Association of hypoglycemic symptoms with patients' rating of their health-related quality of life state: a cross sectional study.

BACKGROUND: To evaluate the association between patient-reported hypoglycemic symptoms with ratings of their health-related quality of life state and patient-reported adverse events in patients with type 2 diabetes mellitus (T2DM). METHODS: This observational, multicenter, cross sectional study was based on a sample of patients with T2DM from seven European countries who added sulfonylurea or thiazolidinedione to metformin monotherapy between January 2001 and January 2006. Included patients were required to have at least one hemoglobin A1c (HbA1c) measurement in the 12 months before enrollment and to not be receiving insulin. Demographic and clinical data from medical records were collected using case report forms. Questionnaires measured patient-reported hypoglycemic symptoms, health-related quality of life (EuroQol visual analogue scale, EQ-5D VAS), and treatment-related adverse events. RESULTS: A total of 1,709 patients were included in the study. Mean patient age was 63 years, 45% were female, mean HbA1c was 7.06%, and 28% were at HbA1c goal (HbA1c < 6.5%). Hypoglycemic symptoms during the 12 months before enrollment were reported by 38% of patients; among whom 68% reported their most severe symptoms were mild, 27% moderate, and 5% severe. Adjusted linear regression analyses revealed that patients reporting hypoglycemic symptoms had significantly lower EQ-5D VAS scores indicating worse patient-reported quality of life (mean difference -4.33, p < 0.0001). Relative to those not reporting symptoms, the adjusted decrement to quality of life increased with greater hypoglycemic symptom severity (mild: -2.68, p = 0.0039; moderate: -6.42, p < 0.0001; severe: -16.09, p < 0.0001). Patients with hypoglycemia reported significantly higher rates of shakiness, sweating, excessive fatigue, drowsiness, inability to concentrate, dizziness, hunger, asthenia, and headache (p < 0.0001 for each comparison). CONCLUSIONS: Hypoglycemic symptoms and symptom severity have an adverse effect on patients' rating of their health related quality of life state. Hypoglycemic symptoms are correlated with treatment-related adverse effects. Minimizing the risk and severity of hypoglycemia may improve patients' quality of life and clinical outcomes. Results are subject to limitations associated with observational studies including the potential biases due to unobserved patient heterogeneity and the use of a convenience sample of patients.

Pre-existing cardiovascular diseases and glycemic control in patients with type 2 diabetes mellitus in Europe: a matched cohort study.

BACKGROUND: Although there is a growing body of evidence showing that patients with type 2 diabetes mellitus (T2DM) have poor glycemic control in general, it is not clear whether T2DM patients with pre-existing cardiovascular diseases (CVD) are more or less likely to have good glycemic control than patients without pre-existing CVD. Our aim was to examine the degree of glycemic control among T2DM patients in Europe with and without pre-existing CVD. METHODS: This is a matched cohort study based on a multi-center, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, United Kingdom, Norway, Finland, Germany, and Poland. Included patients were aged >= 30 years at time of diagnosis of T2DM, had added a SU or a PPARgamma agonist to failing metformin monotherapy (index date) and had pre-existing CVD (cases). A control cohort with T2DM without pre-existing CVD was identified using 1:1 propensity score matching. With difference-in-difference approach, logistic and linear regression analyses were applied to identify differences in glycemic control by CVD during the follow up period, after controlling for baseline demographics, clinical information, and concurrent anti-hyperglycemic medication use. RESULTS: The percentage of case patients with adequate glycemic control relative to control patients during the 1st, 2nd, 3rd, and 4th years after the index date was 19.9 vs. 26.5, 16.8 vs. 26.5, 18.8 vs. 28.3, and 16.8 vs. 23.5 respectively. Cases were significantly less likely to have adequate glycemic control (odds ratio: 0.62; 95% confidence interval: 0.46-0.82) than controls after adjusting for baseline differences, secular trend, and other potential confounding covariates. CONCLUSIONS: T2DM patients with pre-existing CVD tended to have poorer glycemic control than those without pre-existing CVD, all other factors being equal. It suggests that clinicians may need to pay more attention to glycemic control among T2DM patients with CVD.

The impact of acute myocardial infarction and stroke on health care costs in patients with type 2 diabetes in Sweden.

