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1.
AAPS J ; 26(3): 43, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575754

RESUMO

Medication administration via enteral feeding tubes (EFT) is a necessary practice for patients unable to swallow oral dosage forms due to a medical condition or treatment that affects the ability to swallow or the function of the gastrointestinal tract. Off-label administration of oral drug products via EFT raises concerns for pharmaceutical sponsors, regulators, and healthcare practitioners (HCPs) because of the potential risks this practice introduces to both the patient and the caregiver. These risks can be mitigated by generating data-supported instructions that patients and HCPs can use to ensure safe and accurate administration of oral drug products via EFT. This commentary presents an industry perspective on the testing that should be conducted to enable development of product-specific instructions in the labeling to support or advise against administration of oral drug products via enteral feeding tube. The proposal outlined in this commentary takes a risk-based approach, addressing recommendations from both regulatory agencies as well as considerations for expanding this testing to address needs specific to neonatal and pediatric populations.


Assuntos
Nutrição Enteral , Intubação Gastrointestinal , Criança , Recém-Nascido , Humanos , Administração Oral , Preparações Farmacêuticas , Técnicas In Vitro
3.
Exp Physiol ; 109(1): 81-99, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656490

RESUMO

A metabotropic glutamate receptor coupled to phospholipase D (PLD-mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage to PLD activation are well established and indicate it is a highly atypical glutamate receptor. A receptor with the same pharmacology is present in spindle primary sensory terminals where its blockade can totally abolish, and its activation can double, the normal stretch-evoked firing. We report here the first identification of this PLD-mGluR protein, by capitalizing on its expression in primary mechanosensory terminals, developing an enriched source, pharmacological profiling to identify an optimal ligand, and then functionalizing it as a molecular tool. Evidence from immunofluorescence, western and far-western blotting indicates PLD-mGluR is homomeric GluK2, since GluK2 is the only glutamate receptor protein/receptor subunit present in spindle mechanosensory terminals. Its expression was also found in the lanceolate palisade ending of hair follicle, also known to contain the PLD-mGluR. Finally, in a mouse model with ionotropic function ablated in the GluK2 subunit, spindle glutamatergic responses were still present, confirming it acts purely metabotropically. We conclude the PLD-mGluR is a homomeric GluK2 kainate receptor signalling purely metabotropically and it is common to other, perhaps all, primary mechanosensory endings.


Assuntos
Fosfolipase D , Receptores de Glutamato Metabotrópico , Animais , Camundongos , Hipocampo/metabolismo , Terminações Nervosas/metabolismo , Fosfolipase D/metabolismo , Receptores de Glutamato/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo
4.
Sci Total Environ ; 912: 169353, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38104847

RESUMO

Soil microbial communities play a vital role in the biogeochemical cycling and ecological functioning of grassland, but may be affected by common land uses such as cattle grazing. Changes in microbial diversity and network complexity can affect key ecosystem functions such as nutrient cycling. However, it is not well known how microbial diversity and network complexity respond to grazing in the Northern Great Plains. Consequently, it is important to understand whether variation in grazing management alters the diversity and complexity of grassland microbial communities. We compared the effect of intensive adaptive multi-paddock (AMP) grazing and conventional grazing practices on soil microbial communities using 16S/ITS amplicon sequencing. Samples were collected from grasslands in 13 AMP ranches and 13 neighboring, conventional ranches located across the Canadian prairies. We found that AMP grazing increased fungal diversity and evenness, and led to more complex microbial associations. Acidobacteria, Actinobacteria, Gemmatimonadetes, and Bacteroidetes were keystone taxa associated with AMP grazing, while Actinobacteria, Acidobacteria, Proteobacteria, and Armatimonadetes were keystone taxa under conventional grazing. Besides overall grazing treatment effects, specific grazing metrics like cattle stocking rate and rest-to-grazing ratio affected microbial richness and diversity. Bacterial and fungal richness increased with elevated stocking rate, and fungal richness and diversity increased directly with the rest-to-grazing ratio. These results suggest that AMP grazing may improve ecosystem by enhancing fungal diversity and increasing microbial network complexity and connectivity.


