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1.
Am J Psychiatry ; 181(5): 423-433, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38706327

RESUMO

OBJECTIVE: Substance use initiation during early adolescence is associated with later development of substance use and mental health disorders. This study used various domains to predict substance use initiation, defined as trying any nonprescribed substance (e.g., alcohol, tobacco, cannabis), by age 12, using a large longitudinal data set. METHODS: Substance-naive youths from the Adolescent Brain Cognitive Development Study (ages 9-10; N=6,829) were followed for 3 years. A total of 420 variables were examined as predictors of substance use initiation, using a penalized logistic regression with elastic net; domains spanned demographic characteristics, self and peer involvement with substance use, parenting behaviors, mental and physical health, culture and environment, hormones, neurocognitive functioning, and structural neuroimaging. RESULTS: By age 12, 982 (14.4%) children reported substance initiation, with alcohol being the most common. Models with only self-report predictors had similar prediction performance to models adding hormones, neurocognitive factors, and neuroimaging predictors (AUCtest=0.66). Sociodemographic factors were the most robust predictors, followed by cultural and environmental factors, physical health factors, and parenting behaviors. The top predictor was a religious preference of Mormon (coefficient=-0.87), followed by a religious preference for Jewish (coefficient=0.32), and by Black youths (coefficient=-0.32). CONCLUSIONS: Sociodemographic variables were the most robust predictors of substance use initiation. Adding resource-intensive measures, including hormones, neurocognitive assessment, and structural neuroimaging, did not improve prediction of substance use initiation. The application of these large-scale findings in clinical settings could help to streamline and tailor prevention and early intervention efforts.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Feminino , Criança , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estudos Longitudinais , Adolescente , Fatores de Risco , Comportamento do Adolescente/psicologia , Poder Familiar/psicologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-38631877

RESUMO

BACKGROUND: Adolescence is a sensitive stage of oral microbial development that often coincides with the initiation and escalation of alcohol use. Thus, adolescents may be particularly susceptible to alcohol-induced alterations in the oral microbiome, though minimal research has been done in this area. Understanding the connection between the oral microbiome and alcohol use during adolescence is important to understand fully the biological consequences of alcohol use to mitigate potential adverse outcomes. METHODS: Saliva samples were collected from adolescents aged 17-19 who used alcohol heavily (n = 21, 52.4% female) and those who did not use alcohol or any other substances (n = 18, 44.4% female). We utilized 16S rRNA sequencing to examine differences in microbial diversity and composition between the groups. RESULTS: For alpha diversity, evenness was significantly lower in the drinking group than the control group as indicated by Pielou's evenness, Shannon, and Simpson indices. There were no statistically significant findings for beta diversity. Differential abundance analyses revealed higher abundances of Rothia and Corynebacterium in the alcohol-using group using both centered-log-ratio and relative abundance normalization. These genera are known for their high capacity to convert alcohol into acetaldehyde, a toxic metabolite reported to play a role in the neurobiological effects of alcohol. An unclassified Clostridia UCG-014, Streptobacillus, Comamonas, unclassified Lachnospiraceae, and Parvimonas were also identified as significantly different between groups when using only one of the normalization techniques. CONCLUSIONS: This is the first study designed specifically to compare the oral microbiome of adolescents who use alcohol with that of control participants. Our findings reveal distinct alcohol-related differences in microbial composition and taxon abundance, emphasizing the importance of understanding the impact on the oral microbiome of alcohol use during adolescence. Because the oral microbiome is malleable, this study provides foundational work for future prevention and intervention studies.

