Statin use and lung cancer risk in chronic obstructive pulmonary disease patients: a population-based cohort study.

BACKGROUND: Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer. A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins. This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients. METHODS: We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA). We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose). To assess residual confounding, a negative control exposure was used to test the validity of our results. All exposure variables were time-dependent. RESULTS: The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female. There were 12,469 patients who received at least one statin prescription. Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73-1.00) in COPD patients, but this result not statistically significant. Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77-0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96-0.99). Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75-1.10). CONCLUSIONS: The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer. While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy.

Incremental direct medical costs of systemic lupus erythematosus patients in the years preceding diagnosis: A general population-based study.

Objective We estimated the incremental (extra) direct medical costs of a population-based cohort of newly diagnosed systemic lupus erythematosus (SLE) for five years before and after diagnosis, and the impact of sex and socioeconomic status (SES) on pre-index costs for SLE. Methods We identified all adults newly diagnosed with SLE over 2001-2010 in British Columbia, Canada, and obtained a sample of non-SLE individuals from the general population, matched on sex, age, and calendar-year of study entry. We captured costs for all outpatient encounters, hospitalisations, and dispensed medications each year. Using generalised linear models, we estimated incremental costs of SLE each year before/after diagnosis (difference in costs between SLE and non-SLE, controlling for covariates). Similar models were used to examine the impact of sex and SES on costs within SLE. Results We included 3632 newly diagnosed SLE (86% female, mean age 49.6 ± 15.9) and 18,060 non-SLE individuals. Over the five years leading up to diagnosis, per-person healthcare costs for SLE patients increased year-over-year by 35%, on average, with the biggest increases in the final two years by 39% and 97%, respectively. Per-person all-cause medical costs for SLE the year after diagnosis (Year + 1) averaged C$12,019 (2013 Canadian) with 58% from hospitalisations, 24% outpatient, and 18% from prescription medications; Year + 1 costs for non-SLE averaged C$2412. Following adjustment for age, sex, urban/rural residence, socioeconomic status, and prior year's comorbidity score, SLE was associated with significantly greater hospitalisation, outpatient, and medication costs than non-SLE in each year of study. Altogether, adjusted incremental costs of SLE rose from C$1131 per person in Year -5 (fifth year before diagnosis) to C$2015 (Year -2), C$3473 (Year -1) and C$6474 (Year + 1). In Years -2, -1 and +1, SLE patients in the lowest SES group had significantly greater costs than the highest SES. Unlike the non-SLE cohort, male patients with SLE had higher costs than females. Annual incremental costs of SLE males (vs. SLE females) rose from C$540 per person in Year -2, to C$1385 in Year -1, and C$2288 in Year + 1. Conclusion Even years before diagnosis, SLE patients incur significantly elevated direct medical costs compared with the age- and sex-matched general population, for hospitalisations, outpatient care, and medications.

Cognitive status is a determinant of health resource utilization among individuals with a history of falls: a 12-month prospective cohort study.

SUMMARY: Falls are a costly public health problem worldwide. The literature is devoid of prospective data that identifies factors among fallers that significantly drive health care resource utilization. We found that cognitive function--specifically, executive functions--and cognitive status are significant determinants of health resource utilization among older fallers. INTRODUCTION: Although falls are costly, there are no prospective data examining factors among fallers that drive health care resource utilization. We identified key determinants of health resource utilization (HRU) at 6 and 12 months among older adults with a history of falls. Specifically, with the increasing recognition that cognitive impairment is associated with increased falls risk, we investigated cognition as a potential driver of health resource utilization. METHODS: This 12-month prospective cohort study at the Vancouver Falls Prevention Clinic (n = 319) included participants with a history of at least one fall in the previous 12 months. Based on their cognitive status, participants were divided into two groups: (1) no mild cognitive impairment (MCI) and (2) MCI. We constructed two linear regression models with HRU at 6 and 12 months as the dependent variables for each model, respectively. Predictors relating to mobility, global cognition, executive functions, and cognitive status (MCI versus no MCI) were examined. Age, sex, comorbidities, depression status, and activities of daily living were included regardless of statistical significance. RESULTS: Global cognition, comorbidities, working memory, and cognitive status (MCI versus no MCI ascertained using the Montreal Cognitive Assessment (MoCA)) were significant determinants of total HRU at 6 months. The number of medical comorbidities and global cognition were significant determinants of total HRU at 12 months. CONCLUSION: MCI status was a determinant of HRU at 6 months among older adults with a history of falls. As such, efforts to minimize health care resource use related to falls, it is important to tailor future interventions to be effective for people with MCI who fall. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01022866.

