Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.

Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naïve patients were randomized to d4T/didanosine (ddI)- or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P < 5.0 × 10(-8)) and focused on 46 neuropathy-associated genes (threshold, P < 3.5 × 10(-5)). In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P = 8.4 × 10(-4)), in LITAF among Blacks (rs13333308, P = 6.0 × 10(-6)), and in NEFL among Hispanics (rs17763685, P = 5.6 × 10(-6)). Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect

SUGESTÃO DE UM CRITÉRIO DE VIGILÂNCIA DE ESTADO NUTRICIONAL (C.V.E.N.) PARA PRÊ-ESCOLARES

Sugestão de um critério de vigilância de estado nutricional (C. V. E. N.) para pré-escolares O C. V. E. N. consiste no registro das deficiências de crescimento, com base nos conceitos de cronicidade e severidade de WATERLOW & ALLEYNE (1971) e na classificação da altura das crianças, de acordo com a orientação de MARCONDES et al. (1974); põe em evidência a possível influência do tempo e da intensidade de carência alimentar nas deficiências de crescimento apresentadas pelas crianças. Estas deficiências são expressas em números absolutos, ao invés de porcentagens ou índices. A aplicação do Critério de Vigilância de Estado Nutricio-nal mostrou que a sensibilidade deste critério para detectar deficiências de crescimento aproxima-se à sensibilidade da classificação de GOMEZ (1956) — 80% e 84,2%, respectivamente. A equivalência na determinação das deficiências de crescimento entre estes dois critérios é a seguinte: crianças que apresentaram severidade e cronicidade, e que foram classificadas como desnutridas de I e II grau, apresentaram respectivamente, deficiências médias de 0,72 ± 0,57 kg e 6,4 ± 1,38 cm e de 1,40 ± 0,73 kg e 9,6 ± 2,30 cm, significativamente diferentes, ao nível de 0,01%; crianças que apresentaram severidade, apenas, e que foram consideradas como desnutridas de I e II grau apresentaram, respectivamente, deficiências médias de 1,10 ± 0,52 kg e de 2,41 ± 0,42 kg, significativamente diferentes, ao nível de 0,01%.The criterion for Surveying the Nutritional State (C. S. N. S.) for pre-school children consists of reccording growth deficiences based upon concepts of severety and cronicity of WATERLOW & ALLEYNE (1971) and upon orientation of MARCONDES et al. (1974) of classification of children according to their height; it emphasizes the possible influences of time and intensity of malnutrition in growth deficiences presented by children. These deficiences are expressed by absolute numbers, instead of percentages or indexes. The application of C. S. N. S., that has been studied by the author showed that its criterion sensibility to detect growth deficiences is similar to GOMEZ Classification (1956) — 80% and 84,2%, respectively. The equivalence in determining growth deficiences between these two criteria is as follows: children who presented severety and cronicity according to the author's criterion and were classified as malnutrition grade I and II according to GOMEZ, presented each, deficiences media of 0.72 ± 0.57 kg and 6.4 ± 1.38 cm and of 1.40 ± 0.73 kg and 9.6 ± 2.30 cm, with significant differences at 0.01% level; children who presented severety, alone, and who where considered as malnutrition grade I and II, presented each deficiences media of 1.10 ± 0.52 kg and of 2.41 ± 0,42 kg, with significant differences at 0.01% level