BACKGROUND: Estimates of the economic impact of cardiovascular events in patients with type 2 diabetes are scarce. The aim of this study was to determine the health care costs associated with acute myocardial infarction (AMI) and stroke in patients with type 2 diabetes in Sweden. DESIGN: Population-based open cohort study of 9941 patients with type 2 diabetes retrospectively identified in primary care records at 26 centres in Uppsala County. METHODS: Episodes of AMI and stroke suffered by study patients were tracked in the Swedish National Inpatient Register. Annual per patient costs of health care were computed for the years 2000-2004 using register data covering inpatient care, outpatient hospital care, primary care and drugs. Panel data regression was applied to determine the impact of suffering a first or repeat AMI or stroke on health care costs during the year of the event and in subsequent years. RESULTS: Total health care costs of patients suffering a first AMI/stroke increased by 4.1/6.5 during the year of the event [95% confidence interval (CI): 3.1-5.4/4.9-8.5] and by 1.1/1.4 during subsequent years (95% CI: 1.0-1.3/1.2-1.6), controlling for age, sex, the event of amputation and presence of renal failure, heart failure and diabetic eye disease. Total health care costs of patients suffering a first or repeat AMI/stroke increased by 4.1/6.4 during the year of an event (95% CI: 3.2-5.2/5.0-8.1) but were not significantly higher during subsequent years. CONCLUSION: Estimates of the costs related to major cardiovascular complications of type 2 diabetes are critical input to economic evaluations.

Cholesterol reduction yields clinical benefits: meta-analysis including recent trials.

BACKGROUND: Previous meta-analyses reported by Gould et al found significant decreases of 15% in the risk for coronary heart disease (CHD)-related mortality and 11 % in risk for all-cause mortality per decrease of 10% in total cholesterol (TC) level. OBJECTIVE: To evaluate the effects of reducing cholesterol on clinical events after including data from recent clinical trials. METHODS: Using a literature search (MeSH key terms, including: bezafibrate, coronary disease, efficacy, gemfibrozil, hydroxymethylglutaryl-CoA reductase inhibitors, hypercholesterolemia, niacin [nicotinic acids], randomized controlled trials, and treatment outcome; years: 1999-2005), we identified trials published in English that assessed the effects of lipid-modifying therapies on CHD end points, including CHD-related death, myocardial infarction, and angina pectoris. We also included all studies from the previously published meta-analysis. Using the same analytic approach as previously, we determined the effects of net absolute reductions (1 mmol/L [38.7 mg/dL]) in TC and low-density lipoprotein cholesterol (LDL-C) on the relative risks (RRs) for all-cause mortality, CHD-related mortality, any CHD event (mortality or nonfatal myocardial infarction), and non-CHD-related mortality. RESULTS: We included 62 studies involving 216,616 patients, including 126,474 from 24 randomized controlled trials the findings of which were published since the previous meta-analysis (1998). Among all patients, for every 1-mmol/L decrease in TC, there was a 17.5 reduction in RR for all-cause mortality; 24.5 %, for CHD-related mortality; and 29.5% for any CHD event. Corresponding reductions for every 1-mmol/L decrease in LDL-C were 15.6%, 28.0%, and 26.6%, respectively. Similar relationships were observed in patients without CHD. No significant relationship was found between lipid reduction and non-CHD-related mortality risk. CONCLUSIONS: The results from the present analysis support conclusions from previous meta-analyses that cholesterol lowering is clinically beneficial in patients with CHD or at elevated CHD risk. These results also support the previous finding that non-CHD-related mortality is unrelated to lipid reductions.

Development and validation of stroke risk equation for Hong Kong Chinese patients with type 2 diabetes: the Hong Kong Diabetes Registry.