SF-6D and EQ-5D result in widely divergent incremental cost-effectiveness ratios in a clinical trial of older women: implications for health policy decisions.

SUMMARY: Using two instruments (SF-6D and EQ-5D) to estimate quality adjusted life years (QALYs), we conducted an economic evaluation of a 12-month randomized controlled trial with a 12-month follow-up study in older women to evaluate the value for money of two doses of resistance training compared with balance and tone classes. We found that the incremental QALYs estimated from the SF-6D were two- to threefold greater than those estimated from the EQ-5D. INTRODUCTION: Decision makers must continually choose between existing and new interventions. Hence, economic evaluations are increasingly prevalent. The impact of quality-adjusted life year (QALY) estimates using different instruments on the incremental cost-effectiveness ratios (ICERs) is not well understood in older adults. Thus, we compared ICERs, in older women, estimated by the EuroQol-5D (EQ-5D) and the Short Form-6D (SF-6D) to discuss implications on decision making. METHODS: Using both the EQ-5D and the SF-6D, we compared the incremental cost per QALY gained in a randomized controlled trial of resistance training in 155 community-dwelling women aged 65 to 75 years. The 12-month randomized controlled trial included a subsequent 12-month follow-up. Our focus, the follow-up study, included 123 of the 155 participants from the Brain Power study; 98 took part in the economic evaluation (twice-weekly balance and tone exercises, n = 28; once-weekly resistance training, n = 35; twice-weekly resistance training, n = 35). Our primary outcome measure was the incremental cost per QALY gained of once- or twice-weekly resistance training compared with balance and tone exercises. RESULTS: At cessation of the follow-up study, the incremental QALY was -0.051 (EQ-5D) and -0.144 (SF-6D) for the once-weekly resistance training group and -0.081 (EQ-5D) and -0.127 (SF-6D) for the twice-weekly resistance training group compared with balance and tone classes. CONCLUSION: The incremental QALYs estimated from the SF-6D were two- to threefold greater than those estimated from the EQ-5D. Given the large magnitude of difference, the choice of preference-based utility instrument may substantially impact health care decisions.

The cost of fall related presentations to the ED: a prospective, in-person, patient-tracking analysis of health resource utilization.

UNLABELLED: We prospectively collected data on elderly fallers to estimate the total cost of a fall requiring an Emergency Department presentation. Using data collected on 102 falls, we found the average cost per fall causing an Emergency Department presentation of $11,408. When hospitalization was required, the average cost per fall was $29,363. INTRODUCTION: For elderly persons, falls are a major source of mortality, morbidity, and disability. Previous Canadian cost estimates of seniors' falls were based upon administrative data that has been shown to underestimate the incidence of falls. Our objective was to use a labor-intensive, direct observation patient-tracking method to accurately estimate the total cost of falls among seniors who presented to a major urban Emergency Department (ED) in Canada. METHODS: We prospectively collected data from seniors (>70 years) presenting to the Vancouver General Hospital ED after a fall. We excluded individuals who where cognitively impaired or unable to read/write English. Data were collected on the care provided including physician assessments/consultations, radiology and laboratory tests, ED/hospital time, rehabilitation facility time, and in-hospital procedures. Unit costs of health resources were taken from a fully allocated hospital cost model. RESULTS: Data were collected on 101 fall-related ED presentations. The most common diagnoses were fractures (n = 33) and lacerations (n = 11). The mean cost of a fall causing ED presentation was $11,408 (SD: $19,655). Thirty-eight fallers had injuries requiring hospital admission with an average total cost of $29,363 (SD: $22,661). Hip fractures cost $39,507 (SD: $17,932). Among the 62 individuals not admitted to the hospital, the average cost of their ED visit was $674 (SD: $429). CONCLUSIONS: Among the growing population of Canadian seniors, falls have substantial costs. With the cost of a fall-related hospitalization approaching $30,000, there is an increased need for fall prevention programs.

Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias.

AIMS/HYPOTHESIS: Despite the vast body of epidemiological literature on the risk of cancer in people with diabetes, few studies have examined the pattern of cancer risk during different time windows following diabetes onset. The objective of the study was to examine the risks of site-specific cancer in people with incident type 2 diabetes during different time windows following diabetes onset. METHODS: This was a population-based retrospective cohort study. The study period was 1 April 1994 to 31 March 2006; censoring occurred at 31 March 2006, at death or on departure from British Columbia, Canada. Using linked health databases, we identified incident cohorts with and without diabetes, who were matched by age, sex and index year. Following a minimum 2-year cancer washout period, first site-specific cancers were identified prospectively in both cohorts. RESULTS: Within 3 months following diabetes onset, participants with diabetes had significantly increased risks of colorectal, lung, liver, cervical, endometrial, ovarian, pancreatic and prostate cancers. After the initial 3-month period, the risks for colorectal (HR 1.15, 95% CI 1.05, 1.25), liver (HR 2.53, 95% CI 1.93, 3.31) and endometrial (HR 1.58, 95% CI 1.28, 1.94) cancers remained significantly elevated compared with those without diabetes. The diabetes cohort remained at increased risk of pancreatic cancer in later years, but followed a different pattern: HR 3.71 at 3 months-1 year, 2.94 at 1-2 years, 1.78 at 2-3 years and 1.65 at 3-10 years (p value for all <0.01). After an initial period of elevated risk, men with type 2 diabetes subsequently had a decreased risk of prostate cancer (HR 0.82, 95% CI 0.76, 0.88). CONCLUSIONS/INTERPRETATION: People with type 2 diabetes are at increased risk of select cancers; this risk is particularly elevated at the time of diabetes onset, which is likely to be due to increased ascertainment.

Economic evaluation of dose-response resistance training in older women: a cost-effectiveness and cost-utility analysis.

SUMMARY: We estimated the incremental cost-effectiveness of a once-weekly or twice-weekly resistance training intervention compared with balance and tone classes in terms of falls prevented and quality-adjusted life years (QALYs) gained. Both resistance training interventions were more likely to save health care resource money and offer better health outcomes for falls prevention than balance and tone classes. INTRODUCTION: This study aims to estimate the incremental cost-effectiveness and cost-utility of a once-weekly or twice-weekly resistance training intervention compared with twice-weekly balance and tone classes in terms of falls prevented and QALYs gained. METHODS: Economic evaluation was conducted concurrently with a three-arm randomized controlled trial including 155 community-dwelling women aged 65 to 75 years, Mini Mental State Examination ≥24, and visual acuity 20/40 or better. Participants received the once-weekly resistance training (n = 54), the twice-weekly resistance training (n = 51) or the twice-weekly balance and tone (the comparator) classes (n = 50) for 1 year. Measurements included the number of falls for each participant, healthcare resource utilization, and associated costs over 9 months; health status was assessed using the EQ-5D and SF-6D to calculate QALYs. RESULTS: Based on the point estimates from our base case analysis, we found that both once- and twice-weekly resistance training groups were less costly (p < 0.05) and more effective than twice-weekly balance and tone classes. The incremental QALYs assessed using the SF-6D were 0.003 for both the once- and twice-weekly resistance training groups, compared with the twice-weekly balance and tone classes. The incremental QALYs assessed using the EQ-5D were 0.084 for the once-weekly and 0.179 for the twice-weekly resistance training groups, respectively, compared with the twice-weekly balance and tone classes. CONCLUSIONS: An individually tailored resistance training intervention delivered once or twice weekly provided better value for money for falls prevention than balance and tone classes.

