Rigosertib in combination with azacitidine in patients with myelodysplastic syndromes or acute myeloid leukemia: Results of a phase 1 study.

Phase 1 results from a Phase 1/2 study comprise 18 patients with myelodysplastic syndromes (MDS; n = 9), acute myeloid leukemia (AML; n = 8), and chronic myelomonocytic leukemia (CMML; n = 1) who were either hypomethylating agent naïve (n = 10) or relapsed/refractory following prior hypomethylating agent therapy (n = 8) (NCT01926587). Patients received oral rigosertib, an inhibitor of Ras-effector pathways, in 3 successive cohorts (140 mg twice daily, 280 mg twice daily, or 840 mg/day [560 mg morning/280 mg evening]) for 3 weeks of a 4-week cycle. Patients received parenteral azacitidine (75 mg/m2/day × 7 days) during the second week; the cycle repeated every 4 weeks. The combination was well tolerated for a median of 4 (range 1-41) cycles, with 72% of patients experiencing ≥1 serious adverse events. No dose-limiting toxicities were observed. Thus, no maximum tolerated dose was reached. The most frequently reported adverse events were diarrhea (50%), constipation, fatigue, and nausea (each 44%), and pneumonia and back pain (each 33%). Sequential administration demonstrated an overall response rate of 56% in evaluable patients, with responses observed in 7/9 MDS/CMML patients (78%) and 2/7 AML patients (29%). Further clinical studies are warranted to investigate this doublet therapy in patients with myeloid malignancies.

The GOLD ReGISTry: a Global, Prospective, Observational Registry Collecting Longitudinal Data on Patients with Advanced and Localised Gastrointestinal Stromal Tumours.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal sarcomas. This global, prospective registry followed patients with advanced or localised GIST (2007-2011). METHODS: Current and evolving diagnostics, treatments and outcome measures in patients with GIST were assessed. Eligible patients were diagnosed with advanced or localised GIST within 15months of registry entry. No treatment plan was prescribed, and no visit schedule was mandated. Treating physicians recorded patient information, including tumour response, diagnostic methods, medications, surgeries performed, mutation status and adverse events leading to dose/medication changes. Survival outcomes were estimated using the Kaplan-Meier method. Other data were analysed using descriptive statistics. RESULTS: The registry included 1663 patients (advanced GIST, n=1095; localised GIST, n=537). Medications (e.g. tyrosine kinase inhibitor use and dosing), disease progression or recurrence and physician assessment of response to treatment in registry patients were consistent with controlled trials and prevailing clinical recommendations. In advanced GIST, estimated 30-month progression-free survival (PFS) (59.8%) and overall survival (OS) (82.7%) were higher than results from previously reported trials (≈40% and ≈70%, respectively). Consistent with treatment guidelines, the most common initial treatments were imatinib for advanced GIST, and complete surgical resection for localised GIST. Computed tomography scans were the most common imaging technique used at diagnosis and follow-up. Mutation analysis was performed at diagnosis in only 15.3% and 14.5% of patients with advanced and localised GIST, respectively. CONCLUSIONS: In this real-world GIST registry, patients with advanced GIST were treated with imatinib and patients with localised GIST received surgical resection, in accordance with prevailing clinical recommendations.

Nilotinib 300 mg BID as frontline treatment of CML: prospective analysis of the Xpert BCR-ABL monitor system and significance of 3-month molecular response.

Sixty patients with early chronic phase CML (ECPCML) received Nilotinib on a phase II study which included a comparison of the Xpert BCR-ABL Monitor™ PCR system with standardized (IS) BCR-ABL1 real-time quantitative PCR (RQ-PCR). 88% patients achieved MMR with 45% achieving MR4.5. At 3 months BCR-ABL1/ABL1 IS >1% and <10% was associated with a lower likelihood of subsequent MR4.5 compared to patients with lower levels (p = 0.018). No significant difference was observed between methodologies in identifying MMR. Nilotinib induces high molecular response rates in ECPCML and the Xpert BCR-ABL Monitor™ system merits further investigation in this setting.

Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia.

