Instruct: Given a scientific claim, retrieve documents that support or refute the claim.
Query: Cost effectiveness evaluations based on cRCT data accurately reflect prices for patients in actual clinical practice.
BACKGROUND Data on absolute risks of outcomes and patterns of drug use in cost-effectiveness analyses are often based on randomised clinical trials (RCTs). The objective of this study was to evaluate the external validity of published cost-effectiveness studies by comparing the data used in these studies (typically based on RCTs) to observational data from actual clinical practice. Selective Cox-2 inhibitors (coxibs) were used as an example. METHODS AND FINDINGS The UK General Practice Research Database (GPRD) was used to estimate the exposure characteristics and individual probabilities of upper gastrointestinal (GI) events during current exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) or coxibs. A basic cost-effectiveness model was developed evaluating two alternative strategies: prescription of a conventional NSAID or coxib. Outcomes included upper GI events as recorded in GPRD and hospitalisation for upper GI events recorded in the national registry of hospitalisations (Hospital Episode Statistics) linked to GPRD. Prescription costs were based on the prescribed number of tables as recorded in GPRD and the 2006 cost data from the British National Formulary. The study population included over 1 million patients prescribed conventional NSAIDs or coxibs. Only a minority of patients used the drugs long-term and daily (34.5% of conventional NSAIDs and 44.2% of coxibs), whereas coxib RCTs required daily use for at least 6-9 months. The mean cost of preventing one upper GI event as recorded in GPRD was US$104k (ranging from US$64k with long-term daily use to US$182k with intermittent use) and US$298k for hospitalizations. The mean costs (for GPRD events) over calendar time were US$58k during 1990-1993 and US$174k during 2002-2005. Using RCT data rather than GPRD data for event probabilities, the mean cost was US$16k with the VIGOR RCT and US$20k with the CLASS RCT. CONCLUSIONS The published cost-effectiveness analyses of coxibs lacked external validity, did not represent patients in actual clinical practice, and should not have been used to inform prescribing policies. External validity should be an explicit requirement for cost-effectiveness analyses.
IMPORTANCE The American College of Cardiology and the American Heart Association (ACC/AHA) cholesterol treatment guidelines have wide-scale implications for treating adults without history of atherosclerotic cardiovascular disease (ASCVD) with statins. OBJECTIVE To estimate the cost-effectiveness of various 10-year ASCVD risk thresholds that could be used in the ACC/AHA cholesterol treatment guidelines. DESIGN, SETTING, AND PARTICIPANTS Microsimulation model, including lifetime time horizon, US societal perspective, 3% discount rate for costs, and health outcomes. In the model, hypothetical individuals from a representative US population aged 40 to 75 years received statin treatment, experienced ASCVD events, and died from ASCVD-related or non-ASCVD-related causes based on ASCVD natural history and statin treatment parameters. Data sources for model parameters included National Health and Nutrition Examination Surveys, large clinical trials and meta-analyses for statin benefits and treatment, and other published sources. MAIN OUTCOMES AND MEASURES Estimated ASCVD events prevented and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS In the base-case scenario, the current ASCVD threshold of 7.5% or higher, which was estimated to be associated with 48% of adults treated with statins, had an incremental cost-effectiveness ratio (ICER) of $37,000/QALY compared with a 10% or higher threshold. More lenient ASCVD thresholds of 4.0% or higher (61% of adults treated) and 3.0% or higher (67% of adults treated) had ICERs of $81,000/QALY and $140,000/QALY, respectively. Shifting from a 7.5% or higher ASCVD risk threshold to a 3.0% or higher ASCVD risk threshold was estimated to be associated with an additional 161,560 cardiovascular disease events averted. Cost-effectiveness results were sensitive to changes in the disutility associated with taking a pill daily, statin price, and the risk of statin-induced diabetes. In probabilistic sensitivity analysis, there was a higher than 93% chance that the optimal ASCVD threshold was 5.0% or lower using a cost-effectiveness threshold of $100,000/QALY. CONCLUSIONS AND RELEVANCE In this microsimulation model of US adults aged 45 to 75 years [corrected], the current 10-year ASCVD risk threshold (≥7.5% risk threshold) used in the ACC/AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (ICER, $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0% risk threshold) or $150,000/QALY (≥3.0% risk threshold). The optimal ASCVD threshold was sensitive to patient preferences for taking a pill daily, changes to statin price, and the risk of statin-induced diabetes.
