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1.
Can J Pain ; 7(1): 2232838, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37701550

RESUMO

Background: During fiscal year 2021-2022, Veterans Affairs Canada (VAC) reimbursed 18,388 veterans for medicinal cannabis at a cost of $153 million. Yet, it is not known whether the reimbursement program is producing a net benefit for veterans. Aims: This study investigated the views and experiences Canadian that veterans who live with pain have about medicinal cannabis use, including its use for the management of chronic pain, poor sleep, and emotional distress. Methods: Twelve Canadian veterans who live with pain-eight men, four women; split across four focus groups-were recruited to participate in a semistructured discussion around their experiences with medicinal cannabis use. Results: Using inductive thematic analysis, seven broad categories were identified: (1) cannabis use behaviors, (2) reasons for cannabis use, (3) outcomes from cannabis use, (4) facilitators of cannabis use, (5) barriers to cannabis use, (6) stigma around cannabis use, and (7) questions and concerns about cannabis use. Conclusions: Most veterans initiated cannabis use to manage the symptoms of preexisting medical and/or mental health conditions. Despite some negative side effects, most veterans reported improvements in their overall quality of life, sleep, relationships, mood, and pain. Concern remains around the discrepancy between veterans' qualitative reports of beneficial outcomes from medicinal cannabis use and equivocal findings around the benefit-to-harm ratio in the wider literature. Currently, the VAC reimbursement program remains challenged by unclear indication for which veterans, with what condition(s), at what dose, and in what form medical cannabis is most beneficial.


Contexte: Au cours de l'exercice 2021­2022, Anciens Combattants Canada (ACC) a remboursé 18 388 anciens combattants pour le cannabis médicinal, pour un coût de 153 millions de dollars. Pourtant, on ne sait pas si le programme de remboursement donne lieu à un bénéfice net pour les anciens combattants.Objectifs: Cette étude porte sur les points de vue et les expériences des anciens combattants canadiens qui vivent avec la douleur sur la consommation de cannabis médicinal, y compris son utilisation pour la gestion de la douleur chronique, les problèmes de sommeil et la détresse émotionnelle.Méthodes: Douze anciens combattants canadiens qui vivent avec la douleur - huit hommes et quatre femmes répartis en quatre groupes de discussion - ont été recrutés pour participer à une discussion semi-structurée autour de leurs expériences avec la consommation de cannabis médicinal.Résultats: Une analyse thématique inductive a permis d'établir sept grandes catégories : (1) les comportements de consommation de cannabis, (2) les raisons de la consommation de cannabis, (3) résultats de la consommation de cannabis, (4) les facteurs qui facilitent la consommation de cannabis, (5) les obstacles à la consommation de cannabis, (6) la stigmatisation autour de la consommation de cannabis et (7) les questions et préoccupations concernant la consommation de cannabis.Conclusions: La plupart des anciens combattants ont commencé à consommer du cannabis pour gérer les symptômes de maladies préexistantes et/ou des problèmes de santé mentale. Malgré certains effets secondaires négatifs, la plupart des anciens combattants ont signalé une amélioration de leur qualité de vie globale, de leur sommeil, de leurs relations, de leur humeur et de leur douleur. La préoccupation demeure autour de l'écart entre les rapports qualitatifs des anciens combattants décrivant les résultats bénéfiques de la consommation de cannabis médicinal et les résultats équivoques autour du rapport bénéfice/effet néfaste dans la littérature plus large. Actuellement, le programme de remboursement d'ACC reste contesté en raison d'indications peu claires concernant pour quels vétérans, atteints de quelles affections, à quelle dose et sous quelle forme le cannabis médical est le plus bénéfique.