BACKGROUND: We evaluated BCR-ABL1 kinetics in patients treated with nilotinib and analyzed whether a dynamic model of changes in BCR-ABL1 levels over time could be used to predict long-term responses. METHODS: Patients from the nilotinib registration trial (CAMN107A2101; registered at http://www.clinicaltrials.gov as NCT00109707) who had imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase with BCR-ABL1 > 10% (on the international scale [IS]) at baseline and, in the first 6 months, had at least three BCR-ABL1 transcript measurements and an average daily dose of at least 720 mg were included in this analysis (N = 123). RESULTS: More than half of patients (65/123; 53%) had a slow monophasic response and the remainder (58/123; 47%) had a biphasic response, in which patients had a rapid initial decrease in BCR-ABL1 transcripts followed by a more gradual response. The biphasic response type strongly correlated with improved event-free survival (EFS). Data in the first 6 months of follow-up were sufficient to predict EFS at 24 months. CONCLUSIONS: Unlike newly diagnosed patients with Ph+ CML-CP-in whom the majority had a biphasic response-approximately half of patients with imatinib-resistant or -intolerant CML had a slower, monophasic response. Second-line patients who did have a biphasic response had an EFS outlook similar to that of newly diagnosed patients treated with imatinib. Our model was comparable to using BCR-ABL1 (IS) ≤ 10% at 6 months as a threshold for predicting EFS.

Nilotinib population pharmacokinetics and exposure-response analysis in patients with imatinib-resistant or -intolerant chronic myeloid leukemia.

PURPOSE: We evaluated the population pharmacokinetics (PK) and exposure-response relationship of nilotinib in patients with imatinib-resistant or -intolerant chronic myeloid leukemia (CML). METHODS: Concentration data from 493 patients with CML in chronic phase (CML-CP), accelerated phase, or blast crisis were used to perform a population pharmacokinetic analysis using nonlinear mixed-effect modeling. Steady-state nilotinib trough concentrations (Cmin) in individual patients were estimated from the population PK model for correlation with the efficacy and safety variables. Exposure-efficacy analysis was performed in patients with CML-CP, whereas exposure-safety analysis was performed in all patients who had both nilotinib PK data and efficacy/safety measures available. RESULTS: Baseline demographics and CML disease phase did not significantly affect nilotinib PK. Patients with a lower Cmin had significantly longer time to complete cytogenetic response (P = 0.010), longer time to major molecular response (P = 0.012), shorter time to progression (TTP; P = 0.009), and a trend toward lower response rates vs. patients with higher Cmin. A joint effect of prognostic risk score and Cmin on TTP was significant (P < 0.001). Nilotinib Cmin was also associated with the occurrence of all-grade elevations in total bilirubin (P < 0.001) and lipase (P = 0.002) levels. CONCLUSIONS: When tolerability allows, adherence to the nilotinib dose (400 mg twice daily) in order to maintain sufficient Cmin is important in maximizing the efficacy of nilotinib in patients with imatinib-resistant or -intolerant CML.

Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib.

PURPOSE: The association between initial molecular response and longer-term outcomes with nilotinib was examined. PATIENTS AND METHODS: Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). RESULTS: BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to ≤ 1%, > 1% to ≤ 10%, and > 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR-ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of > 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of > 10%. CONCLUSION: Patients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.

Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib.

Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497.

Proinflammatory state, hepcidin, and anemia in older persons.

In patients with overt inflammatory diseases, up-regulated hepcidin impairs iron absorption and macrophage release, causing anemia. Whether the mild proinflammatory state of aging is associated with increased hepcidin is unknown. We characterized the relationships between urinary hepcidin, iron status, anemia, and inflammation in 582 patients 65 years or older participating in the InCHIANTI (Invecchiare in Chianti, "Aging in the Chianti Area") study, a population-based study of aging in Tuscany, Italy. Compared with nonanemic persons, urinary hepcidin (nanograms/milligram of urinary creatinine) was significantly lower in iron deficiency and inflammation anemia compared with no anemia or other anemia types. Urinary hepcidin was positively correlated with log(ferritin) and negatively correlated with the soluble transferrin receptor/log(ferritin) ratio but not correlated with markers of inflammation: interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha, and C-reactive protein (CRP). Lower iron was significantly correlated with higher IL-6 and CRP. Adjusting for confounders, IL-6 and CRP remained significantly associated with serum iron, with no evidence that such a relationship was accounted for by variability in urinary hepcidin. In conclusion, elevated proinflammatory markers were associated with anemia and low iron status, but not with higher urinary hepcidin. Future studies should test whether hepcidin production becomes up-regulated only in situations of overt inflammation.