3.
Drug Alcohol Depend ; 257: 111254, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38457964

RESUMO

BACKGROUND: The objective of this multi-modal neuroimaging study was to identify neuroscience-informed treatment targets for adolescent alcohol use disorder (AUD) by examining potential neural alterations associated with adolescent alcohol use. METHODS: Adolescents (ages 17-19) who heavily used (n=49) or did not use alcohol (n=22) were recruited for a multi-modal neuroimaging protocol, including proton magnetic resonance spectroscopy within the dorsal anterior cingulate cortex (dACC) and an fMRI alcohol cue-reactivity task. The alcohol cue-reactivity task was analyzed across 11 a priori regions-of-interest (ROI), including the dACC, and in an exploratory whole-brain approach. Correlations were run between neurometabolite levels and alcohol cue-reactivity in the dACC. RESULTS: There were no significant group differences in absolute neurometabolite concentrations. Compared to the control group, the alcohol-using group exhibited heightened alcohol cue reactivity in the left amygdala ROI (p=0.04). The whole-brain approach identified higher alcohol cue reactivity in the alcohol-using group compared to controls in the amygdala and occipital regions, and lower reactivity in the parietal lobe. Whole-brain sex effects were noted, with females displaying higher reactivity regardless of group. No significant correlations were found between neurometabolite levels and alcohol cue-reactivity in the dACC. CONCLUSIONS: The null neurometabolic findings may be due to age, relatively low severity of alcohol use, and non-treatment-seeking status of the participants. Females showed overall higher reactivity to alcohol cues, indicating a sex effect regardless of alcohol use history. Higher amygdala reactivity in alcohol-using adolescents suggests that emotional processing related to alcohol cues may be a useful target for future adolescent AUD interventions.


Assuntos
Alcoolismo , Sinais (Psicologia) , Feminino , Humanos , Adolescente , Alcoolismo/diagnóstico por imagem , Alcoolismo/psicologia , Etanol , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neuroimagem , Imageamento por Ressonância Magnética/métodos
4.
Alcohol Clin Exp Res (Hoboken) ; 47(12): 2375-2385, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38151786

RESUMO

BACKGROUND: Accurate assessment of medication adherence is important for understanding pharmacotherapy outcomes across all phases of adolescent substance use disorder (SUD) clinical trials. The objective of this study was to describe and assess the pairwise concordance between three commonly used non-biological medication adherence assessment methods in adolescents who use alcohol to inform the selection of medication adherence measures for use in future youth SUD trials. METHODS: Participants (N = 32, 17-19-years-old) took N-acetylcysteine and placebo, in a randomized cross-over design, for 10 days each. Medication adherence was assessed (20 days total) via pill count, medication videos submitted twice daily, and the Medication Event Monitoring System (MEMS®). Lin's Concordance Correlation Coefficient (CCC) assessed concordance and Bland-Altman plots are reported. Linear mixed-effects models with main effects of medication, treatment block (first medication, second medication), and sequence were also run. RESULTS: Medication videos yielded the lowest (64%) and pill count yielded the highest (89%) adherence estimates. CCC values indicated poor correspondence, except between pill count and MEMS. The Bland-Altman plots showed good pairwise agreement between all methods. Linear mixed-effects models indicated a difference between the first and second cross-over medication, with adherence estimates being lower for the second medication, regardless of whether it was N-acetylcysteine or placebo. CONCLUSIONS: The study yielded important and practical information. First, incorporating more than one method of adherence assessment may capture estimated floor and ceiling adherence in the absence of a biological marker. This is particularly relevant for remote or hybrid studies where bio-marker collection is challenging. Selection of the assessment methods will depend on study goals. Second, the continuation of medication adherence research can benefit each phase of clinical trials and inform rigorous pharmacotherapy evaluation.

5.
Neuropsychopharmacology ; 48(8): 1184-1193, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36878996

RESUMO

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.


Assuntos
Acetilcisteína , Alcoolismo , Humanos , Adolescente , Feminino , Masculino , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico , Alcoolismo/diagnóstico por imagem , Alcoolismo/tratamento farmacológico , Alcoolismo/metabolismo , Consumo de Bebidas Alcoólicas/metabolismo , Etanol , Método Duplo-Cego , Glutationa , Ácido gama-Aminobutírico , Ácido Glutâmico/metabolismo
6.
Drug Alcohol Depend ; 244: 109798, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36774808