2.
Int J Drug Policy ; 120: 104193, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37716112

RESUMO

BACKGROUND: Emerging adults (EAs) have the highest rates of cannabis consumption in Canada and are vulnerable to the potential impacts of frequent cannabis consumption. This study assessed EAs' perceived risk of cannabis consumption across multiple domains of potential harm based on the age (14-year-old, 21-year-old, or 28-year-old) and sex (male or female) of the vignette character, time-point (pre- or post-legalization), and participant's gender. METHODS: Secondary analyses were conducted on data from a pre-legalization study and post-legalization replication. Participants included EAs between 18 and 25 years of age and living in Newfoundland and Labrador. Participants from the pre- and post-legalization studies were matched based on demographic variables and the assigned vignette character. Participants responded to seven items of perceived risk based on their assigned vignette character's (varied by age or sex) almost daily cannabis consumption. RESULTS: Participants (N = 689) viewed cannabis consumption to have greater risks for a 14-year-old compared to a 21- or 28-year-old in all domains except for social life. Prior to legalization, participants who identified as a woman felt that cannabis had more detrimental impacts on social life than participants who identified as a man. Findings also suggested that pre-legalization cannabis consumption by a female was perceived as more detrimental to their social life than pre-legalization consumption by a male and post-legalization consumption by a female. CONCLUSION: EAs do not fully appreciate the risks of cannabis consumption, suggesting that it is imperative for public health strategies to promote increased awareness of the risks of frequent cannabis consumption, and improve cannabis health literacy in this population.

3.
ANZ J Surg ; 93(7-8): 1817-1824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37140189

RESUMO

INTRODUCTION: Endoscopic retrograde cholangio-pancreatography (ERCP) has higher rates of morbidity and mortality compared to upper or lower gastrointestinal tract endoscopy. The availability of magnetic resonance cholangiopancreatography means ERCP is usually performed for therapeutic purposes. Simulation could provide an adjunct to patient-based training in ERCP however models to date have been unconvincing. METHODS: This ERCP simulation model was constructed from moulded meshed silicone by co-designers: Jean Wong and Kai Cheng. The anatomical orientation was based on a combination of anatomical specimens, sectional atlases, and the clinical experience of expert endoscopists. RESULTS: From March to October 2022, we recruited 5 surgeons/gastroenterologists to the expert group and 14 medical students, junior doctors, or surgical/gastroenterological trainees to the novice group. Most experts either agreed or strongly agreed that the simulation anatomy appearance (100%), anatomical orientation (83%), tactile feedback (66%), traversal actions (67%), cannula positioning (66%) and papilla cannulation (67%) resembled the procedure in humans. Experts statistically significantly outperformed novices in obtaining a cannulating position (80% vs. 14%, P = 0.006) and successful papilla cannulation (80% vs. 7%, P = 0.0015) on their first attempt. The novice group had statistically significant improvements in time to obtaining a cannulating position (3.53 vs. 11.5 min, P = 0.006) and passing the duodenoscope to the papilla (2.55 vs. 4 passes, P = 0.009). CONCLUSIONS: The simulator showed statistically significant results in face, content, and construct validity. A follow-up validation study should recruit participants across multiple institutions. External validity could be assessed by comparing expert proceduralist simulator performance against clinical ERCP performance.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Gastroenterologia , Humanos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Projetos Piloto , Silicones , Próteses e Implantes , Gastroenterologia/educação
5.
Langenbecks Arch Surg ; 406(4): 1057-1069, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33770264

