Transforming Possible Risk Into Certain Harm: A Critical Interpretive Synthesis of the Literature on Perinatal Cannabis Use

Substance use in pregnancy has been a prominent public health concern for the last several decades. Since the legalization of cannabis in Canada and across several American states, cannabis use during pregnancy has gained considerable public health, scientific, and media attention. This critical interpretive synthesis explores how the problem of cannabis use in pregnancy is constructed in the scientific literature and illuminates clinical, social, and political responses this construction engenders. The state of empirical evidence regarding the impact of perinatal cannabis use is fraught; a number of studies, of variable quality, have found no associations between cannabis use and adverse neonatal outcomes, while others have found cannabis to be associated with low birthweight and prematurity among other risks. Despite the inconsistent nature of the evidence base, the literature is underpinned by two important assumptions: prenatal cannabis exposure is an asocial phenomenon that can be disentangled from the social determinants of health, and cannabis exposure has detrimental effects on fetal and neonatal health. These assumptions shape indicators of signal and noise in the data by influencing the significance ascribed to particular findings, producing patterns of data interpretation that ultimately transform evidence of potential harms into certain risks and creates the mirage of a cohesive, unambiguous evidence base. We argue that the way that cannabis use in pregnancy is framed as a scientific and public health problem in the literature contributes to the stigmatization of pregnant people who use substances. We caution that failure to consider the interplay between environment, resources and other social determinants of health may ultimately cause undue harm to families and foreclose opportunities for investments that may promote health and well-being

Pulmonary function of a paediatric cohort of patients with postinfectious bronchiolitis obliterans. A long term follow-up

Background: Postinfectious bronchiolitis obliterans (BO) is a chronic respiratory disease that usually follows a severe adenovirus infection. Objective: To determine the evolution of pulmonary function and clinical outcome of children with postinfectious BO during childhood. Methods: The study included patients diagnosed with postinfectious BO in whom at least two spirometries were performed within a minimum interval of 3 months. Results: 46 met the inclusion criteria. The mean (±SD) follow-up period was 12.5 (±3.5) years. 197 spirometries and 41 plethysmographies were performed. Initial (9±3 years old) lung function was as follows (z score, mean±SD): forced vital capacity (FVC) - 3.8±1; forced expiratory volume in 1 s (FEV1) -4.4±1; FEV1/FVC -2.2±1; forced expiratory flow (FEF)25-75 -3.7±1; total lung capacity (TLC) 120±26%; residual volume (RV) 309±108%; and RV/TLC 55±13. During childhood, FVC and FEV1 increased by a mean of 11%/year (95% CI 9.3% to 12.6%; p\u3c0.0001) and 9%/year (95% CI 7.7% to 10.2%; p\u3c0.0001), and the FEV1/FVC ratio decreased by 1.9%/year (95% CI 1% to 2.8; p\u3c0.001). The z score for FVC, FEV1 and FEV1/FVC decreased by 0.07 z score/year (95% CI 0.1 to 0.01; p\u3c0.05), 0.09 z score/year (95% CI 0.1 to 0.05; p\u3c0.01) and 0.04 z score/year (95% CI 0.09 to 0.001; p\u3c0.02), respectively. During the follow-up period, 69% of patients required at least one hospital readmission and five required mechanical ventilation. Nine patients developed a thoracic deformity, and seven whose bronchiectasis did not respond to clinical treatment underwent a lobectomy. Conclusions: After a 12 year follow-up period, pulmonary function remained severely impaired, showing an obstructive pattern with air trapping that slowly improved during childhood. An unequal growth of lung parenchyma over the airways suggests dysinaptic growth. Patients required frequent readmission due to recurrent respiratory infections, and hypoxaemia improved slowly over time

Pulmonary function of a paediatric cohort of patients with postinfectious bronchiolitis obliterans. A long term follow-up

BACKGROUND: Postinfectious bronchiolitis obliterans (BO) is a chronic respiratory disease that usually follows a severe adenovirus infection. OBJECTIVE: To determine the evolution of pulmonary function and clinical outcome of children with postinfectious BO during childhood. METHODS: The study included patients diagnosed with postinfectious BO in whom at least two spirometries were performed within a minimum interval of 3 months. RESULTS: 46 met the inclusion criteria. The mean (±SD) follow-up period was 12.5 (±3.5) years. 197 spirometries and 41 plethysmographies were performed. Initial (9±3 years old) lung function was as follows (z score, mean±SD): forced vital capacity (FVC) -3.8±1; forced expiratory volume in 1 s (FEV1) -4.4±1; FEV1/FVC -2.2±1; forced expiratory flow (FEF)(25-75) -3.7±1; total lung capacity (TLC) 120±26%; residual volume (RV) 309±108%; and RV/TLC 55±13. During childhood, FVC and FEV1 increased by a mean of 11%/year (95% CI 9.3% to 12.6%; p<0.0001) and 9%/year (95% CI 7.7% to 10.2%; p<0.0001), and the FEV1/FVC ratio decreased by 1.9%/year (95% CI 1% to 2.8; p<0.001). The z score for FVC, FEV1 and FEV1/FVC decreased by 0.07 z score/year (95% CI 0.1 to 0.01; p<0.05), 0.09 z score/year (95% CI 0.1 to 0.05; p<0.01) and 0.04 z score/year (95% CI 0.09 to 0.001; p<0.02), respectively. During the follow-up period, 69% of patients required at least one hospital readmission and five required mechanical ventilation. Nine patients developed a thoracic deformity, and seven whose bronchiectasis did not respond to clinical treatment underwent a lobectomy. CONCLUSIONS: After a 12 year follow-up period, pulmonary function remained severely impaired, showing an obstructive pattern with air trapping that slowly improved during childhood. An unequal growth of lung parenchyma over the airways suggests dysinaptic growth. Patients required frequent readmission due to recurrent respiratory infections, and hypoxaemia improved slowly over time.Fil: Colom, Alejandro J.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Maffey, Alberto Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Garcia Bournissen, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Teper, Alejandro Manuel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentin

Predisposition to epilepsy - Does the ABCB1 gene play a role?

We performed a meta-analysis to evaluate the association between ABCB1 C3435T polymorphisms and the prevalence of epilepsy, including all relevant human studies (until June 2009), in which patients with or without epilepsy had undergone genotyping for the ABCB1 gene. Odds ratios (ORs) were calculated using a random effects model. We identified 9 case-control studies that included a total of 3,996 patients (2,454 with epilepsy and 1,542 nonepileptic subjects). No association was found between ABCB1 C3435T polymorphisms and the risk of having epilepsy (odds ratio 1.07, 95% confidence interval 0.76-1.51; p = 0.34). ABCB1 genotyping for epileptic patients is not warranted. © 2010 International League Against Epilepsy

Pediatric Clinical Pharmacology Studies in Chagas Disease

Chagas disease is a neglected parasitic disease endemic in the Americas. It mainly affects impoverished populations and the acute phase of the infection mostly affects children. Many cases have also been detected in nonendemic countries as a result of recent migratory trends. The chronic phase is relatively asymptomatic, but 30% of patients with chronic infection eventually develop cardiac and digestive complications that commonly lead to death or disability. Only two drugs are available for the treatment of Chagas disease, benznidazole and nifurtimox. These drugs have been shown to be effective in the treatment of both acute and early chronic phases in children, but the pharmacokinetics of these drugs have never been studied in this population. We have set out to conduct a pharmacokinetics study of benznidazole in a pediatric population with Chagas disease. The results of this study are expected to allow better estimation of the optimal doses and schedule of pharmacotherapy for Chagas disease in children.Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científic

Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease.

Treatment of Chagas disease with nifurtimox requires age- and body weight-adjusted dosing, resulting in complex dosing instructions. Appropriate formulations are needed for precise and compliant dosing, especially in pediatric patients. We characterized the biopharmaceutical features of a standard nifurtimox 120-mg tablet and a 30-mg tablet developed to improve dose accuracy. Two open-label, randomized crossover studies were conducted in adult outpatients with Chagas disease. One study investigated whether 4 × 30-mg tablets and 1 × 120-mg tablet were bioequivalent and whether tablets can be administered as an aqueous slurry without affecting bioavailability. The second study investigated the effect of a high-calorie/high-fat diet versus fasting on the absorption of nifurtimox after a single 4 × 30-mg dose. Interventions were equivalent if the 90% confidence interval (CI) of their least-squares (LS) mean ratios for both AU

Optimization and biological validation of an in vitro assay using the transfected Dm28c/pLacZ Trypanosoma cruzi strain

There is an urgent need to develop safer and more effective drugs for Chagas disease, as the current treatment relies on benznidazole (BZ) and nifurtimox (NFX). Using the Trypanosoma cruzi Dm28c strain genetically engineered to express the Escherichia coli β-galactosidase gene, lacZ, we have adapted and validated an easy, quick and reliable in vitro assay suitable for high-throughput screening for candidate compounds with anti-T. cruzi activity. In vitro studies were conducted to determine trypomastigotes sensitivity to BZ and NFX from Dm28c/pLacZ strain by comparing the conventional labour-intensive microscopy counting method with the colourimetric assay. Drug concentrations producing the lysis of 50% of trypomastigotes (lytic concentration 50%) were 41.36 and 17.99 μM for BZ and NFX, respectively, when measured by microscopy and 44.74 and 38.94 μM, for the colourimetric method, respectively. The optimal conditions for the amastigote development inhibitory assay were established considering the parasite-host relationship (i.e. multiplicity of infection) and interaction time, the time for colourimetric readout and the incubation time with the β-galactosidase substrate. The drug concentrations resulting in 50% amastigote development inhibition obtained with the colourimetric assay were 2.31 μM for BZ and 0.97 μM for NFX, similar to the reported values for the Dm28c wild strain (2.80 and 1.5 μM, respectively). In summary, a colourimetric assay using the Dm28c/pLacZ strain of T. cruzi has been set up, obtaining biologically meaningful sensibility values with the reference compounds on both trypomastigotes and amastigotes forms. This development could be applied to high-throughput screening programmes aiming to identify compounds with anti-T. cruzi in vitro activity

