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1.
J. sleep res ; : e12863, May 2019. ilus, tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1007059

RESUMO

Overnight extracellular rostral fluid shifts have been shown to be of importance in patients with fluid-retaining states and are associated with a higher prevalence of sleep apnea. Pulmonary hypertension is frequently associated with right ventricular dysfunction and progressive right ventricular failure, and an increased prevalence of sleep apnea has been described. In light of the importance of fluid shifts in the pathophysiology of sleep apnea, we aimed to explore temporal fluid shifts in patients with pulmonary hypertension with and without sleep apnea. Patients with pulmonary hypertension (WHO Group 1 or 4) had overnight extracellular rostral fluid shift assessment before and a minimum of 3 months after initiation of pulmonary hypertension-specific therapy. Fluid shift measurements of extracellular leg, abdominal, thoracic and neck fluid volumes were performed simultaneously. Twenty-nine patients with pulmonary hypertension (age 55 ± 16 years, 69% female) participated. Sleep apnea was diagnosed in 15 subjects (apnea-hypopnea index 14 [8-27] per hr). There were no significant differences in baseline or overnight leg extracellular rostral fluid, abdominal extracellular rostral fluid, thoracic extracellular rostral fluid or neck extracellular rostral fluid between those with and without sleep apnea. There was a significant inverse correlation between the sleep apnea severity and the overnight change in leg extracellular rostral fluid (r = -0.375, p = 0.049). There were no significant differences detected in overnight extracellular rostral fluid shifts from baseline to follow-up. Treatment-naïve patients with pulmonary hypertension both with and without sleep apnea demonstrate overnight extracellular rostral fluid shifts from the legs into the thorax and neck. Pulmonary hypertension-specific treatment, while significantly improving cardiac haemodynamics, had little impact on nocturnal extracellular rostral fluid shifts or the presence of sleep apnea


Assuntos
Humanos , Disfunção Ventricular Esquerda , Apneia Obstrutiva do Sono , Líquido Extracelular
2.
Heliyon ; 5(7): 1-8, Jul 2019.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1006879

RESUMO

Objectives: Our aims were to evaluate HRV in pulmonary hypertension (WHO Group 1 and 4) compared to control subjects, and to assess whether the presence of sleep apnea in those with pulmonary hypertension would be deleterious and cause greater impairment in HRV. Methods: This retrospective case-control study analyzed electrocardiogram segments obtained from diagnostic polysomnography. Results: Forty-one pulmonary hypertension patients were compared to 41 age, sex and apnea-hypopnea index matched healthy controls. The pulmonary hypertension group had decreased high frequency, very low frequency, low frequency, and percentage of normal R-R intervals that differ by > 50 ms compared to control subjects. Moderate to severe right ventricle dysfunction on echocardiography was a predictor of lower high frequency in pulmonary hypertension patients. Conclusions: There were no differences in any HRV measures in pulmonary hypertension patients with or without sleep apnea. Impaired HRV was demonstrated in pulmonary hypertension patients however, the presence of sleep apnea did not appear to further reduce vagal modulation.


Assuntos
Síndromes da Apneia do Sono , Frequência Cardíaca , Hipertensão Pulmonar
3.
Ann Am Thorac Soc ; 16(7): 914-919, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31259634
4.
Artigo em Inglês | MEDLINE | ID: mdl-31296519

RESUMO

BACKGROUND: Patients with advanced cancer are increasingly discharged from inpatient settings following focused symptom management admissions. Thromboprophylaxis (TP) is recommended for patients with cancer admitted to acute care settings; less is known about TP use in palliative care (PC) settings. This study explored the opinions of Canadian medical oncologists (MO) and PC physicians regarding the use of TP for inpatients with advanced cancer. METHODS: A fractional factorial survey designed to evaluate the impact of patient factors (age, clinical setting, reason for admission, pre-admission performance status (Eastern Cooperative Oncology Group; ECOG), and risk of bleeding on anticoagulation) and physician demographics on recommending TP was administered by email to Canadian MO and PC physicians. Each respondent received eight vignettes randomly selected from a set of 32. Hierarchical regression was used to evaluate the odds of prescribing TP adjusted for patient factors. RESULTS: 606 MO and 491 PC physicians were surveyed; response rates were 11.1% and 15.0%, respectively. MO were predominantly male (59.7%); PC female (60.3%); most worked in academic environments (90.3% MO; 73.9% PC). Multivariable hierarchical logistic regression demonstrated that all patient factors except age were associated with prescribing TP (ORs range: from 1.34 (95% CI 1.01 to 1.77) for good ECOG, to 2.53 (95% CI 1.9 to 3.37), for reversible reason for admission). Controlling for these factors, medical specialty was independently associated with recommending TP (OR for MO 2.09 (95% CI 1.56 to 2.8)). CONCLUSIONS: MO have higher odds of recommending TP for inpatients with advanced cancer than PC physicians. Further research exploring the drivers of these differing practices is warranted.

