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1.
Artigo em Inglês | MEDLINE | ID: mdl-38366682

RESUMO

BACKGROUND: Non-obstructive azoospermia (NOA) diagnosis poses challenges for couples seeking parenthood. Microdissection testicular sperm extraction (MD-TESE) excels in retrieving testicular sperm cells for NOA cases. However, limited live birth data in Australian NOA patients hinders accurate counselling. AIMS: This study aimed to determine the likelihood of infertile couples with a male partner diagnosed with NOA conceiving biological children using MD-TESE / intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: A retrospective cohort study included 108 NOA men treated at a public fertility unit and a private fertility centre (May 2009-May 2022). PRIMARY OUTCOME: live birth rate (LBR); secondary outcomes: sperm retrieval rate, pregnancy rate, and neonatal outcomes. RESULTS: Among 108 patients undergoing MD-TESE, the positive sperm retrieval rate (PSRR) was 64.8% (70/108). Histology best predicted sperm retrieval success, with hypo-spermatogenesis yielding a 94.1% PSRR. Age, testicular volume, and hormonal parameters had no significant impact. Mean male age: 35.4 years; mean partner age: 32.7 years. Fertilisation rate: 50.7%. LBR per initiated cycle: 58.7% (37/63); per embryo transfer: 63.8% (37/58); per initially diagnosed NOA man: 34.3% (37/108). Cumulative LBR: 74.1% (43/58); twin rate: 10.8% (4/37). No neonatal deaths or defects were observed among 47 live offspring. CONCLUSION: This study provides valuable data for counselling NOA couples on the probability of conceiving biological offspring. MD-TESE and ICSI yielded favourable PSRR (64.8%) and LBR (63.8%). However, couples should be aware that once NOA is confirmed, the chance of taking home a baby is 34%.

2.
J Cardiothorac Surg ; 18(1): 348, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037117

RESUMO

BACKGROUND: The aim of this review was the creation of uniform protocols to carry out and disclose First-In-Human and preliminary clinical trials of biological mitral valve replacement. The need for consistent methodology in these early trials was highlighted by the observation of significant variability in the methods and protocols used across different research. METHODS: An extensive search through six major databases was carried out to retrieve First-In-Human (FIH) clinical studies evaluating surgically implanted bio-prostheses in the mitral position. RESULTS: Following the PRISMA guideline, a systematic search identified 2082 published articles until March 2023. After removing duplicates (189), 1862 citations were screened, resulting in 22 eligible studies with 3332 patients for analysis. The mitral valve prostheses in these studies ranged from 21 to 37 mm, with the 29 mm size being most prevalent. Patient numbers varied, with the FIH subgroup including 31 patients and the older subgroup including 163 patients. Average study durations differed: the older subgroup lasted 4.57 years, the FIH subgroup 2.85 years, and the early phase studies spanned 8.05 years on average. CONCLUSION: FIH clinical report is essential to assess the significance of clinical data required for a "de novo" surgical implant. In addition, understanding the performance of the device, and recognizing the difficulties associated with the innovation constitute important lessons. These insights could be beneficial for the development of bioprosthetic heart valves and formulating a protocol for an FIH clinical trial.


Assuntos
Bioprótese , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Humanos , Valva Mitral/cirurgia , Desenho de Prótese , Implante de Prótese de Valva Cardíaca/métodos , Falha de Prótese
3.
Front Genet ; 14: 1242180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779907

