Symptomatic osteonecrosis in childhood leukemia survivors: prevalence,risk factors and impact on quality of life in adulthood

Corticosteroid can induce osteonecrosis in children with leukemia. Few studies have been designed to assess the influence of a wide range of cumulative steroid dose on this side effect. Prevalence, risk factors of symptomatic osteonecrosis and its impact on adults’ Quality of Life were assessed in 943 patients enrolled in the French “Leucémies de l''Enfant et de l''Adolescent“ (LEA) cohort of childhood leukemia survivors. During each medical visit, data on previous osteonecrosis diagnosis were retrospectively collected. Patients without a history but with suggestive symptoms were investigated with magnetic resonance imaging. The total steroid dose in equivalent of prednisone was calculated for each patient and its effect on osteonecrosis occurrence was studied in multivariate models. Cumulative incidence was 1.4% after chemotherapy alone versus 6.8% after transplantation (P<0.001). A higher cumulative steroid dose, age over ten years at diagnosis, and treatment with transplantation significantly increased the risk of osteonecrosis. A higher post-transplant steroid dose and age over ten years at time of transplantation were significant factors in the transplanted group. With patients grouped according to steroid dose quartile, cumulative incidence of osteonecrosis reached 3.8% in the chemotherapy group for a dose beyond 5835 mg/m² and 23.8% after transplantation for a post-transplant dose higher than 2055 mg/m². Mean physical composite score of Quality of Life was 44.3 in patients with osteonecrosis versus 54.8% in patients without (P<0.001). We conclude that total and post-transplant cumulative steroid dose may predict the risk of osteonecrosis, a rare late effect with a strong negative impact on physical domains of Quality of Life.     

Social and gender inequalities in depressive symptoms among urban older adults of latin america and the Caribbean

OBJECTIVE: This study examined gender differences in depression by examining differential exposure and vulnerability to socioeconomic factors during the life course. METHODS: The data used for the analyses originated from a cross-national survey of older adults living in seven large Latin American cities. We examined associations between depressive symptomatology and socioeconomic conditions and health indicators in childhood, adulthood, and old age. We used the Geriatric Depression Scale to classify respondents with high levels of depressive symptoms. RESULT: The prevalence of depression in the urban population of Latin America was relatively low, ranging across cities from 0.4 to 5.2% in men and from 0.3 to 9.5% in women. Women were more exposed to social and material disadvantages during their life course than men but were not more vulnerable to them than men. Current socioeconomic conditions and health status as well as functional disabilities mainly accounted for gender differences in the prevalence of depression. Additionally, poor health and hunger during childhood, as well as illiteracy or lack of education, were associated with depression in both men and women. DISCUSSION: Cumulative life course exposure to social and material disadvantage and current material, social, and health conditions explain the higher frequency of depression in women.     

Serum and intraperitoneal pharmacokinetics of cisplatin within intraoperative intraperitoneal chemotherapy: influence of protein binding

Intraperitoneal (i.p.) chemotherapy is a promising therapeutic method to improve the effectiveness of cisplatin in patients with ovarian cancer and peritoneum involvement. Intraperitoneal treatment can be intraoperatively performed just after a complete surgical resection of peritoneal tumor nodules. However, little is known regarding the pharmacokinetics of platinum during intraoperative i.p. chemotherapy (IIC). Serum and i.p. measurements of total and ultrafilterable platinum were performed to determined pharmacokinetic parameters in 11 consecutive patients who received a 2-h IIC with 50 mg/m cisplatin. Protein concentrations were determined in serum and peritoneal liquid at the same times. The cisplatin concentration required to kill OVCAR-3 human ovarian cancer cells and evaluation of cisplatin binding to proteins were determined in vitro. Platinum i.p. concentration decreased rapidly and quickly came under the cytotoxicity threshold (10 mg for 2 h). About 85% of i.p. and serum cisplatin was ultrafilterable during IIC. Platinum concentrations were closely related to protein concentrations. Due to the very low level of serum protein (almost 25 g/l), serum cisplatin binding during chemotherapy was very low (almost 25%), but increased with protein concentration recovery. These pharmacokinetic data show that a sufficient concentration to kill human ovarian cancer is not reached with a single i.p. bath containing 50 mg/m cisplatin for 2 h. A new protocol with a renewed bath and a higher cisplatin concentration is under investigation.     

Anti‐D investigations in individuals expressing weak D Type 1 or weak D Type 2: allo‐ or autoantibodies?

BACKGROUND: Whether anti‐D produced by individuals with a weak D phenotype are allo‐ or autoantibodies remains a matter of debate even though blood transfusion practice is impacted. The aim of our study was to determine the serologic features of anti‐D in individuals expressing the most frequent weak D type in Caucasians that are weak D Type 1 or weak D Type 2, to assess whether anti‐D were allo‐ or autoantibodies. STUDY DESIGN AND METHODS: Serologic D typing and molecular analysis enabled the including of 121 weak D Type 1 individuals and 99 weak D Type 2 individuals in our study. Serologic features of anti‐D included autologous controls, direct antiglobulin test, elution, and titration of anti‐D before and after adsorption of serum on autologous red blood cells (RBCs). RESULTS: Serologic D typing showed a variable reactivity of RBCs expressing weak D Type 1 or weak D Type 2 (4+ to 0). Anti‐D was identified in six weak D Type 1 and six weak D Type 2 individuals, respectively. The serologic data were in favor of autoantibodies. CONCLUSION: A complete anti‐D investigation in individuals with a D variant (weak D or partial D identified by molecular analysis) should be systematically performed before any valid conclusion on the nature of the antibody. Transfusing weak D Type 1 or weak D Type 2 patients with D+ RBC units should be recommended. Weak D Type 1 or weak D Type 2 pregnant women do not need anti‐D immunoprophylaxis.     

Tuberculosis after HAART initiation in HIV-positive patients from five countries with a high tuberculosis burden

BACKGROUND: HAART reduces tuberculosis (TB) incidence in people living with HIV/AIDS but those starting HAART may develop active TB or subclinical TB may become apparent in the immune reconstitution inflammatory syndrome. OBJECTIVE: To measure the incidence rate of notified TB in people receiving HAART in five HIV programmes occurring in low-resource countries with a high TB/HIV burden. METHODS: A retrospective review in five Médecins Sans Frontières programmes (Cambodia, Thailand, Kenya, Malawi and Cameroon) allowed incidence rates of notified TB to be calculated based on follow-up time after HAART initiation. RESULT: Among 3151 patients analysed, 90% had a CD4 cell count of < 200 cells/mul. Median follow-up time ranged from 3.7 months in Thailand or Kenya to 11.1 months in Cambodia. Incidence rates were 7.6, 10.4, 17.6, 14.3 and 4.8/100 person-years for pulmonary TB and 12.7, 4.3, 6.9, 2.1 and 0/100 person-years for extra-pulmonary TB in the programmes in Cambodia, Thailand, Kenya, Malawi and Cameroon, respectively. Overall, 62.3% of pulmonary TB and 54.9% of extra-pulmonary TB were diagnosed within 3 months after HAART initiation. CONCLUSION: High incidence rates of notified TB under HAART in programmes held in poor-resource countries were observed; these were likely to include both undiagnosed prevalent TB at HAART initiation and subclinical TB developing during the immune reconstitution inflammatory syndrome. This raises operational issues concerning TB diagnosis and treatment of TB/HIV-coinfected patients and prompts for urgent TB and HIV care integration.