OBJECTIVE To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care. DESIGN Prospective cohort study. SETTING Five US teaching hospitals between 1989 and 1994. SUBJECTS A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories. MAIN OUTCOME MEASURES Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results. RESULTS By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49 300 ($17 000, $30 500, $56 600) with RHC and $35 700 ($11 300, $20 600, $39 200) without RHC. Mean length of stay in the ICU was 14.8 (5, 9, 17) days with RHC and 13.0 (4, 7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful. CONCLUSION In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study.
BACKGROUND The Italian National Health Service (NHS) provides universal coverage to all citizens, granting primary and hospital care with a copayment system for outpatient and drug services. Financing of Local Health Trusts (LHTs) is based on a capitation system adjusted only for age, gender and area of residence. We applied a risk-adjustment system (Johns Hopkins Adjusted Clinical Groups System, ACG® System) in order to explain health care costs using routinely collected administrative data in the Veneto Region (North-eastern Italy). METHODS All residents in the Veneto Region were included in the study. The ACG system was applied to classify the regional population based on the following information sources for the year 2015: Hospital Discharges, Emergency Room visits, Chronic disease registry for copayment exemptions, ambulatory visits, medications, the Home care database, and drug prescriptions. Simple linear regressions were used to contrast an age-gender model to models incorporating more comprehensive risk measures aimed at predicting health care costs. RESULTS A simple age-gender model explained only 8% of the variance of 2015 total costs. Adding diagnoses-related variables provided a 23% increase, while pharmacy based variables provided an additional 17% increase in explained variance. The adjusted R-squared of the comprehensive model was 6 times that of the simple age-gender model. CONCLUSIONS ACG System provides substantial improvement in predicting health care costs when compared to simple age-gender adjustments. Aging itself is not the main determinant of the increase of health care costs, which is better explained by the accumulation of chronic conditions and the resulting multimorbidity.
OBJECTIVE To conduct an economic analysis of the Hlabisa community-based directly observed therapy management strategy for tuberculosis and to project costs of three alternative strategies. SETTING Hlabisa health district, KwaZulu-Natal, South Africa. METHODS An economic analysis comparing the current tuberculosis management strategy in Hlabisa with three alternative strategies (the Hlabisa strategy prior to 1991 based on hospitalisation, the national strategy and sanatorium care) in terms of costs to both health service and patient and of cost-effectiveness. RESULTS The current Hlabisa strategy was the most cost-effective (R3799 per patient cured), compared with R98307 for the strategy used prior to 1991, R9940 for the national strategy, and R11145 for sanatorium care. Between 71% and 88% of treatment costs lie with the health service, and hospitalisation (R119 per day) is the most expensive item. Prolonged hospitalisation is extremely expensive, but community care is cheaper (community clinic visit, R28; community health worker visit, R7). The total cost of supervising a patient in the community under the current Hlabisa strategy was R503, equivalent to 4.2 days in hospital. Drug costs (R157) are equivalent to just 1.3 days in hospital. CONCLUSION Cost to both health service and patient can be substantially reduced by using community-based directly observed therapy for tuberculosis, a strategy that is cheap and cost-effective in Hlabisa. These findings have important national implications, supporting the goals of the new tuberculosis control programme.
