Dopamine D2 Occupancy as a Biomarker for Antipsychotics: Quantifying the Relationship with Efficacy and Extrapyramidal Symptoms

For currently available antipsychotic drugs, blockade of dopamine D(2) receptors is a critical component for achieving antipsychotic efficacy, but it is also a driving factor in the development of extrapyramidal symptoms (EPS). To inform the clinical development of asenapine, generic mathematical models have been developed for predicting antipsychotic efficacy and EPS tolerability based on D(2) receptor occupancy. Clinical data on pharmacokinetics, D(2) receptor occupancy, efficacy, and EPS for several antipsychotics were collected from the public domain. Asenapine data were obtained from in-house trials. D(2) receptor occupancy data were restricted to published positron emission tomography studies that included blood sampling for pharmacokinetics. Clinical efficacy data were restricted to group mean endpoint data from short-term placebo-controlled trials, whereas EPS evaluation also included some non-placebo-controlled trials. A generally applicable model connecting antipsychotic dose, pharmacokinetics, D(2) receptor occupancy, Positive and Negative Syndrome Scale (PANSS) response, and effect on Simpson-Angus Scale (SAS) was then developed. The empirical models describing the D(2)-PANSS and D(2)-SAS relationships were used successfully to aid dose selection for asenapine phase II and III trials. A broader use can be envisaged as a dose selection tool for new antipsychotics with D(2) antagonist properties in the treatment of schizophrenia.     

Trends of under- and overweight among rural and urban poor women indicate the double burden of malnutrition in Bangladesh

BACKGROUND: Although undernutrition and communicable diseases dominate the current disease burden in resource-poor countries, the prevalence of diet related chronic diseases is increasing. This paper explores current trends of under- and overweight in Bangladeshi women. METHOD: Nationally representative data on reproductive age women from rural Bangladesh (n = 242,433) and selected urban poor areas (n = 39,749) collected by the Nutritional Surveillance Project during 2000-2004 were analyzed. RESULTS: While the prevalence of chronic energy deficiency [CED, body mass index (BMI) < 18.5 kg/m(2)] continues to be major nutritional problem among Bangladeshi women (38.8% rural, 29.7% urban poor; P < 0.001), between 2000-2004, 9.1% of urban poor and 4.1% of rural women were overweight (BMI > or = 25 kg/m(2), P < 0.001). In addition, 9.8% of urban poor and 5.5% of rural women were found to be 'at risk of overweight' (BMI 23.0-<25 kg/m(2)). From 2000 to 2004, prevalence of CED decreased (urban poor: 33.8-29.3%; rural: 42.6-36.6%), while prevalence of overweight increased (urban poor: 6.8-9.1%; rural: 2.8-5.5%). The risk of being overweight was higher among women who were older and of higher socioeconomic status. Rural women with at least 14 years of education had a 8.1-fold increased risk of being overweight compared with non-educated women [95% confidence intervals (CI): 6.6-8.7]. Women living in houses of at least 1000 sq ft (93 m(2)) were 3.7 times more likely to be overweight compared with women living in <250 sq ft (23 m(2)) houses (95% CI: 3.2-4.3). CONCLUSION: The recent increase in overweight prevalence among both urban poor and rural women, along with high prevalence of CED, indicates the emergence of a double burden of malnutrition in Bangladesh.     

Characterization of hemorrhagic fever with renal syndrome caused by hantaviruses, Estonia

Thirty cases of hemorrhagic fever with renal syndrome (HFRS) due to Puumala virus (PUUV), Saaremaa virus (SAAV), and Dobrava virus infection were confirmed in Estonia. Except for the levels of serum creatinine, no remarkable differences were found in the clinical course of HFRS caused by PUUV and SAAV.     