RESUMO

Background: Men diagnosed with Klinefelter syndrome (KS) commonly exhibit non-obstructive azoospermia or rarely having sperm in their ejaculate, rendering them traditionally considered sterile prior to the introduction of intracytoplasmic sperm injection (ICSI). The presence of mosaic KS may mask the classical phenotype, resulting in underdiagnosis throughout their lifetime. Surgical sperm retrieval through Microdissection Testicular Sperm Extraction (Micro-TESE) combined with ICSI has become the gold standard approach, maximizing reproductive outcomes in these individuals. However, it is noteworthy that approximately 7% of men with KS may exhibit sperm in their ejaculate, providing an opportunity for them to achieve biological parenthood through ICSI. Case Presentation: In this report, we present an exceptional case of a 45-year-old man with Mosaic KS and severe oligozoospermia who successfully achieved pregnancy utilizing ICSI with freshly ejaculated sperm. Remarkably, this case represents the oldest recorded instance of a man with Klinefelter syndrome fathering his own biological child using sperm derived from fresh ejaculate. Conclusion: Although this case is exceedingly rare, it underscores the critical importance of exhausting all possibilities to facilitate biological parenthood in men with KS before considering alternative options such as sperm donation or adoption. By recognizing the potential for successful conception using ejaculated sperm in this population, we can provide individuals with mosaic KS the opportunity to fulfill their desire for biological offspring.

4.
J Pers Med ; 13(10)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37888094

RESUMO

Personalized surgery is not just a new trend but rather a patient-specific approach to therapy that makes it possible to adopt a targeted approach for a specific patient and closely mirrors the approach of personalized medicine. However, the application of tailored surgery in the context of cardiovascular replacement surgery has not been systematically reviewed. The ability to customize a device is highly dependent on the collection of radiological image data for precise prosthesis modeling. These facts are essential to "tailor-made" device design for precise prosthesis implantation. According to this study, computed tomography (CT) was the most prominent imaging modality; however, transesophageal echocardiography and echocardiography were also found to be helpful. Additionally, a dynamic finite element simulation was also found to be an attractive alternative to the finite element analysis for an in-silico experiment. Nonetheless, there is a paucity of relevant publications and only sporadic evidence. More clinical studies have been warranted, notwithstanding that the derived data and results from this insight into the use of therapeutic interventions may be evidence of multiple directives in clinical practices and beyond. This study may help the integration of personalized devices for better comprehension of predicted clinical outcomes, thus leading towards enhanced performance gains.

5.
Am J Lifestyle Med ; 16(6): 717-722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389048

RESUMO

We have previously proposed a list of determinants (causes) of modern lifestyle-related chronic disorders, which provides a structure for the emerging discipline of lifestyle medicine. This consists of lifestyle factors with a common immune biomarker (metaflammation) that interact in a systems fashion linked with chronic disease outcomes. We considered this to be a work in progress and later added 3 psychosocial determinants into the causal mix: meaninglessness, alienation, and loss of culture and identity (MAL). Here, we propose adverse childhood experiences (ACEs) as deeper, or even more distal, disease drivers that may act directly or indirectly through MAL to influence later chronic disease. The links with metaflammation and the need for recognition of these embedded scars in the management of lifestyle-related health problems is discussed.

6.
Intern Med J ; 52(11): 1998-2000, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36114725

RESUMO

The COVID-19 pandemic has exposed the deficiencies of the current healthcare system in terms of a disconnect between primary and tertiary care and increasing subspecialisation, the focus on acute episodic care rather than on prevention in a time where chronic disease prevails and an inefficient use of healthcare resources. Herein, we present the case for an alternative model of healthcare delivery - shared medical appointments - which are efficient, effective and empowering and can be transitioned to the virtual environment successfully. We highlight the barriers to implementation and how these can be overcome.


Assuntos
COVID-19 , Humanos , Pandemias/prevenção & controle , Atenção à Saúde
7.
Aust J Prim Health ; 28(6): 573-579, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36038358

RESUMO

BACKGROUND: Overweight and obesity has a bi-directional association with the growing burden of musculoskeletal (MSk) dysfunction and pain. It seems inevitable that MSk practitioners will see increasing numbers of patients who are overweight and or obese and require this to be addressed as part of their management. Little evidence exists to describe the engagement of patients and their MSk practitioner in weight management as an adjunct or direct component of their intervention or therapy. METHODS: A self-administered electronic survey was constructed with 13 items to collect self-reported data from Australian practitioners who have a focus on MSk management. The target group was from a multidisciplinary MSk network of 350 members. RESULTS: A total of 204 completed surveys were analysed from respondents working in one of seven MSk- related professions. It was found that 70% of patients/clients seen by respondents were overweight or obese and that <18% of these patients had weight management included as part of their treatment. CONCLUSIONS: Sixty percent of the respondents in this survey indicated that they do not include weight management as part of their practice despite 70% of their patients/clients being overweight and or obese. With the exception of Medical Practitioners and Exercise Physiologists, in this survey, the other therapists including Chiropractors, Osteopaths, Physiotherapists and Occupational Therapists, indicated that they lacked confidence, knowledge and methods to engage a systematic approach to weight management with their patients/clients.