BACKGROUND PEPFAR, national governments, and other stakeholders are investing unprecedented resources to provide HIV treatment in developing countries. This study reports empirical data on costs and cost trends in a large sample of HIV treatment sites. DESIGN In 2006-2007, we conducted cost analyses at 43 PEPFAR-supported outpatient clinics providing free comprehensive HIV treatment in Botswana, Ethiopia, Nigeria, Uganda, and Vietnam. METHODS We collected data on HIV treatment costs over consecutive 6-month periods starting from scale-up of dedicated HIV treatment services at each site. The study included all patients receiving HIV treatment and care at study sites [62,512 antiretroviral therapy (ART) and 44,394 pre-ART patients]. Outcomes were costs per patient and total program costs, subdivided by major cost categories. RESULTS Median annual economic costs were US$ 202 (2009 USD) for pre-ART patients and US$ 880 for ART patients. Excluding antiretrovirals, per patient ART costs were US$ 298. Care for newly initiated ART patients cost 15-20% more than for established patients. Per patient costs dropped rapidly as sites matured, with per patient ART costs dropping 46.8% between first and second 6-month periods after the beginning of scale-up, and an additional 29.5% the following year. PEPFAR provided 79.4% of funding for service delivery, and national governments provided 15.2%. CONCLUSION Treatment costs vary widely between sites, and high early costs drop rapidly as sites mature. Treatment costs vary between countries and respond to changes in antiretroviral regimen costs and the package of services. Whereas cost reductions may allow near-term program growth, programs need to weigh the trade-off between improving services for current patients and expanding coverage to new patients.
Although interest in clinical guidelines has never been greater, uncertainty persists about whether they are effective. The debate has been hampered by the lack of a rigorous overview. We have identified 59 published evaluations of clinical guidelines that met defined criteria for scientific rigour; 24 investigated guidelines for specific clinical conditions, 27 studied preventive care, and 8 looked at guidelines for prescribing or for support services. All but 4 of these studies detected significant improvements in the process of care after the introduction of guidelines and all but 2 of the 11 studies that assessed the outcome of care reported significant improvements. We conclude that explicit guidelines do improve clinical practice, when introduced in the context of rigorous evaluations. However, the size of the improvements in performance varied considerably.
I present methods for assessing the relative effectiveness of two treatments when they have not been compared directly in a randomized trial but have each been compared to other treatments. These network meta-analysis techniques allow estimation of both heterogeneity in the effect of any given treatment and inconsistency ('incoherence') in the evidence from different pairs of treatments. A simple estimation procedure using linear mixed models is given and used in a meta-analysis of treatments for acute myocardial infarction.
Solitary metastatic brain tumors are the most common intracranial neoplasms encountered by neurosurgeons. Surgical resection of brain metastasis with whole brain radiotherapy (WBR) significantly increases survival in comparison with WBR alone. Stereotactic radiosurgery (SR) seems to provide results that are similar to those of surgical resection. To analyze the economic efficiency of these different treatments, we compared the results of surgical resection and SR as reported in the medical literature between 1974 and 1994. We included studies in which: 1) at least 75% of patients received WBR; 2) study dates were in the computed tomography era (after 1975); 3) operative morbidity, mortality, and median survival were reported; 4) study dates were not included in a more recent update or review; 5) tumor histologies were reported; and 6) the cobalt-60 gamma unit was used for SR. Three surgical resection studies and one SR study met all entry requirements. The WBR baseline was developed from two prospective, randomized trials and used for incremental cost effectiveness analysis. We developed a model of typical resource usage for uncomplicated procedures, reported complications, and subsequent craniotomies (for recurrent tumor or radiation necrosis) for both treatment options. Costs were estimated from the societal viewpoint using the 1992 Medicare Provider Analysis and Review database with average cost:charge ratios for surgery and WBR. A survey of capital and operating costs from five sites was used for radiosurgery. Our analysis revealed that radiosurgery had a lower uncomplicated procedure cost ($20,209 versus $27,587), a lower average complication cost per case ($2,534 versus $2,874), and a lower total cost per procedure ($22,743 versus $30,461), was more cost effective ($24,811 versus $32,149 per life year), and had a better incremental cost effectiveness ($40,648 versus $52,384 per life year) than surgical resection. A sensitivity analysis revealed that large changes in key assumptions would be required to change the analysis outcome. Equalization of the incremental cost effectiveness of the two treatments would require one of the following: 1) a 38.7% reduction in SR annual case volume, 2) a 34.7% increase in SR procedure cost, 3) a 18.8% reduction in surgical resection procedure cost, 4) a 240.5% increase in SR morbidity cost, 5) a 12.7% reduction in SR median survival, 6) a 16.8% increase in surgical resection median survival. Elimination of all surgical resection morbidity cost would still result in superior incremental cost effectiveness for SR.(ABSTRACT TRUNCATED AT 400 WORDS)
