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1.
Artigo em Inglês | MEDLINE | ID: mdl-38196127

RESUMO

AIMS: Catheter-based radiofrequency renal denervation (RF RDN) has recently been approved for clinical use in the European Society of Hypertension guidelines and by the US FDA. This study evaluated the lifetime cost-effectiveness of RF RDN using contemporary evidence. METHODS AND RESULTS: A decision-analytic model based on multivariate risk equations projected clinical events, quality-adjusted life years (QALYs) and costs. The model consisted of seven health states: hypertension alone, myocardial infarction (MI), other symptomatic coronary artery disease, stroke, heart failure (HF), end-stage renal disease, and death. Risk reduction associated with changes in office systolic blood pressure (oSBP) was estimated based on a published meta-regression of hypertension trials. The base case effect size of -4.9 mmHg oSBP (observed vs. sham control) was taken from the SPYRAL HTN-ON MED trial of 337 patients. Costs were based on NHS England data. The incremental cost-effectiveness ratio (ICER) was evaluated against the NICE cost-effectiveness threshold of £20 000-30 000 per QALY gained. Extensive scenario and sensitivity analyses were conducted, including the ON-MED subgroup on three medications and pooled effect sizes. RF RDN resulted in a relative risk reduction in clinical events over 10 years (0.80 for stroke, 0.88 for MI, 0.72 for HF), with an increase in health benefit over a patient's lifetime, adding 0.35 QALYs at a cost of £4 763, giving an ICER of £13 482 per QALY gained. Findings were robust across tested scenarios. CONCLUSION: Catheter-based radiofrequency RDN can be a cost-effective strategy for uncontrolled hypertension in the UK, with an ICER substantially below the NICE cost-effectiveness threshold. Funding: Medtronic Inc.

2.
J Prev Med Public Health ; 57(1): 37-46, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38147822

RESUMO

OBJECTIVES: The objective of this study was to characterize mental health issues among Vietnamese healthcare workers (HCWs) and to identify related factors. METHODS: A cross-sectional study was conducted with 990 HCWs in 2021. Their mental health status was measured using the Depression, Anxiety, and Stress Scale. RESULTS: In total, 49.9%, 52.3%, and 29.8% of respondents were found to have depression, anxiety, and stress, respectively. The multivariable linear regression model revealed that factors associated with increased anxiety scores included depression scores (ß, 0.45; 95% confidence interval [CI], 0.39 to 0.51) and stress scores (ß, 0.46; 95% CI, 0.41 to 0.52). Factors associated with increased depression scores included being frontline HCWs (ß, 0.57; 95% CI, 0.10 to 1.10), stress scores (ß, 0.50; 95% CI, 0.45 to 0.56), and anxiety scores (ß, 0.41; 95% CI, 0.36 to 0.47), while working experience was associated with reduced depression scores (ß, -0.08; 95% CI, -0.16 to -0.01). Factors associated with increased stress scores included working experience (ß, 0.08; 95% CI, 0.00 to 0.16), personal protective equipment interference with daily activities (ß, 0.55; 95% CI, 0.07 to 1.00), depression scores (ß, 0.54; 95% CI, 0.48 to 0.59), and anxiety scores (ß, 0.45; 95% CI, 0.39 to 0.50), while age was associated with reduced stress scores (ß, -0.12; 95% CI, -0.20 to -0.05). CONCLUSIONS: Specific interventions are necessary to enhance and promote the mental health of HCWs so they can successfully cope with the circumstances of the pandemic.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Vietnã/epidemiologia , Saúde Mental , Pandemias , Estudos Transversais , Depressão/epidemiologia , Pessoal de Saúde , Ansiedade/epidemiologia
3.
Heliyon ; 9(9): e20004, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37810012

