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1.
Stat Med ; 43(3): 435-451, 2024 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-38100282

RESUMO

Globally, there were an estimated 9.8 million measles cases and 207 500 measles deaths in 2019. As the effort to eliminate measles around the world continues, modeling remains a valuable tool for public health decision-makers and program implementers. This study presents a novel approach to the use of a yearly transition function that formulates mathematically the vaccine schedules for different age groups while accounting for the effects of the age of vaccination, the timing of vaccination, and disease seasonality on the yearly number of measles cases in a country. The methodology presented adds to an existing modeling framework and expands its analysis, making its utilization more adjustable for the user and contributing to its conceptual clarity. This article also adjusts for the temporal interaction between vaccination and exposure to disease, applying adjustments to estimated yearly counts of cases and the number of vaccines administered that increase population immunity. These new model features provide the ability to forecast and compare the effects of different vaccination timing scenarios and seasonality of transmission on the expected disease incidence. Although the work presented is applied to the example of measles, it has potential relevance to modeling other vaccine-preventable diseases.


Assuntos
Sarampo , Vacinas , Humanos , Lactente , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacinação , Previsões , Surtos de Doenças
2.
Sensors (Basel) ; 24(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38931664

RESUMO

Low-frequency distributed acoustic sensing (LF-DAS) is a diagnostic tool for hydraulic fracture propagation with far-field monitoring using fiber optic sensors. LF-DAS senses strain rate variation caused by stress field change due to fracture propagation. Fiber optic sensors are installed in the monitoring wells in the vicinity of a fractured well. From the strain responses, fracture propagation can be evaluated. To understand subsurface conditions with multiple propagating fractures, a laboratory-scale hydraulic fracture experiment was performed simulating the LF-DAS response to fracture propagation with embedded distributed optical fiber strain sensors under these conditions. The experiment was performed using a transparent cube of epoxy with two parallel radial initial flaws centered in the cube. Fluid was injected into the sample to generate fractures along the initial flaws. The experiment used distributed high-definition fiber optic strain sensors with tight spatial resolutions. The sensors were embedded at two different locations on opposite sides of the initial flaws, serving as observation/monitoring locations. We also employed finite element modeling to numerically solve the linear elastic equations of equilibrium continuity and stress-strain relationships. The measured strains from the experiment were compared to simulation results from the finite element model. The experimentally derived strain and strain-rate waterfall plots from this study show the responses to both fractures propagating, while the fracture at the lower position took most of the fluid during the experiment. Interestingly, a fracture first began propagating from the upper flaw of the two flaws, but once the lower fracture was initiated, it grew much faster than the upper fracture. Both fibers were intercepted by the lower fracture, further verifying the strain signature as a fracture is approaching and intersecting an offset fiber.

3.
Crit Care ; 27(1): 450, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37986015

RESUMO

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.


Assuntos
Estado Terminal , Força da Mão , Adulto , Humanos , Estado Terminal/terapia , Atividades Cotidianas , Resultado do Tratamento , Avaliação de Resultados em Cuidados de Saúde
4.
Ann Oncol ; 33(10): 1052-1060, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35764271

RESUMO

BACKGROUND: In the phase II multicohort CheckMate 142 study, nivolumab plus low-dose (1 mg/kg) ipilimumab provided robust and durable clinical benefit with a manageable safety profile in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) at 13.4- and 25.4-month median follow-up (Overman MJ, Lonardi S, Wong KYM et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773-779. Overman MJ, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: long-term follow-up. J Clin Oncol. 2019;37:635). Here, we present results from the 4-year follow-up of these patients. PATIENTS AND METHODS: Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression. Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1). RESULTS: A total of 119 patients were treated; 76% had ≥2 prior lines of therapy. Median follow-up was 50.9 months (range 46.9-62.7 months). Median duration of therapy was 24.9 months [95% confidence interval (CI) 15.8-33.2 months]. Investigator-assessed ORR increased from 55% (95% CI 45% to 64%) at 13.4 months to 65% (95% CI 55% to 73%) at 50.9 months with a disease control rate of 81% (95% CI 72% to 87%). The complete response rate increased from 3% at 13.4 months to 13% at 50.9 months. Partial responses were observed in 52% of patients; 21% had stable disease, and 12% had progressive disease. Median time to response was 2.8 months (range 1.1-37.1 months), and median duration of response was not reached (range 1.4+ to 58.0+ months). At data cut-off, 37 (48%) patients had ongoing responses. Median progression-free survival was not reached [95% CI 38.4 months-not estimable (NE)], and median overall survival was not reached (95% CI NE). Grade 3-4 treatment-related adverse events (TRAEs) were observed in 32% of patients; 13% of patients had any-grade TRAEs leading to discontinuation. CONCLUSIONS: The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA/genética , Seguimentos , Humanos , Ipilimumab , Instabilidade de Microssatélites , Nivolumabe/uso terapêutico
5.
Phys Rev Lett ; 129(24): 242501, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36563248

