Factors influencing initial implementation of an online community-based exercise intervention with adults living with HIV: a systems approach.

Introduction: Online community-based exercise (CBE) is a digital health intervention and rehabilitation strategy that promotes health among people living with HIV. Our aim was to describe the factors influencing initial implementation of a pilot online CBE intervention with adults living with HIV using a systems approach, as recommended by implementation science specialists. Methods: We piloted the implementation of a 6-month online CBE intervention and 6-month independent exercise follow up, in partnership with the YMCA in Toronto, Canada. We recruited adults living with HIV who identified themselves as safe to engage in exercise. The intervention phase included personalized exercise sessions online with a personal trainer; exercise equipment; access to online exercise classes; and a wireless physical activity monitor. Two researchers documented implementation factors articulated by participants and the implementation team during early implementation, defined as recruitment, screening, equipment distribution, technology orientation, and baseline assessments. Data sources included communication with participants; daily team communication; weekly team discussions; and in-person meetings. We documented implementation factors in meeting minutes, recruitment screening notes, and email communication; and analyzed the data using a qualitative descriptive approach using a systems engineering method called Cognitive Work Analysis. Results: Thirty-three adults living with HIV enrolled in the study (n = 33; median age: 52 years; cis-men: 22, cis-women: 10, non-binary: 1). Fifty-five factors influencing implementation, spanned five layers: (i) Natural, including weather and the COVID-19 virus; (ii) Societal, including COVID-19 impacts (e.g. public transit health risks impacting equipment pick-ups); (iii) Organizational, including information dissemination (e.g. tech support) and logistics (e.g. scheduling); (iv) Personal, including physical setting (e.g. space) and digital setting (e.g. device access); and (v) Human, including health (e.g. episodic illness) and disposition (e.g. motivation). The implementation team experienced heightened needs to respond rapidly; sustain engagement; and provide training and support. Additional organizational factors included a committed fitness training and research team with skills spanning administration and logistics, participant engagement, technology training, physical therapy, and research ethics. Conclusion: Fifty-five factors spanning multiple layers illustrate the complexities of online CBE with adults living with HIV. Initial implementation required a dedicated, rehabilitation-centred, multi-skilled, multi-stakeholder team to address a diverse set of factors.

EQ-5D-5L and SF-6D health utility index scores in patients with myasthenia gravis.

BACKGROUND AND PURPOSE: Health utilities are a preference-based method of valuing health states that are used in healthcare research, such as economic evaluations. There are limited health utility valuation data for patients with myasthenia gravis (MG). The aim of the study was to describe health utilities for patients with MG and different health states, using the EQ-5D-5L and SF-6D utility instruments, and to explore clinical and demographic determinants of utilities in this population. METHODS: Patients completed the EQ-5D-5L and SF-6D. In addition, patients were assessed with the Myasthenia Gravis Foundation of America classification, Myasthenia Gravis Impairment Index and MG-QOL15 as disease-specific measures, and the Neuro-QoL Fatigue scale. We calculated mean utilities for each Myasthenia Gravis Foundation of America severity class. We built regression models for the EQ-5D-5L and SF-6D to determine the clinical and demographic factors that determine patients' valuation of their health state. RESULTS: Among 254 patients, mean EQ-5D-5L health utilities were as follows: Remission, 0.94 ± 0.03; Minimal Manifestations, 0.92 ± 0.04; Class I, 0.89 ± 0.06; Class II, 0.78 ± 0.16; Class III, 0.58 ± 0.24 and Class IV, 0.61 ± 0.22. Mean SF-6D health utilities were as follows: Remission, 0.83 ± 0.07; Minimal Manifestations, 0.86 ± 0.14; Class I, 0.82 ± 0.14; Class II, 0.67 ± 0.12; Class III, 0.56 ± 0.11 and Class IV, 0.50 ± 0.10. The limb/axial scores were more highly correlated to health utilities than ocular or bulbar scores. CONCLUSIONS: We present estimates of health utilities for patients with MG that can be used in cost-utility and decision analyses. Limb/axial symptoms had a higher impact on health utilities than ocular or bulbar symptoms, which might reflect the impact of mobility on health valuation.