RESUMO

BACKGROUND: Most adult daily smokers try their first cigarette during adolescence. Attention-Deficit Hyperactivity Disorder (ADHD) in adolescents is associated with increased risk for cigarette smoking. The impact of ADHD symptoms on smoking cessation among adolescents has been less well-studied. The present secondary data analysis from a clinical trial of varenicline examined ADHD symptoms as a moderator of smoking cessation in adolescents and young adults. METHODS: The double-blind, placebo-controlled trial included treatment-seeking daily cigarette smokers ages 14 - 21 (N = 157) randomized to receive a 12-week course of varenicline or placebo, added to weekly smoking cessation counseling. At pre-treatment assessment, participants were administered a self-report measure of ADHD symptoms, the ADHD - Rating Scale (ADHD-RS). High (≥5) versus low (<5) and continuous ADHD-RS symptom counts in both hyperactive/impulsive (HI) and inattention (IA) domains were examined as predictors of smoking outcomes. RESULTS: Participants with high IA symptoms at baseline were less likely to achieve 7-day point prevalence abstinence (PPA) at weekly visits (p = .001) during active treatment and end-of-treatment (p = .002) compared to those with low IA symptoms. In contrast, high HI symptoms did not predict differences in 7-day PPA or end-of-treatment abstinence versus low symptoms (p's ≥ .07). These findings were not modified by varenicline versus placebo treatment assignment. CONCLUSIONS: ADHD IA symptoms were associated with poorer cessation outcomes among adolescent smokers. These findings warrant additional investigation into how ADHD symptoms may be accounted for in smoking cessation interventions for adolescents and young adults.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Fumar Cigarros , Abandono do Uso de Tabaco , Humanos , Adolescente , Adulto Jovem , Adulto , Vareniclina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Resultado do Tratamento , Método Duplo-Cego
7.
J Patient Saf Risk Manag ; 27(6): 263-267, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36483177

RESUMO

Bacteriophages (phages) are naturally occurring viruses of bacteria that have a long history of use as antimicrobials, known as phage therapy. The antibiotic resistance crisis has driven renewed interest in phage therapy, which has been used on an unlicensed compassionate basis in various Western contexts. The option to use unlicensed medicines exists to allow clinicians to respond to genuine clinical needs arising in their own patients. However, in the UK some clinicians may, in the absence of suitable patients of their own, seek to transfer patients from other NHS trusts into their own Trust. This article sets out why patient transfer is not necessary and the practical, ethical and legal reasons why patients should not be transferred between NHS Trusts for phage therapy. Phage preparations should always be transported to the patient and the patient treated in the Trust in which they would have received care in the absence of phage. We enclose suggested best practice guidelines for adoption across the UK that will protect patient safety and safeguard clinicians and Trusts from potential litigation.

8.
J Am Acad Child Adolesc Psychiatry ; 61(9): 1155-1167, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35367322

RESUMO

OBJECTIVE: Maternal prenatal stress and mood symptoms are associated with risk for child psychopathology. Within the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies (ECHO-FGS), a racially and ethnically diverse cohort, we studied associations between prenatal stress and depressive symptoms with child neurobehavior, and potential mediation by fetal growth velocity (FGV) in low-risk pregnancies. METHOD: For 730 mother-child pairs, we had serial ultrasound measurements, self-reports of prenatal stress and depression, observations of child executive functions and motor skills from 4 to 8 years, and maternal reports of child psychiatric problems. We tested associations between prenatal stress and depressive symptoms with child neurobehavior in regression analyses, and associations with FGV in mixed effect models. Post hoc we tested severity of prenatal symptoms; FGV at 25th, 50th, and 75th percentiles; and moderation by biological sex and by race and ethnicity. RESULTS: Prenatal stress and depressive symptoms were associated with child psychiatric problems, and prenatal depressive symptoms with decrements in executive functions and motor skills, especially in biological male children. Neither prenatal stress nor depressive symptoms were associated with FGV. CONCLUSION: In one of the largest cohorts with observed child outcomes, and the first with broad representation of race and ethnicity in the United States, we found that prenatal stress and depressive symptoms were associated with greater reports of child psychiatric symptoms. Only prenatal depressive symptoms were associated with observed decrements in cognitive abilities, most significantly in biological male children. Stress during low-risk pregnancies may be less detrimental than theorized. There was no mediation by FGV. These findings support the need to attend to even small changes in prenatal distress, as these may have long-lasting implications.


Assuntos
Transtornos Mentais , Efeitos Tardios da Exposição Pré-Natal , Criança , Estudos de Coortes , Depressão , Feminino , Desenvolvimento Fetal , Humanos , Masculino , Mães/psicologia , National Institute of Child Health and Human Development (U.S.) , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Estados Unidos
9.
Pediatr Obes ; 17(8): e12911, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35289494

