Potential Utility of C-reactive Protein for Tuberculosis Risk Stratification Among Patients With Non-Meningitic Symptoms at HIV Diagnosis in Low- and Middle-income Countries.

Background: The World Health Organization recommends initiating same-day antiretroviral therapy (ART) while tuberculosis (TB) testing is under way for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve TB risk stratification in this population. Methods: In this baseline analysis of 498 adults (>18 years) with TB symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP as a continuous variable using generalized linear models. Results: Eighty-seven (17.5%) participants were diagnosed with baseline TB. The median CRP was 33.0 mg/L (interquartile range: 5.1, 85.5) in those with TB, and 2.6 mg/L (interquartile range: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4% and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART and 0.8% to 5.0% would have untreated TB at ART initiation. Conclusions: CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3- to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.

Predictors of Clinical Outcomes among People with HIV and Tuberculosis Symptoms after Rapid Treatment Initiation in Haiti.

Introduction: Few studies have evaluated baseline predictors of clinical outcomes among people with HIV starting antiretroviral therapy (ART) in the modern era of rapid ART initiation. Methods: We conducted a secondary analysis of a randomized controlled trial of two rapid treatment initiation strategies for people with treatment-naïve HIV and tuberculosis symptoms at an urban clinic in Haiti. We used logistic regression models to assess associations between baseline characteristics and (1) retention in care at 48 weeks, (2) HIV viral load suppression at 48 weeks (among participants who underwent viral load testing), and (3) all-cause mortality. Results: 500 participants were enrolled in the study 11/2017-1/2020. Eighty-eight (18%) participants were diagnosed with tuberculosis, and ART was started in 494 (99%). After adjustment, less than secondary education (adjusted odds ratio [AOR] 0.21, 95% CI 0.10-0.46), dolutegravir initiation (AOR 2.57, 95% CI 1.22-5.43), age (AOR 1.42 per 10-year increase, 95% CI 1.01-1.99), and tuberculosis diagnosis (AOR 3.92, 95% CI 1.36-11.28) were significantly associated with retention. Age (AOR 1.36, 95% CI 1.05-1.75), dolutegravir initiation (AOR 1.75, 95% CI 1.07-2.85), and tuberculosis diagnosis (AOR 0.50, 95% CI 0.28-0.89) were associated with viral suppression. Higher CD4 cell count at enrollment (unadjusted odds ratio [OR] 0.69, 95% CI 0.55-0.87) and anemia (OR 4.86, 95% CI 1.71-13.81) were associated with mortality. Conclusions: We identified sociodemographic, treatment-related, clinical, and laboratory-based predictors of clinical outcomes. These characteristics may serve as markers of sub-populations that could benefit from additional interventions to support treatment success after rapid treatment initiation.

Same-day testing with initiation of antiretroviral therapy or tuberculosis treatment versus standard care for persons presenting with tuberculosis symptoms at HIV diagnosis: A randomized open-label trial from Haiti.

BACKGROUND: Same-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment (TB treatment for those diagnosed with TB; ART for those not diagnosed with TB) would be superior to standard care in this population. METHODS AND FINDINGS: We conducted an open-label trial among adults with TB symptoms at initial HIV diagnosis at GHESKIO in Haiti; participants were recruited and randomized on the same day. Participants were randomized in a 1:1 ratio to same-day treatment (same-day TB testing with same-day TB treatment if TB diagnosed; same-day ART if TB not diagnosed) versus standard care (initiating TB treatment within 7 days and delaying ART to day 7 if TB not diagnosed). In both groups, ART was initiated 2 weeks after TB treatment. The primary outcome was retention in care with 48-week HIV-1 RNA <200 copies/mL, with intention to treat (ITT) analysis. From November 6, 2017 to January 16, 2020, 500 participants were randomized (250/group); the final study visit occurred on March 1, 2021. Baseline TB was diagnosed in 40 (16.0%) in the standard and 48 (19.2%) in the same-day group; all initiated TB treatment. In the standard group, 245 (98.0%) initiated ART at median of 9 days; 6 (2.4%) died, 15 (6.0%) missed the 48-week visit, and 229 (91.6%) attended the 48-week visit. Among all who were randomized, 220 (88.0%) received 48-week HIV-1 RNA testing; 168 had <200 copies/mL (among randomized: 67.2%; among tested: 76.4%). In the same-day group, 249 (99.6%) initiated ART at median of 0 days; 9 (3.6%) died, 23 (9.2%) missed the 48-week visit, and 218 (87.2%) attended the 48-week visit. Among all who were randomized, 211 (84.4%) received 48-week HIV-1 RNA; 152 had <200 copies/mL (among randomized: 60.8%; among tested: 72.0%). There was no difference between groups in the primary outcome (60.8% versus 67.2%; risk difference: -0.06; 95% CI [-0.15, 0.02]; p = 0.14). Two new grade 3 or 4 events were reported per group; none were judged to be related to the intervention. The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain. CONCLUSIONS: In patients with TB symptoms at HIV diagnosis, we found that same-day treatment was not associated with superior retention and viral suppression. In this study, a short delay in ART initiation did not appear to compromise outcomes. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov NCT03154320.