Arthrocentesis followed by intra-articular autologous blood injection for the treatment of recurrent temporomandibular joint dislocation.

Temporomandibular joint (TMJ) dislocation is an excessive forward movement of the condyle beyond the articular eminence with complete separation of the articular surfaces and fixation in that position. This study was conducted to assess autologous blood injection to the TMJ for the treatment of chronic recurrent TMJ dislocation. Fifteen patients with bilateral chronic recurrent condylar dislocation were included in the study. Bilateral TMJ arthrocentesis was performed on each patient, followed by the injection of 2ml of autologous blood into the superior joint compartment and 1ml onto the outer surface of the joint capsule. Preoperative and postoperative assessment included a thorough history and physical examination to determine the maximal mouth opening, presence of pain and sounds, frequency of luxation, recurrence rate, and presence of facial nerve paralysis. Eighty percent of the subjects (12 patients) had a successful outcome with no further episodes of dislocation and required no further treatment at their 1-year follow-up, whereas three patients had recurrent dislocation as early as 2 weeks after treatment. Autologous blood injection is a safe, simple, and cost-effective treatment for chronic recurrent TMJ dislocation.

Vitamin K supplementation for the primary prevention of osteoporotic fractures: is it cost-effective and is future research warranted?

UNLABELLED: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. It would be a cost-effective intervention at commonly used thresholds, but high uncertainty around the cost-effectiveness estimates persists. Further research on the effect of vitamin K on fractures is warranted. INTRODUCTION: Vitamin K might have a role in the primary prevention of fractures, but uncertainties about its effectiveness and cost-effectiveness persist. METHODS: We developed a state-transition probabilistic microsimulation model to quantify the cost-effectiveness of various interventions to prevent fractures in 50-year-old postmenopausal women without osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and calcium (at the same doses). An additional analysis explored replacing vitamin K(2) with vitamin K(1) (5 mg/day). RESULTS: Adding vitamin K(2) to vitamin D(3) with calcium reduced the lifetime probability of at least one fracture by 25%, increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95% credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 95% and the population expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin K(1) to vitamin D and calcium reduced the lifetime probability of at least one fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4) and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the EVPI was $414.9 billion. The efficacy of vitamin K was the most important parameter in sensitivity analyses. CONCLUSIONS: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. Given high uncertainty around the cost-effectiveness estimates, further research on the efficacy of vitamin K on fractures is warranted.

Preferences for surveillance strategies for women treated for high-grade precancerous cervical lesions.

OBJECTIVES: Data are lacking on how women view alternative approaches to surveillance for cervical cancer after treatment of high-grade cervical intraepithelial neoplasia. We measured and compared patient preferences (utilities) for scenarios with varying surveillance strategies and outcomes to inform guidelines and cost-effectiveness analyses of post-treatment surveillance options. METHODS: English- or Spanish-speaking women who had received an abnormal Pap test result within the past 2 years were recruited from general gynecology and colposcopy clinics and newspaper and online advertisements in 2007 and 2008. Participation consisted of one face-to-face interview, during which utilities for 11 different surveillance scenarios and their associated outcomes were elicited using the time tradeoff metric. A sociodemographic questionnaire also was administered. RESULTS: 65 women agreed to participate and successfully completed the preference elicitation exercises. Mean utilities ranged from 0.989 (undergoing only a Pap test, receiving normal results) to 0.666 (invasive cervical cancer treated with radical hysterectomy or radiation and chemotherapy). Undergoing both Pap and HPV tests and receiving normal/negative results had a lower mean utility (0.953) then undergoing only a Pap test and receiving normal results (0.989). Having both tests and receiving normal Pap but positive HPV results was assigned an even lower mean utility (0.909). 15.9% of the respondents gave higher utility scores to the Pap plus HPV testing scenario (with normal/negative results) than to the "Pap test alone" scenario (with normal results), while 17.5% gave the Pap test alone scenario a higher utility score. CONCLUSIONS: Preferences for outcomes ending with normal results but involving alternative surveillance processes differ substantially. The observed differences in utilities have important implications for clinical guidelines and cost-effectiveness analyses.