5.
Heart ; 105(19): 1471-1478, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31053610

RESUMO

OBJECTIVE: This study sought to determine the prevalence, predictors, prognostic relevance and evolution of pulmonary hypertension (PH) (mean pulmonary artery pressure ≥25 mm Hg) in adult patients with a subaortic right ventricle (RV) in a biventricular circulation (2V-RV). METHODS: We analysed retrospective data from patients with 2V-RV undergoing cardiac catheterisation in our centre between 2000 and 2018. Echocardiographic assessment of subpulmonary ventricular pressures (left ventricular systolic pressure (LVSP)), age and B-type natriuretic peptide (BNP) were assessed as PH screening tools. Kaplan-Meier curves examined time to a composite outcome of death, transplant or ventricular assist device (VAD). Data from repeat catheterisations were analysed to evaluate PH changes over time, including the effects of therapy. RESULTS: A total of 141 patients (median age 39 (IQR 33-45) years, 68% men) underwent 191 cardiac catheterisations. At baseline, 55% had PH (isolated postcapillary 24%, combined precapillary and postcapillary 26% and precapillary 5%). BNP (area under the curve 0.80; 95% CI 0.72 to 0.88; p<0.0001), but not age at catheterisation or echocardiographic estimates of LVSP were associated with the presence of PH. The absence of PH and BNP <100 pg/mL discriminated a subgroup at very low risk during short-term (2.5 (1.3-3.9) years) follow-up (p<0.0001). Diuretics, milrinone and VAD improved haemodynamics over time. CONCLUSION: PH is prevalent in patients with 2V-RV even when asymptomatic. It is difficult to identify by echocardiography and most importantly, is strongly associated with adverse outcomes. PH affects prognosis and transplant options for this patient group and yet is often amenable to treatment. Awareness of these results ought to lower the threshold for invasive haemodynamic assessment and may change the management of failing patients with 2V-RV.

6.
J Sleep Res ; : e12863, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31099115

RESUMO

Overnight extracellular rostral fluid shifts have been shown to be of importance in patients with fluid-retaining states and are associated with a higher prevalence of sleep apnea. Pulmonary hypertension is frequently associated with right ventricular dysfunction and progressive right ventricular failure, and an increased prevalence of sleep apnea has been described. In light of the importance of fluid shifts in the pathophysiology of sleep apnea, we aimed to explore temporal fluid shifts in patients with pulmonary hypertension with and without sleep apnea. Patients with pulmonary hypertension (WHO Group 1 or 4) had overnight extracellular rostral fluid shift assessment before and a minimum of 3 months after initiation of pulmonary hypertension-specific therapy. Fluid shift measurements of extracellular leg, abdominal, thoracic and neck fluid volumes were performed simultaneously. Twenty-nine patients with pulmonary hypertension (age 55 ± 16 years, 69% female) participated. Sleep apnea was diagnosed in 15 subjects (apnea-hypopnea index 14 [8-27] per hr). There were no significant differences in baseline or overnight leg extracellular rostral fluid, abdominal extracellular rostral fluid, thoracic extracellular rostral fluid or neck extracellular rostral fluid between those with and without sleep apnea. There was a significant inverse correlation between the sleep apnea severity and the overnight change in leg extracellular rostral fluid (r = -0.375, p = 0.049). There were no significant differences detected in overnight extracellular rostral fluid shifts from baseline to follow-up. Treatment-naïve patients with pulmonary hypertension both with and without sleep apnea demonstrate overnight extracellular rostral fluid shifts from the legs into the thorax and neck. Pulmonary hypertension-specific treatment, while significantly improving cardiac haemodynamics, had little impact on nocturnal extracellular rostral fluid shifts or the presence of sleep apnea.