RESUMO

PURPOSE: Surgical resection for elderly patients with gastric cancer is controversial. This study aims to evaluate the preoperative features and postoperative short- and long-term outcomes of elderly patients following surgical resection for gastric adenocarcinoma. METHODS: Between January 2000 and May 2018, a total of 177 consecutive patients underwent curative gastrectomy for gastric adenocarcinoma was retrospectively reviewed. Propensity score matching (PSM) analysis was used to balance confounding covariates between the elderly and non-elderly groups. Clinicopathological characteristics, intraoperative characteristics, postoperative complications and long-term survival outcomes including overall survival (OS) and Disease Specific Survival (DSS) were compared and analysed using the Kaplan-Meier log-rank test. Multivariate cox proportional hazards regression analysis of clinicopathological factors influencing survival were evaluated. RESULTS: There were 50 patients in the elderly group (age ≥ 75 years) and 127 patients in the non-elderly group (age < 75 years). Elderly patients had more comorbid conditions (p < 0.001), lower albumin concentration (p = 0.034), lower haemoglobin levels (p = 0.001), and poorer renal function (p = 0.043). TNM stage was similar between both groups (p = 0.174); however, lymphatic invasion (p = 0.006) and lymph node metastasis (p = 0.029) were higher in the elderly group. Elderly patients were much less likely to receive any chemo- (p < 0.001) or radiotherapy treatment (p = 0.007) with surgical treatment. After PSM, there were 50 patients in each group. Elderly patients were more likely to develop complications (Clavien Dindo ≥ 2: 50% vs. 26%, p = 0.003). The most common postoperative complications were pneumonia (12% vs. 6%, p = 0.498) and delirium (10% vs. 0%, p = 0.066). Elderly patients had a longer median length of hospital stay (median (IQR): 15.6(9.5) vs. 11.3 (9.9), p = 0.030). There were no differences in 30-day mortality (elderly vs. non-elderly: 1% vs. 1%, p = 0.988). Before and after PSM, age remains an independent predictor of postoperative complications. Before PSM, the estimated mean OS for the elderly and non-elderly patients were 108 months (95%CI, 72.5-143.5) and 143 months (95%CI, 123.0-163.8), respectively (p = 0.264). After PSM, the estimated mean OS for the elderly and non-elderly patients were 108 months (95%CI, 72.5-143.5) and 140 months (95%CI, 112.1-168.2), respectively, (p = 0.360). Before PSM, the estimated mean DSS for the elderly and non-elderly patients were 94 months (95%CI, 61.9-127.5) and 121 months (95%CI, 100.9-141.0), respectively (p = 0.405). After PSM, the estimated mean DSS for the elderly and non-elderly patients were 94 months (95%CI, 61.9-127.5) and 115 months (95%CI, 87.3-143.3), respectively (p = 0.721). Age was not an independent predictor of mortality following gastrectomy for gastric cancer in both PSM matched and unmatched cohort. CONCLUSION: Chronological age alone is not a contraindication to curative resection of gastric adenocarcinoma in elderly patients with acceptable risk. Whilst age affects perioperative complications, the incidence of postoperative mortality and overall survival were not significantly different between elderly and non-elderly gastric cancer patients treated with curative surgery. Gastrectomy with D2 lymphadenectomy can also be performed in carefully selected elderly patients by surgeons with expertise in gastric resection along with appropriate perioperative management.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Idoso , Gastrectomia , Humanos , Recém-Nascido , Excisão de Linfonodo , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
6.
ANZ J Surg ; 90(6): 970-977, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811701

RESUMO

BACKGROUND: Adequate training and assessment of competency in surgical trainees are important in minimizing adverse events and achieving good patient outcomes. The purpose was to investigate the current literature on digitally supported methods of facilitating work-based competency assessment of surgical trainees. METHODS: Two concurrent literature searches were performed by two independent researchers using three databases: MEDLINE, Embase and Education Resources Information Center. Eligible studies reported on digitally supported tools for assessing surgical competency in a work-based setting for interns, residents or trainees of a post-graduate surgical programme. Studies focusing primarily on training courses, simulations or other tools for assessing surgical skills in a setting outside of work were excluded. Articles published as abstracts only, articles not published in English and review articles that did not contain original data were excluded. RESULTS: A total of 11 eligible studies were included, with six of these implementing smartphone application-based programmes, and five utilizing web-based programmes. Five studies implemented the 'System for Improving and Measuring Procedural Learning' smartphone application. Studies were based predominantly on general surgery residents, and were limited to the North American context. There was significant variability between studies regarding methodology, including the scoring system used to assess competency. CONCLUSION: This review confirms that digitally supported competency assessment of surgical trainees in a work-based setting is both feasible and effective. Digital platforms allow evaluations to be performed in a timely fashion without significant disturbance to workflow.


Assuntos
Competência Clínica , Cirurgia Geral , Internato e Residência , Educação de Pós-Graduação em Medicina , Cirurgia Geral/educação , Pessoal de Saúde/educação , Humanos , Local de Trabalho
8.
World J Surg Oncol ; 16(1): 136, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986713