RESUMO

BACKGROUND: The prevalence of obesity in US children has more than tripled in the past 40 years; hence, it is critical to identify potentially modifiable factors that may mitigate the risk. OBJECTIVES: To examine the association between maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and child adiposity as measured by BMI, waist circumference and percent body fat in a racial-ethnically diverse cohort. METHODS: In a prospective cohort study of healthy women without chronic disease, we examined the association between pre-pregnancy BMI, GWG and child adiposity. Children ages 4-8 years (n = 816) in the Environmental Influences on Child Health Outcomes-NICHD Fetal Growth Studies were assessed. Trained study staff ascertained maternal pre-pregnancy BMI, GWG and child adiposity. RESULTS: The odds of child obesity (≥95th BMI percentile) increased independently for each unit increase in maternal pre-pregnancy BMI [OR = 1.12 (95% CI: 1.08, 1.17)] and for each 5-kg increase in GWG [OR = 1.25 (95% CI: 1.07, 1.47)]. The odds of child waist circumference (≥85th percentile) also increased independently for pre-pregnancy BMI [OR = 1.09 (95% CI: 1.05, 1.12)] and GWG [OR = 1.18 (95% CI: 1.04, 1.34)]. CONCLUSIONS: Maternal pre-pregnancy BMI and GWG were each independently and positively associated with child obesity and high child waist circumference.


Assuntos
Ganho de Peso na Gestação , Obesidade Infantil , Adiposidade , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Obesidade Infantil/epidemiologia , Gravidez , Estudos Prospectivos , Fatores de Risco , Aumento de Peso
10.
Health Justice ; 10(1): 7, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35175451

RESUMO

BACKGROUND: The purpose of the study was to assess the prevalence of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and to determine whether TBI or PTSD is associated with an increase in general or violent criminal recidivism among a representative sample of released prisoners. In-person interviews were conducted with a stratified random sample of individuals incarcerated with the South Carolina Department of Corrections approximately 90 days prior to the prisoners' releases. In addition to a variety of items and scales, respondents were screened for TBI and were asked whether they had received a current diagnosis of PTSD. Data were merged with arrest data that provided measures of past criminal involvement and indicators of post-release recidivism (arrest). Arrests were coded as "general" for any arrest charge and "violent" for any violent offense charge. RESULTS: Survival analyses indicate that neither TBI nor PTSD predicts time to general recidivism. PTSD (p < 0.01) and age at first arrest (p < 0.01) are significant predictors for violent recidivism and TBI is non-significant at p = 0.09. Results from the negative binomial models indicate that TBI (p < 0.05) and PTSD (p < 0.05) are significantly associated with more post-release violent arrests, but not general arrests. CONCLUSIONS: TBI and PTSD were found to predict violent offending but not general criminal behavior. These findings demonstrate the need for prison officials to identify individuals with a history of TBI and PTSD and to develop appropriate interventions that could be provided during incarceration to reduce the post-release likelihood of violence.

11.
Child Adolesc Obes ; 5(1): 3-15, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35128342

RESUMO

INTRODUCTION: A few studies have identified childhood animal exposure as associated with adiposity, but results are inconsistent and differ in timing. METHODS: We conducted an observational cohort study of children ages 4-8 in the Environmental Influences on Child Health Outcomes [ECHO] study. The main exposure was having a dog in the home and/or regular contact with farm animals during the first year of life. Outcomes of interest were child BMI percentile (adjusted for gender and age) categorized as normal/underweight (<85th percentile), overweight (85th to <95th), and obese (≥95th), and percent fat mass (continuous). Associations were analyzed using multinomial logistic regression and multivariable linear regression, respectively, with and without multiple imputation. RESULTS: First year animal exposure occurred in 245 of 770 (31.8%) children. Children with early animal exposure had 0.53 (95% CI: 0.28, 0.997) times the odds of being in the obese BMI category compared to those exposed to animals after controlling for covariates: maternal pre-pregnancy BMI, race/ethnicity, reported child activity level, receiving food assistance, age child began daycare (<1 year vs 1+), exclusively breastfed x6 months, and NICU admission (n=721). Children with early animal exposure had, on average, 1.5% (95% CI: -3.0, -0.1) less fat mass than exposed children after adjustment for maternal BMI, race/ethnicity, activity, food assistance, breastfeeding, and maternal education (n=548). Multiple imputation did not alter either result. CONCLUSION: These results provide evidence that exposure to dogs or farm animals in the first year of life is associated with lower odds of obesity and lower percent fat mass in childhood.