7.
Respirology ; 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30963672

RESUMO

BACKGROUND AND OBJECTIVE: Osteopontin (OPN) is a pleiotropic cytokine involved in the proliferation of pulmonary artery smooth muscle cells (PA-SMC). OPN is upregulated in the lungs of patients with pulmonary hypertension (PH) associated with pulmonary fibrosis, suggesting that the lung is a source of OPN. We hypothesized that OPN lung expression is elevated in Group I pulmonary arterial hypertension (PAH) and is correlated to haemodynamics. METHODS: Microarray analysis (Affymetrix) was performed after RNA was extracted from explanted lungs in 15 patients with Group I PAH who underwent lung transplantation (LTx) and 11 normal controls. PA pressure levels were recorded intraoperatively, immediately before starting LTx. Serum OPN levels were measured in subjects with PAH, Group II PH and normal controls on the day of right heart catheterization. RESULTS: OPN was among the top five upregulated genes in PAH compared to normal controls, which was confirmed by reverse transcription polymerase chain reaction (RT-PCR). OPN expression was similar and equally elevated in different subtypes of PAH. A strong significant correlation was observed between mean pulmonary arterial pressure and OPN gene expression. Ingenuity pathway analysis showed the involvement of OPN in functions and networks relevant to angiogenesis, cell death and proliferation of PA-SMC. OPN serum levels did not differ in subjects with Group I PAH and Group II PH. CONCLUSION: In the lungs of patients with severe PAH, OPN is highly expressed and the level of expression is significantly correlated to disease severity. OPN may play an important role in the vascular remodelling process of PAH.

8.
Palliat Med ; 33(5): 486-499, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30819046

RESUMO

BACKGROUND: Patients with advanced cancer have an elevated risk of venous thromboembolism. Increasingly, patients are admitted to palliative care settings for brief admissions, with greater numbers of discharges (vs deaths) reported internationally. There is limited guidance around the use of thromboprophylaxis or incidence of venous thromboembolism for these patients. AIM: The aim of this study was to review the use of thromboprophylaxis as well as incidence of venous thromboembolism and bleeding in palliative care units or residential hospices for patients with advanced cancer. DESIGN: A systematic review using Cochrane methods. DATA SOURCES: Medline, Embase and the Cochrane Library were searched up to 28 September 2018 along with a grey literature search; the reference lists of selected papers were hand-searched. Inclusion criteria were original papers assessing thromboprophylaxis use in palliative care units or residential hospices for adult inpatients with cancer. Two reviewers independently selected and appraised papers using a tool designed for disparate data. Heterogeneity in study design made a meta-analysis not possible. RESULTS: A total of 11 full-text papers (9 quantitative and 2 qualitative) and 11 abstracts were included. Thromboprophylaxis use ranged between 4% and 53%; venous thromboembolism rates between 0.5% and 20%; and bleeding incidence was between 0.01% and 9.8%. Risk assessment tools were used infrequently and adherence to international thromboprophylaxis guidelines ranged between 5% and 71%. Physician opinions differed around the use of thromboprophylaxis; patients were largely accepting of thromboprophylaxis if it was offered. CONCLUSION: There is limited evidence around the optimal use of thromboprophylaxis for patients with advanced cancer admitted to palliative care settings. Although some patients may derive benefit, further research in this area is warranted.