Assuntos
Ecossistema , Microbiota , Animais , Bovinos , Humanos , Solo , Pradaria , Microbiologia do Solo , Redes Comunitárias , Canadá , Bactérias
5.
Cleft Palate Craniofac J ; : 10556656231207469, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37844605

RESUMO

OBJECTIVE: To assess the ability of a cleft-specific multi-site learning health network registry to describe variations in cleft outcomes by cleft phenotypes, ages, and treatment centers. Observed variations were assessed for coherence with prior study findings. DESIGN: Cross-sectional analysis of prospectively collected data from 2019-2022. SETTING: Six cleft treatment centers collected data systematically during routine clinic appointments according to a standardized protocol. PARTICIPANTS: 714 English-speaking children and adolescents with non-syndromic cleft lip/palate. INTERVENTION: Routine multidisciplinary care and systematic outcomes measurement by cleft teams. OUTCOME MEASURES: Speech outcomes included articulatory accuracy measured by Percent Consonants Correct (PCC), velopharyngeal function measured by Velopharyngeal Competence (VPC) Rating Scale (VPC-R), intelligibility measured by caregiver-reported Intelligibility in Context Scale (ICS), and two CLEFT-Q™ surveys, in which patients rate their own speech function and level of speech distress. RESULTS: 12year-olds exhibited high median PCC scores (91-100%), high frequency of velopharyngeal competency (62.50-100%), and high median Speech Function (80-91) relative to younger peers parsed by phenotype. Patients with bilateral cleft lip, alveolus, and palate reported low PCC scores (51-91%) relative to peers at some ages and low frequency of velopharyngeal competency (26.67%) at 5 years. ICS scores ranged from 3.93-5.0 for all ages and phenotypes. Speech Function and Speech Distress were similar across phenotypes. CONCLUSIONS: This exploration of speech outcomes demonstrates the current ability of the cleft-specific registry to support cleft research efforts as a source of "real-world" data. Further work is focused on developing robust methodology for hypothesis-driven research and causal inference.

6.
Ecol Evol ; 13(8): e10395, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37589042

RESUMO

Advanced computer vision techniques hold the potential to mobilise vast quantities of biodiversity data by facilitating the rapid extraction of text- and trait-based data from herbarium specimen digital images, and to increase the efficiency and accuracy of downstream data capture during digitisation. This investigation developed an object detection model using YOLOv5 and digitised collection images from the University of Melbourne Herbarium (MELU). The MELU-trained 'sheet-component' model-trained on 3371 annotated images, validated on 1000 annotated images, run using 'large' model type, at 640 pixels, for 200 epochs-successfully identified most of the 11 component types of the digital specimen images, with an overall model precision measure of 0.983, recall of 0.969 and moving average precision (mAP0.5-0.95) of 0.847. Specifically, 'institutional' and 'annotation' labels were predicted with mAP0.5-0.95 of 0.970 and 0.878 respectively. It was found that annotating at least 2000 images was required to train an adequate model, likely due to the heterogeneity of specimen sheets. The full model was then applied to selected specimens from nine global herbaria (Biodiversity Data Journal, 7, 2019), quantifying its generalisability: for example, the 'institutional label' was identified with mAP0.5-0.95 of between 0.68 and 0.89 across the various herbaria. Further detailed study demonstrated that starting with the MELU-model weights and retraining for as few as 50 epochs on 30 additional annotated images was sufficient to enable the prediction of a previously unseen component. As many herbaria are resource-constrained, the MELU-trained 'sheet-component' model weights are made available and application encouraged.