RESUMO

A novel pathway for the formation of multiparticle-multihole excited states in rare isotopes is reported from highly energy- and momentum-dissipative inelastic-scattering events measured in reactions of an intermediate-energy beam of ^{38}Ca on a Be target. The negative-parity, complex-structure final states in ^{38}Ca are observed following the in-beam γ-ray spectroscopy of events in the ^{9}Be(^{38}Ca,^{38}Ca+γ)X reaction in which the scattered projectile loses longitudinal momentum of order Δp_{||}=700 MeV/c. The characteristics of the observed final states are discussed and found to be consistent with the formation of excited states involving the rearrangement of multiple nucleons in a single, highly energetic projectile-target collision. Unlike the far-less-dissipative, surface-grazing reactions usually exploited for the in-beam γ-ray spectroscopy of rare isotopes, these more energetic collisions appear to offer a practical pathway to nuclear-structure studies of more complex multiparticle configurations in rare isotopes-final states conventionally thought to be out of reach with high-luminosity fast-beam-induced reactions.

6.
Crit Care ; 26(1): 240, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933433

RESUMO

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.


Assuntos
Atividades Cotidianas , Estado Terminal , Adulto , Estado Terminal/terapia , Técnica Delphi , Humanos , Insuficiência de Múltiplos Órgãos , Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa , Resultado do Tratamento
7.
Breast Cancer Res Treat ; 187(3): 635-645, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33983492

RESUMO

BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Linfócitos , Linfócitos do Interstício Tumoral , Prognóstico , Receptor ErbB-2/genética
8.
Phys Rev Lett ; 126(15): 152701, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33929230

RESUMO

The discrepancy between observations from γ-ray astronomy of the ^{60}Fe/^{26}Al γ-ray flux ratio and recent calculations is an unresolved puzzle in nuclear astrophysics. The stellar ß-decay rate of ^{59}Fe is one of the major nuclear uncertainties impeding us from a precise prediction. The important Gamow-Teller strengths from the low-lying states in ^{59}Fe to the ^{59}Co ground state are measured for the first time using the exclusive measurement of the ^{59}Co(t,^{3}He+γ)^{59}Fe charge-exchange reaction. The new stellar decay rate of ^{59}Fe is a factor of 3.5±1.1 larger than the currently adopted rate at T=1.2 GK. Stellar evolution calculations show that the ^{60}Fe production yield of an 18 solar mass star is decreased significantly by 40% when using the new rate. Our result eliminates one of the major nuclear uncertainties in the predicted yield of ^{60}Fe and alleviates the existing discrepancy of the ^{60}Fe/^{26}Al ratio.

9.
Colorectal Dis ; 22(11): 1518-1527, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32639663

RESUMO

AIM: Haemorrhoidal disease can severely affect a patient's quality of life. Its classification is commonly based on morphology of the degree of prolapse; however, this does not take into account the symptoms and impact on the quality of life. The aim of this systematic review was to determine the most appropriate instruments that classify the severity of disease according to symptoms. METHOD: A PRISMA-compliant search was conducted in December 2019 to identify studies that described the validation of a haemorrhoidal symptom score. The measurement properties of the scoring systems were assessed based on the consensus-based standards for the selection of health status measurement instruments (COSMIN) methodology for systematic reviews for patient-reported outcome measures. RESULTS: A total of 5288 articles were identified, with five articles included. Three studies developed a scoring system based on a set of core symptoms for a cohort of patients and validated the score against treatment outcomes. One study developed a disease-specific quality of life questionnaire based on symptoms to evaluate disease burden. One study combined both quality of life and symptom measures and tested measurement properties on two cohorts of patients. Only one study demonstrated satisfactory valid, reliable and responsive measurement criteria. CONCLUSION: A single study demonstrated sufficient quality in measurement properties to be recommended for clinical use. Further studies in this area should utilize consensus-based standards for designing and reporting validation research to ensure that the appropriate evidence base is acquired if any further patient-reported outcome measures are to be recommended.