9.
Crit Care Med ; 47(7): 918-925, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30720538

RESUMO

OBJECTIVES: Cellular Immunotherapy for Septic Shock is the first-in-human clinical trial evaluating allogeneic mesenchymal stem/stromal cells in septic shock patients. Here, we sought to determine whether plasma cytokine profiles may provide further information into the safety and biological effects of mesenchymal stem/stromal cell treatment, as no previous study has conducted a comprehensive analysis of circulating cytokine levels in critically ill patients treated with mesenchymal stem/stromal cells. DESIGN: Phase 1 dose-escalation trial. PATIENTS: The interventional cohort (n = 9) of septic shock patients received a single dose of 0.3, 1.0, or 3.0 million mesenchymal stem/stromal cells/kg body weight (n = 3 per dose). The observational cohort received no mesenchymal stem/stromal cells (n = 21). INTERVENTIONS: Allogeneic bone marrow-derived mesenchymal stem/stromal cells. MEASUREMENTS AND MAIN RESULTS: Serial plasma samples were collected at study baseline prior to mesenchymal stem/stromal cell infusion (0 hr), 1 hour, 4 hours, 12 hours, 24 hours, and 72 hours after mesenchymal stem/stromal cell infusion/trial enrollment. Forty-nine analytes comprised mostly of cytokines along with several biomarkers were measured. We detected no significant elevations in a broad range of pro-inflammatory cytokines and biomarkers between the interventional and observational cohorts. Stratification of the interventional cohort by mesenchymal stem/stromal cell dose further revealed patient-specific and dose-dependent perturbations in cytokines, including an early but transient dampening of pro-inflammatory cytokines (e.g., interleukin-1ß, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein 1), suggesting that mesenchymal stem/stromal cell treatment may alter innate immune responses and underlying sepsis biology. CONCLUSIONS: A single infusion of up to 3 million cells/kg of allogeneic mesenchymal stem/stromal cells did not exacerbate elevated cytokine levels in plasma of septic shock patients, consistent with a safe response. These data also offer insight into potential biological mechanisms of mesenchymal stem/stromal cell treatment and support further investigation in larger randomized controlled trials.

10.
Can J Physiol Pharmacol ; 97(4): 306-312, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30557040

RESUMO

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and devastating condition. There is no known cure for IPAH, and current treatment options are not always effective. Autologous myeloid angiogenic cells (MACs) have been explored as a novel therapy for IPAH, but preliminary data from clinical trials show limited beneficial effects. A complete understanding of IPAH MAC function remains elusive. This study was designed to comprehensively compare cell function between IPAH MACs and healthy control MACs. MACs were procured through the culture of peripheral blood mononuclear cells in endothelial selective medium for 7 days. Compared with healthy MACs, IPAH MACs exhibited (1) significantly lower levels of endothelial markers as shown by fluorescence microscopy; (2) a markedly higher rate of apoptosis under both normal culture condition and serum starvation as shown by the TUNEL assay; (3) significantly decreased migration towards vascular endothelial growth factor as shown by a modified Boyden chamber migration assay; and (4) similar vascular endothelial growth factor and endothelial nitric oxide synthase mRNA levels as shown by reverse transcription quantitative PCR. In conclusion, various aspects of IPAH MAC function are impaired. To achieve greater therapeutic benefits, pharmacologic and (or) genetic manipulations to improve IPAH MAC function, particularly to promote cell survival and migration, are warranted.


Assuntos
Apoptose , Movimento Celular , Células Endoteliais/metabolismo , Hipertensão Pulmonar Primária Familiar/patologia , Regulação da Expressão Gênica , Células Mieloides/patologia , Neovascularização Fisiológica , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Proliferação de Células , Hipertensão Pulmonar Primária Familiar/metabolismo , Hipertensão Pulmonar Primária Familiar/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Eur Respir J ; 53(1)2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30545975

RESUMO

Until 20 years ago the treatment of pulmonary arterial hypertension (PAH) was based on case reports and small series, and was largely ineffectual. As a deeper understanding of the pathogenesis and pathophysiology of PAH evolved over the subsequent two decades, coupled with epidemiological studies defining the clinical and demographic characteristics of the condition, a renewed interest in treatment development emerged through collaborations between international experts, industry and regulatory agencies. These efforts led to the performance of robust, high-quality clinical trials of novel therapies that targeted putative pathogenic pathways, leading to the approval of more than 10 novel therapies that have beneficially impacted both the quality and duration of life. However, our understanding of PAH remains incomplete and there is no cure. Accordingly, efforts are now focused on identifying novel pathogenic pathways that may be targeted, and applying more rigorous clinical trial designs to better define the efficacy of these new potential treatments and their role in the management scheme. This article, prepared by a Task Force comprised of expert clinicians, trialists and regulators, summarises the current state of the art, and provides insight into the opportunities and challenges for identifying and assessing the efficacy and safety of new treatments for this challenging condition.

