Characteristics of pulse oximetry and arterial blood gas in patients with fibrotic interstitial lung disease.

BACKGROUND: Fibrotic interstitial lung disease (ILD) is frequently associated with abnormal oxygenation; however, little is known about the accuracy of oxygen saturation by pulse oximetry (SpO2) compared with arterial blood gas (ABG) saturation (SaO2), the factors that influence the partial pressure of carbon dioxide (PaCO2) and the impact of PaCO2 on outcomes in patients with fibrotic ILD. STUDY DESIGN AND METHODS: Patients with fibrotic ILD enrolled in a large prospective registry with a room air ABG were included. Prespecified analyses included testing the correlation between SaO2 and SpO2, the difference between SaO2 and SpO2, the association of baseline characteristics with both the difference between SaO2 and SpO2 and the PaCO2, the association of baseline characteristics with acid-base category, and the association of PaCO2 and acid-base category with time to death or transplant. RESULTS: A total of 532 patients with fibrotic ILD were included. Mean resting SaO2 was 92±4% and SpO2 was 95±3%. Mean PaCO2 was 38±6 mmHg, with 135 patients having PaCO2 <35 mmHg and 62 having PaCO2 >45 mmHg. Correlation between SaO2 and SpO2 was mild to moderate (r=0.39), with SpO2 on average 3.0% higher than SaO2. No baseline characteristics were associated with the difference in SaO2 and SpO2. Variables associated with either elevated or abnormal (elevated or low) PaCO2 included higher smoking pack-years and lower baseline forced vital capacity (FVC). Lower baseline lung function was associated with an increased risk of chronic respiratory acidosis. PaCO2 and acid-base status were not associated with time to death or transplant. INTERPRETATION: SaO2 and SpO2 are weakly-to-moderately correlated in fibrotic ILD, with limited ability to accurately predict this difference. Abnormal PaCO2 was associated with baseline FVC but was not associated with outcomes.

The Clinical Frailty Scale for Risk Stratification in Patients With Fibrotic Interstitial Lung Disease.

BACKGROUND: Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD). RESEARCH QUESTION: Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in patients with fibrotic ILD? STUDY DESIGN AND METHODS: Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits. Patients were stratified into fit (CFS score 1-3), vulnerable (CFS score 4), and frail (CFS score 5-9) subgroups. Cox proportional hazards and logistic regression models with mixed effects were used to estimate time to death or lung transplantation. A derivation and validation cohort was used to establish prognostic performance. Trajectories of functional tests were compared using joint models. RESULTS: Of the 1,587 patients with fibrotic ILD, 858 (54%) were fit, 400 (25%) were vulnerable, and 329 (21%) were frail. Frailty was a risk factor for early mortality (hazard ratio, 5.58; 95% CI, 3.64-5.76, P < .001) in the entire cohort, in individual ILD diagnoses, and after adjustment for potential confounders. Adding frailty to established risk prediction parameters improved the prognostic performance in derivation and validation cohorts. Patients in the frail subgroup had larger annual declines in FVC % predicted than patients in the fit subgroup (-2.32; 95% CI, -3.39 to -1.17 vs -1.55; 95% CI, -2.04 to -1.15, respectively; P = .02). INTERPRETATION: The simple and practical CFS is associated with pulmonary and physical function decline in patients with fibrotic ILD and provides additional prognostic accuracy in clinical practice.

Lung imaging patterns in connective tissue disease-associated interstitial lung disease impact prognosis and immunosuppression response.

OBJECTIVES: Interstitial lung disease (ILD) in connective tissue diseases (CTD) have highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality and immunosuppression response. METHODS: Patients with CTD-ILD had high-resolution chest computed tomography (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern (usual interstitial pneumonia [UIP]; non-specific interstitial pneumonia [NSIP]; organizing pneumonia [OP]; fibrotic hypersensitivity pneumonitis [fHP]; and other). Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. RESULTS: Of 645 CTD-ILD patients, the frequent CTDs were systemic sclerosis (n = 215), rheumatoid arthritis (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with UIP, FVC decline was slower for NSIP (1.1%/year, 95%CI 0.2, 1.9) and OP (3.5%/year, 95%CI 2.0, 4.9), and mortality was lower for NSIP (HR 0.65, 95%CI 0.45, 0.93) and OP (HR 0.18, 95%CI 0.05, 0.57), but higher in fHP (HR 1.58, 95%CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95%CI 1.4, 2.8), with no change for UIP or fHP. CONCLUSION: Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

Integration and Application of Radiologic Patterns From Clinical Practice Guidelines on Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis.

