Background The detection of pulmonary nodules (PNs) is likely to increase, especially with the release of the National Lung Screen Trials. When tissue diagnosis is desired, transthoracic needle ...aspiration (TTNA) is recommended. Several guided-bronchoscopy technologies have been developed to improve the yield of transbronchial biopsy for PN diagnosis: electromagnetic navigation bronchoscopy (ENB), virtual bronchoscopy (VB), radial endobronchial ultrasound (R-EBUS), ultrathin bronchoscope, and guide sheath. We undertook this meta-analysis to determine the overall diagnostic yield of guided bronchoscopy using one or a combination of the modalities described here. Methods We performed a MEDLINE search using “bronchoscopy” and “solitary pulmonary nodule.” Studies evaluating the diagnostic yield of ENB, VB, R-EBUS, ultrathin bronchoscope, and/or guide sheath for peripheral nodules were included. The overall diagnostic yield and yield based on size were extracted. Adverse events, if reported, were recorded. Meta-analysis techniques incorporating inverse variance weighting and a random-effects meta-analysis approach were used. Results A total of 3,052 lesions from 39 studies were included. The pooled diagnostic yield was 70%, which is higher than the yield for traditional transbronchial biopsy. The yield increased as the lesion size increased. The pneumothorax rate was 1.5%, which is significantly smaller than that reported for TTNA. Conclusion This meta-analysis shows that the diagnostic yield of guided bronchoscopic techniques is better than that of traditional transbronchial biopsy. Although the yield remains lower than that of TTNA, the procedural risk is lower. Guided bronchoscopy may be an alternative or be complementary to TTNA for tissue sampling of PN, but further study is needed to determine its role in the evaluation of peripheral pulmonary lesions.
Background and objective. Increasing physical activity (PA) is safe and beneficial in lung cancer (LC) patients. Advanced-stage LC patients are under-studied and have worse symptoms and quality of ...life (QoL). We evaluated the feasibility of monitoring step count in advanced LC as well as potential correlations between PA and QoL. Methods. This is a prospective, observational study of 39 consecutive patients with advanced-stage LC. Daily step count over 1 week (via Fitbit Zip), QoL, dyspnea, and depression scores were collected. Spearman rank testing was used to assess correlations. Correlation coefficients (ρ) >0.3 or <−0.3 (more and less correlated, respectively) were considered potentially clinically significant. Results. Most (83%) of the patients were interested in participating, and 67% of those enrolled were adherent with the device. Of those using the device (n = 30), the average daily step count was 4877 (range = 504-12 118) steps/d. Higher average daily step count correlated with higher QoL (ρ = 0.46), physical (ρ = 0.61), role (ρ = 0.48), and emotional functioning (ρ = 0.40) scores as well as lower depression (ρ = −0.40), dyspnea (ρ = −0.54), and pain (ρ = −0.37) scores. Conclusion. Remote PA monitoring (Fitbit Zip) is feasible in advanced-stage LC patients. Interest in participating in this PA study was high with comparable adherence to other PA studies. In those utilizing the device, higher step count correlates with higher QoL as well as lower dyspnea, pain, and depression scores. PA monitoring with wearable devices in advanced-stage LC deserves further study.
Depression is common among training physicians and may disproportionately affect women. The identification of modifiable risk factors is key to reducing this disease burden and its negative impact on ...patient care and physician career attrition.
To determine the presence and magnitude of a sex difference in depressive symptoms and work-family conflict among training physicians; and if work-family conflict impacts the sex difference in depressive symptoms among training physicians.
A prospective longitudinal cohort study of medical internship in the United States during the 2015 to 2016 academic year in which 3121 interns were recruited across all specialties from 44 medical institutions.
Prior to and during their internship year, participants reported the degree to which work responsibilities interfered with family life using the Work Family Conflict Scale and depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9).
Mean (SD) participant age was 27.5 (2.7) years, and 1571 participants (49.7%) were women. Both men and women experienced a marked increase in depressive symptoms during their internship year, with the increase being statistically significantly greater for women (men: mean increase in PHQ-9, 2.50; 95% CI, 2.26-2.73 vs women: mean increase, 3.20; 95% CI, 2.97-3.43). When work-family conflict was accounted for, the sex disparity in the increase in depressive symptoms decreased by 36%.
Our study demonstrates that depressive symptoms increase substantially during the internship year for men and women, but that this increase is greater for women. The study also identifies work-family conflict as an important potentially modifiable factor that is associated with elevated depressive symptoms in training physicians. Systemic modifications to alleviate conflict between work and family life may improve physician mental health and reduce the disproportionate depression disease burden for female physicians. Given that depression among physicians is associated with poor patient care and career attrition, efforts to alleviate depression among physicians has the potential to reduce the negative consequences associated with this disease.
Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are ...followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase “pilot study” is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well‐designed pilot studies play in the advancement of science and scientific careers. Clin Trans Sci 2011; Volume 4: 332–337
The aim of this study was to evaluate the effect of depression on all-cause and coronary heart disease (CHD) mortality among adults with and without diabetes.
We studied 10,025 participants in the ...population-based National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study who were alive and interviewed in 1982 and had complete data for the Center for Epidemiologic Studies Depression Scale. Four groups were created based on diabetes and depression status in 1982: 1) no diabetes, no depression (reference group); 2) no diabetes, depression present; 3) diabetes present, no depression; and i4) diabetes present, depression present. Cox proportional hazards regression models were used to calculate multivariate-adjusted hazard ratios (HRs) of death for each group compared with the reference group.
Over 8 years (83,624 person-years of follow-up), 1,925 deaths were documented, including 522 deaths from CHD. Mortality rate per 1,000 person-years of follow-up was highest in the group with both diabetes and depression. Compared with the reference group, HRs for all-cause mortality were no diabetes, depression present, 1.20 (95% CI 1.03-1.40); diabetes present, no depression 1.88 (1.55-2.27); and diabetes present, depression present, 2.50 (2.04-3.08). HRs for CHD mortality were no diabetes, depression present, 1.29 (0.96-1.74); diabetes present, no depression 2.26 (1.60-3.21); and diabetes present, depression present, 2.43 (1.66-3.56).
The coexistence of diabetes and depression is associated with a significantly increased risk of death from all causes, beyond that due to having either diabetes or depression alone.
Systemic lupus erythematous (SLE) is a chronic multi-organ autoimmune disease. Genetic and environmental factors contribute to disease onset and severity. Sphingolipids are signaling molecules ...involved in regulating cell functions and have been associated with multiple genetic disease processes. African-Americans are more likely to suffer from SLE morbidity than Whites. The Medical University of South Carolina has banked plasma samples from a well-characterized lupus cohort that includes African-Americans and Whites. This study examined the influence of race on plasma sphingolipid profiles in SLE patients and association of sphingolipid levels with comorbid atherosclerosis and SLE disease activity. Mass spectrometry revealed that healthy African-Americans had higher sphingomyelin levels and lower lactosylcermide levels compared to healthy Whites. SLE patients, irrespective of race, had higher levels of ceramides, and sphingoid bases (sphingosine and dihydrosphingosine) and their phosphates compared to healthy subjects. Compared to African-American controls, African-American SLE patients had higher levels of ceramides, hexosylceramides, sphingosine and dihydrosphingosine 1-phosphate. Compared to White controls, White SLE patients exhibited higher levels of sphingoid bases and their phosphates, but lower ratios of C16:0 ceramide/sphingosine 1-phosphate and C24:1 ceramide/sphingosine 1-phosphate. White SLE patients with atherosclerosis exhibited lower levels of sphingoid bases compared to White SLE patients without atherosclerosis. In contrast, African-American SLE patients with atherosclerosis had higher levels of sphingoid bases and sphingomyelins compared to African-American SLE patients without atherosclerosis. Compared to White SLE patients with atherosclerosis, African-American SLE patients with atherosclerosis had higher levels of select sphingolipids. Plasma levels of sphingosine, C16:0 ceramide/sphingosine 1-phosphate ratio and C24:1 ceramide/sphingosine 1-phosphate ratio significantly correlated with SLEDAI in the African-American but not White SLE patients. The C16:0 ceramide/sphingosine 1-phosphate ratio in SLE patients, and levels of C18:1 and C26:1 lactosylcermides, C20:0 hexosylceramide, and sphingoid bases in SLE patients with atherosclerosis could be dependent on race. Further ethnic studies in SLE cohorts are necessary to verify use of sphingolipidomics as complementary diagnostic tool.
Pulmonary fibrosis is a hallmark of diseases such as systemic sclerosis (SSc, scleroderma) and idiopathic pulmonary fibrosis (IPF). To date, the therapeutic options for patients with pulmonary ...fibrosis are limited, and organ transplantation remains the most effective option. Insulin-like growth factor-binding protein 5 (IGFBP-5) is a conserved member of the IGFBP family of proteins that is overexpressed in SSc and IPF. In this study, we demonstrate that both exogenous and adenovirally expressed IGFBP-5 promote fibrosis by increasing the production of extracellular matrix (ECM) genes and the expression of pro-fibrotic genes in primary human lung fibroblasts. IGFBP-5 increased expression of the pro-fibrotic growth factor CTGF and levels of the matrix crosslinking enzyme lysyl oxidase (LOX). Silencing of IGFBP-5 had different effects in lung fibroblasts from normal donors and patients with SSc or IPF. Moreover, we show that IGFBP-5 increases expression of ECM genes, CTGF, and LOX in human lung tissues maintained in organ culture. Together, our data extend our previous findings and demonstrate that IGFBP-5 exerts its pro-fibrotic activity by directly inducing expression of ECM and pro-fibrotic genes. Further, IGFBP-5 promotes its own expression, generating a positive feedback loop. This suggests that IGFBP-5 likely acts in concert with other growth factors to drive fibrosis and tissue remodeling.