12.
Environ Res ; 203: 111820, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34343551

RESUMO

Perfluoroalkyl substances (PFAS) are widely distributed suspected obesogens that cross the placenta. However, few data are available to assess potential fetal effects of PFAS exposure on children's adiposity in diverse populations. To address the data gap, we estimated associations between gestational PFAS concentrations and childhood adiposity in a diverse mother-child cohort. We considered 6 PFAS in first trimester blood plasma, measured using ultra-high-performance liquid chromatography with tandem mass spectrometry, collected from non-smoking women with low-risk singleton pregnancies (n = 803). Body mass index (BMI), waist circumference (WC), fat mass, fat-free mass, and % body fat were ascertained in 4-8 year old children as measures of adiposity. We estimated associations of individual gestational PFAS with children's adiposity and overweight/obesity, adjusted for confounders. There were more non-Hispanic Black (31.7 %) and Hispanic (42.6 %) children with overweight/obesity, than non-Hispanic white (18.2 %) and Asian/Pacific Islander (16.4 %) children (p < 0.0001). Perfluorooctane sulfonate (PFOS; 5.3 ng/mL) and perfluorooctanoic acid (2.0 ng/mL) had the highest median concentrations in maternal blood. Among women without obesity (n = 667), greater perfluoroundecanoic acid (PFUnDA) was associated with their children having higher WC z-score (ß = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (ß = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (ß = 0.01 %; 95%CI: 0.003, 0.01; p = 0.004), although the association of PFUnDA with fat mass attenuated at the highest concentrations. Among women without obesity, the associations of PFAS and their children's adiposity varied significantly by self-reported race-ethnicity, although the direction of the associations was inconsistent. In contrast, among the children of women with obesity, greater, PFOS, perfluorononanoic acid, and perfluorodecanoic acid concentrations were associated with less adiposity (n = 136). Our results suggest that specific PFAS may be developmental obesogens, and that maternal race-ethnicity may be an important modifier of the associations among women without obesity.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Adiposidade , Criança , Pré-Escolar , Estudos de Coortes , Poluentes Ambientais/toxicidade , Feminino , Fluorocarbonos/toxicidade , Humanos , Obesidade/epidemiologia , Gravidez
13.
Child Obes ; 18(3): 178-187, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34669515

RESUMO

Background: Studies suggest breastfeeding lowers obesity risk in childhood, but generalizability of existing evidence is limited. We examined associations of breastfeeding with childhood overweight, obesity, and percentage body fat, in a racially diverse maternal-child cohort. Methods: This cross-sectional study included 823 children, ages 4-8 years, enrolled in the Environmental Exposures and Child Health Outcomes (ECHO) cohort, a subset of the National Institute of Child Health and Human Development Fetal Growth Studies cohort. Logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for overweight [BMI (kg/m2) 85th to <95th percentile] and obesity (BMI ≥95th percentile) in relation to breastfeeding including duration of exclusive and total breastfeeding. Linear regression was used to evaluate association between breastfeeding and percentage body fat measured by bioelectrical impedance analysis. Results: Fifty-two percent of children were male, 32% non-Hispanic Black, 29% Hispanic, 27% non-Hispanic White, and 13% Asian; 16% were overweight and 13% obese. Six months of exclusive breastfeeding, compared with no breastfeeding, was associated with 60% lower odds of obesity (95% CI 0.18-0.91) adjusting for age, gender, race, socioeconomic status, maternal BMI, and child's activity. Percentage body fat was inversely associated with breastfeeding duration. For none, <6, and ≥6 months of exclusive breastfeeding, adjusted mean percentage body fat was 16.8, 14.5, and 13.4, respectively. Results did not differ by gender, race/ethnicity, or maternal BMI status. Conclusions: Exclusive breastfeeding for the first 6 months of life is inversely and significantly associated with obesity and percentage body fat at ages 4-8 years. These findings support current breastfeeding guidelines.


Assuntos
Aleitamento Materno , Obesidade Infantil , Composição Corporal , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Sobrepeso , Obesidade Infantil/epidemiologia , Fatores de Risco
14.
Br J Clin Pharmacol ; 88(3): 1115-1142, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34390022