Anaemia and the risk of injurious falls in a community-dwelling elderly population.

BACKGROUND: Anaemia in the elderly is associated with a number of health-related functional declines, such as frailty, disability and muscle weakness. These may contribute to falls which, in the elderly, result in serious injuries in perhaps 10% of cases. OBJECTIVE: To investigate whether anaemia increases the risk of injurious falls in an elderly population. METHOD: Health insurance claims and laboratory test results data from January 1999 to April 2004 for 47 530 individuals >or=65 years of age enrolled in over 30 managed care plans were analysed. An open-cohort design was employed to classify patients' observation periods by anaemia status (based on the WHO definition) and haemoglobin (Hb) level category. Injurious falls outcomes were defined as an injurious event claim, within 30 days after a fall claim, for fractures of the hip/pelvis/femur, vertebrae/ribs, humerus or lower limbs; Colles' fracture; or head injuries/haematomas. Univariate and multivariate (adjusted for age, gender, health plan, history of falls, co-morbidities and concomitant medications) analyses were conducted. Subset analyses based on injurious falls of the hip and head were also conducted. RESULTS: In the univariate analysis, anaemia increased the risk of injurious falls by 1.66 times (95% CI 1.41, 1.95) compared with no anaemia. The incidence of injurious falls increased from 6.5 to 15.8 per 1000 person-years when Hb levels decreased from >or=13 to <10 g/dL (trend test: p < 0.001). Multivariate analysis confirmed that Hb levels were significantly associated with the risk of injurious falls (rate ratio = 1.47, 1.39 and 1.14 for Hb levels of <10, 10-11.9 and 12-12.9 g/dL, respectively, compared with Hb >or=13 g/dL; p < 0.001). Even stronger linear negative trends were observed in the subsets of hip and head injurious falls. CONCLUSION: Anaemia was significantly and independently associated with a risk increase for injurious falls. Furthermore, the risk of injurious falls increased as the degree of anaemia worsened. Correction of anaemia, a modifiable risk factor, warrants further investigation as a means of preventing falls in the elderly.

An extended maintenance dosing regimen of epoetin alfa 80,000 U every 3 weeks in anemic patients with cancer receiving chemotherapy.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of epoetin alfa (EPO) at an initial dose of 60,000 Units (U) once weekly (QW) followed by extended dosing of 80,000 U every 3 weeks (Q3W) in patients with chemotherapy-induced anemia (CIA). MATERIALS AND METHODS: Anemic patients (hemoglobin [Hb] < or = 11 g/dl) receiving Q3W chemotherapy for nonmyeloid malignancy were enrolled in this prospective, open-label, single-arm study to receive EPO 60,000 U subcutaneously (SC) QW (initial dosing phase [IDP]) until a target Hb level of 12 g/dl was reached (maximum 12 weeks). Patients who achieved an Hb level of 12 g/dl at any point during the IDP then entered the extended dosing phase (EDP; EPO 80,000 U SC Q3W). Maximum study duration (IDP + EDP) was 24 weeks. The primary endpoint was the proportion of patients achieving a hematopoietic response (Hb increase > or = 2 g/dl from baseline or Hb > or = 12 g/dl) during the IDP. RESULTS: One hundred fifteen patients were enrolled. During the IDP, 76% (84/110) of patients achieved a hematopoietic response, and 15% (17/115) received red blood cell (RBC) transfusion. Sixty-three percent (73/115) of patients entered the EDP, and 88% (64/73) of these patients maintained a mean Hb level > 11.0 and < or =13.0 g/dl. Two of 73 patients received RBC transfusion during the EDP. Adverse events were consistent with the underlying disease and chemotherapy treatment. CONCLUSION: These results suggest that initiation of EPO 60,000 U SC QW is effective in the treatment of CIA and that EPO 80,000 U SC Q3W can be an effective extended dosing option.