Assuntos
Manejo da Obesidade , Humanos , Austrália , Exercício Físico , Atenção Primária à Saúde
8.
J Assist Reprod Genet ; 39(2): 417-425, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35043277

RESUMO

PURPOSE: This study aims to examine whether blastocyst morphology post-warming correlates with live birth. METHODS: In this cohort study, morphological characteristics post-warming were reviewed in all single vitrified-warmed blastocyst transfer cycles performed between November 2016 and May 2017. Immediately before transfer, the degree of blastocoel re-expansion was graded as A, fully expanded; B, partially expanded ≥ 50%; C, partially expanded < 50%; and D, collapsed. The degree of post-warming cell survival was graded on a scale of 50 to 100% and was then classified into 4 groups: very low 50-70%, low 71-80%, moderate 81-90%, and high 91-100%. RESULTS: Overall, 612 cycles were reviewed, of which 196 included PGT-A tested embryos. The live birth rate (LBR) increased from 11.4% in the collapsed blastocysts group to 38.9% in the post-warming full re-expansion group (p < 0.001) and from 6.5% for blastocysts with a very low cell survival rate to 34.7% for blastocysts with high cell survival rate (p = 0.001). LBR was 6.7% for blastocysts with the worst post-warming morphological characteristics, namely, collapsed with very low cell survival rate. On multivariate analyses, partial blastocyst re-expansion ≥ 50%, full re-expansion, and high cell survival rate remained significantly associated with live birth, after controlling for female age, pre-vitrification morphological grading, and PGT-A. A sub-analysis of cycles using PGT-A tested embryos showed similar results. CONCLUSION: Post-warming re-expansion and high cell survival rate are associated with higher LBR in euploid and untested blastocysts. However, embryos with poor post-warming morphology still demonstrate a considerable probability of live birth, and they should not be discarded.


Assuntos
Criopreservação , Nascido Vivo , Blastocisto , Estudos de Coortes , Criopreservação/métodos , Transferência Embrionária/métodos , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Vitrificação
9.
Aust Health Rev ; 46(4): 426-431, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34809748

RESUMO

Personal recovery is central to Australian mental health standards, but promoting recovery-oriented practice remains a wicked problem (ie complex, with definitions and appropriate interventions impacted upon by context and values), with limited evidence regarding effective implementation. This case study re-examines a statewide initiative to enhance recovery-oriented practice in older people's mental health services in New South Wales from the perspective of complex adaptive systems. The initiative consisted of three key strategies: (1) statewide collaborative leadership and practice resources; (2) locally determined and led improvement projects; and (3) evaluating, disseminating and sustaining initiative outcomes. Published outcomes of the initiative, related policy and benchmarking materials and author reflections are used to propose lessons for other services and policy makers. From a systems perspective, a relatively small investment from a state policy unit to enhance a facilitating environment resulted in the emergence of local leaders and voluntary participation of services within 80% of local health districts without funding incentives. Local leaders and activities informed statewide policies and models of care to sustain practice change. Limitations included variability in project scopes and the involvement of people with lived experience, as well as the level of refinement in change management approach. Self-audit and consumer-rated experience suggest resilience of practice and culture change. The outcomes are consistent with conceptualisations of mental health services being complex adaptive systems requiring distributive leadership. Established mechanisms encouraging statewide cooperation between clinicians, service managers and policy makers may have been significant facilitators of engagement in practice change. What is known about this topic? Recovery remains an important concept for older people with mental ill health, with implementation of recovery-oriented practice a wicked problem. What does this paper add? Central policy investment in a collaborative facilitatory environment can stimulate the emergence of local leadership and investment in actions to enhance recovery orientation. As predicted by complex adaptive systems theory, the impact of the leaders developed may be broader than the sum of individual project outcomes. What are the implications for practitioners? A start where you can message can engage and enable leaders in feasible and locally relevant changes consistent with a statewide strategy. This may be a feasible approach to improving recovery orientation in mental health care services for and beyond older people, with potential implications for addressing other wicked problems in health care.