The standard treatment of partial-thickness burns includes topical silver products such as silver sulfadiazine (SSD) cream and enclosed dressings including silver-impregnated foam (Mepilex Ag; Molnlycke Health Care, Gothenburg, Sweden) and silver-laden sheets (Aquacel Ag; ConvaTec, Skillman, NJ). The current state of health care is limited by resources, with an emphasis on evidence-based outcomes and cost-effective treatments. This study includes a decision analysis with an incremental cost-utility ratio comparing enclosed silver dressings with SSD in partial-thickness burn patients with TBSA less than 20%. A comprehensive literature review was conducted to identify clinically relevant health states in partial-thickness burn patients. These health states include successful healing, infection, and noninfected delayed healing requiring either surgery or conservative management. The probabilities of these health states were combined with Medicare CPT reimbursement codes (cost) and patient-derived utilities to fit into the decision model. Utilities were obtained using a visual analog scale during patient interviews. Expected cost and quality-adjusted life years (QALYs) were calculated using the roll-back method. The incremental cost-utility ratio for enclosed silver dressing relative to SSD was $40,167.99/QALY. One-way sensitivity analysis of complication rates confirmed robustness of the model. Assuming a maximum willingness to pay $50,000/QALY, the complication rate for SSD must be 22% or higher for enclosed silver dressing to be cost effective. By varying complication rates for SSD and enclosed silver dressings, the two-way sensitivity analysis demonstrated the cost effectiveness of using enclosed silver dressing at the majority of complication rates for both treatment modalities. Enclosed silver dressings are a cost-effective means of treating partial thickness burns.
BACKGROUND New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly. METHODS We used multiple independent mathematical models in four settings-South Africa, Zambia, India, and Vietnam-to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered 'very cost-effective' if the $/DALY was less than the country's per capita gross domestic product (GDP; South Africa: $8040, Zambia: $1425, India: $1489, Vietnam: $1407) and 'cost-effective' if $/DALY was less than three times per capita GDP. FINDINGS In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from $237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to $749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to $241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost-effective. INTERPRETATION Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets. FUNDING The Bill and Melinda Gates Foundation and World Health Organization.
BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. METHODS We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. FINDINGS Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. FUNDING National Institute for Health Research and the National Institute for Health and Clinical Excellence.
OBJECTIVE Our objective was to assess the cost implications of changing the intensive care unit staffing model from on-demand presence to mandatory 24-hr in-house critical care specialist presence. DESIGN A pre-post comparison was undertaken among the prospectively assessed cohorts of patients admitted to our medical intensive care unit 1 yr before and 1 yr after the change. Our data were stratified by Acute Physiology and Chronic Health Evaluation III quartile and whether a patient was admitted during the day or at night. Costs were modeled using a generalized linear model with log-link and γ-distributed errors. SETTING A large academic center in the Midwest. PATIENTS All patients admitted to the adult medical intensive care unit on or after January 1, 2005 and discharged on or before December 31, 2006. Patients receiving care under both staffing models were excluded. INTERVENTION Changing the intensive care unit staffing model from on-demand presence to mandatory 24-hr in-house critical care specialist presence. MEASUREMENTS AND MAIN RESULTS Total cost estimates of hospitalization were calculated for each patient starting from the day of intensive care unit admission to the day of hospital discharge. Adjusted mean total cost estimates were 61% lower in the post period relative to the pre period for patients admitted during night hours (7 pm to 7 am) who were in the highest Acute Physiology and Chronic Health Evaluation III quartile. No significant differences were seen at other severity levels. The unadjusted intensive care unit length of stay fell in the post period relative to the pre period (3.5 vs. 4.8) with no change in non-intensive care unit length of stay. CONCLUSIONS We find that 24-hr intensive care unit intensivist staffing reduces lengths of stay and cost estimates for the sickest patients admitted at night. The costs of introducing such a staffing model need to be weighed against the potential total savings generated for such patients in smaller intensive care units, especially ones that predominantly care for lower-acuity patients.