International comparison of cost of falls in older adults living in the community: a systematic review.

SUMMARY: Our objective was to determine international estimates of the economic burden of falls in older people living in the community. Our systematic review emphasized the need for a consensus on methodology for cost of falls studies to enable more accurate comparisons and subgroup-specific estimates among different countries. INTRODUCTION: The purpose of this study was to determine international estimates of the economic burden of falls in older people living in the community. METHODS: This is a systematic review of peer-reviewed journal articles reporting estimates for the cost of falls in people aged > or =60 years living in the community. We searched for papers published between 1945 and December 2008 in MEDLINE, PUBMED, EMBASE, CINAHL, Cochrane Collaboration, and NHS EED databases that identified cost of falls in older adults. We extracted the cost of falls in the reported currency and converted them to US dollars at 2008 prices, cost items measured, perspective, time horizon, and sensitivity analysis. We assessed the quality of the studies using a selection of questions from Drummond's checklist. RESULTS: Seventeen studies met our inclusion criteria. Studies varied with respect to viewpoint of the analysis, definition of falls, identification of important and relevant cost items, and time horizon. Only two studies reported a sensitivity analysis and only four studies identified the viewpoint of their economic analysis. In the USA, non-fatal and fatal falls cost US $23.3 billion (2008 prices) annually and US $1.6 billion in the UK. CONCLUSIONS: The economic cost of falls is likely greater than policy makers appreciate. The mean cost of falls was dependent on the denominator used and ranged from US $3,476 per faller to US $10,749 per injurious fall and US $26,483 per fall requiring hospitalization. A consensus on methodology for cost of falls studies would enable more accurate comparisons and subgroup-specific estimates among different countries.

Does a home-based strength and balance programme in people aged > or =80 years provide the best value for money to prevent falls? A systematic review of economic evaluations of falls prevention interventions.

OBJECTIVES: To investigate the value for money of strategies to prevent falls in older adults living in the community. DESIGN: Systematic review of peer reviewed journal articles reporting an economic evaluation of a falls prevention intervention as part of a randomised controlled trial or a controlled trial, or using an analytical model. MEDLINE, PUBMED, EMBASE and NHS EED databases were searched to identify cost-effectiveness, cost-utility and cost-benefit studies from 1945 through July 2008. MAIN OUTCOME MEASURES: The primary outcome measure was incremental cost-effectiveness, cost-utility and cost-benefit ratios in the reported currency and in pounds sterling at 2008 prices. The quality of the studies was assessed using two instruments: (1) an economic evaluation checklist developed by Drummond and colleagues and (2) the Quality of Health Economic Studies instrument. RESULTS: Nine studies meeting our inclusion criteria included eight cost-effectiveness analyses, one cost-utility and one cost-benefit analysis. Three effective falls prevention strategies were cost saving in a subgroup of PARTICIPANTS: (1) an individually customised multifactorial programme in those with four or more of the eight targeted fall risk factors, (2) the home-based Otago Exercise Programme in people > or =80 years and (3) a home safety programme in the subgroup with a previous fall. These three findings were from six studies that scored > or =75% on the Quality of Health Economic Studies instrument. CONCLUSIONS: Best value for money came from effective single factor interventions such as the Otago Exercise Programme which was cost saving in adults 80 years and older. This programme has broad applicability thus warranting warrants health policy decision-makers' close scrutiny.

Valuing the benefit of diagnostic testing for genetic causes of idiopathic developmental disability: willingness to pay from families of affected children.