Assuntos
Serviços de Saúde Mental , Idoso , Austrália , Humanos , Liderança , Saúde Mental , New South Wales
10.
PLoS One ; 16(5): e0250963, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33939757

RESUMO

Time-to-event analysis is a common occurrence in political science. In recent years, there has been an increased usage of machine learning methods in quantitative political science research. This article advocates for the implementation of machine learning duration models to assist in a sound model selection process. We provide a brief tutorial introduction to the random survival forest (RSF) algorithm and contrast it to a popular predecessor, the Cox proportional hazards model, with emphasis on methodological utility for political science researchers. We implement both methods for simulated time-to-event data and the Power-Sharing Event Dataset (PSED) to assist researchers in evaluating the merits of machine learning duration models. We provide evidence of significantly higher survival probabilities for peace agreements with 3rd party mediated design and implementation. We also detect increased survival probabilities for peace agreements that incorporate territorial power-sharing and avoid multiple rebel party signatories. Further, the RSF, a previously under-used method for analyzing political science time-to event data, provides a novel approach for ranking of peace agreement criteria importance in predicting peace agreement duration. Our findings demonstrate a scenario exhibiting the interpretability and performance of RSF for political science time-to-event data. These findings justify the robust interpretability and competitive performance of the random survival forest algorithm in numerous circumstances, in addition to promoting a diverse, holistic model-selection process for time-to-event political science data.


Assuntos
Gerenciamento de Dados/métodos , Condições Sociais/estatística & dados numéricos , Algoritmos , Aprendizado de Máquina , Probabilidade
11.
AIDS ; 35(6): 957-970, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33470609

RESUMO

OBJECTIVE AND DESIGN: People living with HIV (PLH) suffer disproportionately from the chronic diseases exacerbated by smoking tobacco. We performed a systematic review and meta-analysis to establish the relative prevalence of smoking among PLH. METHODS: We included observational studies reporting current smoking rates among PLH and comparators without HIV. We searched Medline, EMBASE, LILACS and SciELO from inception to 31 August 2019. We excluded studies that recruited participants with smoking related illness. We used a random effects model to estimate the odds ratio for current smoking in PLH and people without HIV. We used the Newcastle--Ottawa scale to assess methodological bias. We performed subgroup analysis based on sex and WHO region. We quantified heterogeneity with meta-regression and predictive distributions. PROSPERO registration:CRD42016052608. RESULTS: We identified 6116 studies and included 37. Of 111 258 PLH compared with 10 961 217 HIV-negative participants pooled odds of smoking were 1.64 [(95% confidence interval, 95% CI: 1.45-1.85) (95% prediction interval: 0.66-4.10, I2 = 98.1%)]. Odds for men and women living with HIV were 1.68 [(95% CI: 1.44-1.95) (95% prediction interval: 0.71-3.98, I2 = 91.1%)] and 2.16 [(95% CI: 1.77-2.63) (95% prediction interval: 0.92-5.07, I2 = 81.7%)] respectively. CONCLUSION: PLH are more likely to be smokers than people without HIV. This finding was true in subgroup analyses of men, women and in four of five WHO regions from which data were available. Meta-regression did not explain heterogeneity, which we attribute to the diversity of PLH populations worldwide. Smoking is a barrier to PLH achieving parity in life expectancy and an important covariate in studies of HIV-associated multimorbidity.


Assuntos
Infecções por HIV , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Masculino , Razão de Chances , Gravidez , Prevalência , Fumar/epidemiologia , Fumar Tabaco
12.
Semin Thorac Cardiovasc Surg ; 33(2): 299-302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33171249

RESUMO

Cardiothoracic surgeons are uniquely and expertly positioned to be innovators. Innovation is an iterative process by which unmet needs are identified, a solution is invented, and the results are implemented. A team approach is required, with participation from a variety of experts including the surgeon-innovator. Innovation can be practiced on a multitude of pathways including basic science, clinical science, and commercialization. Economics realities are often the ultimate determinant in the success or failure of any innovative effort. In this manuscript, we aim to define innovation, describe the innovative process, and demonstrate how these principles can, and should, be enacted by cardiothoracic surgeon-innovators.