BACKGROUND Patient experience is increasingly used to assess organizational performance, for example in public reporting or pay-for-performance schemes. Conventional approaches using 95% confidence intervals are commonly used to determine required survey samples or to report performance but these may result in unreliable organizational comparisons. METHODS We analyzed data from 2.2 million patients who responded to the English 2009 General Practice Patient Survey, which included 45 patient experience questions nested within 6 different care domains (access, continuity of care, communication, anticipatory care planning, out-of-hours care, and overall care satisfaction). For each question, unadjusted and case-mix adjusted (for age, sex, and ethnicity) organization-level reliability, and intraclass correlation coefficients were calculated. RESULTS Mean responses per organization ranged from 23 to 256 for questions evaluating primary care practices, and from 1454 to 2758 for questions evaluating out-of-hours care organizations. Adjusted and unadjusted reliability values were similar. Twenty-six questions had excellent reliability (≥0.90). Seven nurse communication questions had very good reliability (≥0.85), but 3 anticipatory care planning questions had lower reliability (<0.70). Reliability was typically <0.70 for questions with <100 mean responses per practice, usually indicating questions which only a subset of patients were eligible to answer. Nine questions had both excellent reliability and high intraclass correlation coefficients (≥0.10) indicating both reliable measurement and substantial performance variability. CONCLUSIONS High reliability is a necessary property of indicators used to compare health care organizations. Using the English General Practice Patient Survey as a case study, we show how reliability and intraclass correlation coefficients can be used to select measures to support robust organizational comparisons, and to design surveys that will both provide high-quality measurement and optimize survey costs.
OBJECTIVE To assess the robustness of patient responses to a new national survey of patient experience as a basis for providing financial incentives to doctors. DESIGN Analysis of the representativeness of the respondents to the GP Patient Survey compared with those who were sampled (5.5 million patients registered with 8273 general practices in England in January 2009) and with the general population. Analysis of non-response bias looked at the relation between practice response rates and scores on the survey. Analysis of the reliability of the survey estimated the proportion of the variance of practice scores attributable to true differences between practices. RESULTS The overall response rate was 38.2% (2.2 million responses), which is comparable to that in surveys using similar methodology in the UK. Men, young adults, and people living in deprived areas were under-represented among respondents. However, for questions related to pay for performance, there was no systematic association between response rates and questionnaire scores. Two questions which triggered payments to general practitioners were reliable measures of practice performance, with average practice-level reliability coefficients of 93.2% and 95.0%. Less than 3% and 0.5% of practices had fewer than the number of responses required to achieve conventional reliability levels of 90% and 70%. A change to the payment formula in 2009 resulted in an increase in the average impact of random variation in patient scores on payments to general practitioners compared with payments made in 2007 and 2008. CONCLUSIONS There is little evidence to support the concern of some general practitioners that low response rates and selective non-response bias have led to systematic unfairness in payments attached to questionnaire scores. The study raises issues relating to the validity and reliability of payments based on patient surveys and provides lessons for the UK and for other countries considering the use of patient experience as part of pay for performance schemes.
Statements like "quality of care is more highly valued than waiting time" can neither be supported nor refuted by comparisons of utility parameters from a traditional discrete choice experiment (DCE). Best--worst scaling can overcome this problem because it asks respondents to perform a different choice task. However, whilst the nature of the best--worst task is generally understood, there are a number of issues relating to the design and analysis of a best--worst choice experiment that require further exposition. This paper illustrates how to aggregate and analyse such data and using a quality of life pilot study demonstrates how richer insights can be drawn by the use of best--worst tasks.
