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1.
Purpose
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging.Methods
This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality).Conclusion
Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.2.
Background
Idiopathic pulmonary fibrosis (IPF) is an incurable, debilitating disease which impairs lung function and eventually leads to death. Currently, there is a lack of effective modifying therapies and treatments for IPF as the underlying epidemiological mechanism is not clearly understood. This leads to difficulty in diagnosing and managing IPF, which results in a high incurment of disease-associated cost. Even though IPF poses a substantial economic burden, there is a lack of research available on cost triggers and healthcare utilization, which can be a barrier to future economic evaluations of new medicines for IPF.Objectives
We aimed to conduct a systematic literature review (SLR) to identify the key cost-generating events of IPF and to gather any related costing information.Results
The data showed that the main events triggering high resource use in patients were the symptoms of IPF progression along with comorbidities and lung transplantations. These events result in a high economic impact through the use of medications, health care professionals, and hospital stays.Conclusion
More research is needed to identify the direct, and indirect, relationships between IPF events and the costs they generate. This would help to further evaluate the area of need for future health technologies and to understand what events should be targeted to reduce the global economic burden of IPF.3.
Maria Mavroudi Despoina Papakosta Theodore Kontakiotis Kaliopi Domvri George Kalamaras Vasiliki Zarogoulidou Paul Zarogoulidis Paschalina Latka Haidong Huang Wolfgang Hohenforst-Schmidt Konstantinos Zarogoulidis 《Sleep & breathing》2018,22(2):393-400
Background
Interstitial lung diseases (ILD) are chronic and restrictive lung diseases with poor survival and quality of life. The aim of this study was to investigate the frequency of sleep disorders in idiopathic pulmonary fibrosis (IPF) and sarcoidosis and to assess patients’ quality of life in relation to these disorders.Methods
Forty patients, 19 with IPF, and 21 with sarcoidosis stage II/III were included. They were compared with 15 healthy subjects. All patients performed all-night polysomnography (PSG) and completed the Epworth, Berlin, and Stop-Bang questionnaires. In order to evaluate the quality of life, all patients completed the Short-Form 36 (SF-36) questionnaire.Results
Of the IPF patients, 68% were diagnosed with mild obstructive sleep apnea (OSA), 5.2% with moderate to severe, 5.2% with severe OSA, and 21% with no OSA. Of patients with sarcoidosis, 52.4% were diagnosed with mild OSA and 4.8% with moderate severity OSA. The remaining 42.8% did not have OSA. The health-related quality of life in both patients with IPF and patients with sarcoidosis was impaired especially in the domains concerning physical health and the level of independence, compared to the control group.Conclusions
In this sample of patients with IPF and sarcoidosis, obstructive sleep apnea is common at least in a mild degree of severity. The SF-36 questionnaire may be a useful tool for the evaluation of the quality of life in these patients.4.
Purpose
The pathophysiology of idiopathic pulmonary fibrosis (IPF) is complex, and its clinical course is difficult to predict. Perceived dyspnea, exercise capacity, and lung physiology have all been associated with mortality outcomes in IPF, but the significance of these relationships is unclear. We sought to investigate the correlation among these variables and their independent predictive capability in determining mortality outcomes.Methods
Four-hundred-thirty-seven patients diagnosed with IPF from three independent centers were included in the study. Medical Research Council Dyspnea Score (MRCDS), 6-min walk distance (6MWD), and pulmonary function tests were determined at baseline. The end-point was 18-month transplant-free survival.Results
Correlations between MRCDS, 6MWD, forced vital capacity (FVC), and diffusing lung capacity for carbon monoxide were either very weak or weak. Calculation of variance inflation factors demonstrated absence of collinearity among these variables. Univariate regression analysis and c-statistics identified MRCDS, 6MWD, and FVC as significant predictors of 18-month transplant-free survival. Multivariate regression analysis retained MRCDS, 6MWD, and FVC as independent predictors of mortality. To ensure generalizability, we confirmed the results in subgroups of patients stratified according to baseline FVC, and further by considering lung transplant as a competing event to death.Conclusions
In a cohort of patients with IPF encompassing a wide range of disease severity, baseline perceived exertional dyspnea, exercise capacity, and lung function are weakly correlated to each other, translating in the absence of collinearity. MRCDS, 6MWD, and FVC are significant and independent predictors of outcome, suggesting that a multi-dimensional assessment of IPF is prognostically appropriate and advantageous.5.
6.