BACKGROUND: Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to apply these approaches concurrently within a single patient. RESEARCH QUESTION: How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines? STUDY DESIGN AND METHODS: Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis. RESULTS: Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91). INTERPRETATION: An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific.

Kidney Transplant Recipients' Perspectives on Cardiovascular Disease and Related Risk Factors After Transplantation: A Qualitative Study.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality among kidney transplant recipients (KTRs). These patients have a high prevalence of risk factors, such as hypertension, diabetes, and dyslipidemia. Despite regular medical care, few of them reach the recommended therapeutic targets. The objective of this study is to describe KTRs' perspectives on CVD and related risk factors, as well as their priorities for posttransplant care. METHODS: Twenty-six KTRs participated in a semistructured interview about their personal experience and offered their perspectives on CVD risk factors posttransplant. The interview was digitally recorded and the transcripts were analyzed using a thematic and content methodology. RESULTS: CVD and related risk factors appear to be underestimated and trivialized. Only 2 of 26 patients identified CVD prevention and treatment as a priority. The most important posttransplant priorities identified by patients were related to immunosuppressive drugs (13 of 26), posttransplant follow-up (10) and graft survival (9). However, 21 of 26 patients stated they wanted to be better informed about posttransplant CVD risk factors. CONCLUSIONS: CVD and related risk factors are not a priority for KTRs, and the importance of CVD is underestimated and trivialized. KTRs did recommend that tailored information be provided by various professionals and at several points in the transplantation process. This knowledge will help us develop a new approach to increase awareness of posttransplant CVD and related risk factors.

Perspectives of Patients, Caregivers and Researchers on Research Priorities in Donation and Transplantation in Canada: A Pilot Workshop.

BACKGROUND: It is vitally important to seek input from key stakeholders to increase the quality and relevance of health-related research and accelerate its adoption into practice. Patients and caregivers have rarely been involved in setting research priorities in the transplantation and donation field. The objectives of this explorative study are: (i) to discuss research priorities within the Canadian National Transplant Research Program during a priority-setting exercise with patients, caregivers, organ donors and researchers and (ii) to compare the identified priorities with research published in 2 prestigious transplantation journals. METHODS: A pilot workshop attended by 10 patients and caregivers and 5 researchers was held in Montréal (Quebec, Canada) in August 2014 to identify research priorities. Priorities were identified using a thematic analysis of the workshop transcription conducted by multiple coders. These priorities were compared with the topics of research articles published in 2 major transplantation journals between 2012 and 2014. RESULTS: The themes of the 10 research priorities identified by study participants were related to different research domains: social, cultural, and environmental health factors (4); biomedical or clinical (4); and research about health systems and services (2). 26.7% of the research articles published were related to the identified priorities. Thirteen percent looked at ways to improve graft survival and 8.5% looked at the development of tolerance, 2 priorities identified by participants. Fewer than 5% examined the other 8 research priorities identified as important by workshop participants. CONCLUSIONS: This is the first study reporting patients' and researchers' priorities in the field of transplantation and donation in Canada. There is a discrepancy between topics that key stakeholders find important and research published in 2 major transplantation journals. The research priorities identified during our initial workshop will be validated through a national survey and workshop.

Strategies to increase living kidney donation: a retrospective cohort study.