Idiopathic developmental disability (DD) has been found to put significant psychological distress on families of children with DD. The cause of the disability, however, is unknown for up to one-half of the affected children. Chromosomal abnormalities identified by cytogenetic analysis are the most frequently recognized cause of DD, although they account for less than 10% of cases. Array genomic hybridization (AGH) is a new diagnostic tool that provides a much higher detection rate for chromosomal imbalance than conventional cytogenetic analysis. This increase in diagnostic capability comes at greater monetary costs, which provides an impetus for understanding how individuals value genetic testing for DD. This study estimated the willingness to pay (WTP) for diagnostic testing to find a genetic cause of DD from families of children with DD. A discrete choice experiment was used to obtain WTP values. When it was assumed that AGH resulted in twice as many diagnoses and a 1-week reduction in waiting time compared with conventional cytogenetic analysis, this study found that families were willing to pay up to CDN$1118 (95% confidence interval, $498-1788) for the expected benefit. These results support the conclusion that the introduction of AGH into the Canadian health care system may increase the perceived welfare of society, but future studies should examine the cost-benefit of AGH vs cytogenetic testing.

Epidemiology and costs associated with genital warts in Canada.

BACKGROUND: Genital warts (condyloma acuminatum) remain one of the most commonly reported sexually transmitted infections (STI) worldwide. Most genital warts are caused by non-oncogenic human papilloma virus. Recurrence is common and many patients receive several rounds of treatment. There are limited data in the literature on the burden of illness and costs associated with genital warts at a population level. METHODS: Episodes of anogenital warts (AGW) were identified from the physician billing database, hospitalisation records and STI clinics from 1998 to 2006. To be included from the physician billing and STI databases, the person had to have a claim that had a diagnosis of condyloma acuminatum (078.11), viral warts (078.1), viral warts unspecified (078.10) or other unspecified warts (078.19), as well as one of the relevant fee codes associated with the treatment of AGW. To be included from the hospital database, the person could be of any age and have a diagnosis of AGW (A63.0), condyloma acuminatum (078.11), viral warts (078.1 or B07), viral warts unspecified (078.10) or other unspecified warts (078.19) in any of the diagnosis fields, as well as one of the relevant procedure codes associated with the treatment of AGW. RESULTS: A total of 39,493 people was diagnosed with AGW and during this period they had a total of 43,586 episodes. The average cost per episode of AGW was $C190 ($C176 for men; $C207 for women). The majority of treatment was with ablative therapy alone (98%). CONCLUSIONS: AGW are associated with a significant burden of illness and costs to the healthcare system.

Cost effectiveness of therapy with combinations of long acting bronchodilators and inhaled steroids for treatment of COPD.

BACKGROUND: Little is known about the combination of different medications in chronic obstructive pulmonary disease (COPD). This study determined the cost effectiveness of adding salmeterol (S) or fluticasone/salmeterol (FS) to tiotropium (T) for COPD. METHODS: This concurrent, prospective, economic analysis was based on costs and health outcomes from a 52 week randomised study comparing: (1) T 18 microg once daily + placebo twice daily (TP group); (2) T 18 microg once daily + S 25 microg/puff, 2 puffs twice daily (TS group); and (3) T 18 microg once daily + FS 250/25 microg/puff, 2 puffs twice daily (TFS group). The incremental cost effectiveness ratios (ICERs) were defined as incremental cost per exacerbation avoided, and per additional quality adjusted life year (QALY) between treatments. A combination of imputation and bootstrapping was used to quantify uncertainty, and extensive sensitivity analyses were performed. RESULTS: The average patient in the TP group generated CAN$2678 in direct medical costs compared with $2801 (TS group) and $4042 (TFS group). The TS strategy was dominated by TP and TFS. Compared with TP, the TFS strategy resulted in ICERs of $6510 per exacerbation avoided, and $243,180 per QALY gained. In those with severe COPD, TS resulted in equal exacerbation rates and slightly lower costs compared with TP. CONCLUSIONS: TFS had significantly better quality of life and fewer hospitalisations than patients treated with TP but these improvements in health outcomes were associated with increased costs. Neither TFS nor TS are economically attractive alternatives compared with monotherapy with T.

Cost-effectiveness of a new interferon-based blood assay, QuantiFERON-TB Gold, in screening tuberculosis contacts.