7.
Environ Toxicol Chem ; 42(12): 2614-2629, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37477462

RESUMO

Bioavailability models, for example, multiple linear regressions (MLRs) of water quality parameters, are increasingly being used to develop bioavailability-based water quality criteria for metals. However, models developed for the Northern Hemisphere cannot be adopted for Australia and New Zealand without first validating them against local species and local water chemistry characteristics. We investigated the applicability of zinc chronic bioavailability models to predict toxicity in a range of uncontaminated natural waters in Australia and New Zealand. Water chemistry data were compiled to guide a selection of waters with different zinc toxicity-modifying factors. Predicted toxicities using several bioavailability models were compared with observed chronic toxicities for the green alga Raphidocelis subcapitata and the native cladocerans Ceriodaphnia cf. dubia and Daphnia thomsoni. The most sensitive species to zinc in five New Zealand freshwaters was R. subcapitata (72-h growth rate), with toxicity ameliorated by high dissolved organic carbon (DOC) or low pH, and hardness having a minimal influence. Zinc toxicity to D. thomsoni (reproduction) was ameliorated by both high DOC and hardness in these same waters. No single trophic level-specific effect concentration, 10% (EC10) MLR was the best predictor of chronic toxicity to the cladocerans, and MLRs based on EC10 values both over- and under-predicted zinc toxicity. The EC50 MLRs better predicted toxicities to both the Australian and New Zealand cladocerans to within a factor of 2 of the observed toxicities in most waters. These findings suggest that existing MLRs may be useful for normalizing local ecotoxicity data to derive water quality criteria for Australia and New Zealand. The final choice of models will depend on their predictive ability, level of protection, and ease of use. Environ Toxicol Chem 2023;42:2614-2629. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Assuntos
Cladocera , Poluentes Químicos da Água , Animais , Modelos Lineares , Nova Zelândia , Concentração de Íons de Hidrogênio , Austrália , Compostos Orgânicos , Zinco/toxicidade , Água Doce , Poluentes Químicos da Água/toxicidade
8.
Pilot Feasibility Stud ; 9(1): 124, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461117

RESUMO

BACKGROUND: The Coronavirus (COVID-19) pandemic has exacerbated the risk for poor physical and mental health outcomes among vulnerable older adults. Multicomponent interventions could potentially prevent or reduce the risk of becoming frail; however, there is limited evidence about utilizing alternative modes of delivery where access to in-person care may be challenging. This randomized feasibility trial aimed to understand how a multicomponent rehabilitation program can be delivered remotely to vulnerable older adults with frailty during the pandemic. METHODS: Participants were randomized to either a multimodal or socialization arm. Over a 12-week intervention period, the multimodal group received virtual care at home, which included twice-weekly exercise in small group physiotherapy-led live-streamed sessions, nutrition counselling and protein supplementation, medication consultation via a videoconference app, and once-weekly phone calls from student volunteers, while the socialization group received only once-weekly phone calls from the volunteers. The RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework was used to evaluate the feasibility of the program. The main clinical outcomes were change in the 5-times sit-to-stand test (5 × STS) and Depression, Anxiety and Stress Scale (DASS-21) scores. The feasibility outcomes were analyzed using descriptive statistics and expressed as frequencies and mean percent with corresponding confidence intervals (CI). Analysis of covariance (ANCOVA) was used for the effectiveness component. RESULTS: The program enrolled 33% (n = 72) of referrals to the study (n = 220), of whom 70 were randomized. Adoption rates from different referral sources were community self-referrals (60%), community organizations (33%), and healthcare providers (25%). At the provider level, implementation rates varied from 75 to 100% for different aspects of program delivery. Participant's adherence levels included virtual exercise sessions 81% (95% CI: 75-88%), home-based exercise 50% (95% CI: 38-62%), protein supplements consumption 68% (95% CI: 55-80%), and medication optimization 38% (95% CI: 21-59%). Most participants (85%) were satisfied with the program. There were no significant changes in clinical outcomes between the two arms. CONCLUSION: The GERAS virtual frailty rehabilitation study for community-dwelling older adults living with frailty was feasible in terms of reach of participants, adoption across referral settings, adherence to implementation, and participant's intention to maintain the program. This program could be feasibly delivered to improve access to socially isolated older adults where barriers to in-person participation exist. However, trials with larger samples and longer follow-up are required to demonstrate effectiveness and sustained behavior change. TRIAL REGISTRATION: ClinicalTrials.gov NCT04500366. Registered August 5, 2020, https://clinicaltrials.gov/ct2/show/NCT04500366.

9.
Mol Pharm ; 20(1): 750-757, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36448927

RESUMO

Vaccine hesitancy and the occurrence of elusive variants necessitate further treatment options for coronavirus disease 2019 (COVID-19). Accumulated evidence indicates that clinically used hypertensive drugs, angiotensin receptor blockers (ARBs), may benefit patients by mitigating disease severity and/or viral propagation. However, current clinical formulations administered orally pose systemic safety concerns and likely require a very high dose to achieve the desired therapeutic window in the lung. To address these limitations, we have developed a nanosuspension formulation of an ARB, entirely based on clinically approved materials, for inhaled treatment of COVID-19. We confirmed in vitro that our formulation exhibits physiological stability, inherent drug activity, and inhibitory effect against SARV-CoV-2 replication. Our formulation also demonstrates excellent lung pharmacokinetics and acceptable tolerability in rodents and/or nonhuman primates following direct administration into the lung. Thus, we are currently pursuing clinical development of our formulation for its uses in patients with COVID-19 or other respiratory infections.