Cost-effectiveness of voluntary HIV screening in Russia.

Russia has one of the world's fastest growing HIV epidemics, and HIV screening has been widespread. Whether such screening is an effective use of resources is unclear. We used epidemiologic and economic data from Russia to develop a Markov model to estimate costs, quality of life and survival associated with a voluntary HIV screening programme compared with no screening in Russia. We measured discounted lifetime health-care costs and quality-adjusted life years (QALYs) gained. We varied our inputs in sensitivity analysis. Early identification of HIV through screening provided a substantial benefit to persons with HIV, increasing life expectancy by 2.1 years and 1.7 QALYs. At a base-case prevalence of 1.2%, once-per-lifetime screening cost $13,396 per QALY gained, exclusive of benefit from reduced transmission. Cost-effectiveness of screening remained favourable until prevalence dropped below 0.04%. When HIV-transmission-related costs and benefits were included, once-per-lifetime screening cost $6910 per QALY gained and screening every two years cost $27,696 per QALY gained. An important determinant of the cost-effectiveness of screening was effectiveness of counselling about risk reduction. Early identification of HIV infection through screening in Russia is effective and cost-effective in all but the lowest prevalence groups.

Current assessment of risk-benefit by regulators: is it time to introduce decision analyses?

Regulatory risk-benefit assessments may overweight small but serious risks relative to benefits. Using terfenadine and torsade de pointes as an exemplar, we illustrate how a different decision may result when outcomes are assessed using quality-adjusted life-years within a decision-analytical framework. The adoption of common measures of health outcome and the use of decision analyses, which will allow uncertainty to be characterized and evidence to be compiled from disparate sources, may inform complex risk-benefit decisions and should be used in conjunction with qualitative assessments.

Adverse quality of life consequences of antiretroviral medications.

To identify the effects of antiretroviral therapy on quality of life, we performed a qualitative content analysis of the Medical Outcomes Study-Human Immunodeficiency Virus (MOS-HIV) Health Survey. We used focus groups to elicit views about antiretroviral effects on quality of life from a purposive sample of treatment-experienced participants. Data were analysed using a grounded theory approach. We appraised the content of the MOS-HIV against the themes identified from our analysis. Participants also completed the MOS-HIV survey and were asked whether the survey captured all important medication-related aspects of quality of life. Participants (n=38) viewed the use of antiretrovirals as a trade-off between poorer quality of life and being alive. The net effect was increased longevity but without hope and future. Features of quality of life included the downstream consequences of side effects and toxicities, tensions with health care providers and loss of independent decision-making, dilemmas regarding drugs and career, burdens of medication-taking responsibilities, and the stress of living life under a pretense and hiding an HIV diagnosis. The MOS-HIV missed or under-emphasised these features. Quality of life concerns of people living with HIV, particularly those related to medication use, are not well captured by the MOS-HIV. A broad concept of quality of life is needed to encompass all dimensions important to people living with HIV.

Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS.

BACKGROUND: Adherence to prescribed regimens is required to derive maximal benefit from many highly active antiretroviral therapy (HAART) regimens in people living with HIV/AIDS. OBJECTIVES: To conduct a systematic review of the research literature on the effectiveness of patient support and education to improve adherence to HAART. SEARCH STRATEGY: A systematic search of electronic databases was performed from January 1996 to May 2005. SELECTION CRITERIA: Randomized controlled trials examining the effectiveness of patient support and education to improve adherence to HAART were considered for inclusion. Only those studies that measured adherence at a minimum of six weeks were included. DATA COLLECTION AND ANALYSIS: Study selection, quality assessments and data abstraction were performed independently by two reviewers. MAIN RESULTS: Nineteen studies involving a total of 2,159 participants met criteria for inclusion. It was not possible to conduct a meta-analysis due to study heterogeneity with respect to populations, interventions, comparison groups, outcomes, and length of follow-up. Sample sizes ranged from 22 to 367. The populations studied ranged from general HIV-positive populations to studies focusing exclusively on children, women, Latinos, or adults with a history of alcohol dependence, to studies focusing almost exclusively on men. Study interventions included cognitive behavioral therapy, motivational interviewing, medication management strategies, and interventions indirectly targeting adherence, such as programs directed to reduce risky sexual behaviours. Ten studies demonstrated a beneficial effect of the intervention on adherence. We found that interventions targeting practical medication management skills, those administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. We also found that interventions targeting marginalized populations such as women, Latinos, or patients with a past history of alcoholism were not successful at improving adherence. We were unable to determine whether effective adherence interventions were associated with improved virological or immunological outcomes. Most studies had several methodological shortcomings leaving them vulnerable to potential biases. AUTHORS' CONCLUSIONS: We found evidence to support the effectiveness of patient support and education interventions intended to improve adherence to antiretroviral therapy. Interventions targeting practical medication management skills, those interventions administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. There is a need for standardization and increased methodological rigour in the conduct of adherence trials.