Anemia and cancer in older persons.

Although the overall prevalence for many cancers is declining, cancer still remains a diagnosis more common in the elderly than in younger individuals. As the population ages, the proportion of patients with cancer who are elderly is expected to increase dramatically. Anemia occurs more often in older individuals for a variety of reasons, and its prevalence in elderly patients with cancer is significantly increasing. Although information on anemia in the elderly is limited, data on cancer patients of all ages have shown that the presence of anemia is associated with poorer prognosis and functional status. The impact of anemia on performance status in patients with cancer is matched by results from a large number of studies indicating negative effects of anemia on a wide variety of performance measures. Despite an apparent reluctance to undertake aggressive therapy in elderly patients with cancer, physicians are using a wider range of treatments with increasing frequency in this older population. Optimizing treatment outcomes in elderly patients with cancer depends on careful determination of performance status as well as the potential of therapies to treat anemia in these patients.

An extended dosing regimen of epoetin alfa 60,000 units every 2 weeks in anemic patients with cancer receiving chemotherapy.

PURPOSE: This open-label study evaluated the safety and efficacy of epoetin alfa 60,000 U once weekly Initialsly followed by 60,000 U every 2 weeks in anemic patients with cancer receiving chemotherapy. PATIENTS AND METHODS: Patients receiving weekly or every- 4-weeks chemotherapy regimens for nonmyeloid malignancy and with hemoglobin (Hb) level /= 1 dose of epoetin alfa. Sixty-eight percent of patients had hematopoietic response (Hb increase >/= 2 g/dL from baseline or Hb level >/= 12 g/dL during the IDP; primary endpoint). Eighty-four patients entered the EDP; 74 of 84 patients (88%) maintained average Hb level between 11 g/dL and 13 g/dL up to time of withdrawal or study completion. Adverse events were consistent with the underlying disease process and chemotherapy treatment. Six patients (4.7%) in the IDP and 8 patients (9.5%) in the EDP experienced clinically relevant thrombotic vascular events. CONCLUSION: In this study, approximately 90% of patients receiving an extended dosing regimen of epoetin alfa 60,000 U every 2 weeks were able to maintain Hb level between 11 g/dL and 13 g/dL.

Anemia, physical disability, and survival in older patients with heart failure.

BACKGROUND: Anemia is common in congestive heart failure, and it has been associated with poor prognosis. The effect of anemia on functional ability in heart failure has not been described. We evaluated the relationship of anemia, physical disability, and survival in patients with heart failure. METHODS AND RESULTS: One-year longitudinal study of 567 non-disabled, hospitalized heart failure patients, age > or = 65 years, enrolled in the Italian Group of Pharmacoepidemiology in the Elderly Study. Anemia was defined according to the World Health Organization criteria. Physical disability was defined as dependence in performing at least 2 basic activities of daily living. After adjustment for disease severity and health-related variables, anemia was associated with higher risk of disability (odds ratio = 2.17; 95% confidence interval [CI] = 1.12-4.24). After stratification according to gender, a strong relationship of anemia and risk of disability persisted in women, but it was reduced in men. Anemic women were significantly more likely to die during the follow-up, even after adjustment for potential confounders (hazard ratio = 2.33; CI = 1.02-5.30). CONCLUSION: Anemia is a predictor of physical disability in older heart failure patients, and in women anemia is associated with increased mortality.

Randomized, open-label comparison of epoetin alfa extended dosing (80 000 U Q2W) vs weekly dosing (40 000 U QW) in patients with chemotherapy-induced anemia.

OBJECTIVE: This randomized, open-label, multicenter study compared the efficacy and safety of epoetin alfa (EPO) 80 000 U every 2 weeks (Q2W) to the FDA-approved regimen of 40 000 U weekly (QW) in patients with chemotherapy-induced anemia. RESEARCH DESIGN AND METHODS: A total of 310 patients with nonmyeloid malignancy and baseline hemoglobin (Hb)

Anemia and cognitive performance in hospitalized older patients: results from the GIFA study.