Assuntos
COVID-19 , Infecções Respiratórias , Animais , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Telmisartan , Sistema Renina-Angiotensina/fisiologia , SARS-CoV-2 , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções Respiratórias/tratamento farmacológico
10.
J Pediatric Infect Dis Soc ; 11(10): 448-451, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-35802023

RESUMO

An 11-month-old male infant with ascending paralysis had an unremarkable initial cerebrospinal fluid (CSF) analysis and imaging. Progressive neurological symptoms resulted in repeated CSF sampling, microscopy, and plasma microbial cell-free DNA next-generation sequencing analysis, that in combination with epidemiology, confirmed the diagnosis.


Assuntos
Angiostrongylus cantonensis , Ácidos Nucleicos Livres , Eosinofilia , Infecções por Strongylida , Lactente , Animais , Masculino , Humanos , Angiostrongylus cantonensis/genética , Infecções por Strongylida/líquido cefalorraquidiano , Infecções por Strongylida/complicações , Infecções por Strongylida/diagnóstico , Eosinofilia/diagnóstico , Paralisia/etiologia
11.
ACS Infect Dis ; 8(4): 825-840, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35263081

RESUMO

FDA-approved and emergency use-authorized vaccines using new mRNA and viral-vector technology are highly effective in preventing moderate to severe disease; however, information on their long-term efficacy and protective breadth against severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) is currently scarce. Here, we describe the durability and broad-spectrum VOC immunity of a prefusion-stabilized spike (S) protein adjuvanted with liquid or lyophilized CoVaccine HT in cynomolgus macaques. This recombinant subunit vaccine is highly immunogenic and induces robust spike-specific and broadly neutralizing antibody responses effective against circulating VOCs (B.1.351 [Beta], P.1 [Gamma], and B.1.617 [Delta]) for at least three months after the final boost. Protective efficacy and postexposure immunity were evaluated using a heterologous P.1 challenge nearly three months after the last immunization. Our results indicate that while immunization with both high and low S doses shorten and reduce viral loads in the upper and lower respiratory tract, a higher antigen dose is required to provide durable protection against disease as vaccine immunity wanes. Histologically, P.1 infection causes similar COVID-19-like lung pathology as seen with early pandemic isolates. Postchallenge IgG concentrations were restored to peak immunity levels, and vaccine-matched and cross-variant neutralizing antibodies were significantly elevated in immunized macaques indicating an efficient anamnestic response. Only low levels of P.1-specific neutralizing antibodies with limited breadth were observed in control (nonvaccinated but challenged) macaques, suggesting that natural infection may not prevent reinfection by other VOCs. Overall, these results demonstrate that a properly dosed and adjuvanted recombinant subunit vaccine can provide protective immunity against circulating VOCs for at least three months.


Assuntos
COVID-19 , SARS-CoV-2 , Adjuvantes Imunológicos , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Macaca , Vacinas de Subunidades Antigênicas
12.
J Pediatr Hematol Oncol ; 44(3): e756-e759, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34486555

RESUMO

The chromosome 8q21.11 deletion syndrome is an extremely rare genetic condition characterized by facial dysmorphic features, Peters anomaly and impaired intellectual development. We report a case of a 2-year-old female with chromosome 8q21.11-q21.2 microdeletion complicated by T-cell lymphoblastic lymphoma. Whole genome single-nucleotide polymorphism microarray detected an interstitial deletion of 8q21.11 to q.21.2, including 16 genes. Autopsy findings revealed a T-cell lymphoblastic lymphoma presenting as an anterior mediastinal mass, encroaching upon the aortic arch, left subclavian artery, left carotid bifurcation and trachea. The genes that may contribute to a neoplastic process are identified (PKIA, IL7, TPD52, PAG1, and FABP5) and discussed in this article.