A novel design for intervention studies is presented, the so called PROBE study (Prospective Randomized Open, Blinded End-point). This design is compared to the classical double-blind design. Among the advantages of the PROBE design are lower cost and greater similarity to standard clinical practice, which should make the results more easily applicable in routine medical care. Since end-points are evaluated by a blinded end-point committee it is obvious that there should be no difference between the two types of trials in this regard.
Background  Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones. Thus, our goal was to systematically evaluate the evidence pertaining to this question. Methods and Findings  We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition. Studies were retrieved from PubMed, contact with experts, and literature cross-referencing. Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome. Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both). Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones. There was considerable heterogeneity between studies (I2 = 72% for the main analysis). Results were similar in studies using clinical and those using administrative databases. No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01). Smaller studies did not differ in their results from larger studies. Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude. Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones. Conclusions  The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes. Differences for specific diseases cannot be excluded, but are likely to be small.
Essentials Direct oral anticoagulants (DOACs) do not require laboratory monitoring currently. DOAC specific measurements were performed at trough in patients with atrial fibrillation. Patients who developed thromboembolic events showed lower DOAC plasma levels. This study supports the concept of measuring DOAC levels at steady state. SUMMARY Background Direct oral anticoagulants (DOACs) are administered at fixed doses without the need for dose adjustment according to laboratory testing. High interindividual variability in drug blood levels has been shown with all DOACs. To evaluate a possible relationship between DOAC C-trough anticoagulant levels and thromboembolic events, 565 consecutive naive patients with atrial fibrillation (AF) were enrolled in this study performed within the START Laboratory Registry. Methods DOAC-specific measurements (diluted thrombin time or anti-activated factor II calibrated for dabigatran; anti-activated FX calibrated for rivaroxaban or apixaban) at C-trough were performed locally at steady state within 15-25 days after the start of treatment. For each DOAC, the interval of C-trough levels, from the limit of quantification to the highest value, was subdivided into four equal classes, and results were attributed to these classes; the median values of results were also calculated. Thromboembolic complications occurring during 1 year of follow-up were recorded. Results Thromboembolic events (1.8%) occurred in 10 patients who had baseline C-trough levels in the lowest class of drug levels. The incidence of thromboembolic events among patients with DOAC C-trough levels in the lowest level class was 2.4%, and that in the remaining groups was 0%. The patients with thrombotic complications also had a higher mean CHA2 DS2 -VASc score than that of the total patient population: 5.3 (95% confidence interval [CI] 4.3-6.3 versus 3.0 (95% CI 2.9-3.1). Conclusion In this study cohort, thrombotic complications occurred only in DOAC-treated AF patients who had very low C-trough levels, with a relatively high CHA2 DS2 -VASc score. Larger studies are warranted to confirm these preliminary observations.
OBJECTIVE To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery. DESIGN Cross sectional observational study of registered and published trials. SETTING Randomised controlled trials of interventions in patients undergoing a surgical procedure. DATA SOURCES The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword "surgery". Recruitment status was extracted from the ClinicalTrials.gov database. A systematic search for studies published in peer reviewed journals was performed; if they were not found, results posted on the ClinicalTrials.gov results database were sought. Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed. MAIN OUTCOME MEASURES Trial discontinuation before completion and non-publication after completion. Logistic regression was used to determine the effect of funding source on publication status, with adjustment for intervention type and trial size. RESULTS Of 818 registered trials found using the keyword "surgery", 395 met the inclusion criteria. Of these, 21% (81/395) were discontinued early, most commonly owing to poor recruitment (44%, 36/81). The remaining 314 (79%) trials proceeded to completion, with a publication rate of 66% (208/314) at a median time of 4.9 (interquartile range 4.0-6.0) years from study completion to publication search. A further 6% (20/314) of studies presented results on ClinicalTrials.gov without a corresponding peer reviewed publication. Industry funding did not affect the rate of discontinuation (adjusted odds ratio 0.91, 95% confidence interval 0.54 to 1.55) but was associated with a lower odds of publication for completed trials (0.43, 0.26 to 0.72). Investigators' email addresses for trials with an uncertain fate were identified for 71.4% (10/14) of discontinued trials and 83% (101/122) of unpublished studies. Only 43% (6/14) and 20% (25/122) replies were received. Email responses for completed trials indicated 11 trials in press, five published studies (four in non-indexed peer reviewed journals), and nine trials remaining unpublished. CONCLUSIONS One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks. To promote future efficiency and transparency, changes are proposed to research governance frameworks to overcome these concerns.