12.
Res Pract Thromb Haemost ; 2(4): 670-677, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30349885

RESUMO

Introduction: Risk factors for exercise limitation after acute pulmonary embolism (PE) are unknown. As a planned sub-study of the prospective, multicenter ELOPE (Evaluation of Long-term Outcomes after PE) Study, we aimed to describe the results of serial imaging by computed tomography pulmonary angiography (CTPA) and perfusion scan during 1 year after a first episode of acute pulmonary embolism, and to assess the association between imaging parameters and exercise limitation at 1 year. Methods: In a prospective cohort study, 100 patients were recruited between June 2010 and February 2013 at five Canadian university-affiliated hospitals. CT pulmonary angiography was performed at baseline and 12 months, perfusion scan at 6 and 12 months, and cardio-pulmonary exercise testing at 1 and 12 months. Imaging parameters included: on CT pulmonary angiography, CT obstruction index (CTO) (% clot burden in the pulmonary vasculature), and on perfusion scan, pulmonary vascular obstruction (PVO) (% perfusion defect). Abnormal cardio-pulmonary exercise test (primary outcome) was defined as percent of predicted peak oxygen uptake (VO2) <80%. Results: Mean (median; SD) CT obstruction index was 28.1% (27.5%; 18.3%) at baseline, 1.2% (0%; 4.3%) at 12 months. Mean (median; SD) pulmonary vascular obstruction was 6.0% (0%; 9.6%) at 6 months, 5.6% (0%; 9.8%) at 12 months. Eighty-six patients had exercise testing at 12 months, and 46.5% had VO2 < 80% predicted. Mean (median; SD) CT obstruction index at 1 year was similar in patients with percent-predicted VO2 peak <80% vs >80% on 1-year cardio-pulmonary exercise testing (1.4% [0%; 5.7%] vs 1.0% [0%; 2.4%]; P = .70). Mean (SD) pulmonary vascular obstruction at 6 and at 12 months was similar in patients with percent-predicted VO2 peak <80% vs >80% (6 months: 5.9% [0%; 10.4%] vs 6.2% [4.5%; 9.0%]; P = .91; 12 months: 5.1% [0%; 10.2%] vs 6.0% [0%; 9.7%]; P = .71). Conclusions: Imaging findings after pulmonary embolism did not predict exercise limitation. Residual thrombus does not appear to explain long-term functional limitation after pulmonary embolism.

13.
Lancet ; 391(10140): 2631-2640, 2018 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-30070222

RESUMO

BACKGROUND: Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery. METHODS: We did a multicentre, international, prospective cohort study at 25 hospitals: five in Canada, seven in the UK, ten in Australia, and three in New Zealand. We recruited adults aged at least 40 years who were scheduled for major non-cardiac surgery and deemed to have one or more risk factors for cardiac complications (eg, a history of heart failure, stroke, or diabetes) or coronary artery disease. Functional capacity was subjectively assessed in units of metabolic equivalents of tasks by the responsible anaesthesiologists in the preoperative assessment clinic, graded as poor (<4), moderate (4-10), or good (>10). All participants also completed the DASI questionnaire, underwent CPET to measure peak oxygen consumption, and had blood tests for measurement of NT pro-BNP concentrations. After surgery, patients had daily electrocardiograms and blood tests to measure troponin and creatinine concentrations until the third postoperative day or hospital discharge. The primary outcome was death or myocardial infarction within 30 days after surgery, assessed in all participants who underwent both CPET and surgery. Prognostic accuracy was assessed using logistic regression, receiver-operating-characteristic curves, and net risk reclassification. FINDINGS: Between March 1, 2013, and March 25, 2016, we included 1401 patients in the study. 28 (2%) of 1401 patients died or had a myocardial infarction within 30 days of surgery. Subjective assessment had 19·2% sensitivity (95% CI 14·2-25) and 94·7% specificity (93·2-95·9) for identifying the inability to attain four metabolic equivalents during CPET. Only DASI scores were associated with predicting the primary outcome (adjusted odds ratio 0·96, 95% CI 0·83-0·99; p=0·03). INTERPRETATION: Subjectively assessed functional capacity should not be used for preoperative risk evaluation. Clinicians could instead consider a measure such as DASI for cardiac risk assessment. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.