Assuntos
Cromossomos Humanos Par 8 , Anormalidades do Olho , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteínas Adaptadoras de Transdução de Sinal , Pré-Escolar , Deleção Cromossômica , Cromossomos , Proteínas de Ligação a Ácido Graxo , Feminino , Humanos , Proteínas de Membrana , Linfócitos T
13.
J Environ Manage ; 303: 114263, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34906831

RESUMO

Grasslands are declining worldwide and are often impacted by industrial activities, including infrastructure development. Current best management practices for low-disturbance development on grasslands include the use of wooden access mats as temporary work platforms and roadways to mitigate soil compaction and rutting due to heavy traffic. We assessed the impacts of heavy traffic (TON), and the impacts of the same heavy equipment driven over top of access mats (AM), on soil physical, hydrological, and nutrient responses in sandy and loamy soils in the Dry Mixedgrass prairies over a 2-year period. We also assessed how the timing (early vs. late in the growing season) and duration (6 vs. 12 vs. 24 weeks) of AM and TON affected the same metrics. Compared to undisturbed soils, TON increased soil penetration resistance (15 cm depth) up to 93% in loamy and up to 101% in sandy soils, and decreased water infiltration rates from 53 to 71%, respectively. Notably, the negative impacts of TON on soil physical characteristics and hydrology were larger in sandy vs. loamy soils, and when moist soils were exposed to traffic early in the growing season. AMs were effective at mitigating soil compaction from industrial traffic when used on sandy soils. However, AM use increased the supply of total nitrogen and other plant macro- and micro-nutrients, particularly in soils subject to longer (12-24 wk) mat placement. Results indicate TON may have long-lasting effects on grassland (particularly sandy) soils, and that AM use represents an effective tool to mitigate traffic impacts. Further, early-season traffic should be avoided when soils are moist (whether with AM or not), and AMs should be placed on soils for limited durations (≤6 wk) to minimize potential nutrient losses.


Assuntos
Nitrogênio , Solo , Plantas , Estações do Ano , Água
14.
J Voice ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34969557

RESUMO

BACKGROUND: Vocal fold nodules are the most common etiology of chronic dysphonia in the pediatric population. Voice therapy is an effective first line of treatment, with increasing evidence supporting the use of telepractice in speech pathology. Despite this, there is limited data on its effectiveness in the pediatric population. The aim of this retrospective study was to investigate the feasibility and efficacy of telepractice in delivering voice therapy to children diagnosed with vocal fold nodules. METHODS: A retrospective review was conducted of patients treated with virtual voice therapy from April 2020 to June 2021. Patients were included if diagnosed with vocal fold nodules, 2-18 years of age, and completed therapy in a virtual format. Data includes demographics, Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) scores and pediatric Voice Handicap Index (pVHI) scores. RESULTS: Twenty-three children were included, 17 (74%) male and six (26%) female (with an age range of 2.4-9.9 years at the start of therapy). Prior to treatment, the average CAPE-V Overall Severity score was 37.9 (SD 13.8); the average posttreatment score was 22.4 (SD 10.2). The average pVHI total score prior to treatment was 26.3 (SD 12.1), with an average posttreatment score of 20.2 (SD 11.7). Patients who underwent virtual voice therapy had improved posttreatment CAPE-V severity scores than those prior to treatment (average difference = -15.5 points; 95% CI: -8.3 to -22.7; P < 0.001). An increased number of therapy sessions was associated with both higher initial CAPE-V severity scores (r = 0.72; P < 0.01) and a greater decrease in posttreatment CAPE-V scores (r = -0.55; P < 0.01). CONCLUSION: Virtual voice therapy may be feasible and efficacious in treating dysphonic children diagnosed with vocal fold nodules. Significant improvements were found in perceptual CAPE-V scores in overall severity; positive changes were also seen in parental measures of quality of life. Delivery of voice therapy in a telehealth format may increase access of care and should be considered as a treatment option.

15.
J Pediatr Hematol Oncol ; 43(8): e1235-e1237, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34673714

RESUMO

Blastomyces is a fungus found in the soil of regions of North America including the Mississippi and Ohio River Valleys. It can be inhaled into the lungs and cause pneumonia and disseminated disease. Although blastomycosis is not widely reported in the sickle cell literature, sickle cell patients may be at increased risk of complications from blastomycosis pneumonia due to their immune compromise and risk of developing acute chest syndrome. We describe the case of a 13-year-old female with homozygous sickle cell disease who presented with pneumonia and acute chest syndrome and was found to have pulmonary blastomycosis.