Potential Utility of C-reactive Protein for Tuberculosis Risk Stratification among Patients with Non-Meningitic Symptoms at HIV Diagnosis in Low- and Middle-Income Countries.

Article Summary: We assessed the association between C-reactive protein (CRP) and Mycobacterium tuberculosis (TB) diagnosis in symptomatic patients at HIV diagnosis. We found that CRP concentrations can improve tuberculosis risk stratification, facilitating decision making about whether (specific) tuberculosis testing is indicated before antiretroviral therapy initiation. Background: The World Health Organization recommends initiating same-day ART while tuberculosis testing is underway for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve tuberculosis risk stratification in this population. Methods: In this baseline analysis of 498 adults (>18 years) with tuberculosis symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP (≥3 mg/dL) using generalized linear models. Results: Eighty-seven (17.5%) patients were diagnosed with baseline TB. The median CRP was 33.0 mg/L (IQR: 5.1, 85.5) in those with TB, and 2.6 mg/L (IQR: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4%, and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART, and 0.8% to 5.0% would have untreated TB at ART initiation. Conclusions: CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3-fold to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.

Retention in Care among Patients with Early HIV Disease in Haiti.

In September 2015, the World Health Organization updated their guidelines to recommend antiretroviral therapy (ART) for all people living with HIV. Countries are now in the process of implementing strategies to provide universal HIV treatment. We analyzed the rate of retention and time to ART eligibility (according to 2013 WHO guidelines) among 3,345 adult patients receiving positive HIV test results between February 1, 2003 and March 31, 2013 at the GHESKIO Clinic in Haiti, with WHO stage 1 or 2 disease and initial CD4 cell count >500 cells/mm3. Among the 3,345 patients, 2,423 (72%) were female, the median age was 33 years, 3,089 (92%) lived in Port-au-Prince, and 1,944 (58%) had attended no school or primary school only. The median initial CD4 cell count was 668 cells/mm3 (IQR: 572-834); over the subsequent 2 years, 1,485 patients (44%) were lost to follow-up and 7 (<1%) died pre-ART, 1,041 (31%) were retained in pre-ART care, and 819 (24%) initiated ART. In multivariate analysis, secondary education (aOR 1.27; 95% CI: 1.10-1.47), female gender (aOR: 1.28; 95% CI: 1.09-1.50), co-habitation (aOR: 1.31; 95% CI: 1.09-1.57), and residence in Port-au-Prince (aOR: 1.43; 95% CI: 1.09-1.88) were associated with retention in care. The median time from baseline CD4 count to ART eligibility was 1.7 years. Prior to the implementation of universal treatment, pre-ART attrition was high among patients who did not qualify for ART at presentation. Though implementing WHO recommendations for universal ART will require service expansion, it will likely result in improved retention for those at risk of being lost to follow-up.

Same-day HIV testing with initiation of antiretroviral therapy versus standard care for persons living with HIV: A randomized unblinded trial.

BACKGROUND: Attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is high worldwide. We assessed whether same-day HIV testing and ART initiation improves retention and virologic suppression. METHODS AND FINDINGS: We conducted an unblinded, randomized trial of standard ART initiation versus same-day HIV testing and ART initiation among eligible adults ≥18 years old with World Health Organization Stage 1 or 2 disease and CD4 count ≤500 cells/mm3. The study was conducted among outpatients at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic infections (GHESKIO) Clinic in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard ART initiation or same-day HIV testing and ART initiation. The standard group initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on the day of testing. The primary study endpoint was retention in care 12 months after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of treatment arm with a modified intention-to-treat analysis, using multivariable logistic regression controlling for potential confounders. Between August 2013 and October 2015, 762 participants were enrolled; 59 participants transferred to other clinics during the study period, and were excluded as per protocol, leaving 356 in the standard and 347 in the same-day ART groups. In the standard ART group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50 copies, and 184 (52%) had <1,000 copies/ml; 20 participants (6%) died. In the same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50 copies/ml, and 212 (61%) had <1,000 copies/ml; 10 (3%) participants died. The unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50 copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group compared to the standard ART group, and the unadjusted RR for being retained with HIV-1 RNA <1,000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain. CONCLUSIONS: Same-day HIV testing and ART initiation is feasible and beneficial in this setting, as it improves retention in care with virologic suppression among patients with early clinical HIV disease. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov number NCT01900080.