OBJECTIVE: We sought to develop stroke risk equations for Chinese patients with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: A total of 7,209 Hong Kong Chinese type 2 diabetic patients without a history of stroke at baseline were analyzed. The data were randomly and evenly divided into the training subsample and the test subsample. In the training subsample, stepwise Cox models were used to develop the risk equation. Validation of the U.K. Prospective Diabetes Study (UKPDS) stroke risk engine and the current stroke equation was performed in the test dataset. The life-table method was used to check calibration, and the area under the receiver operating characteristic curve (aROC) was used to check discrimination. RESULTS: A total of 372 patients developed incident stroke during a median of 5.37 years (interquartile range 2.88-7.78) of follow-up. Age, A1C, spot urine albumin-to-creatinine ratio (ACR), and history of coronary heart disease (CHD) were independent predictors. The performance of the UKPDS stroke engine was suboptimal in our cohort. The newly developed risk equation defined by these four predictors had adequate performance in the test subsample. The predicted stroke-free probability by the current equation was within the 95% CI of the observed probability. The aROC was 0.77 for predicting stroke within 5 years. The risk score was computed as follows: 0.0634 x age (years) + 0.0897 x A1C + 0.5314 x log(10) (ACR) (mg/mmol) + 0.5636 x history of CHD (1 if yes). The 5-year stroke probability can be calculated by: 1 - 0.9707(EXP (Risk Score - 4.5674)). CONCLUSIONS: Although the risk equation performed reasonably well in Chinese type 2 diabetic patients, external validation is required in other populations.

Asthma and allergy medication use and costs among pediatric primary care patients on asthma controller therapy.

As observational studies in children initiating GINA-Step 3 therapies are scarce, we evaluated outcomes and costs in a primary care cohort. Two-yr retrospective cohort study included French children (age: 6-14) continuously followed in BKL-Thalès database who received > or =2 consecutive prescriptions for GINA-Step 3 therapy (=addition of montelukast or other controllers ('other'), such as increasing inhaled-corticosteroid dose (hICS), adding long-acting beta agonist (LABA), or ICS + LABA). After matching on gender and propensity score, medication use [rescue (short-acting beta agonists), acute (antibiotics (AB), oral corticosteroids (OCS)), allergy (antihistamines, nasal steroids) and other respiratory] was estimated via mean number of prescriptions and mean cost (per child/per month), and cost trends. During 12-month follow-up, children adding montelukast (n = 71) vs. 'other' (n = 213) had similar asthma rescue/acute and allergy medication use. Subgroup with asthma and allergic rhinitis (A + AR) adding montelukast used less OCS and AB (p = 0.014). Two-yr cost trends suggest stable asthma/allergy medication use in montelukast group (0.83 euro) compared with increase in 'other' (5.39 euro), which was driven by nasal steroid use [0.32 euro ('other') vs. -0.04 euro (montelukast), p = 0.0013]. In subgroup with A + AR decline in asthma/allergy medication use in montelukast group (-0.47 euro) vs. increase in 'other' (11.05 euro), p = 0.015, was driven by differences in AB and OCS (p = 0.04) and nasal steroid use (p = 0.001). Concomitant asthma/allergy medication use was similar in children adding montelukast or 'other' controllers (hICS, LABA, ICS + LABA), while children with allergic rhinitis on montelukast used less AB. Concomitant medication costs after addition of montelukast remained stable, while 'other' group experienced increase, especially in children with concomitant allergic rhinitis.

Factors associated with the effect-size of thiazolidinedione (TZD) therapy on HbA(1c): a meta-analysis of published randomized clinical trials.

OBJECTIVE: To examine factors affecting the size of the HbA(1c) response to thiazolidinedione (TZD) therapy. RESEARCH DESIGN AND METHODS: Meta-analysis of randomized TZD controlled trials which were identified using PubMed, EBSCO and Sci-lit databases and were published in English. Sociodemographic and clinical data were extracted from each trial. HbA(1c) effect size was defined as either a placebo-subtracted change in HbA(1c) or a change in HbA(1c) from baseline. Weighted multivariable regression was used to examine factors associated with changes in HbA(1c). Bootstrapped smearing estimates were computed to obtain reliable estimates of HbA(1c) effect size. RESULTS: Forty-two trials yielded 60 trial arms which represented 8322 patients treated with thiazolidinediones. Weighted placebo-subtracted change in HbA(1c) was -0.99% +/- 0.02% with an average baseline HbA(1c) of 9.1% +/- 1.0%. Weighted bootstrapped smearing estimate of the placebo-subtracted change in HbA(1c) was -1.02% +/- 0.004%. After controlling for other variables, the baseline HbA(1c) level had a significant negative association with placebo-subtracted HbA(1c) change (p = 0.004) and also with change in HbA(1c) from baseline (p = 0.002). Longer trial duration was associated with greater placebo-subtracted HbA(1c) change (p = 0.01) but not with the change in HbA(1c) from baseline. The multivariable models explained 72% of the variation in placebo-subtracted HbA(1c) change. It was not possible to estimate effects of the run-in period and obesity on TZD effect size. CONCLUSION: Baseline HbA(1c) and trial duration significantly impacted the effect size of TZD therapy on HbA(1c). Age, gender, duration of diabetes and prior use of anti-diabetic therapy were not associated with the TZD effect size.