Assuntos
Cirurgiões , Humanos
13.
Front Endocrinol (Lausanne) ; 11: 570777, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123089

RESUMO

Introduction: Type 2 diabetes (T2DM) is a major health concern with significant personal and healthcare system costs. There is growing interest in using shared medical appointments (SMAs) for management of T2DM. We hypothesize that adding mindfulness to SMAs may be beneficial. This study aimed to assess the feasibility and acceptability of SMAs with mindfulness for T2DM within primary care in Australia. Materials and Methods: We conducted a single-blind randomized controlled feasibility study of SMAs within primary care for people with T2DM living in Western Sydney, Australia. People with T2DM, age 21 years and over, with HbA1c > 6.5% or fasting glucose >7.00 mmol/L within the past 3 months were eligible to enroll. The intervention group attended six 2-h programmed SMAs (pSMAs) which were held fortnightly. pSMAs included a structured education program and mindfulness component. The control group received usual care from their healthcare providers. We collected quantitative and qualitative data on acceptability as well as glycemic control (glycated hemoglobin and continuous glucose monitoring), lipids, anthropometric measures, blood pressure, self-reported psychological outcomes, quality of life, diet, and physical activity using an ActiGraph accelerometer. Results: Over a 2-month period, we enrolled 18 participants (10 females, 8 males) with a mean age of 58 years (standard deviation 9.8). We had 94.4% retention. All participants in the intervention group completed at least four pSMAs. Participants reported that attending pSMAs had been a positive experience that allowed them to accept their diagnosis and empowered them to make changes, which led to beneficial effects including weight loss and better glycemic control. Four pSMA participants found the mindfulness component helpful while two did not. All of the seven participants who contributed to qualitative evaluation reported improved psychosocial wellbeing and found the group setting beneficial. There was a significant difference in total cholesterol levels at 12 weeks between groups (3.86 mmol/L in intervention group vs. 4.15 mmol/L in the control group; p = 0.025) as well as pain intensity levels as measured by the PROMIS-29 (2.11 vs. 2.38; p = 0.034). Conclusion: pSMAs are feasible and acceptable to people with T2DM and may result in clinical improvement. A follow-up fully-powered randomized controlled trial is warranted. Clinical Trial Registration: Australia and New Zealand Clinical Trial Registry, identifier ACTRN12619000892112.


Assuntos
Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/terapia , Atenção Plena/métodos , Comportamento de Redução do Risco , Consultas Médicas Compartilhadas , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Exercício Físico/fisiologia , Exercício Físico/psicologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Plena/tendências , Estudos Prospectivos , Consultas Médicas Compartilhadas/tendências , Método Simples-Cego , Redução de Peso/fisiologia
14.
ACS Omega ; 5(17): 9830-9838, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32391470

RESUMO

The compound dimethyl sulfide (DMS) links terrestrial and oceanic sulfur with the atmosphere because of its volatility. Atmospheric DMS is responsible for cloud formation and radiation backscattering and has been implicated in climate control mitigation. The enzyme DMS C-monooxygenase degrades DMS and has been classified as a two-component FMNH2-dependent monooxygenase. This enzyme requires a flavin reductase B subunit to supply electrons to the monooxygenase A subunit where DMS conversion occurs. One form of the enzyme from Hyphomicrobium sulfonivorans has been isolated and characterized. In this work, a putative DMS C-monooxygenase has been identified with bioinformatics in Arthrobacter globiformis. We report the expression, purification, and characterization of the DmoB flavin reductase subunit, termed DmoB, from A. globiformis. Data support DmoB preference and optimal activity for the cosubstrates flavin mononucleotide (FMN) and NADH. FMN binds at a 1:1 stoichiometry with high affinity (K d = 1.11 µM). The reductase is able to generate product with the A subunit from H. sulfonivorans expressed in Escherichia coli, albeit at a lower turnover than the natively expressed enzyme. No static protein-protein interactions were observed under the conditions tested between the two subunits. These results provide new details in the classification of enzymes involved in the sulfur cycling pathway and emerging forms of the enzyme DMS monooxygenase.