RESUMO

The food selection and processing stage are important stages to prevent food poisoning. A good level of knowledge and practice regarding food selection and processing among people who are responsible for the family meals are important. In this study, we aimed to investigate the knowledge and practice of primary food caregivers regarding food poisoning prevention in food selection and processing and identify the factors that influence these outcomes. The current study applied a cross-sectional study to investigate 422 primary food caregivers in urban areas in Vietnam. Data were collected using a structured questionnaire, and knowledge and practice were assessed based on pre-defined criteria. The data were analyzed using descriptive statistics, chi-square test, and logistic regression. Our study found that 78.9% of people had good knowledge regarding food poisoning prevention in food selection and processing. Furthermore, 84.4% of people had correct practice in this regard. Our study also revealed that household income level and educational level were associated with knowledge and practice, respectively. The proportion of correct practice was higher in the group with good knowledge (90.4%) compared to the remaining group (61.8%). The results indicated that the proportion of good knowledge and practice were high among food caregivers, but further efforts are needed to improve the knowledge and practice of food caregivers with lower household income and educational levels. The findings also emphasize the importance of communication campaigns to enhance knowledge related to food poisoning prevention.

4.
Neurol Ther ; 12(6): 2133-2146, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37824047

RESUMO

INTRODUCTION: Tonic motor activation (TOMAC) therapy is a novel non-pharmacologic treatment approach for patients suffering from medication-refractory restless legs syndrome (RLS). The objective of this study was to explore the potential cost-effectiveness of TOMAC in the US healthcare system. METHODS: A decision-analytic Markov model was constructed to project strategy-specific treatment costs and benefits over 3 years and lifetime. Cohort characteristics (mean age 57.4 years, 39.8% male) and treatment effects were derived from the sham-controlled RESTFUL study. Study-observed International RLS Study Group (IRLS) scores were used to estimate changes in healthcare resource utilization and quality of life based on mapping algorithms informed by published data. The incremental cost-effectiveness ratio (ICER) was evaluated against established willingness-to-pay thresholds of $50,000/$150,000 per QALY to determine cost-effectiveness. Extensive scenario analyses were performed, including longer-term extension study data. RESULTS:  TOMAC and sham reduced IRLS scores from baseline 25.3 to 18.10 and 21.60, respectively, at 4 weeks (treatment effect - 3.4 vs. sham), with an increase in utility from 0.80 to 0.84 (0.75-0.84 vs. baseline). Over 3 years and lifetime, the TOMAC vs. sham effect size corresponded to an added 0.10 and 0.49 QALYs (2.36 vs. 2.26; 12.59 vs. 12.10) at incremental costs of $8061 and $36,373 ($36,707 vs. $28,646; $224,040 vs.$187,667), resulting in ICER estimates of $83,822 and $73,600, respectively. Compared to baseline, TOMAC resulted in ICER estimates of $29,569 and $23,690 over 3 years and lifetime, respectively. TOMAC remained cost-effective or dominant across all scenarios, with ICERs ranging from $10,530-$83,822 and - $8061 to $29,569 vs. sham and baseline, respectively. Larger TOMAC effect sizes, achieved per extension study data, further increased cost-effectiveness. CONCLUSION:  Based on this exploratory analysis of published trial data, TOMAC therapy appears to offer meaningful improvements in patient health-related quality at net costs that render it a cost-effective intervention. Further analyses are warranted.

5.
Surg Endosc ; 37(10): 7759-7766, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37580581

RESUMO

BACKGROUND: Diverting ileostomy and colostomy after total mesorectal excision reduces the risk of complications related to anastomotic leakages but is associated with a reduction in health-related quality of life and long-term economic consequences that are unknown. Our objective was to estimate the lifetime costs of stoma placement after rectal cancer resection in the U.S., England, and Germany. METHODS: Input parameters were derived from quasi-systematic literature searches. Decision-analytic models with survival from colorectal cancer-adjusted life tables and country-specific stoma reversal proportions were created for the three countries to calculate lifetime costs. Main cost items were stoma maintenance costs and reimbursement for reversal procedures. Discounting was applied according to respective national guidelines. Sensitivity analysis was conducted to explore the impact of parameter uncertainty onto the results. RESULTS: The cohort starting ages and median survival were 63 and 11.5 years for the U.S., 69 years and 8.5 years for England, and 71 and 6.5 years for Germany. Lifetime discounted stoma-related costs were $26,311, £9512, and €10,021, respectively. All three models were most sensitive to the proportion of ostomy reversal, age at baseline, and discount rate applied. CONCLUSION: Conservative model-based projections suggest that stoma care leads to significant long-term costs. Efforts to reduce the number of patients who need to undergo a diverting ostomy could result in meaningful cost savings.


