformin. DESIGN: This was an observational, cross-sectional, multi-centre study. SETTING: A total of 98 primary care centres in France during October to December 2005. PATIENTS: A total of 400 patients with type 2 diabetes, who were > or = 35 years old and who had been treated with metformin and a sulphonylurea for at least 6 months, completed questionnaires during their usual primary care office visit. MAIN OUTCOME MEASURES: Frequency and severity of hypoglycaemic symptoms in the past 6 months, the Worry subscale of the Hypoglycaemic Fear Survey-II (HFS-II) and the EuroQol-5 Dimensions (EQ-5D) questionnaire. RESULTS: A total of 136 (34%) patients reported experiencing hypoglycaemia, of whom 78 (58%) experienced mild, 40 (30%) experienced moderate and 16 (12%) experienced severe or very severe symptoms. Mean score on the HFS-II Worry scale was higher for patients who reported having hypoglycaemia than for those who did not (19.0 vs. 10.2; p < 0.0001) and increased with severity of hypoglycaemic symptoms. In linear regression analyses, more severe symptoms of hypoglycaemia were significantly associated with higher scores on the HFS-II Worry scale (p = 0.0162) among patients with hypoglycaemic symptoms. Summary scores on the EQ-5D were lower for patients who reported hypoglycaemia than for those who did not (p = 0.0001) and, in multivariate analysis, the experience of hypoglycaemia was negatively associated with the EQ-5D summary score (p < 0.0001). CONCLUSION: The occurrence and severity of hypoglycaemic symptoms were associated with increased patient worry about hypoglycaemia and lower health-related quality of life among type 2 diabetic patients being treated with both metformin and a sulphonylurea.

Hypoglycaemic symptoms, treatment satisfaction, adherence and their associations with glycaemic goal in patients with type 2 diabetes mellitus: findings from the Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) Study.

AIMS: This study was undertaken to evaluate (i) factors associated with patient-reported hypoglycaemia; (ii) association of patient-reported hypoglycaemic symptoms with treatment satisfaction and barriers to adherence and (iii) association between treatment satisfaction, adherence and glycaemic control among patients with type 2 diabetes who added a sulphonylurea or a thiazolidinedione to ongoing metformin. METHODS: This observational, cross-sectional, multicentre study was conducted in seven countries (Finland, France, Germany, Norway, Poland, Spain and UK) from June 2006 to February 2007. Patients with type 2 diabetes who added a sulphonylurea or a thiazolidinedione to ongoing metformin therapy on a date (index date) from January 2001 through January 2006 and who had at least one haemoglobin A1C (HbA1C) measurement in the 12-month period before the visit date were eligible. Questionnaires were used to ascertain patients' reports of hypoglycaemic symptoms, treatment satisfaction, and treatment adherence. The Treatment Satisfaction Questionnaire for Medication was used to measure patients' treatment satisfaction. An adherence and barriers questionnaire was used to measure patients' adherence to treatment. Glycaemic control was based on documented HbA1C measurements within the prior 12 months. RESULTS: The mean +/- s.d. age was 62.9 +/- 10.6 years, and the mean +/- s.d. duration of diabetes was 7.8 +/- 5.1 years. HbA1C in this population of patients who had failed metformin monotherapy and were treated with oral antihyperglycaemic agents was below the International Diabetes Federation goal of 6.5% in only 477 (27.9%) patients. Approximately 38% of patients reported hypoglycaemic symptoms during the past year. Hypoglycaemia was significantly more likely in patients with a history of macrovascular complications of diabetes (OR = 1.346; 95% CI = 1.050-1.725) and with no regular physical activity (OR = 1.295; 95% CI = 1.037-1.618). Patients reporting hypoglycaemia had significantly lower treatment satisfaction scores (71.6 +/- 17.6 vs. 76.3 +/- 16.8; p < 0.0001 for global satisfaction). Compared with their counterparts reporting no hypoglycaemic symptoms, patients with such symptoms were also significantly more likely to report barriers to adherence, including being unsure about instructions (37.0 vs. 30.5%; p = 0.0057). Patients at HbA1C goal had significantly higher treatment satisfaction and adherence compared with those who were not. CONCLUSIONS: Patients' reports of hypoglycaemic symptoms are common in European outpatients with type 2 diabetes and are associated with significantly lower treatment satisfaction and with barriers to adherence. In addition, being at HbA1C goal is associated with treatment satisfaction and adherence.