RESUMO

BACKGROUND: There has been worldwide debate on lymphadenectomy for gastric cancer, with increasing consensus on performing an extended (D2) resection. There is a paucity of data in Australia. Our aim is to compare overall outcomes between a D1 and D2 lymphadenectomy for gastric cancer in a single specialist unit. METHODS: We performed a retrospective analysis on patients who underwent a curative primary gastric resection for gastric adenocarcinoma between January 1996 and April 2016, primary outcomes included overall survival (OS) and disease-free survival (DFS). Propensity score matching (PSM) analysis was used to balance covariates between D1/D1+ and D2 groups. Kaplan-Meier survival curves of D1/D1+ versus D2 were constructed and evaluated using the log-rank test with subgroup analyses for pathological node (pN) status. Multiple Cox proportional hazards model was used to determine predictors of overall survival. RESULTS: Two hundred four patients underwent a gastrectomy, 54 had D1/D1+, and 150 had a D2 lymphadenectomy. After PSM, there were 39 patients in each group, the 10-year OS for D1/D1+ was 52.1 and 76.2% for D2 (p = 0.008), and 10-year DFS was 35% for D1 and 58.1% for D2 (p = 0.058). Subgroup analysis showed that node-negative (N0) patients had improved 5-year OS for D2 (90.9%), compared to D1/D1+ (76.4%) (p = 0.028). There was no difference in operative mortality between the groups (D1 vs D2: 2 vs 0%, p = 0.314), nor in post-operative complications (p = 0.227). Multiple Cox analysis showed advanced tumor stage (stages III and IV), and lymphadenectomy type (D1) and the presence of postoperative complications were independent predictors of poor overall survival. CONCLUSIONS: D2 lymphadenectomy with spleen and pancreas preservation can be performed safely on patients with gastric adenocarcinoma. Significant improvement in overall survival is observed in patients with N0 disease who underwent D2 lymphadenectomy without increasing operative morbidity or mortality. This paper supports the notion of a global consensus for a D2 lymphadenectomy, particularly in the Western context.


Assuntos
Adenocarcinoma , Gastrectomia , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Idoso , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Cirurgiões
9.
Int J Pharm ; 536(2): 530-535, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-28495584

RESUMO

A small amount of food is commonly used to aid administration of medicines to children to improve palatability and/or swallowability. However the impact of this co-administered food on the absorption and subsequent pharmacokinetic profile of the drug is unknown. Existing information on food effects is limited to standard protocols used to evaluate the impact of a high fat meal in an adult population using the adult medication. In the absence of a substantial body of data, there are no specific guidelines available during development of paediatric products relating to low volumes of potentially low calorie food. This paper brings together expertise to consider how the impact of co-administered food can be risk assessed during the development of a paediatric medicine. Two case studies were used to facilitate discussions and seek out commonalities in risk assessing paediatric products; these case studies used model drugs that differed in their solubility, a poorly soluble drug that demonstrated a positive food effect in adults and a highly soluble drug where a negative food effect was observed. For poorly soluble drugs risk assessments are centred upon understanding the impact of food on the in vivo solubility of the drug which requires knowledge of the composition of the food and the volumes present within the paediatric gastrointestinal tract. Further work is required to develop age appropriate in vitro and in silico models that are representative of paediatric populations. For soluble drugs it is more important to understand the mechanisms that may lead to a food effect, this may include interactions with transporters or the impact of the food composition on gastro-intestinal transit or even altered gastric motility. In silico models have the most promise for highly soluble drug products although it is essential that these models reflect the relevant mechanisms involved in potential food effects. The development of appropriate in vitro and in silico tools is limited by the lack of available clinical data that is critical to validate any tool. Further work is required to identify globally acceptable and available vehicles that should be the first option for co-administration with medicines to enable rapid and relevant risk assessment.


Assuntos
Interações Alimento-Droga , Animais , Biofarmácia , Criança , Alimentos , Humanos , Preparações Farmacêuticas/administração & dosagem
10.
ANZ J Surg ; 87(12): 997-1000, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28768364

RESUMO

BACKGROUND: Competency in surgical training is a topic of much recent discussion, with concern regarding the adequacy of current training schemes to achieve competency. Most programmes use caseload and primary operator rates to assess trainee progression. Some trainees still lack technical competence even when recommended procedural numbers are met. It is possible that current measures of individual's capabilities used in surgical education are outdated. METHODS: Logbook data of New South Wales general surgical trainees between 2010 and 2012 was obtained through General Surgeons Australia. The top 10 most common operations recorded in trainee logbooks were identified. Individual trainee data were grouped by the surgical education and training year and primary operator versus assistant experience. The data were analysed focusing on the primary operator rate, comparing between trainee levels to identify progression. RESULTS: A total of 183 319 operations were recorded in New South Wales general surgery trainee logbooks. A positive association was demonstrated between trainee seniority and primary operator rates for the most common procedures, indicating trainee's continual progression in experience as they advance. However, laparoscopic inguinal hernia repair, oversew of gastroduodenal ulcer, open cholecystectomy and right hemicolectomy showed poor primary operator rates among trainees regardless of trainee year, despite these operations being among the 10 most common. CONCLUSION: General surgical trainees accumulate operative experience with progression through the surgical education and training programme, highlighting expected technical progression and competency of trainees for common procedures. For less common or more complicated procedures, the use of entrustable professional activities and accompanying simulation training could be used to achieve the necessary technical expertise.