BACKGROUND: Anemia represents a major risk factor for adverse health-related events in older persons. The aim of this study was to evaluate the association between hemoglobin levels/anemia and cognitive function in hospitalized older persons. METHOD: Data are from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study. Hemoglobin levels (in g/dL) were measured upon admission to hospital; anemia was defined according to the WHO criteria. Cognitive performance was assessed by the Abbreviated Mental Test (AMT) on admission; an AMT score <7 defined cognitive impairment. Logistic regressions and analyses of covariance were performed to evaluate the relationship between cognitive status and hemoglobin levels/anemia. RESULTS: Mean age of the sample (n = 13,301) was 72.0 years. Participants with cognitive impairment presented a higher prevalence of anemia (47%) compared to those without cognitive impairment (35%, p < 0.001). Adjusted logistic regressions showed that hemoglobin levels/anemia were significantly associated with cognitive impairment (OR = 0.96, 95%CI = 0.94-0.99, p = 0.004, and OR = 1.32, 95%CI = 1.18-1.48, p < 0.001, respectively). Patients with anemia and cognitive impairment at the hospital admission presented a higher number of impaired Activities of Daily Living compared to those with only one or none of the studied conditions (p for trend < 0.001). CONCLUSION: Low hemoglobin levels and anemia are independently associated with cognitive performance in older persons admitted to acute care units.

Epoetin alfa increases hemoglobin levels and improves quality of life in anemic geriatric cancer patients receiving chemotherapy.

GOAL: To evaluate epoetin alfa (EPO) treatment of anemia in geriatric cancer patients receiving chemotherapy, a retrospective subgroup analysis was conducted of anemic cancer patients > or =65 years of age from three 16-week community-based studies of thrice-weekly (TIW) or once-weekly (QW) EPO for chemotherapy-related anemia (CRA). PATIENTS AND METHODS: Analyses were conducted on the overall geriatric population (> or =65 years) and by age subgroup (65-74, 75-84, and > or =85 years), and compared with younger patients (<65 years) for each individual study and for pooled data. MAIN RESULTS: Some 3,634 geriatric patients were compared with 3,467 younger patients. From baseline to final measurement, EPO therapy significantly increased Hb by 2.0 g/dl in patients > or =65 years and 1.9 g/dl in patients <65 years (P<0.0001) and reduced transfusion utilization in both groups (P<0.006). Both age groups also had significant improvements in quality of life (QOL), measured by the 100-mm Linear Analog Assessment Scale (LASA). In younger patients, mean LASA changes were significantly greater than those in geriatric patients (P<0.05); however, QOL improvements in both age groups were clinically meaningful. There were no significant differences across geriatric age subgroups or between TIW and QW regimens for Hb change or QOL improvement. Overall hematopoietic response rate to EPO was 65.4% for patients > or =65 years and 64.7% for patients <65 years. Predictors of greater hematopoietic response (based on a pooled analysis) included lower body weight, baseline Hb, and baseline serum erythropoietin levels; better tumor response; and history of EPO dose reduction and longer time on study. CONCLUSIONS: Anemic geriatric patients receiving EPO for CRA responded comparably to younger patients <65 years and should be treated similarly.

Meaningful change and responsiveness in common physical performance measures in older adults.