Asthma rescue and allergy medication use among asthmatic children with prior allergy prescriptions who initiated asthma controller therapy.

BACKGROUND: Asthma and allergic rhinitis are frequently comorbid conditions. Montelukast is effective in treating both diseases and may reduce total medication use among children with asthma and allergic rhinitis. OBJECTIVE: To determine the differences in respiratory and allergy medication use and costs, as proxies for control, in pediatric patients with asthma and allergy who initiated asthma controller therapy. METHODS: A 24-month, retrospective, pre-post cohort study using a pharmacy claims database of children (age < 16 years) with 2 or more consecutive asthma controller prescriptions and 1 or more allergy prescription (within 12 months before initial controller prescription). Children taking inhaled corticosteroids (ICSs) and montelukast were matched one to one based on age, days of prior allergic rhinitis therapy supply, duration of controller therapy, and propensity score. Differences in costs of rescue or acute asthma medications, prescription allergy medications, other respiratory medications, and the number of days of rescue or acute asthma medication use and allergy medication use were calculated. RESULTS: A total of 1,236 children were matched into ICS and montelukast groups (n = 618 each). Montelukast patients had a smaller cost increase overall compared with ICS patients (combined cost for rescue or acute asthma medications, allergy medications, and other respiratory medications: $5.55 vs $12.08, P < .001). Cost increase for rescue or acute asthma medications was significantly lower in the montelukast group ($0.94 vs $3.82, P = .003). The cost increase for allergy medications ($5.29 vs $10.06, P < .001) was also significantly lower in the montelukast group. Patients taking montelukast also had fewer days of therapy with asthma rescue medication and allergy medication compared with patients taking ICSs. CONCLUSIONS: Initiating therapy with montelukast was associated with better asthma and allergy control demonstrated via lower increase in use and costs of asthma rescue and allergy medications compared with initiating ICS therapy.

Real-world effectiveness of lipid-lowering therapy in male and female outpatients with coronary heart disease: relation to pre-treatment low-density lipoprotein-cholesterol, pre-treatment coronary heart disease risk, and other factors.

BACKGROUND: Determinants of the real-world effectiveness of lipid-lowering therapy have been rarely assessed in an unselected observational coronary heart disease (CHD) community cohort over time. DESIGN: Randomly drawn patients (n=605) from randomly drawn practices (n=62) were retrospectively followed for a median of 3.6 years (1998-2002) on lipid-lowering therapy (98% statins). METHODS: Coronary heart disease population-averaged estimates and variances accounting for repeated measurements within patients were obtained using generalized estimating equations. RESULTS: Post-treatment low-density lipoprotein-cholesterol (LDL-C) was 124 mg/dl in men and 141 mg/dl in women and was independently associated (all P<0.05) with pre-treatment LDL-C (+3.7 mg/dl per 10 mg/dl increment), female sex (+14.0 mg/dl), coronary bypass (-9.5 mg/dl), drug-treated diabetes mellitus (-6.8 mg/dl), and era 2002/2001 versus 1999/2000 (-6.4 mg/dl) in age-adjusted multivariate analyses. Holding pre-treatment LDL-C constant post-treatment LDL-C was associated with pre-treatment Framingham CHD risk in men (-13.9 mg/dl per doubling of risk), whereas LDL-C control in women resembled that in low-risk men. The likelihood of attaining LDL-C <100 mg/dl was 0.28 in men and 0.17 in women and was likewise associated with the above factors. CONCLUSION: Low-density lipoprotein-cholesterol control remained low despite lipid-lowering therapy across a wide range of pre-treatment LDL-C and pre-treatment CHD risk. Low-density lipoprotein-cholesterol control in women was inferior to that in men, a finding that warrants attention and clarification.

