Prospective Acid Reflux Study of Iran (PARSI): Methodology and study design

<p>Abstract</p> <p>Background</p> <p>Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients.</p> <p>Methods</p> <p>We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years.</p> <p>Discussion</p> <p>Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.</p

Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation.

Studies demonstrate that Tropheryma whipplei (T. whipplei) is present in the lungs of healthy individuals without acute respiratory symptoms or acute respiratory infection and is more common in the lungs of HIV-infected individuals and in smokers. The impact of T. whipplei colonization in the lung on local inflammation and pulmonary dysfunction in HIV-infected individuals is currently unknown. In this study, we performed specific polymerase chain reaction (PCR) and sequencing for T. whipplei in bronchoalveolar lavage (BAL) and induced sputum (IS) samples in 76 HIV-infected participants from three clinical sites. Pulmonary function and proinflammatory cytokine and chemokine levels in BAL were measured. Frequency of T. whipplei in either BAL or IS was 43.4%. The sensitivity and specificity of IS compared to BAL for detection of T. whipplei was 92.3% and 84.2%, respectively, and isolates of T. whipplei in the BAL and IS in the same subject shared genetic identity. Pulmonary function measures were not associated with T. whipplei colonization, and proinflammatory cytokine and chemokine levels in BAL and plasma as well as percentages of inflammatory cells in BAL and IS were not higher in colonized individuals. Overall, these results indicate that T. whipplei colonization in the lung is common, but may not be associated with decreased pulmonary function or inflammation in HIV-infected individuals

Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation.

Studies demonstrate that Tropheryma whipplei (T. whipplei) is present in the lungs of healthy individuals without acute respiratory symptoms or acute respiratory infection and is more common in the lungs of HIV-infected individuals and in smokers. The impact of T. whipplei colonization in the lung on local inflammation and pulmonary dysfunction in HIV-infected individuals is currently unknown. In this study, we performed specific polymerase chain reaction (PCR) and sequencing for T. whipplei in bronchoalveolar lavage (BAL) and induced sputum (IS) samples in 76 HIV-infected participants from three clinical sites. Pulmonary function and proinflammatory cytokine and chemokine levels in BAL were measured. Frequency of T. whipplei in either BAL or IS was 43.4%. The sensitivity and specificity of IS compared to BAL for detection of T. whipplei was 92.3% and 84.2%, respectively, and isolates of T. whipplei in the BAL and IS in the same subject shared genetic identity. Pulmonary function measures were not associated with T. whipplei colonization, and proinflammatory cytokine and chemokine levels in BAL and plasma as well as percentages of inflammatory cells in BAL and IS were not higher in colonized individuals. Overall, these results indicate that T. whipplei colonization in the lung is common, but may not be associated with decreased pulmonary function or inflammation in HIV-infected individuals

Factors Associated With Progression of Lung Function Abnormalities in HIV-Infected Individuals

BACKGROUND:HIV is an independent risk factor for chronic obstructive pulmonary disease; however, baseline risk factors for lung function decline remain largely unknown in this population. METHODS:HIV-infected participants in the Pittsburgh Lung HIV Cohort with at least 3 pulmonary function measurements between 2007 and 2016 were included. Pulmonary function testing including postbronchodilator (BD) spirometry and diffusion capacity for carbon monoxide (DLco) was performed every 18 months. We used a mixed-effect linear model to evaluate factors associated with pulmonary function testing and DLco decline and logistic regression models to evaluate factors associated with rapid FEV1 decline (defined as &gt;80 mL per year) and any DLco decline. RESULTS:Two hundred eighty-five HIV-infected participants were included. Median baseline CD4 cell count was 521 cells per micro liter, 61.9% had an undetectable HIV viral load at baseline, and 78.5% were receiving ART. Approximately 20% of participants met Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for a diagnosis of chronic obstructive pulmonary disease at baseline. Older age and baseline GOLD stage 1 compared with stage 0 were associated with faster decline in post-BD FEV1%, whereas female sex was associated with slower decline. Similarly, female sex was associated with slower decline in DLco%. HIV-related factors including CD4 cell count, viral load, and ART use were not significantly associated with pulmonary function decline. CONCLUSIONS:Older age, male sex, and higher baseline GOLD stage were associated with more rapid post-BD FEV1% decline in HIV-infected individuals