BACKGROUND: Recent approval of interferon-gamma release assays that are more specific for Mycobacterium tuberculosis has given new options for the diagnosis of latent tuberculosis infection (LTBI). OBJECTIVE: To assess the cost-effectiveness of Quanti-FERON-TB Gold (QFT-G) vs. the tuberculin skin test (TST) in diagnosing LTBI in contacts of active TB cases using a decision analytic Markov model. METHODS: Three screening strategies--TST alone, QFT-G alone and sequential screening of TST then QFT-G--were evaluated. The model was further stratified according to ethnicity and bacille Calmette-Guérin (BCG) vaccination status. Data sources included published studies and empirical data. Results were reported in terms of the incremental net monetary benefit (INMB) of each strategy compared with the baseline strategy of TST-based screening in all contacts. RESULTS: The most economically attractive strategy was to administer QFT-G in BCG-vaccinated contacts, and to reserve TST for all others (INMB CA$3.70/contact). The least cost-effective strategy was QFT-G for all contacts, which resulted in an INMB of CA$-11.50 per contact. Assuming a higher prevalence of recent infection, faster conversion of QFT-G, a higher rate of TB reactivation, reduction in utility or greater adherence to preventive treatment resulted in QFT-G becoming cost-effective in more subgroups. CONCLUSIONS: Selected use of QFT-G appears to be cost-effective if used in a targeted fashion.

Cost-effectiveness of continuous positive airway pressure therapy in patients with obstructive sleep apnea-hypopnea in British Columbia.

BACKGROUND: Obstructive sleep apnea-hypopnea (OSAH) is a common disorder characterized by recurrent collapse of the upper airway during sleep. Patients experience a reduced quality of life and an increased risk of motor vehicle crashes (MVCs). Continuous positive airway pressure (CPAP), which is the first-line therapy for OSAH, improves sleepiness, vigilance and quality of life. OBJECTIVE: To assess the cost-effectiveness of CPAP therapy versus no treatment for OSAH patients who are drivers. METHODS: A Markov decision analytical model with a five-year time horizon was used. The study population consisted of male and female patients, between 30 and 59 years of age, who were newly diagnosed with moderate to severe OSAH. The model evaluated the cost-effectiveness of CPAP therapy in reducing rates of MVCs and improving quality of life. Utility values were obtained from previously published studies. Rates of MVCs under the CPAP and no CPAP scenarios were calculated from Insurance Corporation of British Columbia data and a systematic review of published studies. MVCs, equipment and physician costs were obtained from the British Columbia Medical Association, published cost-of-illness studies and the price lists of established vendors of CPAP equipment in British Columbia. Findings were examined from the perspectives of a third-party payer and society. RESULTS: From the third-party payer perspective, CPAP therapy was more effective but more costly than no CPAP (incremental cost-effectiveness ratio [ICER] of $3,626 per quality-adjusted life year). From the societal perspective, the ICER was similar ($2,979 per quality-adjusted life year). The ICER was most dependent on preference elicitation method used to obtain utility values, varying almost sixfold under alternative assumptions from the base-case analysis. CONCLUSION: After considering costs and impact on quality of life, as well as the risk of MVCs in individuals with OSAH, CPAP therapy for OSAH patients is a highly efficient use of health care resources. Provincial governments who do not provide funding for CPAP therapy should reconsider.

Not all "quality-adjusted life years" are equal.

BACKGROUND: There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. METHODS: Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. RESULTS: Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively. CONCLUSION: Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated.

Adverse drug reactions associated with first-line anti-tuberculosis drug regimens.