Background
Little is known about self-help associations and their possibilities. Obstacles often prevent early contacts between affected people.Objectives
The psychosocial support given by self-help associations in different phases is evaluated.Materials and methods
Based on the experience of the Deutsche ILCO and from cooperation with other organizations and institutions, various dimensions of self-help groups are investigated.Results
On the professional side, there is a lack of knowledge and of attitude. Suitable structures are rare.Conclusions
The removal of barriers and development of effective structures are overdue.7.
Giovanni B. Gaeta Massimo Puoti Nicola Coppola Teresa Santantonio Raffaele Bruno Antonio Chirianni Massimo Galli 《Infection》2018,46(2):183-188
Aim
This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC).Methods
This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations.Results
Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments.Conclusions
Early treatment with DAA should be offered when available.8.
J. Daryl Thornton Catherine Sullivan Jeffrey M. Albert Maria Cedeño Bridget Patrick Julie Pencak Kristine A. Wong Margaret D. Allen Linda Kimble Heather Mekesa Gordon Bowen Ashwini R. Sehgal 《Journal of general internal medicine》2016,31(8):832-839
BACKGROUND
Low organ donation rates remain a major barrier to organ transplantation.OBJECTIVE
We aimed to determine the effect of a video and patient cueing on organ donation consent among patients meeting with their primary care provider.DESIGN
This was a randomized controlled trial between February 2013 and May 2014.SETTING
The waiting rooms of 18 primary care clinics of a medical system in Cuyahoga County, Ohio.PATIENTS
The study included 915 patients over 15.5 years of age who had not previously consented to organ donation.INTERVENTIONS
Just prior to their clinical encounter, intervention patients (n?=?456) watched a 5-minute organ donation video on iPads and then choose a question regarding organ donation to ask their provider. Control patients (n?=?459) visited their provider per usual routine.MAIN MEASURES
The primary outcome was the proportion of patients who consented for organ donation. Secondary outcomes included the proportion of patients who discussed organ donation with their provider and the proportion who were satisfied with the time spent with their provider during the clinical encounter.KEY RESULTS
Intervention patients were more likely than control patients to consent to donate organs (22 % vs. 15 %, OR 1.50, 95%CI 1.10–2.13). Intervention patients were also more likely to have donation discussions with their provider (77 % vs. 18 %, OR 15.1, 95%CI 11.1–20.6). Intervention and control patients were similarly satisfied with the time they spent with their provider (83 % vs. 86 %, OR 0.87, 95%CI 0.61–1.25).LIMITATION
How the observed increases in organ donation consent might translate into a greater organ supply is unclear.CONCLUSION
Watching a brief video regarding organ donation and being cued to ask a primary care provider a question about donation resulted in more organ donation discussions and an increase in organ donation consent. Satisfaction with the time spent during the clinical encounter was not affected.TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT016971379.
Thierry H. Le Jemtel Rohan Samson Gregory Milligan Abhishek Jaiswal Suzanne Oparil 《Current hypertension reports》2018,20(9):77
Purpose of the Review
Low-grade systemic inflammation increases residual cardiovascular risk. The pathogenesis of low-grade systemic inflammation is not well understood.Recent Findings
Visceral adipose tissue accumulates when the subcutaneous adipose tissue can no longer store excess nutrients. Visceral adipose tissue inflammation initially facilitates storage of nutrients but with time become maladaptive and responsible for low-grade systemic inflammation. Control of low-grade systemic inflammation requires reversal of visceral adipose tissue accumulation with intense and sustained aerobic exercise or bariatric surgery. Alternatively, pharmacologic inhibition of the inflammatory signaling pathway may be considered.Summary
Reversal visceral adipose tissue accumulation lowers residual cardiovascular risk.10.
Lena M. Biehl Rebeca Cruz Aguilar Fedja Farowski Werner Hahn Angela Nowag Hilmar Wisplinghoff Maria J. G. T. Vehreschild 《Infection》2018,46(6):871-874
Purpose
We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections.Methods
FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed.Results
The patient remained without symptoms after FMT.Conclusions
Underlying mechanisms of action need to be addressed in depth by future research.11.