RESUMO

AIMS: We profile the lack of specific regulation for direct-to-patient postal supply (DTP) of clinical trial medications (investigational medicinal products, IMPs) calling for increased efficiency of patient-centred multi-country remote clinical trials. METHODS: Questionnaires emailed to 28 European Economic Area (EEA) Medical Product Licensing Authorities (MPLAs) and Swissmedic MPLA were analysed in 2019/2020. The questionnaire asked whether DTP of IMPs was legal, followed by comparative legal analysis profiling relevant national civil and criminal liability provisions in 30 European jurisdictions (including The Netherlands), finally summarising accessible COVID-19-related guidance in searches of 30 official MPLA websites in January 2021. RESULTS: Twenty MPLAs responded. Twelve consented to response publication in 2021. DTP was not widely authorised, though different phrases were used to explain this. Our legal review of national laws in 29 EEA jurisdictions and Switzerland did not identify any specific sanctions for DTP of IMPs; however, we identified potential national civil and criminal liability provisions. Switzerland provides legal clarity where DTP of IMPs is conditionally legal. MPLA webpage searches for COVID-19 guidance noted conditional acceptance by 19 MPLAs. CONCLUSIONS: Specific national legislation authorising DTP of IMPs, defining IMP categories, and conditions permitting the postage and delivery by courier in an EEA-wide clinical trial, would support innovative patient-centred research for multi-country remote clinical trials. Despite it appearing more acceptable to do this between EU Member States, provided each EU MPLA and ethics board authorises it, temporary Covid-19 restrictions in national Good Clinical Practice (GCP) guidance discourages innovative research into the safety and effectiveness of clinical trial medications.


Assuntos
Drogas em Investigação , Legislação de Medicamentos , Ensaios Clínicos como Assunto , Drogas em Investigação/uso terapêutico , União Europeia , Humanos , Tratamento Farmacológico da COVID-19
15.
Artigo em Inglês | MEDLINE | ID: mdl-33396261

RESUMO

Asthma in children poses a significant clinical and public health burden. We examined the association between reported neighborhood traffic (a proxy for traffic-related air pollution) and asthma among 855 multi-racial children aged 4-8 years old who participated in the Environmental Influences on Child Health Outcomes (ECHO) cohort. We hypothesized that high neighborhood traffic density would be associated with the prevalence of asthma. Asthma/asthma-like symptoms (defined as current and/or past physician diagnosed asthma, past wheezing, or nighttime cough or wheezing in the past 12 months) was assessed by parental report. The relationship between neighborhood traffic and asthma/asthma-like symptoms was assessed using logistic regression. The prevalence of asthma/asthma-like symptoms among study participants was 23%, and 15% had high neighborhood traffic. Children with significant neighborhood traffic had a higher odds of having asthma/asthma-like symptoms than children without neighborhood traffic [adjusted OR = 2.01 (95% CI: 1.12, 3.62)] after controlling for child's race-ethnicity, age, sex, maternal education, family history of asthma, play equipment in the home environment, public parks, obesity and prescribed asthma medication. Further characterization of neighborhood traffic is needed since many children live near high traffic zones and significant racial/ethnic disparities exist.


Assuntos
Asma , Disparidades nos Níveis de Saúde , Características de Residência , Poluição Relacionada com o Tráfego , Asma/epidemiologia , Asma/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Humanos , Sons Respiratórios , Estados Unidos
16.
J Emerg Trauma Shock ; 12(3): 185-191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543641

RESUMO

BACKGROUND: A large number of patients live with undiagnosed HIV and/or hepatitis C despite broadened national screening guidelines. European studies, however, suggest many patients falsely believe they have been screened during a prior hospitalization. This study aims to define current perceptions among trauma and emergency general surgery (EGS) patients regarding HIV and hepatitis C screening practices. METHODS: Prospective survey administered to adult (>18 years old) acute care surgery service (trauma and EGS) patients at a Level 1 academic trauma center. The survey consisted of 13 multiple choice questions: demographics, whether admission tests included HIV and hepatitis C at index and prior hospital visits and whether receiving no result indicated a negative result, prior primary care screening. Response percentages calculated in standard fashion. RESULTS: One hundred and twenty-five patients were surveyed: 80 trauma and 45 EGS patients. Overall, 32% and 29.6% of patients believed they were screened for HIV and hepatitis C at admission. There was no significant difference in beliefs between trauma and EGS. Sixty-eight percent of patients had a hospital visit within 10 years of these, 49.3% and 44.1% believe they had been screened for HIV and hepatitis C. More EGS patients believed they had a prior screen for both conditions. Among patients who believed they had a prior screen and did not receive any results, 75.9% (HIV) and 80.8% (hepatitis C) believed a lack of results meant they were negative. Only 28.9% and 23.6% of patients had ever been offered outpatient HIV and hepatitis C screening. CONCLUSIONS: A large portion of patients believe they received admission or prior hospitalization HIV and/or hepatitis C screening and the majority interpreted a lack of results as a negative diagnosis. Due to these factors, routine screening of trauma/EGS patients should be considered to conform to patient expectations and national guidelines, increase diagnosis and referral for medical management, and decrease disease transmission.