Health Services Utilization Among Fee-for-Service Medicare and Medicaid Patients Under Age 65 with Behavioral Health Illness at an Urban Safety Net Hospital.

BACKGROUND: In 2011, fee-for-service patients with both Medicare and Medicaid (dual eligible) sustained $319.5 billion in health care costs. OBJECTIVE: To describe the emergency department (ED) use and hospital admissions of adult dual eligible patients aged under 65 years who used an urban safety net hospital. METHODS: This was a retrospective database analysis of patients aged between 18 and 65 years with Medicare and Medicaid, who used an urban safety net academic health center between January 1, 2011, and December 31, 2011. We compared patients with and without behavioral health illness. The main outcome measures were hospital admission and ED use. Chi-square and Wilcoxon rank-sum tests were used for descriptive statistics on categorical and continuous variables, respectively. Greedy propensity score matching was used to control for confounding factors. Rate ratios (RR) and 95% confidence intervals (CI) were determined after matching and after adjusting for those variables that remained significantly different after matching. RESULTS: In 2011, 10% of all fee-for-service dual eligible patients aged less than 65 years in Massachusetts were seen at Boston Medical Center. Data before propensity score matching showed significant differences in age, sex, race/ethnicity, marital status, education, employment, physical comorbidities, and Charlson Comorbidity Index score between patients with and without behavioral health illness. Analysis after propensity score matching found significant differences in sex, Hispanic race, and other education and employment status. Compared with patients without behavioral health illness, patients with behavioral health illness had a higher RR for hospital admissions (RR = 2.07; 95% CI = 1.81-2.38; P < 0.001) and ED use (RR = 1.61; 95% CI = 1.46-1.77; P < 0.001). Results were robust after adjusting for characteristics that remained statistically significantly different after propensity score matching. CONCLUSIONS: Adult dual eligible patients aged less than 65 years with behavioral health illness in the Medicaid fee-for-service plan had significantly higher rates of hospital admission and ED use compared with dual eligible patients without behavioral health illness at the largest urban safety net medical center in New England. Safety net hospitals care for a large proportion of dual eligible patients with behavioral health illness. Further research is needed to elucidate the systems-related and patient-centered factors contributing to the utilization behaviors of this patient population. DISCLOSURES: This research was funded in part by a National Research Service Award (T3HP10028-14-01). The authors have no conflicts of interests to disclose. Cancino had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design were contributed by Cancino, Jack, and Burgess, with assistance from Cremieux. Cancino and Cremieux took the lead in data collection, along with Jack and Burgess, and data interpretation was performed by Jarvis, Cummings, and Cooper, along with the other authors. The manuscript was written primarily by Cancino, along with Jack and Burgess, and revised primarily by Cancino, along with the other authors.

The impact of bariatric surgery on comorbidities and medication use among obese patients.

BACKGROUND: The risks and benefits of bariatric surgery have rarely been evaluated in large multiyear patient samples. This study identifies the short- and long-term impact of bariatric surgery on comorbidities and medication use among obese patients. METHODS: A comprehensive analysis of 5,502 obese patients who underwent bariatric surgery was performed. Submissions of reimbursement claims, including diagnostics and medication use, were compared in the 90 days preceding the surgery and 30 up to 1,110 days following the surgery. Presurgery and postsurgery frequency counts were performed on diagnostics and medication use to identify trends. RESULTS: Among 5,502 patients, significant decreases in the prevalence of reported comorbidities were observed during the short-term postsurgery period and sustained for up to 3 years of follow-up. Compared to the presurgery period, significant decreases (p < 0.05) were observed after 3 years for total cardiovascular disorders (43.6% vs. 14.2%), diabetes mellitus (19.9% vs. 7.7%), chronic obstructive pulmonary disease and other respiratory conditions (57.7% vs. 16.2%), diseases of the musculoskeletal system and connective tissue (32.6% vs. 27.7%), and mental disorders (30.7% vs. 14.8%). Over the same period, the frequency of medication use decreased significantly for a number of conditions including infections, pain, respiratory, cardiovascular, gastroenterologic, lipidemic, and diabetic conditions. Anemia, however, increased from 3.8% to 9.9%, and use of nutritional supplements increased significantly. CONCLUSION: Bariatric surgery was associated with significant reductions in reported claims for short- and long-term health outcomes and reduced medication use for major disease categories.