Asthma-related health care resource use among asthmatic children with and without concomitant allergic rhinitis.

OBJECTIVE: To determine the incremental effect of allergic rhinitis on health care resource use in children with asthma. DESIGN: Population-based historical cohort study. SETTING: Data in a general practice database in the United Kingdom during 1998 to 2001. PATIENTS: Children 6 to 15 years old with asthma and with >or=1 asthma-related visits to a general practitioner (GP) during a 12-month follow-up period. MAIN OUTCOME MEASURES: Asthma-related hospitalizations, GP visits, and prescription drug costs during the 12-month follow-up period for patients with and without comorbid allergic rhinitis. RESULTS: Of 9522 children with asthma, 1879 (19.7%) had allergic rhinitis recorded in the GP medical records. Compared with children with asthma alone, children with comorbid allergic rhinitis experienced more GP visits (4.4 vs 3.4) and more of them were hospitalized for asthma (1.4% vs 0.5%) during the 12-month follow-up period. In multivariable regression analyses, comorbid allergic rhinitis was an independent predictor of hospitalization for asthma (odds ratio: 2.34; 95% confidence interval [CI]: 1.41-3.91) and was associated with increases in the number of asthma-related GP visits (mean increase: 0.53; 95% CI: 0.52-0.54) and asthma drug costs (mean increase pound: 6.7; 95% CI: 6.5-7.0). The association between allergic rhinitis and higher costs of prescriptions for asthma drugs was independent of asthma severity, measured indirectly by the intensity of use of asthma drugs. CONCLUSIONS: Children with comorbid allergic rhinitis incurred greater prescription drug costs and experienced more GP visits and hospitalizations for asthma than did children with asthma alone. A unified treatment strategy for asthma and allergic rhinitis, as recommended by the Allergic Rhinitis and Its Impact on Asthma initiative, might reduce the costs of treating these conditions.

Statins are less effective in common daily practice among patients with hypercholesterolemia: the REALITY-PHARMO study.

BACKGROUND: To study the use and effectiveness of lipid-lowering drugs with respect to lowering of cholesterol levels in routine daily practice. METHODS: 20 392 patients for whom lipid levels records were available between January 1991 and December 2001 were included in this retrospective population based cohort study. From this group of patients 1899 patients started treatment during the study period and had at least one baseline cholesterol measurement during the six months prior to the initiation of lipid lowering drugs and at least one cholesterol measurement after initiation. A patient was defined to be 'at goal' if the patient had a total cholesterol less than 5.0 mmol/L. RESULTS: Our results indicate that only 30.2% of all treated patients achieved goal in the first year of treatment. After the introduction of new guidelines in 1998, recommending more aggressive treatment, the goal attainment percentage rose from 22.4% of those patients treated before 1998 to 42.3% for those in whom treatment was initiated after 1998. CONCLUSION: The percentage of patients achieving guideline recommended goal is low in real-life even in patients treated with high dose statins.

Resource use and cost of care for patients hospitalised with community acquired pneumonia: impact of adherence to infectious diseases society of america guidelines.