The impact of home nocturnal hemodialysis on end-stage renal disease therapies: a decision analysis.

Home nocturnal hemodialysis (HNHD) is cost-effective relative to in-center hemodialysis (IHD) in short-run analyses. The effect in long-run analyses, when technique failures, declining benefits, delayed training, transplantation and death are considered, is unknown. We used decision analysis techniques to examine the relative cost-effectiveness of HNHD and IHD, projecting future costs and health effects over a lifetime with end-stage renal disease. We developed a Markov state-transition model comparing two strategies: only IHD or starting on IHD and subsequently transferring to HNHD. The model incorporates transplantation. In the base case, half the population was eligible for transplantation, with (1/3) of grafts from live donors. The time to transplant was 0.75 years for live and 5 years for deceased donor transplants. The delay before initiation of HNHD was 5 years. Costs and outcomes were discounted at 3% per annum. Model parameters were derived from a literature review. We also conducted one-way sensitivity analyses and Monte Carlo simulations. The HNHD strategy was associated with a quality-adjusted survival estimate of 5.79 quality-adjusted life years (QALYs), with lifetime costs of $538 094. The values for IHD were 5.31 QALYs and $543 602, respectively. Thus, HNHD is cost saving while improving quality of life. The incremental cost-utility ratio was consistently less than $50 000 per QALY in sensitivity and Monte Carlo analyses. Important determinants of cost-effectiveness were transplantation time and whether benefits declined over time. Our model suggests that HNHD improves quality-adjusted survival over IHD at an economically attractive cost-effectiveness ratio.

Decision analysis with cumulative prospect theory.

BACKGROUND: Individuals sometimes express preferences that do not follow expected utility theory. Cumulative prospect theory adjusts for some phenomena by using decision weights rather than probabilities when analyzing a decision tree. METHODS: The authors examined how probability transformations from cumulative prospect theory might alter a decision analysis of a prophylactic therapy in AIDS, eliciting utilities from patients with HIV infection (n = 75) and calculating expected outcomes using an established Markov model. They next focused on transformations of three sets of probabilities: 1) the probabilities used in calculating standard-gamble utility scores; 2) the probabilities of being in discrete Markov states; 3) the probabilities of transitioning between Markov states. RESULTS: The same prophylaxis strategy yielded the highest quality-adjusted survival under all transformations. For the average patient, prophylaxis appeared relatively less advantageous when standard-gamble utilities were transformed. Prophylaxis appeared relatively more advantageous when state probabilities were transformed and relatively less advantageous when transition probabilities were transformed. Transforming standard-gamble and transition probabilities simultaneously decreased the gain from prophylaxis by almost half. Sensitivity analysis indicated that even near-linear probability weighting transformations could substantially alter quality-adjusted survival estimates. CONCLUSION: The magnitude of benefit estimated in a decision-analytic model can change significantly after using cumulative prospect theory. Incorporating cumulative prospect theory into decision analysis can provide a form of sensitivity analysis and may help describe when people deviate from expected utility theory.

Cost-effectiveness of androgen suppression therapies in advanced prostate cancer.