Assuntos
Neoplasias Retais , Estomas Cirúrgicos , Humanos , Qualidade de Vida , Neoplasias Retais/cirurgia , Reto/cirurgia , Ileostomia/métodos , Colostomia/métodos , Anastomose Cirúrgica , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle
6.
J Prev Med Public Health ; 56(4): 319-326, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37551070

RESUMO

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has increased the workload of healthcare workers (HCWs), impacting their health. This study aimed to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and identify factors associated with poor sleep among HCWs in Vietnam during the COVID-19 pandemic. METHODS: In this cross-sectional study, 1000 frontline HCWs were recruited from various healthcare facilities in Vietnam between October 2021 and November 2021. Data were collected using a 3-part self-administered questionnaire, which covered demographics, sleep quality, and factors related to poor sleep. Poor sleep quality was defined as a total PSQI score of 5 or higher. RESULTS: Participants' mean age was 33.20±6.81 years (range, 20.0-61.0), and 63.0% were women. The median work experience was 8.54±6.30 years. Approximately 6.3% had chronic comorbidities, such as hypertension and diabetes mellitus. About 59.5% were directly responsible for patient care and treatment, while 7.1% worked in tracing and sampling. A total of 73.8% reported poor sleep quality. Multivariate logistic regression revealed significant associations between poor sleep quality and the presence of chronic comorbidities (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.17 to 5.24), being a frontline HCW directly involved in patient care and treatment (OR, 1.59; 95% CI, 1.16 to 2.16), increased working hours (OR, 1.84; 95% CI,1.37 to 2.48), and a higher frequency of encountering critically ill and dying patients (OR, 1.42; 95% CI, 1.03 to 1.95). CONCLUSIONS: The high prevalence of poor sleep among HCWs in Vietnam during the COVID-19 pandemic was similar to that in other countries. Working conditions should be adjusted to improve sleep quality among this population.


Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Adulto , Masculino , COVID-19/epidemiologia , Pandemias , Qualidade do Sono , Estudos Transversais , Vietnã/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Pessoal de Saúde
7.
Int J Technol Assess Health Care ; 39(1): e32, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37277322

RESUMO

OBJECTIVES: To assess the potential cost-effectiveness of neuromuscular electrical stimulation (NMES) for treatment of mild obstructive sleep apnea (OSA). METHODS: A decision-analytic Markov model was developed to estimate health state progression, incremental cost, and quality-adjusted life year (QALY) gain of NMES compared to no treatment, continuous airway pressure (CPAP), or oral appliance (OA) treatment. The base case assumed no cardiovascular (CV) benefit for any of the interventions, while potential CV benefit was considered in scenario analyses. Therapy effectiveness was based on a recent multi-center trial for NMES, and on the TOMADO and MERGE studies for OA and CPAP. Costs, considered from a United States payer perspective, were projected over lifetime for a 48-year-old cohort, 68% of whom were male. An incremental cost-effectiveness ratio (ICER) threshold of USD150,000 per QALY gained was applied. RESULTS: From a baseline AHI of 10.2 events/hour, NMES, OA and CPAP reduced the AHI to 6.9, 7.0 and 1.4 events/hour respectively. Long-term therapy adherence was estimated at 65-75% for NMES and 55% for both OA and CPAP. Compared to no treatment, NMES added between 0.268 and 0.536 QALYs and between USD7,481 and USD17,445 in cost, resulting in ICERs between USD15,436 and USD57,844 per QALY gained. Depending on long-term adherence assumptions, either NMES or CPAP were found to be the preferred treatment option, with NMES becoming more attractive with younger age and assuming CPAP was not used for the full night in all patients. CONCLUSIONS: NMES might be a cost-effective treatment option for patients with mild OSA.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Análise Custo-Benefício , Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/terapia , Serviços de Saúde , Estimulação Elétrica
8.
Eur Heart J Qual Care Clin Outcomes ; 9(6): 575-582, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36057838