Assuntos
Competência Clínica/estatística & dados numéricos , Cirurgia Geral/educação , Hérnia Inguinal/cirurgia , Procedimentos Cirúrgicos Operatórios/educação , Austrália/epidemiologia , Cirurgia Geral/estatística & dados numéricos , Cirurgia Geral/tendências , Hérnia Inguinal/complicações , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , New South Wales/epidemiologia , Treinamento por Simulação/métodos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos
11.
AAPS PharmSciTech ; 18(8): 2841-2853, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28560506

RESUMO

The presented study describes the development of a membrane permeation non-sink dissolution method that can provide analysis of complete drug speciation and emulate the in vivo performance of poorly water-soluble Biopharmaceutical Classification System class II compounds. The designed membrane permeation methodology permits evaluation of free/dissolved/unbound drug from amorphous solid dispersion formulations with the use of a two-cell apparatus, biorelevant dissolution media, and a biomimetic polymer membrane. It offers insight into oral drug dissolution, permeation, and absorption. Amorphous solid dispersions of felodipine were prepared by hot melt extrusion and spray drying techniques and evaluated for in vitro performance. Prior to ranking performance of extruded and spray-dried felodipine solid dispersions, optimization of the dissolution methodology was performed for parameters such as agitation rate, membrane type, and membrane pore size. The particle size and zeta potential were analyzed during dissolution experiments to understand drug/polymer speciation and supersaturation sustainment of felodipine solid dispersions. Bland-Altman analysis was performed to measure the agreement or equivalence between dissolution profiles acquired using polymer membranes and porcine intestines and to establish the biomimetic nature of the treated polymer membranes. The utility of the membrane permeation dissolution methodology is seen during the evaluation of felodipine solid dispersions produced by spray drying and hot melt extrusion. The membrane permeation dissolution methodology can suggest formulation performance and be employed as a screening tool for selection of candidates to move forward to pharmacokinetic studies. Furthermore, the presented model is a cost-effective technique.


Assuntos
Biomimética/métodos , Química Farmacêutica/métodos , Felodipino/metabolismo , Animais , Dessecação , Composição de Medicamentos/métodos , Felodipino/química , Felodipino/farmacologia , Previsões , Congelamento , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/fisiologia , Tamanho da Partícula , Polímeros/química , Polímeros/metabolismo , Polímeros/farmacologia , Solubilidade , Suínos , Difração de Raios X
12.
Int J Pharm ; 510(1): 210-20, 2016 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-27311354

RESUMO

The Dynamic Gastric Model (DGM) is an in-vitro system which aims to closely replicate the complex mixing, dynamic biochemical release and emptying patterns of the human stomach. In this study, the DGM was used to understand how the polymer content of hydrophilic matrices influences drug release in fasted and fed dissolution environments. Matrices containing a soluble model drug (caffeine) and between 10 and 30% HPMC 2208 (METHOCEL(®) K4M CR) were studied in the DGM under simulated fasted and fed conditions. The results were compared with compendial USP I and USP II dissolution tests. The USP I and II tests clearly discriminated between formulations containing different polymer levels, whereas the fasted DGM test bracketed drug release profiles into three groups and was not able to distinguish between some different formulations. DGM tests in the fed state showed that drug release was substantially influenced by the presence of a high fat meal. Under these conditions, there was a delay before initial drug release, and differences between matrices with different polymer contents were no longer clear. Matrices containing the typical amount of HPMC polymer (30% w/w) exhibited similar release rates under fed and fasted DGM conditions, but matrices with lower polymer contents exhibited more rapid drug release in the fasted state. In both the fasted and fed states erosion mechanisms appeared to dominate drug release in the DGM: most likely a consequence of the changing, cylindrical forces exerted during simulated antral cycling. This is in contrast to the USP tests in which diffusion played a significant role in the drug release process. This study is one of the first publications where a series of extended release (ER) formulations have been studied in the DGM. The technique appears to offer a useful tool to explore the potential sensitivity of ER formulations with respect to the gastric environment, especially the presence of food.


