A three-year naturalistic follow-up of patients receiving clozapine: Report from India

INTRODUCTION: Clozapine is a first-line drug for treatment-resistant schizophrenia, but studies dealing with long-term outcome are lacking, so we decided to carry out such a study. METHODS: Patients with treatment-resistant schizophrenia who were recruited in an open-label study three years ago were re-evaluated using the same parameters: BPRS, PANSS and a side-effect rating checklist. RESULTS: Nineteen out of 25 patients who participated in the initial study were available for re-evaluation. Two patients had changed to conventional neuroleptic medication, and were excluded from the study. A significant reduction in psychopathology was observed in 85% of patients. An improvement in social functioning was evident, with seven patients pursuing a career independently, and another six working with their family members since being started on clozapine. All the patients were on clozapine monotherapy, and the average daily dose was 248.21 mg. No patient required hospitalization and there was no incidence of granulocytopenia. CONCLUSIONS: A significant improvement in the psychopathology and social functioning of patients was observed with much lower doses of clozapine than has been reported elsewhere. The doses used for maintenance were lower than those used in the acute phase of treatment. (Int J Psych Clin Pract 2002; 6: 167-171 )     

Newborn care practices and health seeking behavior in urban slums and villages of Anand, Gujarat

Health status of neonates in urban slums has not been studied in smaller towns. A questionnaire was administered to 154 families of 10 urban slums of Anand (population — 197351) and 160 families from 6 villages of Anand district. The socioeconomic and education status of the slum dwellers versus rural participants were significantly lower (P<0.001). Antenatal care (79.9 vs 94.4%, P<0.001), hospital delivery (82.5 vs 93.8%, P=0.002), neonatal follow-up (27.9 vs 78.8%, P<0.001), health seeking (56.5 vs 91.3%, P<0.001), essential newborn care and exclusive breastfeeding (6.5 vs 85.6%, P<0.001) were also lower in urban slums, as compared to villages, Care seeking was low in urban slums, Hindus and illiterate mothers. Health care and socioeconomic status of neonates in slums of smaller cities is poorer than in surrounding villages.     

Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States

Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs.     

Podocyte loss involves MDM2‐driven mitotic catastrophe

Podocyte apoptosis as a pathway of podocyte loss is often suspected but rarely detected. To study podocyte apoptosis versus inflammatory forms of podocyte death in vivo, we targeted murine double minute (MDM)‐2 for three reasons. First, MDM2 inhibits p53‐dependent apoptosis; second, MDM2 facilitates NF‐κB signalling; and third, podocytes show strong MDM2 expression. We hypothesized that blocking MDM2 during glomerular injury may trigger p53‐mediated podocyte apoptosis, proteinuria, and glomerulosclerosis. Unexpectedly, MDM2 blockade in early adriamycin nephropathy of Balb/c mice had the opposite effect and reduced intra‐renal cytokine and chemokine expression, glomerular macrophage and T‐cell counts, and plasma creatinine and blood urea nitrogen levels. In cultured podocytes exposed to adriamycin, MDM2 blockade did not trigger podocyte death but induced G2/M arrest to prevent aberrant nuclear divisions and detachment of dying aneuploid podocytes, a feature of mitotic catastrophe in vitro and in vivo. Consistent with these observations, 12 of 164 consecutive human renal biopsies revealed features of podocyte mitotic catastrophe but only in glomerular disorders with proteinuria. Furthermore, delayed MDM2 blockade reduced plasma creatinine levels, blood urea nitrogen, tubular atrophy, interstitial leukocyte numbers, and cytokine expression as well as interstitial fibrosis. Together, MDM2‐mediated mitotic catastrophe is a previously unrecognized variant of podocyte loss where MDM2 forces podocytes to complete the cell cycle, which in the absence of cytokinesis leads to podocyte aneuploidy, mitotic catastrophe, and loss by detachment. MDM2 blockade with nutlin‐3a could be a novel therapeutic strategy to prevent renal inflammation, podocyte loss, glomerulosclerosis, proteinuria, and progressive kidney disease. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.