Assuntos
Hemorroidas , Qualidade de Vida , Hemorroidas/diagnóstico , Humanos , Medidas de Resultados Relatados pelo Paciente , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
Colorectal Dis ; 22(2): 187-194, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31491051

RESUMO

AIM: Excisional haemorrhoidectomy is the gold standard for management of advanced symptomatic haemorrhoids. Although an effective treatment, it is associated with significant postoperative morbidity with pain, bleeding and a high readmission rate. This study seeks to investigate potential risk factors that may predict unplanned 30-day readmissions following excisional haemorrhoidectomy. METHOD: A retrospective cohort review of all haemorrhoidectomies performed at Counties Manukau District Health Board, Auckland, New Zealand, between January 2012 and December 2017 was performed. Baseline demographic data, readmission data and potential variables for readmission were recorded. Univariate and multivariate logistic regression analyses were performed to determine significant variables for readmission within 30 days. RESULTS: In total, 485 cases of excisional haemorrhoidectomy were included in the final analysis with 62 (12.8%) unplanned readmissions. The demographics between the no readmission and unplanned readmission groups were similar. Multivariate logistic regression analysis demonstrated that male gender (P = 0.018) and the use of non-diathermy devices (P = 0.017) were significant risk factors for readmission. Initial dispensing of opioid analgesia did not decrease the risk of readmission. CONCLUSION: This study suggests that male gender and surgical technique are associated with increased risk of readmission.


Assuntos
Hemorroidectomia/efeitos adversos , Hemorroidas/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Fatores Sexuais , Adulto , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
11.
Climacteric ; 23(3): 311-315, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32107945

RESUMO

Objective: This study aimed to investigate the association of endogenous and exogenous estrogen exposure with risk of incident dementia in the oldest-old (age 90+ years).Methods: Participants were part of The 90+ Study, a longitudinal study begun in 2003 of aging and dementia among people aged 90+ years. Menstrual, reproductive, and menopausal data were collected in the 1980s as part of the population-based Leisure World Cohort Study. Cognitive status at baseline was determined from an in-person neurological evaluation with biannual follow-up through June 2019. Hazard ratios (HRs) of dementia associated with estrogen-related variables were estimated using Cox regression analysis. No adjustment was made for multiple comparisons.Results: A total of 424 women without dementia at baseline had at least one follow-up evaluation. The mean age was 68.5 years at enrollment in the Leisure World Cohort Study, 93.2 years at enrollment in The 90+ Study, and 96.5 years at last follow-up. During follow-up (mean 3.4 years) dementia was diagnosed in 209 (49%) participants. No individual menstrual, reproductive, menopausal, or estrogen replacement variable was associated with risk of incident dementia after age 90 years. However, women with a high endogenous estrogen exposure index (summarizing exposure from menarche to menopause) had a non-significant 25% lower risk (HR = 0.75, 95% confidence interval 0.53-1.06).Conclusions: Prior exposure to estrogen, endogenous or exogenous, had little effect on risk of dementia in the 10th decade of life.