Assuntos
Gorduras na Dieta , Jejum , Esvaziamento Gástrico , Interações Hidrofóbicas e Hidrofílicas , Modelos Biológicos , Polímeros/química , Química Farmacêutica , Gorduras na Dieta/administração & dosagem , Polímeros/análise
13.
Int J Pharm ; 511(2): 1151-7, 2016 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-27349792

RESUMO

The aim of this research survey was to understand current global thinking around the need for and development of a paediatric biopharmaceutics classification system (pBCS) to be used for the development of paediatric medicines and regulatory purposes (e.g. Biowaivers). A literature review highlighted the paucity of data in this area and therefore a survey was developed to better understand this topic to identify areas of common thinking and highlight future research needs. Global experts in paediatric biopharmaceutics were identified from existing networks and public forums. An online survey was developed and circulated broadly to maximise participation. Sixty individuals (including academics, health care professionals, pharmaceutical industry scientists and regulators) completed the survey, bringing together their views on the need for a pBCS. The results highlighted that the area of greatest concern was the definition of BCS II and IV drugs within this population and additional research is required to generate evidence to underpin this issue. In questions relating to permeability and dissolution consensus was generally reached within the expert population suggesting that little additional research is required to define suitable criteria. More than 90% of those experts who participated agreed that a pBCS would be useful for paediatric populations with a greater need identified for the younger populations (newborn and infants compared to adolescents). The results presented will facilitate further discussion and research into the evidence to underpin a relevant pBCS. These results highlight the need for additional evidence and guidance in this area.


Assuntos
Biofarmácia/classificação , Pediatria/classificação , Inquéritos e Questionários , Adolescente , Biofarmácia/tendências , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Pediatria/tendências
14.
Eur J Pharm Biopharm ; 94: 485-92, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26143369

RESUMO

Percolation theory has been used for several years in the design of HPMC hydrophilic matrices. This theory predicts that a minimum threshold content of polymer is required to provide extended release of drug, and that matrices with a lower polymer content will exhibit more rapid drug release as a result of percolation pathways facilitating the faster penetration of the aqueous medium. At present, percolation thresholds in HPMC matrices have been estimated solely through the mathematical modelling of dissolution data. This paper examines whether they can be also identified in a novel way: through the use of confocal laser scanning fluorescence microscopy (CLSM) to observe the morphology of the emerging gel layer during the initial period of polymer hydration and early gel formation at the matrix surface. In this study, matrices have been prepared with a polymer content of 5-30% w/w HPMC 2208 (Methocel K4M), with a mix of other excipients (a soluble drug (caffeine), lactose, microcrystalline cellulose and magnesium stearate) to provide a typical industrially realistic formulation. Dissolution studies, undertaken in water using USP apparatus 2 (paddle) at 50rpm, provided data for the calculation of the percolation threshold through relating dissolution kinetic parameters to the excipient volumetric fraction of the dry matrix. The HPMC percolation threshold estimated this way was found to be 12.8% v/v, which was equivalent to a matrix polymer content of 11.5% w/w. The pattern of polymer hydration and gel layer growth during early gel layer formation was examined by confocal laser scanning fluorescence microscopy (CLSM). Clear differences in gel layer formation were observed. At polymer contents above the estimated threshold a continuous gel layer was formed within 15min, whereas matrices with polymer contents below the threshold were characterised by irregular gel layer formation with little evidence of HPMC particle coalescence. According to percolation theory, this implies that a continuous cluster of HPMC particles was not formed. The images provide the first direct evidence of how the percolation threshold may be related to the success or failure of early gel layer development in HPMC matrices. It also shows how extended release characteristics are founded on the successful coalescence of hydrated polymer particles to form a continuous coherent diffusion barrier, which can then inhibit further percolation of the hydration medium. The correlation between percolation thresholds estimated from dissolution and imaging techniques suggests that confocal imaging may provide a more rapid method for estimating the percolation thresholds, facilitating the rational design of HPMC extended release matrices at lower polymer contents with minimal risk of dose dumping.