BACKGROUND: Standard treatment of active tuberculosis (TB) consists of isoniazid (INH), rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB). Although this regimen is effective in treating active TB, it is associated with many adverse drug reactions (ADRs) and poses a significant challenge to completion of treatment. OBJECTIVES: To examine the incidence of major ADRs and risk factors associated with first-line anti-tuberculosis medications. METHODS: This study evaluated patients receiving treatment for active TB from a population-based database (2000-2005). The nature of the ADRs, likelihood of association with the study medications and severity were evaluated. RESULTS: A total of 1061 patients received treatment, of whom 318 (30%) had at least one major ADR. The overall incidence of all major ADRs was 7.3 events per 100 person-months (95%CI 7.2-7.5): 23.3 (95%CI 23.0-23.7) when on all four first-line drugs, 13.6 (95%CI 13.3-14.0) when on RMP, INH and PZA, and 2.4 (95%CI 2.3-2.6) when on INH and RMP. Adjusted hazard ratio (HR) revealed that combination regimens containing PZA, females, subjects aged 35-59 and >or=60 years, baseline aspartate aminotransferase >or=80 U/l and drug resistance were associated with any major event. CONCLUSIONS: First-line anti-tuberculosis drugs are associated with significant ADRs. There are several risk factors associated with the development of ADRs, including exposure to regimens containing PZA.

A dexamethasone-induced protein stimulates delta 9-desaturase activity in rat liver microsomes.

The effect of dexamethasone on the oxidative desaturation of [1-14C]palmitic to palmitoleic acid on rat liver microsomes, was studied. After 12 h of dexamethasone injection (1 mg/rat) a significant increase in delta 9-desaturase activity, was observed. This effect was also produced by a factor present in a 110,000 X g supernatant soluble fraction obtained after washing crude microsomes from dexamethasone-treated rats with a low ionic strength solution. The dexamethasone-induced factor was present not only in the liver cytosolic fraction of treated animals but also in the cytosol of isolated HTC cells previously incubated with the hormone. Dexamethasone would act via a newly synthesized modulatory factor. The effect depends on an unchanged protein structure, since its biological activity is impaired by trypsin digestion.

Modulation of delta 6 and delta 5 rat liver microsomal desaturase activities by dexamethasone-induced factor.

This report supports evidence for the existence of a dexamethasone-induced factor that modulates fatty acid desaturase activities. Dexamethasone at a dose of 1 mg/rat produced a significant decrease in microsomal delta 6 and delta 5 desaturation activity 12 h after the injection. Both desaturase activities were depressed by a soluble factor present in the cytosolic fraction of cells, since the supernatant of microsomes separated at 110,000 X g from hormonal-treated rat liver homogenates, added to crude or washed control microsomes, was able to inhibit in vitro linoleic and homo-gamma-linolenic conversion to gamma-linolenic and arachidonic acids, respectively. The inhibitory factor was loosely bound to microsomes, since it was also present in a soluble fraction obtained after washing crude microsomes from dexamethasone-treated rats with a low-ionic-strength solution. Besides, trypsin digestion deactivates the dexamethasone-induced factor. Therefore, the depressing effect of glucocorticoids on delta 6 and delta 5 desaturation capacity depends on an unchanged protein structure present in the cytosolic fraction of the cell and whose biosynthesis is brought about by hormonal induction.

Systematic review of the treatment of early Lyme disease.

Lyme disease is a rapidly emerging infectious disease and there are still many unanswered questions with respect to appropriate laboratory tests required for diagnosis of early Lyme disease, types of antimicrobials required for treatment and duration of therapy. A qualitative systematic review was used to summarise the existing data for the treatment of early Lyme disease. Eleven antibacterial therapy trials and 3 cost-effectiveness analyses met the inclusion criteria for this review. Antibacterial regimens that have been studied include phenoxymethylpenicillin (penicillin V), amoxicillin, amoxicillin/probenecid, tetracycline, doxycycline, cefuroxime axetil, erythromycin, roxithromycin, azithromycin and ceftriaxone. The data support the use of oral beta-lactam antibacterials [phenoxymethylpenicillin (penicillin V), amoxicillin, cefuroxime axetil] and oral tetracyclines as effective first-line treatment modalities for early Lyme disease. Oral macrolides are considered second-line agents as their clinical efficacy has been less than that of the beta-lactams and tetracyclines. Courses of therapy ranging from 10 to 21 days are supported by the available evidence, although the optimal duration of therapy is unknown.