15.
Am J Lifestyle Med ; 14(2): 114-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231472

RESUMO

Most advances in humanity have been related to the discovery or introduction of new innovations and/or technology. There should be no suggestion that all technology is pathological or that major advances in health, science, and well-being have not come from industrial and technological advances. However, just like the invention of the wheel would have no doubt caused people to be injured and modern lifesaving medicines can have side effects, modern technology can have a downside, which needs to be recognized. This article explores some of the pathologies linked to small screen and internet technologies (personal computers, communication devices, and the internet). The uptake and impact of this set of technologies is pivotal in redefining our lifestyle behaviors and environment: the way we work, shop, seek entertainment, communicate, socialize, reproduce, interact with the environment, and seek information.

16.
Am J Lifestyle Med ; 14(2): 147-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231480

RESUMO

Lifestyle medicine commenced in Australia in response to the rise in chronic diseases following the epidemiological transition that began in the 1980s. Today, it is flourishing with an annual conference, a variety of multidisciplinary members, and a developed pedagogy for the "art-science."

18.
J Thromb Haemost ; 18(2): 422-438, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31654551

RESUMO

BACKGROUND: Thromboprophylaxis has the potential to reduce venous thromboembolism (VTE) following lower limb immobilization resulting from injury. OBJECTIVES: We aimed to estimate the effectiveness of thromboprophylaxis, compare different agents, and identify any factors associated with effectiveness. METHODS: We undertook a systematic review and network meta-analysis (NMA) of randomized trials reporting VTE or bleeding outcomes that compared thromboprophylactic agents with each other or to no pharmacological prophylaxis, for this indication. An NMA was undertaken for each outcome or agent used, and a series of study-level network meta-regressions examined whether population characteristics, type of injury, treatment of injury, or duration of thromboprophylaxis were associated with treatment effect. RESULTS: Data from 6857 participants across 13 randomized trials showed that, compared with no treatment, low molecular weight heparin (LMWH) reduced the risk of any VTE (odds ratio [OR]: 0.52; 95% credible interval [CrI]: 0.37-0.71), clinically detected deep vein thrombosis (DVT) (OR: 0.39; 95% CrI: 0.12-0.94) and pulmonary embolism (PE) (OR: 0.16; 95% CrI: 0.01-0.74), whereas fondaparinux reduced the risk of any VTE (OR: 0.13; 95% CrI: 0.05-0.30) and clinically detected DVT (OR: 0.10; 95% CrI: 0.01-0.86), with inconclusive results for PE (OR: 0.40; 95% CrI: 0.01-7.53). CONCLUSIONS: Thromboprophylaxis with either fondaparinux or LMWH appears to reduce the odds of both asymptomatic and clinically detected VTE in people with temporary lower limb immobilization following an injury. Treatment effects vary by outcome and are not always conclusive. We were unable to identify any treatment effect modifiers other than thromboprophylactic agent used.


Assuntos
Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular , Humanos , Extremidade Inferior , Metanálise em Rede , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/prevenção & controle
19.
Pharmacoeconomics ; 38(2): 193-204, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31761997