RESUMO

AIMS: Renal denervation has been shown to lower blood pressure in sham-controlled trials and represents a device-based treatment option for hypertension. We sought to project clinical event reductions after radiofrequency renal denervation using a novel modelling approach. METHODS AND RESULTS: The Global SYMPLICITY Registry is a global, prospective all-comer registry to evaluate safety and efficacy after renal denervation. For this analysis, change in office systolic blood pressure from baseline was calculated from reported follow-up in the Global SYMPLICITY Registry. Relative risks for death and other cardiovascular events as well as numbers needed to treat for event avoidance were obtained for the respective blood pressure reductions based on previously reported meta-regression analyses for the full cohort and high-risk subgroups including type 2 diabetes, chronic kidney disease, resistant hypertension, and high basal cardiovascular risk. Average baseline office systolic blood pressure and reduction estimates for the full cohort (N = 2651) were 166±25 and -14.8 ± 0.4 mmHg, respectively. Mean reductions in blood pressure ranged from -11.0--21.8 mmHg for the studied high-risk subgroups. Projected relative risks ranged from 0.57 for stroke in the resistant hypertension cohort to 0.92 for death in the diabetes cohort. Significant absolute reductions in major adverse cardiovascular events over 3 years compared with the projected control (8.6 ± 0.7% observed vs. 11.7 ± 0.9% for projected control; P < 0.01) were primarily due to reduced stroke incidence. The robustness of findings was confirmed in sensitivity and scenario analyses. CONCLUSION: Model-based projections suggest radiofrequency renal denervation for patients with uncontrolled hypertension adds considerable clinical benefit across a spectrum of different cohort characteristics.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Acidente Vascular Cerebral , Humanos , Estudos Prospectivos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Simpatectomia/métodos , Resultado do Tratamento , Hipertensão/epidemiologia , Hipertensão/cirurgia , Hipertensão/tratamento farmacológico , Sistema de Registros
9.
Nephrology (Carlton) ; 27(11): 859-868, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36068700

RESUMO

AIM: The recent IN.PACT AV Access study found drug-coated balloon therapy to be associated with reduced reinterventions compared to percutaneous transluminal angioplasty using standard balloons in the management of arteriovenous fistula stenosis. The economic implications of drug-coated balloon use in Asia, including Japan and Korea, remain unknown. METHODS: A decision-analytic model was developed to calculate strategy-specific costs for Korea and Japan through 5-year follow-up. The analysis assumed maintained therapy benefit beyond current trial follow-up of 1 year in the base case, with several alternative scenarios explored in sensitivity analysis. Costs were derived from claims and reimbursement data, and projections were evaluated at 3 and 5 years post-index procedure. RESULTS: Model-projected access circuit reintervention events for drug-coated versus standard balloons were 1.70 versus 2.76 (-1.06) and 2.53 versus 4.10 (-1.57) at 3 and 5 years in the base case. Corresponding 3- and 5-year costs were ₩6 211 103 versus ₩7 605 553 (-₩1 394 451) and ₩7 766 051 versus ₩10 124 954 (-₩2 358 904) in Korea, and ¥1 469 824 versus ¥1 504 161 (-¥34 337) and ¥1 956 931 versus ¥2 106 632 (-¥149 701) in Japan. In scenario analyses, drug-coated balloons remained cost saving at 3- and 5-year follow-up in Korea, but required up to 5 years to reach cost-savings in Japan. Drug-coated balloon use in reinterventions increased projected savings, as did younger treatment age. CONCLUSION: Treatment of arteriovenous fistulas with the IN.PACT AV drug-coated balloon, based on preliminary data, may lead to meaningful reductions in reintervention costs that would render it cost-saving at timeframes of around 1 year in Korea and between 3 and 5 years in Japan.


Assuntos
Angioplastia com Balão , Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Fármacos Cardiovasculares , Angioplastia com Balão/métodos , Materiais Revestidos Biocompatíveis , Constrição Patológica , Humanos , Japão , Paclitaxel , Diálise Renal/métodos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
11.
Am J Physiol Lung Cell Mol Physiol ; 321(4): L736-L749, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34346778