BACKGROUND: The costs and side effects of several antiandrogen therapies for advanced prostate cancer differ substantially. We estimated the cost-effectiveness of antiandrogen therapies for advanced prostate cancer. METHODS: We performed a cost-effectiveness analysis using a Markov model based on a formal meta-analysis and literature review. The base case was assumed to be a 65-year-old man with a clinically evident, local recurrence of prostate cancer. The model used a societal perspective and a time horizon of 20 years. Six androgen suppression strategies were evaluated: diethylstilbestrol (DES), orchiectomy, a nonsteroidal antiandrogen (NSAA), a luteinizing hormone-releasing hormone (LHRH) agonist, and combinations of an NSAA with an LHRH agonist or orchiectomy. Outcome measures were survival, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios. RESULTS: DES, the least expensive therapy, had a discounted lifetime cost of $3600 and the lowest quality-adjusted survival, 4.6 QALYs. At a cost of $7000, orchiectomy was associated with 5.1 QALYs, resulting in an incremental cost-effectiveness ratio of $7500/QALY relative to DES. All other strategies-LHRH agonists, NSAA, and both combined androgen blockade strategies-had higher costs and lower quality-adjusted survival than orchiectomy. These results were sensitive to the quality of life associated with orchiectomy and the efficacy of combined androgen blockade, and they changed little when prostate-specific antigen results were used to guide therapy. Under a wide range of other assumptions, the cost-effectiveness of orchiectomy relative to DES was consistently less than $20 000/QALY. Androgen suppression therapies were most cost-effective if initiated after patients became symptomatic from prostate metastases. CONCLUSIONS: For men who accept it, orchiectomy is likely to be the most cost-effective androgen suppression strategy. Combined androgen blockade is the least economically attractive option, yielding small health benefits at high relative costs.

The cost effectiveness of voluntary prenatal and routine newborn HIV screening in the United States.

OBJECTIVE: To evaluate the cost effectiveness of voluntary prenatal and routine postnatal HIV screening in the cohort of pregnant women and newborns in the United States. DESIGN: Cost-effectiveness analysis. We developed a decision model to analyze the cost effectiveness of enhanced prenatal screening and routine newborn screening for HIV. We also analyzed the incremental cost effectiveness of routine newborn screening when improved voluntary prenatal screening is already in place. PARTICIPANTS: Analysis of the cohort of pregnant women and newborns in the United States. INTERVENTIONS: Enhanced prenatal screening, or routine newborn screening for HIV. MAIN OUTCOME MEASURES: Infections averted, life expectancy, costs, and incremental cost effectiveness. RESULTS: Improved participation in voluntary prenatal HIV screening would result in an additional 1.1 million women being screened annually, would identify an additional 527 HIV-infected mothers annually, would avert 150 infections in newborns, and would cost $8,900 U.S. per life-year gained. Routine newborn HIV screening would test 3.9 million infants annually, would identify 1061 HIV-infected mothers, would avert 266 infections in newborns, and would cost $7,000 U.S. per life-year gained. If improved voluntary prenatal screening is already in place, routine newborn screening would avert an additional 135 infections in newborns, at an incremental cost of $10, 600 U.S. per life-year gained. The screening programs are likely to be cost effective over a wide range of assumptions regarding key factors in the analysis. CONCLUSIONS: Improved voluntary prenatal HIV screening of women and routine screening of newborns are cost effective. Routine newborn screening becomes less attractive as the rate of voluntary prenatal screening increases. Improved participation in voluntary prenatal screening has the added benefit that mothers maintain their right to determine whether they are tested for HIV.

Economic methods for measuring the quality of life associated with HIV infection.