Population pharmacokinetics of amikacin in neonatal intensive care unit patients

Background Amikacin treatment requires close monitoring of blood concentrations to increase the probability that levels achieved are both effective and safe. Aims We described population pharmacokinetics parameters of amikacin in newborns from a Neonatal Intensive Care Unit with suspected or documented sepsis. Methods A nonlinear mixed-effect model approach was used to analyse the data. Results Twenty seven neonates were enrolled. Final parameter estimates were: Ke(h-1)=0.232x(CR) Exp-0.85; V(mL/kg)=497. Conclusion Weight and serum creatinine are associated with neonatal amikacin volume of distribution and elimination constant rate, respectively. The presence of sepsis may decrease amikacin elimination, although this observation should be further explored. These results could help to individualize amikacin dosage for neonates

Validation of apolipoprotein A-1 and fibronectin fragments as markers of parasitological cure for congenital chagas disease in children treated with benznidazole

Background. No reliable tests or validated biomarkers exist to ensure parasitological cure following treatment of Chagas disease (CD) patients chronically infected with Trypanosoma cruzi. As seroreversion, the only marker of cure, happens more quickly in children, we investigated the correlation between previously identified biomarkers and seroreversion in children. Methods. Thirty CD children (age 1 month to 10 years) diagnosed as T. cruzi positive (time point S0) were treated with benznidazole (BZ) 5-8 mg/kg/d for 60 days. At least 2 serological tests were used to evaluate treatment efficacy from the end of treatment (S1) until seroreversion (S2). Thirty children (age 1 month to 10 years) and 15 adults were used as healthy controls (HCs). Immunoblot and a proteomic-based assay were used to validate previously identified fragments of apolipoprotein A-1 (ApoA1) and fibronectin (FBN) as CD biomarkers. Results. Correlation between seroreversion and absence of ApoA1 and FBN fragments by immunoblot was observed in 30/30 (100%) and 29/30 (96.6%) CD children, respectively. ApoA1 and FBN fragments were absent at the end of BZ treatment in 20/30 (66.6%) and 16/30 (53.3%) children, respectively. Absence of fragments in serum profiles was confirmed by mass spectrometry. Using intact protein analysis, a 28 109-Da protein identified as full-length ApoA1 by tandem mass spectrometry was detected in HC serum samples. Conclusions. These data confirm that ApoA1 and FBN fragments can discriminate between healthy and T. cruzi-infected samples. Correlation with seroreversion was shown for the first time; results suggest predictive capacity potentially superior to serology, making them potentially useful as surrogate biomarkers.Fil: Ruiz Lancheros, Elizabeth. National Reference Centre For Parasitology; CanadáFil: Rasoolizadeh, Asieh. National Reference Centre For Parasitology; CanadáFil: Chatelain, Eric. No especifíca;Fil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Moscatelli, Guillermo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Ndao, Momar. National Reference Centre For Parasitology; Canad

Estudios bioanalíticos en la farmacología del paciente coinfectado Chagas/HIV

En Argentina se estiman en 126.000 a las personas infectadas con HIV y en 1.600.000 a las infectadas con Trypanosoma cruzi y no es infrecuente en la práctica clínica el diagnostico de coinfección. Las reactivaciones por T. cruzi, como infecciones oportunistas tiene una mortalidad de entre 79 y 100%, indicando ser una situación de altísimo riesgo para el paciente. El tratamiento farmacológico tripanocida con Benznidazol (BNZ) en la fase crónica es una estrategia para reducir el riesgo de la reactivación en pacientes con HIV. Sin embargo, la información sobre la interacción del BNZ, con los medicamentos antirretrovirales es inexistente, escaso el conocimiento respecto de la cinética parasitaria y viral y su asociación con la clínica en los pacientes coinfectados. Objetivos y Metodología: Revalidar bioanalítica para medir BNZ en plasma y líquido céfalo raquídeo (LCR) mediante HPLC/UV/MS-MS, en presencia de antiretrovirales, y su adecuación como método multianalito para estudios farmacocinéticos y farmacológicos. Evaluar muestras de pacientes HIV seropositivos y Chagas en su etapa silenciosa y pacientes HIV inmunodeprimidos con Chagas reactivado, ambos bajo tratamiento con BNZ y comedicación antiretroviral. Resultados De muestras de 7 pacientes en distintos estadíos de la enfermedad: dos muestras de LCR presentaron valores de BNZ bajos (&lt; 1 μg/mL) y el resto presentó niveles no detectables. De las muestras de plasma cerca del 70% presentaron concentraciones por encima del valor asumido como tripanocida (2 μg/mL). La información generada y su vinculación con la clínica pretenden aportar a la mejora de los protocolos preventivos del tratamiento en pacientes HIV seropositivosFil: Fleitas, Ulises. Universidad Nacional de La PlataFil: Fernández, Marisa. Universidad Nacional de La PlataFil: Prospitti, Anabella. Universidad Nacional de La PlataFil: Marson, María Elena. Universidad Nacional de La PlataFil: Mastrantonio, Guido. Universidad Nacional de La PlataFil: Garcia Bournissen, Facundo. Universidad Nacional de La Plat