Exact and efficient inference procedure for meta-analysis and its application to the analysis of independent 2 x 2 tables with all available data but without artificial continuity correction.

Recently, meta-analysis has been widely utilized to combine information across comparative clinical studies for evaluating drug efficacy or safety profile. When dealing with rather rare events, a substantial proportion of studies may not have any events of interest. Conventional methods either exclude such studies or add an arbitrary positive value to each cell of the corresponding 2 x 2 tables in the analysis. In this article, we present a simple, effective procedure to make valid inferences about the parameter of interest with all available data without artificial continuity corrections. We then use the procedure to analyze the data from 48 comparative trials involving rosiglitazone with respect to its possible cardiovascular toxicity.

A study on the economic impact of bariatric surgery.

OBJECTIVE: To evaluate the private third-party payer return on investment for bariatric surgery the United States. STUDY DESIGN: Morbidly obese patients aged 18 years or older were identified in an employer claims database of more than 5 million beneficiaries (1999-2005) using International Classification of Diseases, Ninth Revision, Clinical Modification code 278.01. Each of 3651 patients who underwent bariatric surgery during this period was matched to a control subject who was morbidly obese and never underwent bariatric surgery. Bariatric surgery patients and controls were matched based on patient demographics, selected comorbidities, and costs. METHODS: Total healthcare costs for bariatric surgery patients and their controls were recorded for 6 months before surgery through the end their continuous enrollment. To account for potential differences in patient characteristics, we calculated the cost differential by estimating a Tobit model. A return on investment was estimated from the resulting coefficients. Costs were inflation adjusted to 2005 US dollars using the Consumer Price Index for Medical Care, and the cost savings were discounted by 3.07%, the month Treasury bill rate during the same period. RESULTS: The mean bariatric surgery investment ranged from approximately $17,000 to $26,000. After controlling for observable patient characteristics, we estimated all costs to have been recouped within 2 years for laparoscopic surgery patients and within 4 years for open surgery patients. CONCLUSIONS: Downstream savings associated with bariatric surgery are estimated to offset the initial costs in 2 to 4 years. Randomized or quasiexperimental studies would be useful to confirm this conclusion, as unobserved characteristics may influence the decision to undergo surgery and cannot be controlled for in this analysis.

The economic consequences of generic substitution for antiepileptic drugs in a public payer setting: the case of lamotrigine.

Generic substitution of antiepileptic drugs (AEDs) may increase pharmacy utilization, thus counterbalancing per-pill savings. The purpose of our study was to analyze the economic impact of government-mandated switching from branded to generic lamotrigine. Patients in a Canadian public pharmacy claims database using branded lamotrigine (Lamictal GlaxoSmithKline, UK) in 2002 converted to generic lamotrigine in 2003 and were observed from July 2002 to March 2006. Patients used branded lamotrigine for >or=90 days pre-generic entry and had >or=1 claim for generic lamotrigine post-generic entry. For the generic period, observed per-patient monthly drug costs were calculated as the sum of costs for lamotrigine, other AEDs, and non-AEDs. Expected per-patient drug costs were estimated assuming lamotrigine dose and other prescription drug utilization in the generic period were identical to those observed during the brand period. Differences between observed and expected costs were compared. Among 1,142 branded lamotrigine users, overall average monthly drug costs per person were expected to decrease by $30.55 due to lower pill costs. Instead, they fell by $11.98 from the brand to the generic periods (p < 0.001). Because of dosage changes, lamotrigine costs decreased by $29.92 instead of the anticipated $33.87 (p < 0.001). Increased pharmacy utilization caused other AED costs to rise by $6.29 versus the expected $0.36 (p < 0.001), while non-AED drug cost increased by $11.64 rather than by $2.95 (p < 0.001). We concluded that conversion to generic lamotrigine resulted in lower than expected cost savings. Further research is necessary to determine whether this is due to reduced effectiveness and/or tolerability. Payers may weigh smaller-than-expected cost reductions against a possible decrease in effectiveness to assess the relevance of mandatory generic switching of lamotrigine.