RESUMO

Normal lungs do not express α-Klotho (Klotho) protein but derive cytoprotection from circulating soluble Klotho. It is unclear whether chronic supranormal Klotho levels confer additional benefit. To address this, we tested the age-related effects of modest Klotho overexpression on acute lung injury (ALI) and recovery. Transgenic Klotho-overexpressing (Tg-Kl) and wild-type (WT) mice (2 and 6 mo old) were exposed to hyperoxia (95% O2; 72 h; injury; Hx) then returned to normoxia (21% O2; 24 h; recovery; Hx-R). Control mice were kept in normoxia. Renal and serum Klotho, lung histology, and bronchoalveolar lavage fluid oxidative damage markers were assessed. Effects of hyperoxia on Klotho release were tested in human embryonic kidney cells stably expressing Klotho. A549 lung epithelial cells transfected with Klotho cDNA or vector were exposed to cigarette smoke; lactate dehydrogenase and double-strand DNA breaks were measured. Serum Klotho decreased with age. Hyperoxia suppressed renal Klotho at both ages and serum Klotho at 2 mo of age. Tg-Kl mice at both ages and 2-mo-old WT mice survived Hx-R; 6-mo-old Tg-Kl mice showed lower lung damage than age-matched WT mice. Hyperoxia directly inhibited Klotho expression and release in vitro; Klotho transfection attenuated cigarette smoke-induced cytotoxicity and DNA double-strand breaks in lung epithelial cells. Young animals with chronic high baseline Klotho expression were more resistant to ALI. Chronic constitutive Klotho overexpression in older Tg-Kl animals attenuated hyperoxia-induced lung damage and improves survival and short-term recovery despite an acute reduction in serum Klotho during injury. We conclude that chronic enhancement of Klotho expression increases resilience to ALI.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Glucuronidase/sangue , Glucuronidase/metabolismo , Fumaça/efeitos adversos , Lesão Pulmonar Aguda/patologia , Animais , Linhagem Celular , Citoproteção/genética , Citoproteção/fisiologia , Quebras de DNA de Cadeia Dupla , Dano ao DNA/genética , Feminino , Glucuronidase/genética , Células HEK293 , Humanos , Hiperóxia , Proteínas Klotho , L-Lactato Desidrogenase/análise , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Transgênicos
12.
J Appl Physiol (1985) ; 129(5): 1051-1061, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32909918

RESUMO

Cell-free secretory products (secretome) of human induced pluripotent stem cells (iPSCs) have been shown to attenuate tissue injury and facilitate repair and recovery. To examine whether iPSC secretome facilitates mechanically induced compensatory responses following unilateral pneumonectomy (PNX), litter-matched young adult female hounds underwent right PNX (removing 55%-58% of lung units), followed by inhalational delivery of either the nebulized-conditioned media containing induced pluripotent stem cell secretome (iPSC CM) or control cell-free media (CFM); inhalation was repeated every 5 days for 10 treatments. Lung function was measured under anesthesia pre-PNX and 10 days after the last treatment (8 wk post-PNX); detailed quantitative analysis of lung ultrastructure was performed postmortem. Pre-PNX lung function was similar between groups. Compared with CFM control, treatment with iPSC CM attenuated the post-PNX decline in lung diffusing capacity for carbon monoxide and membrane diffusing capacity, accompanied by a 24% larger postmortem lobar volume and distal air spaces. Alveolar double-capillary profiles were 39% more prevalent consistent with enhanced intussusceptive angiogenesis. Frequency distribution of the harmonic mean thickness of alveolar blood-gas barrier shifted toward the lowest values, whereas alveolar septal tissue volume and arithmetic septal thickness were similar, indicating septal remodeling and reduced diffusive resistance of the blood-gas barrier. Thus, repetitive inhalational delivery of iPSC secretome enhanced post-PNX alveolar angiogenesis and septal remodeling that are associated with improved gas exchange compensation. Results highlight the plasticity of the remaining lung units following major loss of lung mass that are responsive to broad-based modulation provided by the iPSC secretome.NEW & NOTEWORTHY To examine whether the secreted products of human induced pluripotent stem cells (iPSCs) facilitate innate adaptive responses following loss of lung tissue, adult dogs underwent surgical removal of one lung, then received repeated administration of iPSC secretory products via inhalational delivery compared with control treatment. Inhalation of iPSC secretory products enhanced capillary formation and beneficial structural remodeling in the remaining lung, leading to improved lung function.