OBJECTIVE: The objective of this study was to compare the inpatient resource use and cost of care for patients hospitalised with community-acquired pneumonia (CAP) who were treated with preferred antibacterial therapy according to the 1998 Infectious Diseases Society of America (IDSA) guidelines with those who were not treated with preferred therapy. METHODS: A multicentre, observational study was conducted in Florida between 1999 and 2000. Hospitalised adult patients (aged > or = 18 years) started on antibacterial therapy for suspected or confirmed CAP were enrolled in the study. Data collected included patient demographic characteristics, pneumonia risk class, resource use (pharmacy, laboratory, radiology, respiratory services, hospital room and board) and economic data. Risk classification according to Fine et al.'s criteria was determined for each patient. Patient's antibacterial therapy was classified as being preferred or non-preferred according to the 1998 IDSA guidelines. Resource utilisation and cost of care were compared between these two groups. RESULTS: Ninety-nine patients were enrolled in the study. The average age was 60.6 years +/- 20.5 years. The percentage of patients in each risk class (according to Fine et al.) were 11.1% in class I, 39.4% in class II, 29.3% in class III, 16.2% in class IV and 4% in class V. The mean cost of hospitalisation per admission (excluding physician cost) was US 3,490 dollars +/- US 3,058 dollars (median US 2,430 dollars) with hospital room/board accounting for the largest percentage (83.7%), followed by laboratory (8.1%), antibacterial (4.6%), radiology (2.6%) and respiratory (0.9%) cost centres [year 2000 values]. The majority of patients (75.8%) received preferred antibacterials according to the IDSA guidelines. The group treated with preferred antibacterials had a shorter mean length of hospital stay (4.5 vs 6.8 days, p = 0.002), a lower total cost of hospitalisation (mean US 3,009 dollars +/- US 2,682 dollars vs US 4,992 dollars +/- US 3,686 dollars; median US 2,047 dollars vs US 3,805 dollars, p = 0.021) and lower antibacterial costs (mean US 117 dollars +/- US 79 dollars vs US 301 dollars +/- US 409 dollars; median US 97 dollars vs US 171 dollars, p = 0.038) compared with patients who did not receive preferred therapy. CONCLUSION: Implementation of protocols according to IDSA guidelines may result in cost savings to institutions wishing to reduce the economic burden associated with treating hospitalised patients for CAP.

Variations in pediatric asthma hospitalization rates and costs between and within Nordic countries.

BACKGROUND: We assessed variations in hospitalization parameters and costs among asthmatic children in four Nordic countries by geographic location and age groups. METHODS: Cross-sectional, county-level aggregate data on asthma-related hospitalizations in 1999, obtained from public national databases for children < 15 years old from Denmark, Sweden, Norway, and Finland, together with country-specific asthma management cost were used to estimate the incidence of first hospital admission (per 1,000), length of hospital stay (LOS), and hospitalization cost. Longitudinal patient-specific data from 1998/1999 were used to calculate the relative hazard of readmission (RHR) using a multivariate Cox proportional hazards model. RESULTS: Nordic incidence of first hospital admission in 1999 was 2.17 per 1,000 children, readmission was noted in 16% of the patients, mean LOS was 2.64 days, and total hospitalization cost was almost 14 million dollars. Hospitalization incidence, RHR, and costs were significantly higher in children < 5 years old compared with school children 6 to 14 years old. Hospital LOS, incidence of first hospital admission, and cost per child were the highest in Denmark, though RHR did not differ significantly from Sweden. CONCLUSIONS: Large variations in all parameters were observed between and within countries. Given the similarities among the four countries studied, these results may, among other reasons, indicate different efficiencies of the various asthma management plans between and within them. The presented measures of hospitalization patterns could prove to be valuable quality-of-care measures to guide further improvements in asthma management.

Association between diarrhea and quality of life in HIV-infected patients receiving highly active antiretroviral therapy.

Diarrhea is a common symptom that many HIV patients experience either as a consequence of HIV infection or of highly active antiretroviral therapy (HAART). A multicenter, prospective observational study was conducted in 11 AIDS clinics in Italy to determine the effect of diarrhea on health-related quality of life among patients receiving HAART. The study enrolled 100 consecutive HIV positive patients who had diarrhea while on HAART. For each enrolled patient a control patient with matching disease stage who did not have diarrhea was identified using existing data from another prospective observational study conducted in 34 AIDS clinics (including the 11 in current study). Quality of life was measured by MOS-HIV Health Survey (MOS-HIV). Paired t-test and multiple regression analysis were used to compare the quality of life among patients with and without diarrhea. Mean patient age was 40 +/- 7 years; 69% were male. Mean CD4 cell count was 342 +/- 239 cells/mm3; 59% had AIDS. Of the cases, 49 patients had severe diarrhea (> 5 bowel movements or > 3 watery per day) and 46 patients had moderate diarrhea (3-5 bowel movements). Compared to matched control patients, cases experiencing diarrhea while on HAART had significantly lower MOS-HIV scores in all domains. The significant adverse effect of diarrhea on quality of life should be considered when choosing the appropriate antiretroviral drugs regimen.