BACKGROUND: Living kidney transplantation (LKT) offers the best medical outcomes for organ recipients. Historically, our centre had a low rate of LKT. In 2009, in an effort to increase living organ donation (LOD), a dedicated team was created. Its mandate was to promote LOD at our centre and at referring centres, to coordinate assessments of living organ donors, to facilitate the process, and to ensure long-term follow-up after the donation. In November 2010, our centre joined the national living donor paired exchange registry (LDPE). OBJECTIVE: To document the impact of the LOD team and LDPE registry on LOD rates at our centre. DESIGN: Retrospective cohort study. SETTING: Single center study in a university hospital with an adult kidney transplant program. PATIENTS: Using our electronic database, we included all potential living organ donors who contacted our centre from 01/01/2005 to 31/12/2008 and from 01/01/2009 to 31/12/2012. Follow-up was conducted until 31/12/2013. MEASUREMENTS: Number of transplantations from living donors, number of potential donors who contacted the centre, donor and recipient characteristics. METHODS: We compared the number of transplantations from living donors performed and the number of potential donors who contacted the centre before and after the creation of the LOD team and participation in the LDPE. RESULTS: A total of 50 renal transplantations were performed using organs from living donors during the first time period, whereas this increased to 73 in the 2009-2012 cohort (incidence rate difference (IRD): 0.030, 95% confidence interval (CI) 0.003-0.056). We also observed a significant increase in the number of individuals who contacted our centre to donate a kidney. During the 2005-2008 period (cohort 1), 191 individuals interested in donating a kidney contacted our centre, whereas this figure was 304 during the 2009-2012 period (cohort 2) (IRD: 0.143, 95% CI 0.091-0.196). LIMITATIONS: Single center study, relatively low sample size. CONCLUSION: The implementation of a LOD team, combined with our participation in the LDPE registry, was associated with a significant increase in the actual number of living kidney transplantations performed. These data support initiatives such as the creation of dedicated LOD teams and LDPE registry to increase LKT.

CONTEXTE: Le meilleur traitement pour les patients atteints d'insuffisance rénale est la transplantation rénale à partir d'un donneur vivant (DV). Historiquement, notre centre hospitalier réalisait une faible proportion de greffes rénales à partir de DV. En 2009, nous avons créé une équipe dédiée au don vivant afin d'augmenter le nombre de transplantations rénales à partir de DV. Cette équipe avait pour mandat de promouvoir le don vivant dans notre centre et dans les centres périphériques, de coordonner et faciliter l'évaluation des DV et s'assurer d'un suivi à long terme des DV. A partir de novembre 2010, notre centre s'est joint au registre canadien de donneurs vivants jumelés par échange de bénéficiaires (DVEB). OBJECTIF: Évaluer l'impact de l'équipe dédiée au don vivant et de la participation au registre canadien de DVEB sur le nombre de donneurs potentiels ayant contacté notre centre et le nombre de transplantation effectuées à partir de DV. TYPE D'ÉTUDE: Etude de cohorte rétrospective. LIEU DE L'ÉTUDE: Centre de santé universitaire offrant un programme de transplantation rénale adulte. PATIENTS: Tous les DV qui ont contacté notre centre entre le 01/01/2005 et le 31/12/2008 et entre le 01/01/2009 et le 31/12/2012. Nous avons effectué un suivi jusqu'au 31/12/2013. MESURES: Nombre de transplantations effectuées à partir de DV, nombre de donneurs potentiels ayant contacté notre centre, caractéristiques des donneurs et des receveurs. MÉTHODOLOGIE: Nous avons comparé le nombre de transplantations à partir de DV ainsi que le nombre de donneurs potentiels qui ont contacté notre centre avant et après la création d'une équipe dédiée au don vivant et la participation au registre de DVEB. RÉSULTATS: Nous avons réalisé 50 transplantations à partir de DV dans la première période, et 73 dans la deuxième (différence du taux d'incidence (DTI) : 0.030, intervalle de confiance de 95% (IC) 0.003-0.056). Entre 2005 et 2008, 191 individus ont manifesté un intérêt à être DV en contactant notre centre, alors que ce chiffre a augmenté à 304 pour la période 2009-2012 (DTI: 0.143, IC 95% 0.091-0.196). LIMITES: Étude avec un petit nombre de patients, provenant d'un seul centre de santé. CONCLUSION: La création d'une équipe de DV et la participation au registre canadien de DVEB sont associés à un accroissement du nombre de donneurs vivants effectifs. Ces données supportent l'efficacité d'initiatives telles la mise en place d'équipes dédiées au don vivant et le registre canadien de DVEB afin d'augmenter le nombre de transplantations à partir de DV.