The economic impact of a partnership-measurement model of disease management: Improving Cardiovascular Outcomes in Nova Scotia (ICONS).

Improving Cardiovascular Outcomes in Nova Scotia (ICONS) was a five-year, community partnership-based disease-management project that sought, as a primary goal, to improve the care and outcomes of patients with heart disease in Nova Scotia. This program, based on a broad stakeholder partnership, provided repeated measurement and feedback on practices and outcomes as well as widespread communication and education among all partners. From a clinical viewpoint, ICONS was successful. For example, use of proven therapies for the target diseases improved and re-hospitalization rates decreased. Stakeholders also perceived a sense of satisfaction because of their involvement in the partnership. However, the universe of health stakeholders is large, and not many have had an experience similar to ICONS. These other health stakeholders, such as decision-makers concerned with the cost of care and determining the value for cost, might, nonetheless, benefit from knowledge of the ICONS concepts and results, particularly economic analyses, as they determine future health policy. Using budgetary data on actual dollars spent and a robust input-output methodology, we assessed the economic impact of ICONS, including trickle-down effects on the Canadian and Nova Scotian economies. The analysis revealed that the $6.22 million invested in Nova Scotia by the private sector donor generated an initial net increase in total Canadian wealth of $5.32 million and a global net increase in total Canadian wealth of $10.23 million, including $2.27 million returned to the different governments through direct and indirect taxes. Thus, the local, provincial and federal governments are important beneficiaries of health project investments such as ICONS. The various government levels benefit from the direct influx of private funds into the publicly funded healthcare sector, from direct and indirect tax revenues and from an increase in knowledge-related employment. This, of course, is in addition to the clinical benefits associated with the partnership-measurement disease-management model. Because of their uniquely simultaneous roles as beneficiary and major resource provider, the public payer can play an early and active role in such partnerships to enhance its efficiencies and increase the likelihood of sustainability if the original concepts are proven of value.

Do drugs reduce utilisation of other healthcare resources?

BACKGROUND: Drug expenditures per capita have drastically increased over the last quarter century in Canada, with a share of overall healthcare costs rising from 8.8% in 1980 to 16.8% in 2002. Pressure to curb expenditure on drugs has increased accordingly, but containing drug expenditure might increase costs elsewhere in the healthcare sector. OBJECTIVE: To measure substitution patterns between drugs and other healthcare resources over the last 25 years and thus assess whether containing drug costs might result in higher expenditure elsewhere in the healthcare system. METHODS AND DATA: A production function approach was used, in which life expectancy was modelled as a function of per capita drugs and non-drug healthcare resources, among other factors. Estimates are used to calculate a marginal rate of substitution, or trade-off, between drugs and non-drug healthcare resources, for a given level of life expectancy in the population. The model is estimated from a societal perspective, with panel data techniques using Canadian provincial-level data on health expenditure and spending on physicians per capita for the period 1980-2002, as well as individual survey data on lifestyle habits such as cigarette consumption and body mass index. RESULT: Using life expectancy at birth for males as the production function, increasing drug spending by Can 1.00 dollars (constant 2003 values) was accompanied by a decrease of Can 1.48 dollars in non-drug, non-physician healthcare resources over the study period, without affecting life expectancy at birth. Results using life expectancy at birth for females as the production function showed a decrease of Can 1.05 dollars in non-drug, non-physician healthcare resources over the same period. CONCLUSION: Using life expectancy as a general health indicator, results suggest that increases in drug spending could be more than offset by decreases in other healthcare spending without affecting the health of the population. This suggests that better access to drugs may be an effective strategy to decrease overall healthcare costs. Freeing up healthcare dollars by reallocating spending towards drugs could provide opportunities for overall healthcare cost savings without negatively impacting the health of the population.

Relationship between hemoglobin level and quality of life in anemic patients with chronic kidney disease receiving epoetin alfa.