17.
J Trauma Acute Care Surg ; 86(4): 642-650, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30633100

RESUMO

BACKGROUND: Previous work demonstrated diagnostic delays in blunt small bowel perforation (SBP) with increased mortality and inability of scans to reliably exclude the diagnosis. We conducted a follow-up multicenter study to determine if these challenges persist 15 years later. METHODS: We selected adult cases with blunt injury, International Classification of Diseases, Ninth Revision or current procedural terminology (CPT) indicating small bowel surgery, no other major injury and at least one abdominal computed tomography (CT) within initial 6 hours. Controls had blunt trauma with abdominal CT but not SBP. After institutional review board approval, data from each center were collected and analyzed. RESULTS: Data from 39 centers (from October 2013 to September 2015) showed 127,919 trauma admissions and 94,743 activations. Twenty-five centers were Level 1. Centers submitted 77 patients (mean age, 39; male, 68%; mean length of stay, 11.3 days) and 131 controls (mean age, 44; male, 64.9%; length of stay, 3.6 days). Small bowel perforation cases were 0.06% of admissions and 0.08% of activations. Mean time to surgery was 8.7 hours (median, 3.7 hours). Initial CT showed free air in 31 cases (43%) and none in controls. Initial CT was within normal in three cases (4.2%) and 84 controls (64%). Five cases had a second scan; two showed free air (one had an initial normal scan). One death occurred among the patients (mortality, 1.4%; and time to surgery, 16.9 hours). Regression analysis showed sex, abdominal tenderness, distention, peritonitis, bowel wall thickening, free fluid, and contrast extravasation were significantly associated with SBP. CONCLUSIONS: Blunt SBP remains relatively uncommon and continues to present a diagnostic challenge. Trauma centers have shortened time to surgery with decreased case mortality. Initial CT scans continue to miss a small number of cases with potentially serious consequences. We recommend (1) intraperitoneal abnormalities on CT scan should always evoke high suspicion and (2) strong consideration of additional diagnostic/therapeutic intervention by 8 hours after arrival in patients who continue to pose a clinical challenge. LEVEL OF EVIDENCE: Observational study, level III.


Assuntos
Perfuração Intestinal/cirurgia , Intestino Delgado/lesões , Ferimentos não Penetrantes/cirurgia , Adulto , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/mortalidade , Intestino Delgado/cirurgia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/mortalidade
18.
J Trauma Acute Care Surg ; 85(5): 977-983, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30358756

RESUMO

BACKGROUND: In the United States, millions of patients are living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) (0.44% and 1.5%) and many are currently undiagnosed. Because highly effective treatments are now available, early identification of these patients is extremely important to achieve improved clinical outcomes. Prior data and trauma-associated risk factors suggest a higher prevalence of both diseases in the trauma population. We hypothesized that a screening program could be successfully initiated among trauma activation patients and that a referral and linkage-to-care program could be developed. METHODS: Hepatitis C virus and HIV screening tests were added to standard trauma activation laboratory orders at an academic Level I Trauma Center. Confirmatory viral load was sent when indicated. Patients with positive results were educated about their disease and referred to disease-specific follow-up. Data were collected prospectively from January 1, 2016, until June 30, 2017. Total and new diagnosis, referral rates, and linkage-to-care rates were analyzed. RESULTS: One thousand eight hundred ninety-eight patients arrived as trauma activations. One thousand two hundred seventeen (64.1%) patients were screened (Level A, 75.6%; Level B, 60.2%). Seven percent of the screened patients were initially positive, and 5.5% were confirmed positive. Rates of both HIV (1.1%) and HCV (4.4%) were almost triple the national average. Overall, 3.3% screened positive for a new diagnosis. For HCV, the rate of new diagnosis was twice the national average (3%). Over 85% of all cases were referred for follow-up, and the combined linkage-to-care rate was 43.3%. CONCLUSION: The majority of patients were screened and referred for follow-up, indicating successful implementation of our trauma screening program. Routine screening of trauma patients should be considered to increase diagnosis rate, increase linkage-to-care rates, and decrease disease transmission. These screening efforts would help bridge the health care gap that exists in the trauma population due to lower insurance rates and limited access to primary care. LEVEL OF EVIDENCE: Therapeutic/Care management, level III.