Assuntos
Células-Tronco Pluripotentes Induzidas , Pulmão , Pneumonectomia , Animais , Cães , Feminino , Humanos , Pulmão/fisiologia , Pulmão/cirurgia , Medidas de Volume Pulmonar , Capacidade de Difusão Pulmonar
13.
FASEB Bioadv ; 1(11): 675-687, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32123814

RESUMO

Alpha-Klotho (αKlotho), produced by the kidney and selected organs, is essential for tissue maintenance and protection. Homozygous αKlotho-deficiency leads to premature multi-organ degeneration and death; heterozygous insufficiency leads to apoptosis, oxidative stress, and increased injury susceptibility. There is inconsistent data in the literature regarding whether αKlotho is produced locally in the lung or derived from circulation. We probed murine and human lung by immunohistochemistry (IHC) and immunoblot (IB) using two monoclonal (anti-αKlotho Kl1 and Kl2 domains) and three other common commercial antibodies. Monoclonal anti-Kl1 and anti-Kl2 yielded no labeling in lung on IHC or IB; specific labeling was observed in kidney (positive control) and also murine lungs following tracheal delivery of αKlotho cDNA, demonstrating specificity and ability to detect artificial pulmonary expression. Other commercial antibodies labeled numerous lung structures (IHC) and multiple bands (IB) incompatible with known αKlotho mobility; labeling was not abolished by blocking with purified αKlotho or using lungs from hypomorphic αKlotho-deficient mice, indicating nonspecificity. Results highlight the need for rigorous validation of reagents. The lung lacks native αKlotho expression and derives full-length αKlotho from circulation; findings could explain susceptibility to lung injury in extrapulmonary pathology associated with reduced circulating αKlotho levels, for example, renal failure. Conversely, αKlotho may be artificially expressed in the lung, suggesting therapeutic opportunities.

14.
J Appl Physiol (1985) ; 125(5): 1411-1423, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30091664

RESUMO

A colony of deer mice subspecies ( Peromyscus maniculatus sonoriensis) native to high altitude (HA) has been maintained at sea level for 18-20 generations and remains genetically unchanged. To determine if these animals retain responsiveness to hypoxia, one group (9-11 wk old) was acclimated to HA (3,800 m) for 8 wk. Age-matched control animals were acclimated to a lower altitude (LA; 252 m). Maximal O2 uptake (V̇o2max) was measured at the respective altitudes. On a separate day, lung volume, diffusing capacity for carbon monoxide (DLCO), and pulmonary blood flow were measured under anesthesia using a rebreathing technique at two inspired O2 tensions. The HA-acclimated deer mice maintained a normal V̇o2max relative to LA baseline. Compared with LA control mice, antemortem lung volume was larger in HA mice in a manner dependent on alveolar O2 tension. Systemic hematocrit, pulmonary blood flow, and standardized DLCO did not differ significantly between groups. HA mice showed a higher postmortem alveolar-capillary hematocrit, larger alveolar ducts, and smaller distal conducting structures. In HA mice, absolute volumes of alveolar type I epithelia and endothelia were higher whereas that of interstitia was lower than in LA mice. These structural changes occurred without a net increase in whole-lung septal tissue-capillary volumes or surface areas. Thus, deer mice bred and raised to adulthood at LA retain phenotypic plasticity and adapt to HA without a decrement in V̇o2max via structural (enlarged airspaces, alveolar septal remodeling) and nonstructural (lung expansion under hypoxia) mechanisms and without an increase in systemic hematocrit or compensatory lung growth. NEW & NOTEWORTHY Deer mice ( Peromyscus maniculatus) are robust and very active mammals that are found across the North American continent. They are also highly adaptable to extreme environments. When introduced to high altitude they retain remarkable adaptive ability to the low-oxygen environment via lung expansion and remodeling of existing lung structure, thereby maintaining normal aerobic capacity without generating more red blood cells or additional lung tissue.