Purpose of Review
Organ fibrosis is a lethal component of scleroderma. The hallmark of scleroderma fibrosis is extensive extracellular matrix (ECM) deposition by activated myofibroblasts, specialized hyper-contractile cells that promote ECM remodeling and matrix stiffening. The purpose of this review is to discuss novel mechanistic insight into myofibroblast activation in scleroderma.Recent Findings
Matrix stiffness, traditionally viewed as an end point of organ fibrosis, is now recognized as a critical regulator of tissue fibrogenesis that hijacks the normal physiologic wound-healing program to promote organ fibrosis. Here, we discuss how matrix stiffness orchestrates fibrosis by controlling three fundamental pro-fibrotic mechanisms: (a) mechanoactivation of myofibroblasts, (b) integrin-mediated latent transforming growth factor beta 1 (TGF-β1) activation, and (c) activation of non-canonical TGF-β1 signaling pathways. We also summarize novel therapeutic targets for anti-fibrotic therapy based on the mechanobiology of scleroderma.Summary
Future research on mechanobiology of scleroderma may lead to important clinical applications such as improved diagnosis and treatment of patients with scleroderma and other fibrotic-related diseases.12.
BACKGROUND
Educating medical students about health disparities may be one step in diminishing the disparities in health among different populations. According to adult learning theory, learners’ opinions are vital to the development of future curricula.DESIGN
Qualitative research using focus group methodology.OBJECTIVES
Our objectives were to explore the content that learners value in a health disparities curriculum and how they would want such a curriculum to be taught.PARTICIPANTS
Study participants were first year medical students with an interest in health disparities (n?=?17).APPROACH
Semi-structured interviews consisting of 12 predetermined questions, with follow-up and clarifying questions arising from the discussion. Using grounded theory, codes were initially developed by the team of investigators, applied, and validated through an iterative process.MAIN RESULTS
The students perceived negative attitudes towards health disparities education as a potential barrier towards the development of a health disparities curriculum and proposed possible solutions. These solutions centered around the learning environment and skill building to combat health disparities.CONCLUSIONS
While many of the students’ opinions were corroborated in the literature, the most striking differences were their opinions on how to develop good attitudes among the student body. Given the impact of the provider on health disparities, how to develop such attitudes is an important area for further research.13.
Grant R. Martsolf Ryan Kandrack Robert A. Gabbay Mark W. Friedberg 《Journal of general internal medicine》2016,31(7):723-731
Background
Medical home initiatives encourage primary care practices to invest in new structural capabilities such as patient registries and information technology, but little is known about the costs of these investments.Objectives
To estimate costs of transformation incurred by primary care practices participating in a medical home pilot.Design
We interviewed practice leaders in order to identify changes practices had undertaken due to medical home transformation. Based on the principles of activity-based costing, we estimated the costs of additional personnel and other investments associated with these changes.Setting
The Pennsylvania Chronic Care Initiative (PACCI), a statewide multi-payer medical home pilot.Participants
Twelve practices that participated in the PACCI.Measurements
One-time and ongoing yearly costs attributed to medical home transformation.Results
Practices incurred median one-time transformation-associated costs of $30,991 per practice (range, $7694 to $117,810), equivalent to $9814 per clinician ($1497 to $57,476) and $8 per patient ($1 to $30). Median ongoing yearly costs associated with transformation were $147,573 per practice (range, $83,829 to $346,603), equivalent to $64,768 per clinician ($18,585 to $93,856) and $30 per patient ($8 to $136). Care management activities accounted for over 60% of practices’ transformation-associated costs. Per-clinician and per-patient transformation costs were greater for small and independent practices than for large and system-affiliated practices.Limitations
Error in interviewee recall could affect estimates. Transformation costs in other medical home interventions may be different.Conclusions
The costs of medical home transformation vary widely, creating potential financial challenges for primary care practices—especially those that are small and independent. Tailored subsidies from payers may help practices make these investments.Primary Funding Source
Agency for Healthcare Research and Quality14.
Purpose
Interleukin (IL)-25 and IL-33 induce IL-5 production by various types of cells, such as type 2 helper T (Th2) cells and type 2 innate lymphoid cells. The number of Th2 cells and concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) are increased in patients with eosinophilic pneumonia (EP). To examine the contribution of IL-25 and IL-33 to eosinophilic inflammation of the lung in humans, we evaluated IL-5, IL-25 and IL-33 levels in the BALF of patients with EP.Methods
IL-5, IL-25, and IL-33 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), idiopathic pulmonary fibrosis (IPF), and sarcoidosis.Results
The absolute number of eosinophils, and IL-5 levels, but not IL-33 levels, in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. IL-25 levels in the BALF were significantly higher in patients with CEP, but not in patients with AEP, than in patients with IPF and sarcoidosis. The absolute number of eosinophils was significantly correlated with the IL-5 concentration in the BALF of patients with EP. IL-5 concentrations were significantly correlated with IL-25 concentrations in the BALF of patients with CEP, but not in patients with AEP. IL-5 levels were not correlated with IL-33 levels in the BALF of patients with EP.Conclusions
Our findings suggest that IL-25 plays an important role via IL-5 in eosinophilic lung inflammation in patients with CEP.15.