Assuntos
Infecções por HIV/diagnóstico , Hepatite C/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Ferimentos e Lesões/diagnóstico , Testes Diagnósticos de Rotina , Diagnóstico Precoce , Humanos , Educação de Pacientes como Assunto , Centros de Traumatologia/estatística & dados numéricos
19.
J Intensive Care Med ; 33(7): 424-429, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27837045

RESUMO

OBJECTIVE: Stress gastropathy is a rare complication of the intensive care unit stay with high morbidity and mortality. There are data that support the concept that patients tolerating enteral nutrition have sufficient gut blood flow to obviate the need for prophylaxis; however, no robust studies exist. This study assesses the incidence of clinically significant gastrointestinal bleeding in surgical trauma intensive care unit (STICU) patients at risk of stress gastropathy secondary to mechanical ventilation receiving enteral nutrition without pharmacologic prophylaxis. DESIGN: A retrospective cohort study of records from 2008 to 2013. SETTING: Adult patients in a single-center STICU were included. PATIENTS: Patients were included if they received full enteral nutrition while on mechanical ventilation. Exclusion criteria were coagulopathy, glucocorticoid use, prior-to-admission acid-suppressive therapy use, direct trauma or surgery to the stomach, failure to tolerate goal enteral nutrition, orders to allow natural death, and deviation from the intervention. INTERVENTION: Pharmacologic stress ulcer prophylaxis was discontinued once enteral nutrition was providing full caloric requirements for patients requiring mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: A total of 200 patients were included. The median age was 42 years, 83.0% were male, and 96.0% were trauma patients. The incidence of clinically significant gastrointestinal bleeding was 0.50%, with a subset analysis of traumatic brain injury patients yielding an incidence of 0.68%. Rates of ventilator-associated pneumonia and Clostridium difficile infection were low at 1.0 case/1000 ventilator days and 0.2 events/1000 patient days, respectively. Hospital all-cause mortality was 2.0%. Cost savings of US$121/patient stay were realized. CONCLUSION: Stress gastropathy is rare in this population. Surgical and trauma patients at risk for stress gastropathy did not benefit from continued pharmacologic prophylaxis once they tolerated enteral nutrition. Pharmacologic prophylaxis may safely be discontinued in this patient population. Further investigation is warranted to determine whether continued prophylaxis after attaining enteral feeding goals is detrimental.


Assuntos
Estado Terminal/terapia , Nutrição Enteral , Hemorragia Gastrointestinal/prevenção & controle , Úlcera Gástrica/prevenção & controle , Estresse Psicológico/fisiopatologia , Adulto , Feminino , Hemorragia Gastrointestinal/etiologia , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , Úlcera Gástrica/etiologia , Estresse Psicológico/complicações
20.
Am Surg ; 83(11): 1308-1314, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29183537

RESUMO

Trauma care has traditionally focused on prehospital and hospital settings, yet many injured patients report emotional distress in the postacute care setting, which is known to impair recovery. The objective of this study was to assess postdischarge emotional recovery and communication preferences. An observational cohort of 100 adult patients from our Level 1 Trauma Center was surveyed one to two months postdischarge. Among those employed preinjury, 44 per cent had not returned to work. Nearly half screened positive for emotional issues (posttraumatic stress disorder, depression, and/or psychological distress); of these, only 35 per cent considered getting professional help and only 10 per cent received help. The barrier most cited (58%) was cost; 42 per cent did not know how or where to get help. Most participants responded "no" or "I don't know" when asked if they had received information about coping with negative emotions after injury and how to seek help from a doctor to address these emotions. Two-thirds preferred to receive such information via phone call from a health care provider or by text. Eighty-nine per cent owned a cellphone. Our trauma systems are failing to provide comprehensive care or look at the ultimate outcomes of our patients, yet modern technology could provide needed resources to patients in novel ways.


Assuntos
Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Idoso , Ansiedade/etiologia , Meios de Comunicação/estatística & dados numéricos , Depressão/etiologia , Emoções , Feminino , Comportamento de Busca de Ajuda , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Avaliação das Necessidades , Gravidez , Psicometria , Recuperação de Função Fisiológica , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos Relacionados ao Uso de Substâncias/etiologia , Centros de Traumatologia , Adulto Jovem
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