Assuntos
Demência/epidemiologia , Estrogênios/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Estudos de Coortes , Demência/etiologia , Terapia de Reposição de Estrogênios , Estrogênios/administração & dosagem , Feminino , Idoso Fragilizado , Humanos , Estudos Longitudinais , Fatores de Risco
12.
Int J Audiol ; 59(1): 16-23, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486696

RESUMO

Objective: To determine audiology student perceptions of two simulated learning environments (SLE) in paediatric audiology.Design: A one-shot case study design.Study sample: Fifteen audiology students who completed questionnaires after participating in two SLEs, one simulating auditory brainstem response (ABR) assessments of neonates in a hospital ward and one simulating visually reinforced orientation audiometry (VROA) assessments of young children in an audiology clinic.Results: The students responded positively to 11/11 areas of audiometric testing and client interaction in both SLEs, to 7/7 aspects of their interactions with the mannequins in both SLEs, and to 8/8 aspects of their interactions with fellow students playing the role of parent in the ABR SLE and 7/8 of these aspects in the VROA SLE. The students reported low levels of anxiety towards both SLEs but rated the ABR SLE more highly than the VROA SLE in areas of preparedness, effectiveness, realism, pre-SLE training, reinforcement of lecture content, and overall usefulness.Conclusions: The participating students responded positively to almost all aspects of both SLEs. Further research is warranted using research designs capable of determining if these SLEs directly improve student abilities as they transition from academic settings to clinical placements in paediatric audiology.


Assuntos
Audiologistas/psicologia , Audiologia/educação , Pediatria/educação , Treinamento por Simulação/métodos , Estudantes de Ciências da Saúde/psicologia , Adulto , Audiologistas/educação , Criança , Feminino , Humanos , Masculino
13.
Diabet Med ; 36(9): 1092-1099, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30955221

RESUMO

AIMS: Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA1c , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA1c in those with long duration (> 5 years) Type 1 diabetes. METHODS: We conducted a cross-sectional case-control study of 221 people (median age 24 years) with Type 1 diabetes. We confirmed ongoing endogenous insulin secretion by measuring C-peptide after a mixed-meal tolerance test. We compared self-reported hypoglycaemia (n = 160), HbA1c , insulin dose and microvascular complications (n = 140) in those with preserved and low C-peptide. RESULTS: Stimulated median (IQR) C-peptide was 114 (43, 273) pmol/l and < 3 (< 3, < 3) pmol/l in those with preserved and low C-peptide respectively. Participants with preserved C-peptide had lower reported monthly rates of hypoglycaemia, with 21% fewer symptomatic episodes, 5.9 vs. 7.5 [incidence rate ratio (IRR) 0.79, P = 0.001], and 65% fewer asymptomatic episodes, 1.0 vs. 2.9 (IRR 0.35, P < 0.001). Those with preserved C-peptide had a lower insulin dose (0.68 vs. 0.81 units/kg, P = 0.01) but similar HbA1c (preserved 69 vs. low 67 mmol/mol, P = 0.06). CONCLUSIONS: Adults with Type 1 diabetes and preserved endogenous insulin production receiving usual care in the UK have lower daily insulin doses and fewer self-reported hypoglycaemic episodes, but no difference in HbA1c . This is consistent with non-intensive treatment in previous studies, and suggests a need to consider therapy intensification to gain full benefit of preserved endogenous insulin.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemia/sangue , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Glicemia/análise , Glicemia/metabolismo , Automonitorização da Glicemia , Peptídeo C/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Reino Unido/epidemiologia , Adulto Jovem
14.
Epilepsia ; 60(9): 1829-1837, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31329272

RESUMO

OBJECTIVE: Pharmacokinetics (PK) of antiseizure drugs differ considerably between rats and humans. Rodents require larger and more frequent doses to maintain therapeutic drug levels. This study uses the antiseizure drug (ASD) carbamazepine (CBZ) to validate the application of a previously described automated drug delivery system for delivering chronic oral medication to rats. METHODS: Treatment-naive, male Sprague-Dawley rats were treated with oral CBZ, 75 mg/kg every 6 hours for 10 days, via the automated feeder. Blood samples were collected on day 0 (acute), day 2 (steady-state), and day 9 (chronic) and used to measure plasma CBZ and carbamazepine-10,11-epoxide (CBZ-E) concentrations via high-performance liquid chromatography. The PK of CBZ and CBZ-E were modeled using Monolix v2018R1. The acute and chronic tolerability of CBZ was evaluated using the open field test. RESULTS: CBZ and CBZ-E concentrations were best described by a one-compartment parent-metabolite model with first-order absorption and elimination kinetics. Observed and predicted CBZ concentrations were maintained within the therapeutic window (4-12 µg/mL) for the duration of the study. There was no change in open-field test activity following acute or chronic oral dosing of 75 mg/kg CBZ compared to a pretreatment baseline (P > 0.4). SIGNIFICANCE: Oral administration of CBZ dosed q.i.d. in rats using an automated drug delivery system results in therapeutic concentrations of CBZ and its active metabolite. This study represents the first PK validation for this previously described preclinical drug delivery system.