OBJECTIVES: To evaluate the relationship between hemoglobin (Hb) level and quality of life (QOL) in anemic patients with non-dialysis chronic kidney disease receiving epoetin alfa. PATIENTS AND METHODS: A post-hoc analysis using data from a multicenter, open-label, prospective study of epoetin alfa for anemia in patients with chronic kidney disease not on dialysis was conducted. The relationship between Hb and QOL was analyzed using correlation and longitudinal analyses, the latter adjusting for sample selection bias. The Linear Analog Scale Assessment (LASA) and the Kidney Disease Questionnaire (KDQ) subscales were used to measure QOL. The impact of an incremental 1 g/dL increase in Hb level on LASA and KDQ scores was determined using an incremental analysis. RESULTS: A total of 1183 and 1044 patients formed the study populations for the LASA and KDQ analyses, respectively. There was a positive and significant relationship between Hb levels and QOL (p < 0.05). Using non-linear regression analysis, we characterized the sigmoid-shape of the relationship between Hb levels and QOL scores. Hemoglobin change was a statistically significant determinant of QOL improvement for both LASA and KDQ scales (p < 0.05). The model predicted that, based on a 2 unit change in Hb, the greatest incremental QOL improvement per unit of Hb increase occurred when Hb was in the range of 11 to 12 g/dL. CONCLUSIONS: This study demonstrates that, beyond the well-known relationship between Hb increases and QOL improvements, the maximal incremental gain in QOL occurred when Hb reached 11 to 12 g/dL. This suggests that treating anemic patients with non-dialysis chronic kidney disease until their Hb level reaches 12 g/dL will result in the greatest QOL improvement per Hb unit increase. The analyses were conducted based on an open-label study of epoetin alfa and could be further validated using a randomized, controlled trial, comparing incremental gains in QOL associated with treatment initiation at varying levels of Hb across arms.

The relative dosing of epoetin alfa and darbepoetin alfa in chronic kidney disease.

OBJECTIVE: The purpose of this study was to review and analyze current research to evaluate the dose ratio of epoetin alfa and darbepoetin alfa for the treatment of anemia in chronic kidney disease (CKD) and to identify determinants of the variation in epoetin alfa:darbepoetin alfa dose ratios across studies. METHODS: A systematic review of the literature for comparative switch and non-switch studies of epoetin alfa and darbepoetin alfa treatments in CKD for the period 2000-2005 was performed. Two reviewers independently assessed the quality of the information. Data on the study design and outcomes were collected for each selected study. The dose ratio from epoetin alfa to darbepoetin alfa was calculated for each study, and the results were reported stratified by study characteristics. To control for differences in study design and characteristics that could explain the variability in the relative dosages of the two agents across studies, multivariate regression analysis was conducted. Based on these results, a dose conversion ratio for Canada was estimated. RESULTS: A total of 21 studies involving 16 378 patients exposed to epoetin alfa or darbepoetin alfa in CKD were identified. Univariate analysis of the dose ratios indicated a mean dose ratio of 217:1 (IU of epoetin alfa:mug of darbepoetin alfa). Results from the multivariate analysis demonstrated that the study design (i.e., switch study versus straight comparison studies) and geographical coverage (i.e., United States) affected the results. Based on the multivariate analysis, the dose conversion ratio between epoetin alfa and darbepoetin alfa for Canada was 169:1. CONCLUSIONS: Despite limitations associated with switching studies and the limited total number of studies available, this systematic review based on aggregated results provides further evidence to the clinical community that the dose conversion ratio for epoetin alfa:darbepoetin alfa in CKD patients in Canada is approximately 169:1. At that ratio, treatment with epoetin alfa is 11-18% cheaper than treatment with darbepoetin alfa in Canada.

Hospital cost flexibility in the presence of many outputs: a public-private comparison.

This paper develops flexibility measures in the context of a multi-firm output based on a generalized average cost function. We then apply this methodology to assess and compare the relative flexibility of hospital services in Québec and California based on two very complete data sets. Results indicate that there is no clear distinction between private and public institutions and that there is no clear distinction between Québec and California hospitals. However, there are clear differences in flexibility among different outputs. This last result suggests that there are bottlenecks in the health care system and calls for a targeted approach on the part of hospital administrators, whether public or private, in Québec or California.

Public and private pharmaceutical spending as determinants of health outcomes in Canada.

Canadian per capita drug expenditures increased markedly in recent years and have become center stage in the debate on health care cost containment. To inform public policy, these costs must be compared with the benefits provided by these drugs. This paper measures the statistical relationship between drug spending in Canadian provinces and overall health outcomes. The analysis relies on more homogenous data and includes a more complete set of controls for confounding factors than previous studies. Results show a strong statistical relationship between drug spending and health outcomes, especially for infant mortality and life expectancy at 65. This relationship is almost always stronger for private drug spending than for public drug spending. The analysis further indicates that substantially better health outcomes are observed in provinces where higher drug spending occurs. Simulations show that if all provinces increased per capita drug spending to the levels observed in the two provinces with the highest spending level, an average of 584 fewer infant deaths per year and over 6 months of increased life expectancy at birth would result.