INTRODUCTION Recent studies in septic patients showed that adverse effects of hydroxyethyl starches (HESs) possibly outweigh their benefits in severely impaired physiological haemostasis. It remains unclear whether this also applies to patient populations that are less vulnerable. In this meta-analysis, we evaluated the impact of various HES generations on safety and efficacy endpoints in patients undergoing cardiac surgery. METHODS We searched the PubMed, Embase and Cochrane Central Register of Controlled Trials databases for randomised controlled trials (RCTs) in the English or German language comparing the use of HES to any other colloid or crystalloid during open heart surgery. RESULTS Blood loss and transfusion requirements were higher for older starches with mean molecular weights more than 200 kDa compared to other volume substitutes. In contrast, this effect was not observed with latest-generation tetrastarches (130/0.4), which performed even better when compared to albumin (blood loss of tetrastarch versus albumin: standardised mean difference (SMD), -0.34; 95% CI, -0.63, -0.05; P = 0.02; versus gelatin: SMD, -0.06; 95% CI, -0.20, 0.08; P = 0.39; versus crystalloids: SMD, -0.05; 95% CI, -0.20, 0.10; P = 0.54). Similar results were found for transfusion needs. Lengths of stay in the intensive care unit or hospital were significantly shorter with tetrastarches compared to gelatin (intensive care unit: SMD, -0.10; 95% CI, -0.15, -0.05; P = 0.0002) and crystalloids (hospital: SMD, -0.52; 95% CI, -0.90, -0.14; P = 0.007). CONCLUSIONS In this meta-analysis of RCTs, we could not identify safety issues with tetrastarches compared with other colloid or crystalloid solutions in terms of blood loss, transfusion requirements or hospital length of stay in patients undergoing cardiac surgery. The safety data on coagulation with older starches raise some issues that need to be addressed in future trials.
BACKGROUND HIV and tuberculosis (TB) services are provided free of charge in many sub-Saharan African countries, but patients still incur costs. METHODS Patient-exit interviews were conducted in primary health care clinics in rural South Africa with representative samples of 200 HIV-infected patients enrolled in a pre-antiretroviral treatment (pre-ART) program, 300 patients receiving antiretroviral treatment (ART), and 300 patients receiving TB treatment. For each group, we calculated health expenditures across different spending categories, time spent traveling to and using services, and how patients financed their spending. Associations between patient group and costs were assessed in multivariate regression models. RESULTS Total monthly health expenditures [1 USD = 7.3 South African Rand (ZAR)] were ZAR 171 [95% confidence interval (CI): 134 to 207] for pre-ART, ZAR 164 (95% CI: 141 to 187) for ART, and ZAR 122 (95% CI: 105 to 140) for TB patients (P = 0.01). Total monthly time costs (in hours) were 3.4 (95% CI: 3.3 to 3.5) for pre-ART, 5.0 (95% CI: 4.7 to 5.3) for ART, and 3.2 (95% CI: 2.9 to 3.4) for TB patients (P < 0.01). Although overall patient costs were similar across groups, pre-ART patients spent on average ZAR 29.2 more on traditional healers and ZAR 25.9 more on chemists and private doctors than ART patients, whereas ART patients spent ZAR 34.0 more than pre-ART patients on transport to clinics (P < 0.05 for all results). Thirty-one percent of pre-ART, 39% of ART, and 41% of TB patients borrowed money or sold assets to finance health care. CONCLUSIONS Patients receiving nominally free care for HIV/TB face large private costs, commonly leading to financial distress. Subsidized transport, fewer clinic visits, and drug pick-up points closer to home could reduce costs for ART patients, potentially improving retention and adherence. Large expenditure on alternative care among pre-ART patients suggests that transitioning patients to ART earlier, as under HIV treatment-as-prevention policies, may not substantially increase patients' financial burden.