OBJECTIVES: To estimate the magnitude of small meaningful and substantial individual change in physical performance measures and evaluate their responsiveness. DESIGN: Secondary data analyses using distribution- and anchor-based methods to determine meaningful change. SETTING: Secondary analysis of data from an observational study and clinical trials of community-dwelling older people and subacute stroke survivors. PARTICIPANTS: Older adults with mobility disabilities in a strength training trial (n=100), subacute stroke survivors in an intervention trial (n=100), and a prospective cohort of community-dwelling older people (n=492). MEASUREMENTS: Gait speed, Short Physical Performance Battery (SPPB), 6-minute-walk distance (6MWD), and self-reported mobility. RESULTS: Most small meaningful change estimates ranged from 0.04 to 0.06 m/s for gait speed, 0.27 to 0.55 points for SPPB, and 19 to 22 m for 6MWD. Most substantial change estimates ranged from 0.08 to 0.14 m/s for gait speed, 0.99 to 1.34 points for SPPB, and 47 to 49 m for 6MWD. Based on responsiveness indices, per-group sample sizes for clinical trials ranged from 13 to 42 for substantial change and 71 to 161 for small meaningful change. CONCLUSION: Best initial estimates of small meaningful change are near 0.05 m/s for gait speed, 0.5 points for SPPB, and 20 m for 6MWD and of substantial change are near 0.10 m/s for gait speed, 1.0 point for SPPB, and 50 m for 6MWD. For clinical use, substantial change in these measures and small change in gait speed and 6MWD, but not SPPB, are detectable. For research use, these measures yield feasible sample sizes for detecting meaningful change.

Anemia and recovery from disability in activities of daily living in hospitalized older persons.

OBJECTIVES: To evaluate the predictive value of hemoglobin levels upon hospital admission on recovery from activity of daily living (ADL) disability during hospital stay in older patients. DESIGN: Longitudinal observational study. SETTING: Geriatric and internal medicine acute care units. PARTICIPANTS: Data are from 5,675 patients aged 65 and older enrolled in the Italian Group of Pharmacoepidemiology in the Elderly Study with ADL disability upon hospital admission. MEASUREMENTS: ADL disability was defined as inability to perform or need for assistance in performing one or more ADLs. Recovery from ADL disability was defined as independence in ADLs upon hospital discharge. Anemia was defined according to the World Health Organization criteria. Sociodemographic and clinical characteristics were considered as potential confounders. RESULTS: Mean age was 80.5 years; 57.7% of subjects were female. Prevalence of anemia was 46.8%. A total of 536 (9.4%) participants regained independence in all six ADLs at hospital discharge. Patients with anemia had a lower rate of recovery from ADL disability than those with normal hemoglobin levels (7.0% vs 11.6%; P<.001). Adjusted analyses confirmed that anemia was inversely associated with the likelihood of ADL recovery (odds ratio=0.71, 95% confidence interval=0.57-0.88). The probability of ADL recovery in anemic patients was higher at higher hemoglobin concentrations. CONCLUSION: In older hospitalized patients, anemia is inversely associated with the likelihood of regaining ADL independence during a hospital stay.

Anemia in old age is associated with increased mortality and hospitalization.

BACKGROUND: Anemia is common in old age and has been shown to affect older persons' physical function. To more fully understand the detrimental health effects of anemia, we examined the relationship of anemia with death and hospitalization outcomes in a large community-based sample of older persons. METHODS: Data are from 3607 persons, aged 71 years or older, participating in the National Institute on Aging (NIA)-sponsored Established Populations for Epidemiologic Studies of the Elderly (EPESE) study. Anemia was defined according to World Health Organization (WHO) criteria as a hemoglobin concentration below 12 g/dL in women and below 13 g/dL in men. Data on subsequent mortality and hospital admissions over 4 years were obtained from death records and the Medicare database. RESULTS: Anemia was present in 451 of the 3607 (12.5%) participants. During the follow-up period, anemic persons were more likely to die than were nonanemic persons (37.0% vs 22.1%, p<.001). Also, anemic persons were more often hospitalized (65.9% vs 54.6%, p<.001) and spent more days in hospital (25.0 vs 13.7, p<.001). After adjustment for demographics and baseline comorbidities, anemia significantly predicted subsequent mortality and hospitalization (relative risk=1.61, 95% confidence interval, 1.34-1.93; and relative risk=1.27, 95% confidence interval, 1.12-1.45, respectively). After excluding persons with prevalent diseases at baseline, anemia remained significantly associated with increased risks of mortality and hospitalization. A higher hemoglobin level was significantly associated with lower risks of mortality and hospitalization (p for trend<.001 for both). CONCLUSIONS: These findings indicate that late-life anemia characterizes persons at risk for important clinical health outcomes, and demonstrate the importance of clinical awareness of anemia even if the person is without apparent clinical disease.