Assuntos
Preparações de Ação Retardada , Excipientes/química , Géis/química , Derivados da Hipromelose/química , Microscopia Confocal/métodos , Química Farmacêutica , Liberação Controlada de Fármacos , Cinética , Solubilidade , Comprimidos
15.
J Infus Nurs ; 37(6): 424-31, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25376319

RESUMO

An observational retrospective study audited the incidence of adverse events in 300 consecutive inpatients receiving a single, premade total nutrient admixture. No patient experienced critically high triglycerides; 16% of patients had a metabolic adverse event, including raised bilirubin, urea, creatinine, or liver enzymes. Line sepsis occurred on 30 occasions representing 0.67 infections per 1000 catheter days. Mortality was significantly higher in dialysis, nonsurgical, and intensive care unit patients. The use of a standard formulation for all parenterally nourished patients does not lead to an unacceptable incidence or severity of metabolic complications; however, it did not meet the protein requirements of surgical or critically ill patients.


Assuntos
Nutrição Parenteral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Clin Nutr ; 30(6): 774-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21723650

RESUMO

BACKGROUND & AIMS: Major upper gastrointestinal surgery results in permanent alterations to the gastrointestinal tract, and previously been shown to impair nutritional status. The aim of this study was to assess long term nutritional status and quality of life in people having had major upper gastrointestinal surgery, and the relationship between the two measures. METHODS: People having had major upper gastrointestinal surgery greater than 6 months ago were recruited. Nutrition assessment included weight, anthropometry, Subjective Global Assessment, dietary intake and assessment of gastrointestinal symptoms; quality of life was assessed using the EORTC QLQ-C30 questionnaire. Associations between nutritional status, type of surgery and quality of life were analysed. RESULTS: Thirty people were recruited with fourteen people showing a degree of malnutrition according to subjective global assessment. Total gastrectomy and oesophagectomy surgery resulted in significantly higher percent weight loss than those having undergone pancreaticoduodenectomy (p = 0.01). Subjective global assessment correlated with quality of life (p = 0.003). Subjective global assessment and gastrointestinal symptoms were both significant variables in explaining quality of life (p < 0.001). CONCLUSIONS: Nutritional status in this group was significantly compromised, and impacted on quality of life. Individualised nutrition intervention to address malnutrition and gastrointestinal symptoms should be integrated into post surgery management.


Assuntos
Desnutrição/etiologia , Desnutrição/fisiopatologia , Estado Nutricional/fisiologia , Qualidade de Vida , Trato Gastrointestinal Superior/cirurgia , Idoso , Antropometria , Peso Corporal/fisiologia , Estudos Transversais , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Inquéritos e Questionários
17.
Talanta ; 74(5): 1166-74, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-18371766

RESUMO

The aroma profile of cocoa products was investigated by headspace solid-phase micro-extraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS). SPME fibers coated with 100 microm polydimethylsiloxane coating (PDMS), 65 microm polydimethylsiloxane/divinylbenzene coating (PDMS-DVB), 75 microm carboxen/polydimethylsiloxane coating (CAR-PDMS) and 50/30 microm divinylbenzene/carboxen on polydimethylsiloxane on a StableFlex fiber (DVB/CAR-PDMS) were evaluated. Several extraction times and temperature conditions were also tested to achieve optimum recovery. Suspensions of the samples in distilled water or in brine (25% NaCl in distilled water) were investigated to examine their effect on the composition of the headspace. The SPME fiber coated with 50/30 microm DVB/CAR-PDMS afforded the highest extraction efficiency, particularly when the samples were extracted at 60 degrees C for 15 min under dry conditions with toluene as an internal standard. Forty-five compounds were extracted and tentatively identified, most of which have previously been reported as odor-active compounds. The method developed allows sensitive and representative analysis of cocoa products with high reproducibility. Further research is ongoing to study chocolate making processes using this method for the quantitative analysis of volatile compounds contributing to the flavor/odor profile.


Assuntos
Cacau/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Sólida/métodos , Manipulação de Alimentos , Compostos Orgânicos/análise , Reprodutibilidade dos Testes , Volatilização
18.
World J Gastroenterol ; 13(43): 5781-2, 2007 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-17963310

RESUMO

Heterotopic pancreatic tissue within the stomach is rare and dysplasia within heterotopic pancreatic tissue is very rare. We present the first report of a patient with concurrent occurrence of heterotopic pancreas in the stomach with a gastrointestinal stromal tumour.