Assuntos
Aclimatação , Altitude , Pulmão/fisiologia , Peromyscus/fisiologia , Respiração , Animais , Biometria , Pulmão/ultraestrutura , Masculino , Tamanho do Órgão , Peromyscus/anatomia & histologia , Testes de Função Respiratória
15.
BMC Med Genomics ; 11(1): 61, 2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30037347

RESUMO

BACKGROUND: Giant cell arteritis (GCA) is the most common form of vasculitis affecting elderly people. It is one of the few true ophthalmic emergencies but symptoms and signs are variable thereby making it a challenging disease to diagnose. A temporal artery biopsy is the gold standard to confirm GCA, but there are currently no specific biochemical markers to aid diagnosis. We aimed to identify a less invasive method to confirm the diagnosis of GCA, as well as to ascertain clinically relevant predictive biomarkers by studying the transcriptome of purified peripheral CD4+ and CD8+ T lymphocytes in patients with GCA. METHODS: We recruited 16 patients with histological evidence of GCA at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and aimed to collect blood samples at six time points: acute phase, 2-3 weeks, 6-8 weeks, 3 months, 6 months and 12 months after clinical diagnosis. CD4+ and CD8+ T-cells were positively selected at each time point through magnetic-assisted cell sorting. RNA was extracted from all 195 collected samples for subsequent RNA sequencing. The expression profiles of patients were compared to those of 16 age-matched controls. RESULTS: Over the 12-month study period, polynomial modelling analyses identified 179 and 4 statistically significant transcripts with altered expression profiles (FDR < 0.05) between cases and controls in CD4+ and CD8+ populations, respectively. In CD8+ cells, two transcripts remained differentially expressed after 12 months; SGTB, associated with neuronal apoptosis, and FCGR3A, associatied with Takayasu arteritis. We detected genes that correlate with both symptoms and biochemical markers used for predicting long-term prognosis. 15 genes were shared across 3 phenotypes in CD4 and 16 across CD8 cells. In CD8, IL32 was common to 5 phenotypes including Polymyalgia Rheumatica, bilateral blindness and death within 12 months. CONCLUSIONS: This is the first longitudinal gene expression study undertaken to identify robust transcriptomic biomarkers of GCA. Our results show cell type-specific transcript expression profiles, novel gene-phenotype associations, and uncover important biological pathways for this disease. In the acute phase, the gene-phenotype relationships we have identified could provide insight to potential disease severity and as such guide in initiating appropriate patient management.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Perfilação da Expressão Gênica , Arterite de Células Gigantes/genética , Arterite de Células Gigantes/imunologia , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Fenótipo , Fatores de Tempo
16.
Transplantation ; 102(10): e447-e453, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30028418

RESUMO

BACKGROUND: Live donor nephrectomy is an operation that places the donor at risk of complications without the possibility of medical benefit. Rigorous donor selection and assessment is therefore essential to ensure minimization of risk and for this reason robust national guidelines exist. Previous studies have demonstrated poor adherence to donor guidelines. METHODS: We developed a clinical decision support system (CDSS), based on national living donor guidelines, to facilitate the identification of contraindications, additional investigations, special considerations, and the decision as to nephrectomy side in potential living donors. The CDSS was then tested with patient data from 45 potential kidney donors. RESULTS: The CDSS comprises 17 core tasks completed by either patient or nurse, and 17 optional tasks that are triggered by certain patient demographics or conditions. Decision rules were able to identify contraindications, additional investigations, special considerations, and predicted operation side in our patient cohort. Seventeen of 45 patients went on to donate a kidney, of whom 7 had major contraindications defined in the national guidelines, many of which were not identified by the clinical team. Only 43% of additional investigations recommended by national guidelines were completed, with the most frequently missed investigations being oral glucose tolerance testing and routine cancer screening. CONCLUSIONS: We have demonstrated the feasibility of turning a complex set of national guidelines into an easy-to-use machine-readable CDSS. Comparison with real-world decisions suggests that use of this CDSS may improve compliance with guidelines and informed consent tailored to individual patient risks.


Assuntos
Sistemas de Apoio a Decisões Clínicas/organização & administração , Seleção do Doador/organização & administração , Transplante de Rim/efeitos adversos , Doadores Vivos , Nefrectomia/efeitos adversos , Tomada de Decisão Clínica/métodos , Sistemas de Apoio a Decisões Clínicas/normas , Seleção do Doador/normas , Feminino , Fidelidade a Diretrizes/organização & administração , Fidelidade a Diretrizes/normas , Implementação de Plano de Saúde , Humanos , Consentimento Livre e Esclarecido/normas , Rim/cirurgia , Avaliação em Enfermagem/organização & administração , Avaliação em Enfermagem/normas , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/normas , Estudos Retrospectivos , Inquéritos e Questionários
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