Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents.

AIM: We aimed to find the optimal route of iron supplementation in patients with malignancy and iron deficiency (true or functional) anemia not receiving erythropoiesis stimulating agents (ESA). METHODS: Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) <12 g/dL and serum ferritin <100 mcg/mL, transferrin saturation <20% or hypochromic red blood cells >10% were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, quality of life (QoL), toxicity, response and overall survival. RESULTS: A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm. Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and -0.16 g/dL (SD: 1.36) in oral arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients (14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade) developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron and none on oral iron had hypersensitivity, P = 0.06. QoL was not significantly different between the two arms. CONCLUSION: IV iron was not superior to oral iron in patients with malignancy on chemotherapy and iron deficiency anemia.

Health-related quality of life in patients with metastatic, relapsed, or inoperable squamous cell carcinoma of the head and neck in India.

OBJECTIVE: The objective of this study was to evaluate changes in health related quality of life (HRQoL) in patients with metastatic head and neck (H&N) cancer randomized to receive metronomic (methotrexate and celecoxib) or cisplatin chemotherapy. METHODS: Patients older than 18 years, with a Karnofsky Performance score of ≥70, and diagnosed with metastatic, locally advanced inoperable or recurrent head and neck (H&N) cancer not amenable to surgery or radiation were randomized (1:1) to receive metronomic or cisplatin chemotherapy. All patients were recruited from the Tata Memorial Hospital, Mumbai, India. In addition to demographic and baseline clinical characteristics, patients were asked to rate their HRQoL using the EORTC QLQ-C30 and the EORTC QLQ-H&N35 questionnaires (Indian versions) at baseline and at the end of each chemo cycle (every 3 weeks) till the end of study or early termination. RESULTS: Of the 110 patients screened, 87 agreed to participate in the study. Mean age of the study population was 47.5 years (S.D. ±10.04) for the metronomic group and 47.2 years (S.D. ±9.89) for the cisplatin group. Overall quality of life was not significantly different between the two treatment groups from baseline to end of treatment. However, there was a statistically significant improvement in Pain QLQ-C30 score from baseline to week 3 (OR = 3.14, p = 0.036) and week 6 (OR = 3.33, p = 0.034) in the metronomic arm compared with the cisplatin arm. CONCLUSION: In addition to improvements in survival, understanding the impact of treatment options on changes in HRQoL is important as it can aid physicians in making treatment and rehabilitation decisions for patients with advanced inoperable H&N cancer.

Treatment Costs of Stroke Related to Nonvalvular Atrial Fibrillation Patients in India-A Multicenter Observational Study.

OBJECTIVE: The objective of this study was to quantify the direct medical and nonmedical costs of stroke among patients with nonvalvular atrial fibrillation in India. METHODS: An observational, multicenter cost-of-illness study was conducted within large tertiary care hospitals across three metropolitan cities in India. Medical chart records of eligible patients who were hospitalized during the study period were reviewed. A standardized data collection form was designed and used to capture resources expended in the treatment and management of stroke during the inpatient stay. In addition, direct medical and nonmedical outpatient care resources and informal care burden were captured using a detailed questionnaire, following the patients' discharge. Factors associated with acute care costs were investigated using multivariate linear regression analysis. RESULTS: Data were collected on a total of 400 patients with incident strokes. Their mean age was 61.4 ± 9.4 years. About 84% of the patients were diagnosed with ischemic stroke. On average, patients spent 16 ± 10 days in the hospital. Total mean direct health care costs per patient amounted to `504,973 (US $8,020) during the first year, with about 47% (mean `235,471; US $3,750) of the total costs due to the index hospitalization. The modified Rankin scale score was strongly associated with costs, whereby severely disabled patients had 32% higher costs (P = 0.001) compared with moderately disabled patients during the first 3 months postdischarge. CONCLUSIONS: Overall, the financial burden associated with medical care for patients with stroke with atrial fibrillation along with rehabilitation and long-term care costs places a significant demand on health services in India.

Cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals in Mexico.

OBJECTIVE: Maraviroc is the first approved drug in a new class of antiretrovirals, the CCR5 antagonists. The objective of this study was to predict the long-term clinical impact and cost-effectiveness of maraviroc in treatment-experienced adults with HIV/AIDS in Mexico. METHODS: The AntiRetroviral Analysis by Monte Carlo Individual Simulation (ARAMIS) model was adapted to the Mexican context to predict clinical and economic outcomes of treating with optimized background therapy (OBT) versus testing for viral tropism status and treating with OBT ± maraviroc accordingly in treatment-experienced adults in Mexico. Baseline characteristics and efficacy were from the MOTIVATE trials' screening cohort. Costs and population mortality data were specific to Mexico. Results were reported from the perspective of health care payers in 2008 Mexican pesos (converted to 2008 US$ in parentheses). RESULTS: Compared to treatment with OBT alone, treatment with OBT ± maraviroc contingent on tropism test result increased projected undiscounted life expectancy and discounted quality-adjusted life expectancy from 7.54 to 8.71 years and 4.42 to 4.92 quality-adjusted life years (QALYs), respectively, at an incremental cost of $228,215 (US$21,329). The resultant incremental cost-effectiveness ratio (ICER) was $453,978 (US$42,429) per QALY gained. The ICER was somewhat lower when maraviroc was modeled in individuals susceptible to ≤ 2 components of OBT ($407,329; US$38,069), while the ICER was higher in individuals susceptible to ≥3 OBT components ($718,718; US$67,171). CONCLUSION: In treatment-experienced individuals with HIV/AIDS in Mexico, maraviroc may be cost-effective, particularly in individuals with limited options for active antiretroviral therapy (ART).