Systematic literature reviews are widely used as an aid to evidence based decision making. For example, reviews of randomised controlled trials are regularly used to answer questions about the effectiveness of healthcare interventions. The high profile of systematic reviews as a cornerstone of evidence based medicine, however, has led to several misconceptions about their purpose and methods. Among these is the belief that systematic reviews are applicable only to randomised controlled trials and that they are incapable of dealing with other forms of evidence, such as from non-randomised studies or qualitative research. The systematic literature review is a method of locating, appraising, and synthesising evidence. The value of regularly updated systematic reviews in the assessment of effectiveness of healthcare interventions was dramatically illustrated by Antman and colleagues, who showed that review articles failed to mention advances in treatment identified by an updated systematic review.1  It is nearly a quarter of a century since Gene Glass coined the term “meta-analysis” to refer to the quantitative synthesis of the results of primary studies.2 The importance of making explicit efforts to limit bias in the review of literature, however, has been emphasised by social scientists at least since the 1960s.3 In recent years systematic reviews have found an important role in health services research, and the growing interest in evidence based approaches to decision making makes it likely that their use will increase. Not everybody accepts that systematic reviews are necessary or desirable, and as one moves further away from the clinical applications of systematic reviews cynicism about their utility grows. Several arguments are commonly used to reject a wider role for systematic reviews, and these arguments are often based on major misconceptions about the history, purpose, methods, and uses of systematic reviews. I have examined eight common myths about …
Efforts to improve the outcomes of patients with mental illness often have involved incorporating the skills of a variety of health care professionals into collaborative care models. For over 30 years, clinical pharmacists have contributed to these care models in capacities ranging from educator to consultant to provider. This systematic review evaluates the quantity and quality of medical literature examining the impact of pharmacists in mental health from 1972-2003. Although we identified approximately 35 publications describing the roles of clinical pharmacists in this regard, only 16 were of sufficient scientific rigor to permit evaluation and comparison. The 16 studies were divided equally between inpatient and outpatient settings and were conducted in a variety of health care organizations (e.g., Veterans Administration, health maintenance organizations, community mental health clinics, and nursing homes). Nine of the studies examined the role of pharmacists in providing treatment recommendations and patient education, five featured pharmacists as providers (with prescriptive authority), and the remaining two described the impact pharmacists have in delivering education to the psychiatric staff. Six of the 16 studies were prospective, but only three of these incorporated a randomization procedure for patients or facilities. Collectively, the results of the 16 studies were positive, demonstrating improvements in outcomes, prescribing practices, patient satisfaction, and resource use. Unfortunately, most of the investigations were small, and significant limitations in study design limited further comparison. Given the long history and anecdotal success of pharmacists in mental health care settings, additional multicenter cost-effectiveness trials are warranted to further support the role of the psychiatric pharmacist.
The marginal costs and benefits of converting malaria programmes from a control to an elimination goal are central to strategic decisions, but empirical evidence is scarce. We present a conceptual framework to assess the economics of elimination and analyse a central component of that framework-potential short-term to medium-term financial savings. After a review that showed a dearth of existing evidence, the net present value of elimination in five sites was calculated and compared with effective control. The probability that elimination would be cost-saving over 50 years ranged from 0% to 42%, with only one site achieving cost-savings in the base case. These findings show that financial savings should not be a primary rationale for elimination, but that elimination might still be a worthy investment if total benefits are sufficient to outweigh marginal costs. Robust research into these elimination benefits is urgently needed.