Assuntos
Nível de Saúde , Complicações Pós-Operatórias/etiologia , Idoso , Teste de Esforço , Tolerância ao Exercício , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade
14.
Cardiovasc Res ; 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29878071

RESUMO

Aims: The assumption of equivalence between right ventricular and pulmonary arterial systolic pressure is fundamental to several assessments of right ventricular or pulmonary vascular hemodynamic function. Our aims were to 1) determine whether systolic pressure gradients develop across the right ventricular outflow tract in healthy adults during exercise, 2) examine the potential correlates of such gradients, and 3) consider the effect of such gradients on calculated indices of right ventricular function. Methods and Results: Healthy untrained and endurance-trained adult volunteers were studied using right-heart catheterization at rest and during submaximal cycle ergometry. Right ventricular and pulmonary artery pressures were simultaneously transduced, and cardiac output was determined by thermodilution. Systolic pressures, peak and mean gradients, and indices of chamber, vascular, and valve function were analyzed offline. Summary data are reported as mean ± standard deviation or median [interquartile range]. No significant right ventricular outflow tract gradients were observed at rest (mean gradient = 4 [3-5] mmHg), and calculated effective orifice area was 3.6±1.0 cm2. Right ventricular systolic pressure increases during exercise were greater than that of pulmonary artery systolic pressure. Accordingly, mean gradients developed during light exercise (8 [7-9] mmHg) and increased during moderate exercise (12 [9-14] mmHg, p < 0.001). The magnitude of the mean gradient was linearly related to cardiac output (r2 = 0.70, p < 0.001). Conclusions: In healthy adults without pulmonic stenosis, systolic pressure gradients develop during exercise, and the magnitude is related to blood flow rate.

15.
J Cardiopulm Rehabil Prev ; 38(6): 419-424, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29952810

RESUMO

PURPOSE: Little is known about the oxygen requirements during physical exertion or exercise in individuals with interstitial lung disease (ILD). This study examined exertional oxygen requirements, the relationships between exertional oxygen use, exercise capacity and aerobic training parameters, and predictors of change in exertional oxygen requirements during pulmonary rehabilitation (PR). METHODS: A retrospective study of lung transplant candidates with advanced ILD who underwent at least 4 wk of outpatient PR between 2004 and 2014 was undertaken. Data were extracted at baseline, 4 wk, and 6 mo. Exertional oxygen was prescribed during PR to support continuous, moderate-intensity aerobic training. RESULTS: The study cohort (n = 375) had a median age of 61 y (55-66 y), were 57% male, and most were diagnosed with idiopathic pulmonary fibrosis (n = 214). A variety of oxygen delivery systems were used and exertional oxygen requirements increased after 4 wk (0.5 [0.4-0.6] vs 0.5 [0.4-0.73], P < .001, n = 375) and 6 mo (0.44 [0.36-0.5] vs 0.5 [0.4-0.55], P < .001, n = 196) of PR. A higher exertional oxygen requirement was associated with lower 6-min walk distance and lower aerobic training intensity at all time points. There were no identified predictors of the change in exertional oxygen requirements. CONCLUSIONS: Individuals with advanced ILD had high exertional oxygen requirements to participate in moderate-intensity aerobic training, which increased over time. Exertional oxygen needs may affect exercise prescription and response during PR in ILD patients.

16.
Clin Kidney J ; 11(3): 310-314, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29942494

RESUMO

Cobalamin C (cblC) deficiency is the most commonly inherited inborn error of vitamin B12 metabolism. It is characterized by multisystem involvement with severe neurological, hematological, renal and cardiopulmonary manifestations. Disease is most commonly diagnosed early in the first decade of life. We report a case of a 20-year-old woman who developed severe pulmonary arterial hypertension while under nephrologic follow-up for chronic kidney disease. She had initially presented at 14 years of age with visual disturbance and acute renal failure and been diagnosed with thrombotic thrombocytopenic purpura on the basis of kidney biopsy findings of thrombotic microangiopathy and compatible ADAMTS13 (a disentegrin and metalloproteinase with a thrombospondin type 1 motif member 13). When cblC deficiency was eventually diagnosed, remarkable improvement in cardiopulmonary function was evident upon initiation of treatment. This case highlights the importance of a timely diagnosis and initiation of treatment for cblC deficiency. Clinical diagnosis may be challenged by asynchronous organ symptom presentation and by misleading laboratory tests, in this case: an initial low ADAMTS13. A simple test of plasma homocysteine level should be encouraged in cases of thrombotic microangiopathy and/or pulmonary artery hypertension.

