Combination of socio-demographic and clinical co-variates for predicting treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase / 中华血液学杂志

Objective: To explore the impacts of socio-demographic and clinical co-variates on treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitor (TKI) and identified the predictive models for them. Methods: Data of newly diagnosed adult patients with CML-CP receiving first-line TKI and having complete socio-demographic data and clinical information were reviewed. Cox model was used to identify the independent variables associated with complete cytogenetic response (CCyR) , major molecular response (MMR) , molecular response 4 (MR(4)) and molecular response 4.5 (MR(4.5)) , as well as failure-free survival (FFS) , progression-free survival (PFS) , overall survival (OS) and CML-related OS. Results: A total of 1414 CML-CP patients treated with first-line imatinib (n=1176) , nilotinib (n=170) or dasatinib (n=68) were reviewed. Median age was 40 (18-83) years and 873 patients (61.7% ) were males. Result of the multivariate analysis showed that lower educational level (P<0.001-0.070) and EUTOS long-term survival intermediate or high-risk (P<0.001-0.009) were significantly associated with lower cumulative incidences of CCyR, MMR, MR(4) and MR(4.5), as well as the inferior FFS, PFS, OS and CML-related OS. In addition, those who were males, from rural households, had white blood cells (WBC) ≥120×10(9)/L, hemoglobin (HGB) <115 g/L and treated with first-line imatinib had significantly lower cumulative incidences of cytogenetic and/or molecular responses. Being single, divorced or widowed, having, rural household registration, WBC≥120×10(9)/L, HGB<15 g/L, and comorbidity (ies) was significantly associated with inferior FFS, PFS, OS, and/or CML-related OS. Thereafter, the patients were classified into several subgroups using the socio-demographic characteristics and clinical variables by cytogenetic and molecular responses, treatment failure and disease progression, as well as overall survival and CML-related OS, respectively. There were significant differences in treatment responses and outcomes among the subgroups (P<0.001) . Conclusion: Except for clinical co-variates, socio-demographic co-variates significantly correlated with TKI treatment responses and outcomes in CML-CP patients. Models established by the combination of independent socio-demographic and clinical co-variates could effectively predict the responses and outcome.

Occupancy dynamics of South American sea-lions in Brazilian haul-outs / Dinâmica de ocupação do leão-marinho-do-sul no Brasil

Along the Brazilian coast only two haul-outs of South American sea lions (Otaria flavescens) are known: Ilha dos Lobos and Molhe Leste, both located in the southernmost state of Brazil, Rio Grande do Sul. Most sea lions observed in these haul-outs are adult and sub-adult males. It is supposed that the species' presence in these areas is due to food supply and absence of parental assistance by males. This study analysed the use of these haul-outs by O. flavescens between 1993 and 2002 based on counting data of observed individuals. Bayesian generalised linear mixed models were used to evaluate differences in abundance between areas, long term trends and seasonal patterns. Results showed that for O. flavescens abundance had a long term trend of increased average occupancy over the study period, with seasonal variation reaching the highest within-year value in August (Ilha dos Lobos) and October (Molhe Leste). The novel application of this powerful statistical modelling approach resulted in a useful tool to quantify occupancy dynamic.

Ao longo da costa do Brasil apenas duas colônias não-reprodutivas de leões-marinhos-do-sul (Otaria flavescens) são conhecidas: Ilha dos Lobos e Molhe Leste, ambas localizadas no estado do Rio Grande do Sul. A maioria dos leões-marinhos observados nestas colônias são machos adultos e sub-adultos. Supõe-se que a presença da espécie nestas áreas está relacionada ao forrageamento e a ausência de cuidado parental pelos machos. Este estudo analisou a dinâmica de ocupação e abundância de O. flavescens nas colônias não-reprodutivas entre 1993 e 2002, baseado em uma série temporal de dados de contagens de indivíduos. Modelos lineares generalizados mistos Bayesianos foram usados para avaliar diferença na abundância entre áreas, tendência de uso em longo prazo e padrões sazonais. Os resultados mostram que a abundância de O. flavescens variou sazonalmente, atingindo pico intra-anual em agosto (Ilha dos Lobos) e outubro (Molhe Leste), acompanhado de um aumento da ocupação média dos refúgios ao longo do período de estudo. A nova aplicação desta poderosa forma de modelagem estatística mostrou-se útil para quantificar a dinâmica de ocupação.

Clinical pharmacokinetics of vancomycin in the neonate: a review

Neonatal sepsis is common and is a major cause of morbidity and mortality. Vancomycin is the preferred treatment of several neonatal staphylococcal infections. The aim of this study was to review published data on vancomycin pharmacokinetics in neonates and to provide a critical analysis of the literature. A bibliographic search was performed using PubMed and Embase, and articles with a publication date of August 2011 or earlier were included in the analysis. Vancomycin pharmacokinetic estimates, which are different in neonates compared with adults, also exhibit extensive inter-neonatal variability. In neonates, several vancomycin dosing schedules have been proposed, mainly based on age (i.e., postmenstrual and postnatal), body weight or serum creatinine level. Other covariates [e.g., extracorporeal membrane oxygenation (ECMO), indomethacin or ibuprofen, and growth restriction] of vancomycin pharmacokinetics have been reported in neonates. Finally, vancomycin penetrates cerebrospinal fluid (range = 7-42%). Renal function drives vancomycin pharmacokinetics. Because either age or weight is the most relevant covariate of renal maturation, these covariates should be considered first in neonatal vancomycin dosing guidelines and further adjusted by renal dysfunction indicators (e.g., ECMO and ibuprofen/indomethacin). In addition to the prospective validation of available dosing guidelines, future studies should focus on the relevance of therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates.