Developing a Training Program to Diversify the Biomedical Research Workforce

The National Institutes of Health has made considerable investments to diversify the biomedical research workforce. Towards this goal, the authors partnered with representatives from several minority-serving institutions (MSIs) to develop training for the next generation of researchers. To ensure the most effective training program, the authors conducted a needs assessment with junior and senior investigators from the partnering MSIs. In 2016, the authors conducted focus groups and interviews with 23 junior investigators as well as in-depth interviews with 6 senior investigators from the partnering institutions with the goal of identifying specific areas of training and support that would help junior investigators at MSIs develop and sustain research careers. The data were transcribed and coded, and thematic analysis was conducted. The authors determined four areas in which training and support were needed: training in the "informal curriculum" (skills not covered in traditional clinical research courses), protected time for research training, opportunities to create career-advancing work products, and networking opportunities. The themes that were identified informed the development of the LEADS (Leading Emerging and Diverse Scientists to Success) program. The program consists of 10 instructor-led online modules each lasting approximately one month in duration with weekly synchronous sessions. Scholars are expected to be able to devote at least 20% of their time to the program

Glucocorticoid use in acute respiratory failure from pulmonary causes and association with early changes in the systemic host immune response

Abstract Background Glucocorticoids are commonly used in patients with or at-risk for acute respiratory distress syndrome (ARDS), but optimal use remains unclear despite well-conducted clinical trials. We performed a secondary analysis in patients previously enrolled in the Acute Lung Injury and Biospecimen Repository at the University of Pittsburgh. The primary aim of our study was to investigate early changes in host response biomarkers in response to real-world use of glucocorticoids in patients with acute respiratory failure due to ARDS or at-risk due to a pulmonary insult. Participants had baseline plasma samples obtained on study enrollment and on follow-up 3 to 5 days later to measure markers of innate immunity (IL-6, IL-8, IL-10, TNFr1, ST2, fractalkine), epithelial injury (sRAGE), endothelial injury (angiopoietin-2), and host response to bacterial infections (procalcitonin, pentraxin-3). In our primary analyses, we investigated the effect of receiving glucocorticoids between baseline and follow-up samples on host response biomarkers measured at follow-up by doubly robust inverse probability weighting analysis. In exploratory analyses, we examined associations between glucocorticoid use and previously characterized host response subphenotypes (hyperinflammatory and hypoinflammatory). Results 67 of 148 participants (45%) received glucocorticoids between baseline and follow-up samples. Dose and type of glucocorticoids varied. Regimens that used hydrocortisone alone were most common (37%), and median daily dose was equivalent to 40 mg methylprednisolone (interquartile range: 21, 67). Participants who received glucocorticoids were more likely to be female, to be on immunosuppressive therapy at baseline, and to have higher baseline levels of ST-2, fractalkine, IL-10, pentraxin-3, sRAGE, and TNFr1. Glucocorticoid use was associated with decreases in IL-6 and increases in fractalkine. In exploratory analyses, glucocorticoid use was more frequent in participants in the hyperinflammatory subphenotype (58% vs 40%, p = 0.05), and was not associated with subphenotype classification at the follow-up time point (p = 0.16). Conclusions Glucocorticoid use varied in a cohort of patients with or at-risk for ARDS and was associated with early changes in the systemic host immune response

Additional file 1 of Glucocorticoid use in acute respiratory failure from pulmonary causes and association with early changes in the systemic host immune response

Additional file 1: Table S1. Prior studies of glucocorticoid use in patients with acute respiratory distress syndrome (ARDS) or at-risk for ARDS due to severe pneumonia. Table S2. Conversion table for glucocorticoids [17]. Table S3. Clinical characteristics of ARDS and patients at-risk from a pulmonary insult who were excluded due to biomarker availability compared to patients who were included. Table S4. Clinical characteristics comparing patients with ARDS and patients at-risk for ARDS from a pulmonary insult included in the study. Table S5. Clinical characteristics comparing patients by pre-existing immunosuppression status. Table S6. Clinical characteristics by type(s) of glucocorticoid administered between baseline and follow-up samples. Table S7. Systemic host immune response biomarkers measured at follow-up time point. Table S8. Sensitivity analyses of the association between glucocorticoid use and systemic host immune response biomarkers at follow-up. Table S9. Clinical characteristics by host response subphenotype at baseline. Table S10. Clinical characteristics by host response subphenotype and receipt of glucocorticoids. Table S11. Sensitivity analyses of the association between glucocorticoid use and systemic host immune response biomarkers at follow-up in the hypoinflammatory phenotype subgroup. Table S12. Sensitivity analyses of the association between glucocorticoid use and systemic host immune response biomarkers at follow-up in the hyperinflammatory phenotype subgroup. Figure S1. Kaplan–Meier curves for 90-day survival and liberation from mechanical ventilation. Survival curves are adjusted for propensity score. Adjusted hazard ratio for survival (HR 0.96 [95% CI 0.46–2.01], p = 0.908) and time to liberation (HR 1.03 [95% CI 0.68–1.54, p = 0.905]) did not suggest differences between groups. Hazard ratio generated from Cox proportional hazard modeling with robust regression and proportional hazards assumption tested and not violated in both cases