Assuntos
Anticonvulsivantes/farmacocinética , Carbamazepina/farmacocinética , Sistemas de Liberação de Medicamentos , Administração Oral , Animais , Masculino , Ratos , Ratos Sprague-Dawley
15.
Epilepsia ; 60(3): 475-484, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30669183

RESUMO

OBJECTIVE: Medication nonadherence directly contributes to poor seizure control. A lack of emphasis on correcting poor adherence and failures in patient adherence can result in unwarranted alterations to a patient's drug regimen. We have modeled nonadherent patients in an animal model of epilepsy to study how alterations to pharmacotherapy, made without consideration of a patient's adherence, result in changes to seizure control. METHODS: Newly diagnosed rats with epilepsy were treated with carbamazepine (CBZ) during a 4-week baseline period to establish their baseline seizure rate in the presence of 50% adherence. Next, animals were randomized to one of three treatment interventions and monitored for 6 weeks. Groups included: (1) no change in therapy-rats continued the 50% adherent paradigm; (2) dose escalation-the dose of CBZ was doubled, and the 50% adherent paradigm continued; and (3) nonadherence corrected-rats continued the initial dose of CBZ, but the adherence rate was adjusted to 100% (ie, fully adherent). RESULTS: The rats in the no change in therapy arm displayed a 61% increase in seizure burden over the 6-week intervention phase. Similarly, rats in the dose escalation arm had a 66% worsening of their daily seizure burden. In contrast, rats in the nonadherence corrected arm displayed a 33% reduction in their daily seizure burden; a significant improvement when compared to the normalized seizure burden scores of rats in the other two treatment arms (P < 0.01). SIGNIFICANCE: We found that failure to correct medication nonadherence resulted in an increase in daily seizure burden in rats, even following dose escalation. In the presence of nonadherence, dose escalation worsened seizure control. In contrast, correcting nonadherence alone resulted in improved seizure control. These findings suggest that improving adherence should be prioritized over dose escalation in the clinical management of uncontrolled epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Adesão à Medicação , Convulsões/prevenção & controle , Animais , Anticonvulsivantes/administração & dosagem , Carbamazepina/administração & dosagem , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia/psicologia , Masculino , Ratos , Ratos Sprague-Dawley
16.
World J Surg ; 43(3): 659-695, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30426190

RESUMO

BACKGROUND: This is the fourth updated Enhanced Recovery After Surgery (ERAS®) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded recommendations for each ERAS item within the ERAS® protocol. METHODS: A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS® protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly. CONCLUSIONS: The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS® Society in this comprehensive consensus review.


Assuntos
Colo/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Eletivos , Assistência Perioperatória , Guias de Prática Clínica como Assunto , Reto/cirurgia , Protocolos Clínicos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos Eletivos/métodos , Humanos , Assistência Perioperatória/métodos , Recuperação de Função Fisiológica
17.
J Intellect Disabil Res ; 63(12): 1441-1452, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31497918