Cost-effectiveness of sitagliptin-based treatment regimens in European patients with type 2 diabetes and haemoglobin A1c above target on metformin monotherapy.

OBJECTIVE: Sitagliptin is a novel oral incretin enhancer that acts by inhibiting the dipeptidyl peptidase 4 enzyme and is indicated in Europe as a treatment adjunct to metformin (MF), sulphonylurea (SU), MF plus SU and diet and exercise, in the management of type 2 diabetes mellitus. The objective of the current analysis was to evaluate the cost-effectiveness of adding sitagliptin to the regimens of patients with haemoglobin A1c (HbA1C) above the International Diabetes Federation goal (6.5%) while on MF in six European countries: Austria, Finland, Portugal, Scotland (United Kingdom), Spain and Sweden. METHODS: A discrete event simulation model, which employed the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model risk equations for predicting risks of diabetes-related complication, was used. Lifetime costs and benefits were projected for alternative treatment strategies of adding sitagliptin, compared with adding rosiglitazone or a SU to MF in patients not at HbA1C goal on MF monotherapy. Changes in HbA1C as well as side effects associated with these different treatment strategies were based on clinical trial data. Mean baseline values from local epidemiologic studies involving patients with type 2 diabetes not at HbA1C goal on MF monotherapy were included in the current analysis. Costs of medications, side effects and direct costs of diabetes-related complications were based on country-specific data. UKPDS-based disutility weights associated with diabetes complications were incorporated. Disutilities associated with medication side effects were based on published data. All future costs and benefits were discounted according to local guidelines on cost-effectiveness analysis. One-way sensitivity analyses were conducted by varying key input parameters. FINDINGS: The discounted incremental cost-effectiveness ratios (ICER) associated with the addition of sitagliptin to MF, compared with adding rosiglitazone, in the different countries analysed ranged from treatment with sitagliptin being dominant (cost saving with improved health outcome) to its being cost-effective [4,766 euros per quality-adjusted life year (QALY)]. Treatment with sitagliptin added to MF was cost-effective compared with adding a SU, with discounted ICER values ranging from 5949 euros/QALY to 20,350 euros/QALY across countries. Sensitivity analyses showed that these results were robust to changes in input parameters, including clinical efficacy, costs and utility weights for both diabetes-related complications and hypoglycaemia. CONCLUSIONS: Compared with adding rosiglitazone or a SU to MF, adding sitagliptin to MF is projected to be either cost saving or cost-effective for patients with type 2 diabetes who are not at HbA1C goal on MF.

Risk factors for vitamin D inadequacy among women with osteoporosis: an international epidemiological study.

A serum 25-hydroxyvitamin D [25(OH)D] level of 75 nmol/l (30 ng/ml) has been proposed as the minimum for adequate vitamin D nutrition as lower levels are associated with increases in serum parathyroid hormone in otherwise healthy adults. Amongst 2589 community-dwelling, postmenopausal women with osteoporosis from 18 countries, recruited to determine risk factors for vitamin D inadequacy, 64% had vitamin D inadequacy. General health, education, ethnicity, sun exposure, skin reactivity, diet, recent travel to sunny climates, vitamin D supplementation, body mass index (BMI), season and latitude were assessed using logistic regression models. Asian ethnicity, BMI >or=30 kg/m(2), living in non-equatorial countries, inadequate vitamin D supplementation, poor/fair health, no education about vitamin D, skin reactivity and no recent travel to sunny areas were significant predictors. Several modifiable risk factors are associated with vitamin D inadequacy worldwide, suggesting potentially simple ways to increase vitamin D and improve bone health in postmenopausal women.