Assuntos
Síndrome Torácica Aguda/patologia , Anemia Falciforme/fisiopatologia , Blastomyces/isolamento & purificação , Blastomicose/complicações , Pneumopatias Fúngicas/complicações , Pneumonia/complicações , Síndrome Torácica Aguda/etiologia , Adolescente , Blastomicose/microbiologia , Feminino , Humanos , Pneumopatias Fúngicas/microbiologia , Pneumonia/microbiologia , Prognóstico
16.
Arch Environ Contam Toxicol ; 81(4): 521-530, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34170356

RESUMO

Rare earth elements (REEs) are increasingly critical to the high-technology and low-carbon economy. With a shift to sustainable socioeconomic development that aims to be less fossil fuel dependent, global demand for REEs continues to rise, despite their uncertain supply chain and high environmental impact of production. Here, we review recent research on REEs, including global reserve assessment, REE-based applications, major REE production pathways, environmental impacts, and the potential to leverage circular economies within the REE industry. The main objective of this review is to provide an overall socioeconomic and environmental perspective of the REE industry with a central focus on environmental impacts of various REE-related activities. The literature reveals significant interest in extracting REEs from secondary materials (e.g., tailings, bauxite residues, coal combustion ash) and electronic wastes. However, some of these REE recovery processes are not yet economically profitable and environmental-friendly. Continued technological advancements and increasing demands for REEs may entice countries with recently discovered REE reserves to break the current monopolistic REE supply chain. Furthermore, the sustainability of REE usage may also depend on consumer awareness of environmental and human health impacts associated with end-of-life electronics that contain REEs. On the other hand, REEs may show promise in sustainable agriculture and environmental applications. Nevertheless, further research on REE ecotoxicological impacts is required to establish environmental regulations that protect the environment and human health.


Assuntos
Resíduo Eletrônico , Metais Terras Raras , Cinza de Carvão , Meio Ambiente , Humanos
17.
Eur J Pharm Biopharm ; 164: 66-74, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33878434

RESUMO

A pediatric formulation workshop entitled "Pediatric Formulations: Challenges of Today and Strategies for Tomorrow" was held to advance pediatric drug product development efforts in both pre-competitive and competitive environments. The workshop had four main sessions discussing key considerations of Formulation, Analytical, Clinical and Regulatory. This paper focuses on the clinical session of the workshop. It provides an overview of the discussion on the interconnection of pediatric formulation design and development, clinical development strategy and pediatric clinical pharmacology. The success of pediatric drug product development requires collaboration of multi-disciplinary teams across the pharmaceutical industry, consortiums, foundations, academia and global regulatory agencies. Early strategic planning is essential to ensure alignment among major stakeholders of different functional teams. Such an alignment is particularly critical in the collaboration between formulators and clinical pharmacology teams.


Assuntos
Desenvolvimento de Medicamentos/métodos , Preparações Farmacêuticas/química , Química Farmacêutica/métodos , Criança , Indústria Farmacêutica/métodos , Humanos , Farmacologia Clínica/métodos
18.
Eur J Pharm Biopharm ; 164: 54-65, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33878432

RESUMO

A workshop on "Pediatric Formulation Development: Challenges of Today and Strategies for Tomorrow" was organized jointly by the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI), the U.S. Food and Drug Administration (FDA) and the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Drug Product Pediatric Working Group (PWG). This multi-disciplinary, pediatric focused workshop was held over a two-day period (18-19 Jun 2019) and consisted of participants from industry, regulatory agencies, academia and other organizations from both US and Europe. The workshop consisted of sequential sessions on formulation, analytical, clinical, and regulatory and industry lessons learned and future landscape. Each session began with a series of short framing presentations, followed by facilitated breakout sessions and panel discussion. The formulation session was dedicated to three main topics pertaining to drug product acceptability, excipients in pediatrics and oral administration device considerations. The analytical session discussed key considerations for dosing vehicle selection and analytical strategies for testing of different dosage forms, specifically mini-tablets (multiparticulates). The clinical session highlighted the influence of pediatric pharmacokinetics prediction on formulation design, pediatric drug development strategies and clinical considerations to support pediatric formulation design. The regulatory and industry lessons learned and future landscape session explored the regional differences that exist in regulatory expectations, requirements for pediatric formulation development, and key patient-centric factors to consider when developing novel pediatric formulations. This session also discussed potential collaboration opportunities and tools for pediatric formulation development. This manuscript summarizes the key discussions and outcomes of all the sessions in the workshop with a broadened review and discussion of the topics that were covered.