17.
Rheum Dis Clin North Am ; 44(2): 203-213, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29622292

RESUMO

A challenge to the use of observational data to study treatment effects is the issue of confounding. Noncomparability of exposed and nonexposed subjects can lead to biased estimation of the treatment effect. The propensity score is a balancing score that can be used to form matched groups, or pairs, that are not systematically different and enable nonbiased comparisons between groups. This article reviews propensity score methods with an illustrative example of the application of propensity score matching in an observational study of an uncommon disease (systemic sclerosis).

18.
Rheum Dis Clin North Am ; 44(2): 361-370, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29622302

RESUMO

The use of applied Bayesian methods is increasing in rheumatology. Using the Bayes theorem, past evidence is updated with new data. Preexisting data are expressed as a prior probability distribution or prior. New observations are expressed as a likelihood. Through explicit incorporation of preexisting data and new data, this process informs how this new information should change the way we think. In this article, the authors highlight the use of applied Bayesian methods in the study of rheumatic diseases.

19.
Am J Respir Crit Care Med ; 197(3): 337-347, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28960096

RESUMO

RATIONALE: In septic animal models mesenchymal stem (stromal) cells (MSCs) modulate inflammation, enhance tissue repair and pathogen clearance, and reduce death. OBJECTIVES: To conduct a phase I dose escalation trial of MSCs in septic shock with the primary objective of examining the safety and tolerability of MSCs. METHODS: We enrolled nine participants within 24 hours of admission to the ICU. A control cohort of 21 participants was enrolled before starting the MSC interventional cohort to characterize expected adverse events (AEs) and to serve as a comparator for the intervention cohort. Three separate MSC dose cohorts, with three participants per cohort, received a single intravenous dose of 0.3, 1.0, and 3.0 × 106 cells/kg. A prespecified safety plan monitored participants for the occurrence of AEs; cytokines were collected at prespecified time points. MEASUREMENTS AND MAIN RESULTS: Ages of participants in the interventional versus observational cohorts were median of 71 (range, 38-91) and 61 (range, 23-95). Acute Physiology and Chronic Health Evaluation scores were median of 25 (range, 11-28) and 26 (range, 17-32). MSC doses ranged from 19 to 250 million cells. There were no prespecified MSC infusion-associated or serious unexpected AEs, nor any safety or efficacy signals for the expected AEs or the measured cytokines between the interventional and observational cohorts. CONCLUSIONS: The infusion of freshly cultured allogenic bone marrow-derived MSCs, up to a dose of 3 million cells/kg (250 million cells), into participants with septic shock seems safe. Clinical trial registered with www.clinicaltrials.gov (NCT02421484).

20.
Chest ; 154(3): 678-690, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29253554

RESUMO

Heparin-induced thrombocytopenia (HIT) is associated with clinically significant morbidity and mortality. Patients who are critically ill are commonly thrombocytopenic and exposed to heparin. Although HIT should be considered, it is not usually the cause of thrombocytopenia in the medical-surgical ICU population. A systematic approach to the patient who is critically ill who has thrombocytopenia according to clinical features, complemented by appropriate laboratory confirmation, should lead to a reduction in inappropriate laboratory testing and reduce the use of more expensive and less reliable anticoagulants. If the patient is deemed as being at intermediate or high risk for HIT or if HIT is confirmed by means of the serotonin-release assay, heparin should be stopped, heparin-bonded catheters should be removed, and a direct antithrombin or fondaparinux should be initiated to reduce the risk of thrombosis. Warfarin is absolutely contraindicated in the acute phase of HIT; if administered, its effects must be reversed by using vitamin K.

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