An Assessment of the Potential Impact of Fortification of Staples and Condiments on Micronutrient Intake of Young Children and Women of Reproductive Age in Bangladesh

Bangladesh has experienced rapid economic growth and achieved major health improvements in the past decade, but malnutrition rates remain high. A nationally representative study conducted in 2011 assessed the dietary habits of 841 children 24–59 months old; 1428 children 6–14 years old; and 1412 non-pregnant, non-lactating women. The study’s objective was to assess dietary intakes of key micronutrients and the consumption pattern of potentially fortifiable foods, and then to model the potential impact of fortification of key staple foods. The current intakes of several micronutrients, namely, iron, zinc, folate, vitamin A and vitamin B12, were found to be insufficient to meet the needs of Bangladesh’s children and women. The fortification of rice with iron and zinc and edible oil with vitamin A has the potential to fill a significant part of the nutrient gap, as these are consumed widely and in significant amounts. Wheat flour and sugar are not as promising food vehicles in the Bangladeshi context, as they were consumed by a smaller portion of the population and in smaller amounts. In conclusion, fortification of rice and oil is recommended to address the large gap in micronutrient intakes.     

Risk factors for nightblindness among women of childbearing age in Cambodia

OBJECTIVE: To characterize risk factors for nightblindness among nonpregnant women of childbearing age, a group recently recognized to be at high risk of vitamin A deficiency in some developing countries. DESIGN: Case-control study. SETTING: The study included >15 000 households in National Micronutrient Survey of Cambodia conducted in 2000. SUBJECTS: The prevalence of nightblindness among 13 358 nonpregnant women was 2.0%. A total of 328 nonpregnant women with nightblindness were matched by province with 1009 nonpregnant women without nightblindness. METHODS: Univariate and multivariate logistic regression models were used to estimate odds ratios (ORs) as estimates of the relative risk of factors associated with nightblindness. RESULTS: In a final model, materials in the wall of the house (OR 1.4, 95% confidence interval (CI) 0.9-2.0), land ownership < or =0.5 hectares (OR 1.4, 95% CI 1.0-1.9), nightblindness in last pregnancy (OR 44.5, 95% CI 29.2-67.8), parity >3 (OR 1.5, 95% CI 1.0-2.1), diarrhea within the last 2 weeks (OR 1.9, 95% CI 1.3-2.8), maternal body mass index <18.5 (OR 1.8, 95% CI 1.2-2.7), and lack of consumption of vitamin A-rich animal foods in the last 24 h (1-60 retinol equivalents (RE) OR 1.1, 95% CI 0.7-1.6; > or =60 RE, OR 0.7, 95% CI 0.4-1.0) were associated with nightblindness among nonpregnant women. CONCLUSIONS: Women of childbearing age in Cambodia with low socioeconomic status, low consumption of vitamin A-rich animal foods, a history of nightblindness during the previous pregnancy, parity >3, malnutrition, and diarrhea have a higher risk of nightblindness. SPONSORSHIP: United States Agency for International Development (442-G-00-95-00515-00).     

Validation of a rapid enzyme immunoassay for the quantitation of retinol-binding protein to assess vitamin A status within populations

OBJECTIVE: To compare the prevalence of vitamin A deficiency (VAD) among Cambodian preschool children as determined by the retinol-binding protein-enzyme immunoassay (RBP-EIA) and direct measurement of serum retinol by high-performance liquid chromatography (HPLC). SETTING AND SUBJECTS: Sera from 359 children were randomly selected from archived specimens collected in a national VAD prevalence survey in Cambodia. METHODS: Sera were first analyzed for retinol content by HPLC and then subjected to analysis using RBP-EIA to determine serum RBP concentrations. National Institute of Standards and Technology and control sera were used to ensure quality and accuracy for each set of analyses. To classify VAD, the same cutoff point of <0.70 micromol/l was employed for each indicator. RESULTS: Overall, the prevalence of VAD based on serum retinol was 22.3% (95% confidence interval (CI): 18.0, 26.6), whereas the RBP-EIA indicated a VAD prevalence of 20.9% (95% CI: 16.7, 25.1). A simple linear regression model indicated an R2 of 0.79, and a receiver operating curve analysis revealed an area under the curve of 0.92. CONCLUSIONS: We found no significant difference between the results of RBP-EIA compared to retinol analyzed by HPLC in estimating the prevalence of VAD. Use of the test could enable public health authorities to assess the extent of VAD and track progress in control programs in resource-poor settings.