Adam Wright Skye Aaron Diane L. Seger Lipika Samal Gordon D. Schiff David W. Bates 《Journal of general internal medicine》2018,33(11):1868-1876
Background
Drug-drug interaction (DDI) alerts in electronic health records (EHRs) can help prevent adverse drug events, but such alerts are frequently overridden, raising concerns about their clinical usefulness and contribution to alert fatigue.Objective
To study the effect of conversion to a commercial EHR on DDI alert and acceptance rates.Design
Two before-and-after studies.Participants
3277 clinicians who received a DDI alert in the outpatient setting.Intervention
Introduction of a new, commercial EHR and subsequent adjustment of DDI alerting criteria.Main Measures
Alert burden and proportion of alerts accepted.Key Results
Overall interruptive DDI alert burden increased by a factor of 6 from the legacy EHR to the commercial EHR. The acceptance rate for the most severe alerts fell from 100 to 8.4%, and from 29.3 to 7.5% for medium severity alerts (P?<?0.001). After disabling the least severe alerts, total DDI alert burden fell by 50.5%, and acceptance of Tier 1 alerts rose from 9.1 to 12.7% (P?<?0.01).Conclusions
Changing from a highly tailored DDI alerting system to a more general one as part of an EHR conversion decreased acceptance of DDI alerts and increased alert burden on users. The decrease in acceptance rates cannot be fully explained by differences in the clinical knowledge base, nor can it be fully explained by alert fatigue associated with increased alert burden. Instead, workflow factors probably predominate, including timing of alerts in the prescribing process, lack of differentiation of more and less severe alerts, and features of how users interact with alerts.16.
17.
Jason M. Glanz Komal J. Narwaney Shane R. Mueller Edward M. Gardner Susan L. Calcaterra Stanley Xu Kristin Breslin Ingrid A. Binswanger 《Journal of general internal medicine》2018,33(10):1646-1653
Background
Naloxone is a life-saving opioid antagonist. Chronic pain guidelines recommend that physicians co-prescribe naloxone to patients at high risk for opioid overdose. However, clinical tools to efficiently identify patients who could benefit from naloxone are lacking.Objective
To develop and validate an overdose predictive model which could be used in primary care settings to assess the need for naloxone.Design
Retrospective cohort.Setting
Derivation site was an integrated health system in Colorado; validation site was a safety-net health system in Colorado.Participants
We developed a predictive model in a cohort of 42,828 patients taking chronic opioid therapy and externally validated the model in 10,708 patients.Main Measures
Potential predictors and outcomes (nonfatal pharmaceutical and heroin overdoses) were extracted from electronic health records. Fatal overdose outcomes were identified from state vital records. To match the approximate shelf-life of naloxone, we used Cox proportional hazards regression to model the 2-year risk of overdose. Calibration and discrimination were assessed.Key Results
A five-variable predictive model showed good calibration and discrimination (bootstrap-corrected c-statistic?=?0.73, 95% confidence interval [CI] 0.69–0.78) in the derivation site, with sensitivity of 66.1% and specificity of 66.6%. In the validation site, the model showed good discrimination (c-statistic?=?0.75, 95% CI 0.70–0.80) and less than ideal calibration, with sensitivity and specificity of 82.2% and 49.5%, respectively.Conclusions
Among patients on chronic opioid therapy, the predictive model identified 66–82% of all subsequent opioid overdoses. This model is an efficient screening tool to identify patients who could benefit from naloxone to prevent overdose deaths. Population differences across the two sites limited calibration in the validation site.18.
Purpose
To determine the predictive value of qSOFA (quick Sequential Organ Failure Assessment) in Malawian patients with suspected infection.Methods
Prospective observational study in a tertiary referral hospital in Malawi.Results
Predictive ability of qSOFA was reasonable [AUROC 0.73 (95% CI 0.68–0.78)], increasing to 0.77 (95% CI 0.72–0.82) when classifying all patients with altered mental status as high risk. Adding HIV status as a variable to the qSOFA score did not improve predictive value.Conclusion
qSOFA is a simple tool that can aid risk stratification in resource-limited settings.19.
Heritage J Robinson JD Elliott MN Beckett M Wilkes M 《Journal of general internal medicine》2007,22(10):1429-1433