Assuntos
Desenvolvimento de Medicamentos/métodos , Preparações Farmacêuticas/química , Comprimidos/química , Química Farmacêutica/métodos , Criança , Excipientes/química , Humanos , Pediatria/métodos
19.
JMIR Res Protoc ; 10(2): e23767, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595443

RESUMO

BACKGROUND: Social integration and mental health are vital aspects of healthy aging. However, close to half of Canadians older than 80 years report feeling socially isolated. Research has shown that social isolation leads to increased mortality and morbidity, and various interventions have been studied to alleviate loneliness among older adults. This proposal presents an evaluation of an intervention that provides one-on-one coaching, is intergenerational, provides both educational and socialization experiences, and increases technology literacy of older adults to overcome loneliness. OBJECTIVE: This paper describes the protocol of a randomized, mixed-methods study that will take place in Ontario, Canada. The purpose of this study is to evaluate if an intergenerational technology literacy program can reduce social isolation and depression in older adults via quantitative and qualitative outcome measures. METHODS: This study is a randomized, mixed-methods, feasibility trial with 2 conditions. Older adults in the intervention condition will receive 1 hour of weekly technological assistance to send an email to a family member, for 8 weeks, with the assistance of a volunteer. Participants in the control condition will not receive any intervention. The primary outcomes are loneliness, measured using the University of California, Los Angeles Loneliness Scale, and depression, measured using the Center for Epidemiologic Studies Depression scale, both of which are measured weekly. Secondary outcomes are quality of life, as assessed using the Older People's Quality of Life-Brief version, and technological literacy, evaluated using the Computer Proficiency Questionnaire-12, both of which will be administered before and after the intervention. Semistructured interviews will be completed before and after the intervention to assess participants' social connectedness, familiarity with technology, and their experience with the intervention. The study will be completed in a long-term care facility in Southwestern Ontario, Canada. Significance was set at P<.05. RESULTS: This study was funded in April 2019 and ethical approval was obtained in August 2019. Recruitment for the study started in November 2019. The intervention began in February 2020 but was halted due to the COVID-19 pandemic. The trial will be restarted when safe. As of March 2020, 8 participants were recruited. CONCLUSIONS: Information and communication technology interventions have shown varying results in reducing loneliness and improving mental health among older adults. Few studies have examined the role of one-on-one coaching for older adults in addition to technology education in such interventions. Data from this study may have the potential to provide evidence for other groups to disseminate similar interventions in their respective communities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23767.

20.
Pediatr Dev Pathol ; 24(2): 142-147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33439111

RESUMO

TRAP pregnancies involving monochorionic triplets are extremely rare, calculated to be 1 in 4.5 million. We report two cases of monochorionic triplet pregnancies with an acardiac triplet. In one case, the mother was a 33-year-old G2P1 who underwent dilation and evacuation at 20 weeks due to poor prognosis. The other case involved a 21-year-old G1P0 mother presenting in advanced preterm labor at 21 weeks who elected expectant management. Seventeen cases of monochorionic triplets with TRAP were identified in the literature. Invasive intervention was performed in 10 cases; 9 cases resulted in the survival of the nonacardiac twins and 1 case resulted in the survival of 1 fetus. Our two cases had common sonographic features which included polyhydramnios of all fetuses. Placental features shared between both cases included being large for gestational age and velamentous insertion of the acardiac twin. The acardiac twins in both of our cases were hydropic and demonstrated developed pelvis and lower extremities. One had an omphalocele. Most case reports in the literature review demonstrate similar findings. Two cases of monochorionic triplets with TRAP and acardiac twin are herein described. Successful treatment by invasive interventions have been described in this condition, highlighting the importance of early diagnosis.


Assuntos
Transfusão Feto-Fetal/diagnóstico , Cardiopatias Congênitas/diagnóstico , Gravidez de Trigêmeos , Aborto Eugênico , Adulto , Feminino , Morte Fetal , Transfusão Feto-Fetal/patologia , Cardiopatias Congênitas/patologia , Humanos , Gravidez , Ultrassonografia Pré-Natal
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