Satisfactory cross-cultural validity of the ACTG symptom distress module in HIV-1-infected antiretroviral-naive patients.

BACKGROUND: Multinational clinical trials commonly include different language versions of patient-reported outcomes (PRO) instruments without considering the question of their cross-cultural validity. The inclusion of a PRO instrument, the Adult AIDS Clinical Trial Group Symptom Distress Module (SDM), in an multinational clinical trial in HIV-1 antiretroviral-naive patients offered an opportunity to explore the methods to assess cross-cultural validity of PRO instruments in the context of clinical trials. PURPOSE: To assess the cross-cultural validity of the SDM across seven cultural groups in the setting of a multinational HIV clinical trial. METHODS: Twenty-five language versions of the SDM were included in a Phase IIb/III trial comparing maraviroc with efavirenz (each in combination with zidovudine/ lamivudine) conducted in 12 countries to assess symptoms perceived by HIV-1-infected antiretroviral-naive patients. Differential item functioning (DIF) detection and the STATIS method were combined in a pragmatic approach to assess the cross-cultural validity of the SDM using pre-antiretroviral treatment data from 759 patients. RESULTS: Statistically significant DIF between cultural groups was observed for four items: fatigue; fevers; anxiety; and headache. However, examination of these items by linguists did not lead to meaningful explanations for the statistical differences. With the STATIS approach, the Bantu and European Germanic groups were the furthest from the Occidental English group. LIMITATIONS: The assessment of cross-cultural validity had to be performed on some very small samples and on data aggregated by cultural groups, which suggests the need for a cautious interpretation of the results. CONCLUSIONS: Given the heterogeneity of cultures considered, the absence of meaningful explanations for statistically significant differences between cultural groups supports the cross-cultural validity of the SDM versions included in this trial. Thus, this study demonstrated that it is feasible to conduct assessment of crosscultural validity of PRO instruments using data collected in the setting of multinational clinical trials.

GI risk factors and use of GI protective agents among patients receiving nonsteroidal antiinflammatory drugs.

BACKGROUND: Patient characteristics increase the risk of gastrointestinal (GI) complications associated with nonsteroidal antiinflammatory drugs (NSAIDs). Patients at risk may not be prescribed protective therapies that might mitigate their risk of NSAID-associated GI complications. OBJECTIVE: To assess GI risk among Veterans Affairs (VA) patients on NSAID therapy, determine whether therapy conformed to VA guidelines for lessening the risk of GI complications, and identify patient risk factors associated with conformance. METHODS: Using databases from 3 VA medical centers, we retrospectively identified patients receiving NSAIDs and obtained data regarding age, history of GI bleed over 8 years, GI adverse effects associated with NSAIDs, diagnoses, and medication history over one year. We inferred health status from age-adjusted Charlson comorbidity index values. Each patient's risk of developing GI complications over one year was calculated using these data. Among patients at significant or substantial risk, we assessed conformance to VA guidelines. We used logistic regression to identify risk factors associated with conformance and determine adjusted ORs (AORs) with 95% CIs for each risk factor. RESULTS: There were 19 122 patients receiving NSAIDs. Of 4589 patients at significant risk and 1246 at substantial risk, 1161 (25.3%) and 356 (28.6%), respectively, were prescribed guideline-conformant therapy. Risk factors associated with conformance (p < or = 0.001) among patients at significant risk were rheumatoid arthritis (AOR 1.34; 95% CI 1.13 to 1.58) and GI adverse effects (AOR 1.53; 95% CI 1.42 to 1.64). For substantial risk patients, risk factors associated with conformance (p < or = 0.031) were rheumatoid arthritis (AOR 1.65; 95% CI 1.37 to 1.98), concomitant corticosteroids (AOR 1.21; 95% CI 1.02 to 1.43), GI hospitalization (AOR 2.01; 95% CI 1.57 to 2.59), and GI adverse effects (AOR 1.79; 95% CI 1.47 to 2.18). CONCLUSIONS: Many patients at risk for GI adverse events do not receive guideline-conformant therapy. Educational interventions to improve conformance could focus on specific risk factors for GI complications.