BACKGROUND: Quality of life is measured as utilities for cost-effectiveness analyses. OBJECTIVE: To test the adequacy of three common utility elicitation methods for individuals with Human Immunodeficiency Virus (HIV) disease. MEASUREMENTS: HIV-positive participants (n = 75) rated three standardized health states (symptomatic HIV infection, minor AIDS defining illness, and major AIDS defining illness) with two utility elicitation methods (Standard Gamble [SG], and Time Trade-off [TTO]) and one value method (Visual Analog [VA]). Participants also rated their own health with one utility method (Health Utilities Index [HUI]) and one conventional quality of life method (Medical Outcomes Study--HIV Health Survey [MOS-HIV]). RESULTS: For all states, SG and TTO scores ranged from near 0.00 (equivalent to death) to 1.00 (best possible quality of life). Mean scores for symptomatic HIV were similar with the SG (0.80) and TTO (0.81) but higher than with the VA (0.70). Similar results were observed for minor AIDS defining illnesses (0.65, 0.65, 0.46 respectively) and major AIDS defining illnesses (0.42, 0.44, 0.25 respectively). Discrepant SG and TTO scores were observed in many individuals and were not explained by demographic characteristics. As expected, HUI scores of an individual's own health were related to the disease state. Four of ten MOS-HIV subscales (overall health, physical functioning, role functioning, and pain) were also related to disease state. HUI scores were correlated with the MOS-HIV score for overall health and for all MOS-HIV subscales except health transition. CONCLUSIONS: Mean utility scores for HIV-related health states elicited by the Standard Gamble and Time Trade-off were similar but a large degree of individual variation persists. Economic methods provide imprecise estimates of the quality of life associated with HIV infection.

Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer.

OBJECTIVES: With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis. SEARCH STRATEGY: The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references. SELECTION CRITERIA: We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included. DATA COLLECTION AND ANALYSIS: The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine. MAIN RESULTS: Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)

Preventing Mycobacterium avium complex in patients who are using protease inhibitors: a cost-effectiveness analysis.

BACKGROUND: Practice guidelines recommending Mycobacterium avium complex (MAC) prophylaxis for patients with HIV disease were based on clinical trials in which individuals did not receive protease inhibitors. OBJECTIVE: To estimate the cost-effectiveness of strategies for MAC prophylaxis in patients whose treatment regimen includes protease inhibitors. DESIGN: Decision analysis with Markov modelling of the natural history of advanced HIV disease. Five strategies were evaluated: no prophylaxis, azithromycin, rifabutin, clarithromycin and a combination of azithromycin plus rifabutin. MAIN OUTCOME MEASURES: Survival, quality of life, quality-adjusted survival, health care costs and marginal cost-effectiveness ratios. RESULTS: Compared with no prophylaxis, rifabutin increased life expectancy from 78 to 80 months, increased quality-adjusted life expectancy from 50 to 52 quality-adjusted months and increased health care costs from $233000 to $239800. Ignoring time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $44300 per life year. Adjusting for time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $41500 per quality-adjusted life year (QALY). In comparison with rifabutin, azithromycin was associated with increased survival, increased costs and an incremental cost-effectiveness ratio of $54300 per QALY. In sensitivity analyses, prophylaxis remained economically attractive unless the lifetime chance of being diagnosed with MAC was less than 20%, the rate of CD4 count decline was less than 10 x 10(6) cells/l per year, or the CD4 count was greater than 50 x 10(6) cells/l. CONCLUSION: MAC prophylaxis increases quality-adjusted survival at a reasonable cost, even in patients using protease inhibitors. When not contraindicated, starting azithromycin or rifabutin when the patient's CD4 count is between 50 and 75 x 10(6) cells/l is the most cost-effective strategy. The main determinants of cost-effectiveness are CD4 count, viral load, place of residence and patient preference.

Interpreting small differences in functional status: the Six Minute Walk test in chronic lung disease patients.

Functional status measurements are often difficult to interpret because small differences may be statistically significant but not clinically significant. How much does the Six Minute Walk test (6MW) need to differ to signify a noticeable difference in walking ability for patients with chronic obstructive pulmonary disease (COPD)? We studied individuals with stable COPD (n = 112, mean age = 67 yr, mean FEV1 = 975 ml) and estimated the smallest difference in 6MW distances that was associated with a noticeable difference in patients' subjective comparison ratings of their walking ability. We found that the 6MW was significantly correlated with patients' ratings of their walking ability relative to other patients (r = 0.59, 95% confidence interval [CI]: 0.54 to 0.63). Distances needed to differ by 54 m for the average patient to stop rating themselves as "about the same" and start rating themselves as either "a little bit better" or "a little bit worse" (95% CI: 37 to 71 m). We suggest that differences in functional status can be statistically significant but below the threshold at which patients notice a difference in themselves relative to others; an awareness of the smallest difference in walking distance that is noticeable to patients may help clinicians interpret the effectiveness of symptomatic treatments for COPD.