Structural and functional partitioning of bread wheat chromosome 3B.

We produced a reference sequence of the 1-gigabase chromosome 3B of hexaploid bread wheat. By sequencing 8452 bacterial artificial chromosomes in pools, we assembled a sequence of 774 megabases carrying 5326 protein-coding genes, 1938 pseudogenes, and 85% of transposable elements. The distribution of structural and functional features along the chromosome revealed partitioning correlated with meiotic recombination. Comparative analyses indicated high wheat-specific inter- and intrachromosomal gene duplication activities that are potential sources of variability for adaption. In addition to providing a better understanding of the organization, function, and evolution of a large and polyploid genome, the availability of a high-quality sequence anchored to genetic maps will accelerate the identification of genes underlying important agronomic traits.

Transplant professionals' proposals for the implementation of an altruistic unbalanced paired kidney exchange program.

BACKGROUND: Kidney recipients in the O blood group are at a disadvantage in kidney exchange programs (KEPs) because they can only receive an organ from O blood group donors. A way to remedy this unfair situation is through altruistic unbalanced paired kidney exchange (AUPKE) where a compatible pair (CP) consisting of an O donor and a non-O recipient is invited to participate in a KEP. There is no established AUPKE program in Canada. The aim of this study was to gather transplant professionals' views on the conditions necessary for the implementation of an AUPKE program. METHODS: Nineteen Canadian transplant professionals took part in semistructured interviews. The content of these interviews was analyzed using a qualitative data analysis method. RESULTS: Respondents' recommendations focused on the following: (i) the logistics of AUPKE (e.g., not delaying the transplantation for the CP, retrieving organs locally, providing a good quality organ to the CP, and maintaining anonymity); (ii) the transplantation teams (e.g., establishing a consensus among members and ensuring sufficient resources); (iii) information provided to CPs; and (iv) research (e.g., looking into all transplant options for O recipients, studying all potential impacts of KEPs and AUPKE). CONCLUSION: The respondents in our study made the following recommendations for the implementation of an AUPKE program: (i) CPs should not be disadvantaged, (ii) measures should be taken to ensure that all transplant team members agree to participate and that there are sufficient resources for implementation, (iii) comprehensive information should be provided to the CP, and (iv) further research is needed on AUPKE.

How is organ transplantation depicted in internal medicine and transplantation journals.

BACKGROUND: In their book Spare Parts, published in 1992, Fox and Swazey criticized various aspects of organ transplantation, including the routinization of the procedure, ignorance regarding its inherent uncertainties, and the ethos of transplant professionals. Using this work as a frame of reference, we analyzed articles on organ transplantation published in internal medicine and transplantation journals between 1995 and 2008 to see whether Fox and Swazey's critiques of organ transplantation were still relevant. METHODS: Using the PubMed database, we retrieved 1,120 articles from the top ten internal medicine journals and 4,644 articles from the two main transplantation journals (Transplantation and American Journal of Transplantation). Out of the internal medicine journal articles, we analyzed those in which organ transplantation was the main topic (349 articles). A total of 349 articles were randomly selected from the transplantation journals for content analysis. RESULTS: In our sample, organ transplantation was described in positive terms and was presented as a routine treatment. Few articles addressed ethical issues, patients' experiences and uncertainties related to organ transplantation. The internal medicine journals reported on more ethical issues than the transplantation journals. The most important ethical issues discussed were related to the justice principle: organ allocation, differential access to transplantation, and the organ shortage. CONCLUSION: Our study provides insight into representations of organ transplantation in the transplant and general medical communities, as reflected in medical journals. The various portrayals of organ transplantation in our sample of articles suggest that Fox and Swazey's critiques of the procedure are still relevant.