Assuntos
Coristoma/complicações , Tumores do Estroma Gastrointestinal/complicações , Pâncreas , Gastropatias/complicações , Adulto , Coristoma/diagnóstico , Coristoma/patologia , Cistos , Epitélio/patologia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Gastropatias/diagnóstico , Gastropatias/patologia
19.
Eur J Nutr ; 46(6): 307-14, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17623227

RESUMO

BACKGROUND: Lactitol (4-beta-D: -galactopyranosyl-D: -glucitol) is a sugar alcohol used as a sweetener. Previous studies have shown that it has a beneficial effect on intestinal microflora. AIMS OF THE STUDY: To determine whether low doses of lactitol had beneficial effects without eliciting adverse gastrointestinal symptoms. METHODS: Faecal bacterial populations (total anaerobes, total aerobes, enterobacteria, bifidobacteria and lactobacilli), faecal pH and faecal short chain fatty acids (SCFA) were studied in a randomized longitudinal study of 75 non-adapted healthy adults before and after consumption of low doses of lactitol. Subjects consumed 25 g tablets of milk chocolate containing 10 g sweetener as sucrose:lactitol in ratios of 10:0, 5:5 or 0:10 daily for 7 d. RESULTS: No significant changes in faecal bacterial counts occurred in the 10:0 or 5:5 sucrose:lactitol groups. There were no significant changes in faecal anaerobes, aerobes, Enterobacteriaceae or lactobacilli during the study period in subjects consuming 0:10 sucrose:lactitol but there was a significant increase (P = 0.017) in bifidobacteria. There were no significant changes in faecal pH and SCFA for the 10:0 or 5:5 sucrose:lactitol groups but a significant decrease (P = 0.02) in faecal pH and significant increases (P = 0.001) in concentrations of propionic and butyric acids were observed in the 0:10 sucrose:lactitol group. There were few adverse symptoms of gastrointestinal intolerance to the daily consumption of 10 g lactitol. CONCLUSIONS: The results show that low doses of lactitol can beneficially affect the faecal flora without eliciting gross symptoms of intolerance and that lactitol can be classified as a prebiotic.


Assuntos
Ácidos Graxos Voláteis/análise , Fezes/microbiologia , Álcoois Açúcares/farmacologia , Edulcorantes/farmacologia , Adolescente , Adulto , Catárticos/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Flatulência/induzido quimicamente , Flatulência/epidemiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Estudos Longitudinais , Masculino , Probióticos , Álcoois Açúcares/efeitos adversos , Edulcorantes/efeitos adversos
20.
ANZ J Surg ; 77(4): 247-52, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17388828

RESUMO

BACKGROUND: With poor cure rates in gastric cancer using surgery alone, the safety, efficacy and feasibility of preoperative and postoperative chemotherapy was investigated. METHODS: Patients with advanced but operable gastric or cardio-oesophageal adenocarcinoma were staged using endoscopy, computed tomography scan and laparoscopy. If considered potentially resectable, they received chemotherapy (epirubicin, cisplatin and 5-fluorouracil) for 9 weeks before and after surgery. RESULTS: Of 59 participants entered, two were found to have metastatic disease and were excluded from the analysis. Of the participants, 10 were women and 47 men; their median age was 58 years (range 27-83 years) and median performance status 0 (range 0-1). Two of the 57 participants commencing chemotherapy did not undergo surgery (one sudden death, one new liver metastases). Grade 3 and 4 preoperative and postoperative toxicity rates were, respectively, neutropenia 22 and 18%, emesis 12 and 14% and other non-haematological toxicity <10 and <10%. Of the 55 who underwent surgery, 40 had apparently curative resections (clear or positive microscopic margins), 2 died after surgery (anastomotic leak, sepsis) and 16 had postoperative complications. Of these, 27 participants commenced postoperative chemotherapy and 21 completed it. Median progression-free survival and overall survival were 19.6 and 22 months, respectively. CONCLUSION: Epirubicin, cisplatin and protracted venous infusion of 5-fluorouracil chemotherapy was well-tolerated in the preoperative setting and did not appear to increase complication rates of surgery for advanced and operable stomach cancer. These findings demonstrate the feasibility of this strategy in the Australasian clinical setting and are in keeping with the results of a recently reported randomized trial, which demonstrated a significant survival advantage using this chemotherapy regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Resultado do Tratamento
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