Reliability of Covariates in Baseline Survey of a Cohort Study: Epidemiological Investigation on Cancer Risk Among Residents Who Reside Near the Nuclear Power Plants in Korea / 예방의학회지

OBJECTIVES: We evaluated the reliability of the possible covariates of the baseline survey data collected for the Epidemiological Investigation on Cancer Risk Among Residents Who Reside Near the Nuclear Power Plants in Korea. METHODS: Follow-up surveys were conducted for 477 participants of the cohort at less than 1 year after the initial survey. The mean interval between the initial and follow-up surveys was 282.5 days. Possible covariates were identified by analyzing the correlations with the exposure variable and associations with the outcome variables for all the variables. Logistic regression analysis with stepwise selection was further conducted among the possible covariates to select variables that have covariance with other variables. We considered that these variables can be representing other variables. Seven variables for the males and 3 variables for the females, which had covariance with other possible covariates, were selected as representative variables. The Kappa index of each variable was calculated. RESULTS: For the males, the Kappa indexes were as follow; family history of cancer was 0.64, family history of liver diseases in parents and siblings was 0.56, family history of hypertension in parents and siblings was 0.51, family history of liver diseases was 0.50, family history of hypertension was 0.44, a history of chronic liver diseases was 0.53 and history of pulmonary tuberculosis was 0.36. For females, the Kappa indexes were as follow; family history of cancer was 0.58, family history of hypertension in parents and siblings was 0.56 and family history of hypertension was 0.47. CONCLUSIONS: Most of the possible covariates showed good to moderate agreement.

Factors Affecting Hand Tremor and Postural Sway in Children

Objectives: It is crucial to consider covariates relevant for outcome variables in developing dose-effect relations of environmental hazardous toxins. The aim of this study was to clarify the covariates affecting hand tremor and postural sway in children. Methods: Hand tremor and postural sway, as well as hair mercury concentrations, were measured in 155 boys and 148 girls at age 7 years. Results: Current mercury concentrations in child hair ranged from 0.35 to 6.32 μg/g (geometric mean, 1.71 μg/g for boys and 1.58 μg/g for girls), and were not significantly correlated with the neuromotor parameters. All hand tremor and postural sway parameters, except for tremor intensity at 1–6 Hz with non-dominant hand, were significantly larger in the boys than in the girls. Using multiple regression analysis, some postural sway parameters were related negatively to age in the boys and girls (p<0.05), and positively to height (p<0.05). Similarly, hand tremor parameters were positively related to age, height and heart rate either in the boys or in the girls (p<0.05). Also, there were positive relationships between tremor intensity at 1–6 Hz and transversal and sagittal sways at 1–2 Hz and 2–4 Hz (p<0.05). Conclusions: Heart rate and postural sway, together with age, sex, and height, should be considered in interpreting hand tremor in children. Hand tremor or postural sway may not be so sensitive or specific to methylmercury exposures at levels of less than 7 μg/g in hair.

Factors affecting hand tremor and postural sway in children

<p><b>OBJECTIVES</b>It is crucial to consider covariates relevant for outcome variables in developing dose-effect relations of environmental hazardous toxins. The aim of this study was to clarify the covariates affecting hand tremor and postural sway in children.</p><p><b>METHODS</b>Hand tremor and postural sway, as well as hair mercury concentrations, were measured in 155 boys and 148 girls at age 7 years.</p><p><b>RESULTS</b>Current mercury concentrations in child hair ranged from 0.35 to 6.32 μg/g (geometric mean, 1.71 μg/g for boys and 1.58 μg/g for girls), and were not significantly correlated with the neuromotor parameters. All hand tremor and postural sway parameters, except for tremor intensity at 1-6 Hz with non-dominant hand, were significantly larger in the boys than in the girls. Using multiple regression analysis, some postural sway parameters were related negatively to age in the boys and girls (p<0.05), and positively to height (p<0.05). Similarly, hand tremor parameters were positively related to age, height and heart rate either in the boys or in the girls (p<0.05). Also, there were positive relationships between tremor intensity at 1-6 Hz and transversal and sagittal sways at 1-2 Hz and 2-4 Hz (p<0.05).</p><p><b>CONCLUSIONS</b>Heart rate and postural sway, together with age, sex, and height, should be considered in interpreting hand tremor in children. Hand tremor or postural sway may not be so sensitive or specific to methylmercury exposures at levels of less than 7 μg/g in hair.</p>