RESUMO

BACKGROUND: People with intellectual disability (ID) experience age-related changes earlier in life, and as such, falls among people with ID are of serious concern. Falls can cause injury and consequently reduce quality of life. Limited studies have investigated the incidence of falls among people with ID and the associated risk factors. The purpose of this study was to investigate the incidence of falls and risk factors for falling in people with ID living in the community. METHODS: A prospective observational cohort (n = 78) of community-dwelling adults with ID. Characteristics measured at baseline included falls history, medication use, balance and mobility. Falls were reported for 6 months using monthly calendars and phone calls. Data were analysed using univariate and multivariate logistic regression to identify risk factors associated with falling. RESULTS: Participants [median (interquartile range) age 49 (43-60) years, female n = 32 (41%)] experienced 296 falls, with 36 (46.2%) participants having one or more falls. The incidence of falls was 5.7 falls (injurious falls = 0.8) per person year (one outlier removed from analysis). A history of falls [adjusted odds ratio (OR): 6.37, 95% confidence interval (CI) (1.90-21.34)] and being ambulant [adjusted OR: 4.50, 95% CI (1.15-17.67)] were associated with a significantly increased risk of falling. Falls were significantly less frequent among participants taking more than four medications [adjusted OR: 0.22, 95% CI (0.06-0.83)] and participants who were continent [adjusted OR: 0.25, 95% CI (0.07-0.91)]. CONCLUSIONS: People with ID fall at a younger age compared with the broader community. The associated falls risk factors also differ to older community-dwelling adults. Health professionals should prioritise assessment and management of falls risk in this population.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Deficiência Intelectual/epidemiologia , Adulto , Feminino , Humanos , Incidência , Deficiência Intelectual/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
18.
BMC Surg ; 19(1): 85, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286905

RESUMO

BACKGROUND: Enterovesical fistula (EVF) is a abnormal connection between the intestine and the bladder. The aim of the study was to analyze whether closure of the defect in the bladder wall during surgery is always necessary. METHODS: Fifty-nine patients with benign EVF undergoing surgical treatment were enrolled. A one-stage surgical procedure was performed in all patients. After the separation of the diseased bowel segment, methylene blue was introduced. Through a catheter into the bladder. Only patients with urinary bladder leakage were sutured. RESULTS: The most common intestinal fistula involving the urinary bladder was colovesical fistula, observed in 53% of cases. Two-thirds of patients had diverticular disease as the underlying pathology. There was no relationship between suturing of the bladder and perioperative complications. Recurrent EVF was observed in one patient with bladder suturing and in two patients without suture. CONCLUSIONS: These findings suggest that closure of the bladder defect is not necessary in cases where a leak is not demonstrated from the bladder intraoperatively. This study is limited by its retrospective design and small numbers and a randomized controlled trial is recommended to answer this question definitively.


Assuntos
Fístula Intestinal/etiologia , Fístula da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Técnicas de Sutura , Fístula da Bexiga Urinária/etiologia
19.
BMC Med Educ ; 19(1): 263, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311546

RESUMO

BACKGROUND: Adequate clinical skills training is a challenge for present day medical education. Simulation Based Education (SBE) is playing an increasingly important role in healthcare education worldwide to teach invasive procedures. The impact of this teaching on students along with retention of what is taught is not fully understood. The purpose of this study was to evaluate the retention levels of practical skills taught and assessed by SBE and to explore the degree of re-training required to restore decayed performance. In exploring this aim, the study further investigates how skilled performance decays over time and which dimensions of clinical skills were more likely to decay. METHODS: Study participants were 51 final year medical students. They were provided with online pre-course videos and procedural guides asynchronously with repeatedly access. 7 of the skills taught over 2 years using task trainers were selected. Following demonstration from faculty, students practiced in small groups with faculty facilitated supervision and peer support prior to formal testing. Score sheets with itemised procedure checklists detailing the minimum passing standard (MPS) for each skill were designed. To test retention of skills, 18 months later, there was an unannounced test to demonstrate proficiency in the skills. Students were asked to complete a questionnaire indicating how many times and where they had practiced or performed the skills. RESULTS: 55% of the students were deficient in 3 or more skills and 4% were not competent in 5 or more skills. A significant number of students had never practiced some skills following the initial teaching session. A relationship was noted with the number of times students self-declared that they had practiced and their performance. Decay is evident in both psychomotor and cognitive domains of the skills. CONCLUSION: A curriculum with deliberate practice significantly increases the competence of students in defined clinical skills. Deliberate practice of clinical skills, under supervision of an engaged instructor, is a key component of the mastery model. Experiences and assessments in the clinical setting need to be augmented with focus on direct observation and focused feedback to reinforce the skills acquired in the simulated setting.


Assuntos
Competência Clínica , Currículo , Educação de Graduação em Medicina/métodos , Retenção Psicológica , Treinamento por Simulação/métodos , Estudos de Coortes , Feminino , Humanos , Irlanda , Masculino , Estudos Prospectivos , Estudantes de Medicina/estatística & dados numéricos , Adulto Jovem
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