RESUMO

BACKGROUND AND OBJECTIVE: The extrapolation of estimated hazard functions can be an important part of cost-effectiveness analyses. Given limited follow-up time in the sample data, it may be expected that the uncertainty in estimates of hazards increases the further into the future they are extrapolated. The objective of this study was to illustrate how the choice of parametric survival model impacts on estimates of uncertainty about extrapolated hazard functions and lifetime mean survival. METHODS: We examined seven commonly used parametric survival models and described analytical expressions and approximation methods (delta and multivariate normal) for estimating uncertainty. We illustrate the multivariate normal method using case studies based on four representative hypothetical datasets reflecting hazard functions commonly encountered in clinical practice (constant, increasing, decreasing, or unimodal), along with a hypothetical cost-effectiveness analysis. RESULTS: Depending on the survival model chosen, the uncertainty in extrapolated hazard functions could be constant, increasing or decreasing over time for the case studies. Estimates of uncertainty in mean survival showed a large variation (up to sevenfold) for each case study. The magnitude of uncertainty in estimates of cost effectiveness, as measured using the incremental cost per quality-adjusted life-year gained, varied threefold across plausible models. Differences in estimates of uncertainty were observed even when models provided near-identical point estimates. CONCLUSIONS: Survival model choice can have a significant impact on estimates of uncertainty of extrapolated hazard functions, mean survival and cost effectiveness, even when point estimates were similar. We provide good practice recommendations for analysts and decision makers, emphasizing the importance of considering the plausibility of estimates of uncertainty in the extrapolated period as a complementary part of the model selection process.


Assuntos
Ensaios Clínicos como Assunto , Análise Custo-Benefício , Modelos Econômicos , Modelos de Riscos Proporcionais , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Humanos , Funções Verossimilhança , Método de Monte Carlo , Análise de Sobrevida , Incerteza
20.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875422

RESUMO

Poor maternal nutrition during gestation can have immediate and life-long negative effects on offspring growth and health. In livestock, this leads to reduced product quality and increased costs of production. Based on previous evidence that both restricted- and overfeeding during gestation decrease offspring muscle growth and alter metabolism postnatally, we hypothesized that poor maternal nutrition during gestation would reduce the growth and development of offspring muscle prenatally, reduce the number of myogenic progenitor cells, and result in changes in the global expression of genes involved in prenatal muscle development and function. Ewes were fed a control (100% NRC)-, restricted (60% NRC)-, or overfed (140% NRC) diet beginning on day 30 of gestation until days 45, 90, and 135 of gestation or until parturition. At each time point fetuses and offspring (referred to as CON, RES, and OVER) were euthanized and longissimus dorsi (LM), semitendinosus (STN), and triceps brachii (TB) were collected at each time point for histological and RNA-Seq analysis. In fetuses and offspring, we did not observe an effect of diet on cross-sectional area (CSA), but CSA increased over time (P < 0.05). At day 90, RES and OVER had reduced secondary:primary muscle fiber ratios in LM (P < 0.05), but not in STN and TB. However, in STN and TB percent PAX7-positive cells were decreased compared with CON (P < 0.05). Maternal diet altered LM mRNA expression of 20 genes (7 genes downregulated in OVER and 2 downregulated in RES compared with CON; 5 downregulated in OVER compared with RES; false discovery rate (FDR)-adj. P < 0.05). A diet by time interaction was not observed for any genes in the RNA-Seq analysis; however, 2,205 genes were differentially expressed over time between days 90 and 135 and birth (FDR-adj. P < 0.05). Specifically, consistent with increased protein accretion, changes in muscle function, and increased metabolic activity during myogenesis, changes in genes involved in cell cycle, metabolic processes, and protein synthesis were observed during fetal myogenesis. In conclusion, poor maternal nutrition during gestation contributes to altered offspring muscle growth during early fetal development which persists throughout the fetal stage. Based on muscle-type-specific effects of maternal diet, it is important to evaluate more than one type of muscle to fully elucidate the effects of maternal diet on offspring muscle development.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Fenômenos Fisiológicos da Nutrição Materna , Desenvolvimento Muscular , Músculo Esquelético/embriologia , Ovinos/embriologia , Ovinos/fisiologia , Fenômenos Fisiológicos da Nutrição Animal/genética , Animais , Dieta/veterinária , Regulação para Baixo/genética , Feminino , Desenvolvimento Fetal/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Imuno-Histoquímica/veterinária , Masculino , Fenômenos Fisiológicos da Nutrição Materna/genética , Desenvolvimento Muscular/genética , Gravidez , Análise de Sequência de RNA/veterinária , Ovinos/genética , Fatores de Tempo , Regulação para Cima/genética , Vitaminas/administração & dosagem
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