Population-wide reductions in cardiovascular disease (CVD) have not been equally shared in the African American community due to a higher burden of CVD risk factors such as metabolic disorders and ...obesity. Differential concentrations of sphingolipids such as ceramide, sphingosine, and sphingosine 1-phosphate (S1P) has been associated with the development of CVD, metabolic disorders (MetD), and obesity. Whether African Americans have disparate expression levels of sphingolipids that explain higher burdens of CVD remains unknown.
A cross sectional analysis of plasma concentrations of ceramides, sphingosine, and S1P were measured from 8 whites and 7 African Americans without metabolic disorders and 7 whites and 8 African Americans with metabolic disorders using high performance liquid chromatography/tandem mass spectrometry methodology (HPLC/MS-MS). Subjects were stratified by both race and metabolic status. Subjects with one or more of the following physician confirmed diagnosis: diabetes, hypertension, hypercholesterolemia, or dyslipidemia were classified as having metabolic disease (MetD). Data was analyzed using a Two-Way ANOVA and Tukey's post hoc test.
Total ceramide levels were increased in African Americans compared to African Americans with MetD. Ceramide C16 levels were higher in whites with MetD compared to African Americans with MetD (p<0.05). Ceramide C20 levels were higher in whites with MetD compared to whites. Ceramide C20 levels were higher in African Americans compared to African Americans with MetD. Furthermore, whites with MetD had higher levels of C20 compared to African Americans with MetD (p<0.0001). Ceramide C24:0 and C24:1 in African Americans was higher compared to African Americans with MetD (p<0.05). The plasma concentration of Sph-1P ceramide was higher in African Americans vs whites (p = 0.01). Lastly, ceramide C20 negatively correlated with hemoglobin A1c (HbA1c) levels in our study cohort.
Plasma ceramide concentration patterns are distinct in African Americans with MetD. Further research with larger samples sizes are needed to confirm these findings and to understand whether racial disparities in sphingolipid concentrations have potential therapeutic implications for CVD-related health outcomes.
Background Vasoconstrictor therapy has been advocated as treatment for hepatorenal syndrome (HRS). Our aim was to explore across all tested vasoconstrictors whether achievement of a substantial ...increase in arterial blood pressure is associated with recovery of kidney function in HRS. Study Design Pooled analysis of published studies identified by electronic database search. Setting & Population Data pooled across 501 participants in 21 studies. Selection Criteria for Studies Human studies evaluating the efficacy of a vasoconstrictor administered for 72 hours or longer in adults with HRS type 1 or 2. Intervention Vasoconstrictor therapy. Outcomes & Measurements Cohorts' mean arterial pressure (MAP), serum creatinine level, urinary output, and plasma renin activity (PRA) at baseline and subsequent times during treatment. Linear regression models were constructed to estimate mean daily changes in MAP, serum creatinine level, urinary output, and PRA for each study subgroup. Correlations were used to assess for association between variables. Results An increase in MAP is associated strongly with a decrease in serum creatinine level, but is not associated with an increase in urinary output. Associations were stronger when analyses were restricted to randomized clinical trials and were not limited to cohorts with either lower baseline MAP or lower baseline serum creatinine level. Most studies tested terlipressin as vasoconstrictor, whereas fewer studies tested ornipressin, midodrine, octreotide, or norepinephrine. Excluding cohorts of participants treated with terlipressin or ornipressin did not eliminate the association. Furthermore, a decrease in PRA correlated with improvement in kidney function. Limitations Studies were not originally designed to test our question. We lacked access to individual patient data. Conclusions An increase in MAP during vasoconstrictor therapy in patients with HRS is associated with improvement in kidney function across the spectrum of drugs tested to date. These results support consideration for a goal-directed approach to the treatment of HRS.
New technology has resulted in bronchoscopy being increasingly used for diagnosing pulmonary lesions. Reported yield from these procedures varies widely with few randomized clinical trials. This ...study compares the diagnostic yield of a thin bronchoscope and radial endobronchial ultrasound (R-EBUS) with standard bronchoscopy and fluoroscopy (SB-F) in lung lesions.
Patients presenting for diagnostic bronchoscopic evaluation at five centers were randomized to undergo SB-F or R-EBUS with a thin bronchoscope (TB-EBUS). If SB-F was nondiagnostic, crossover to the TB-EBUS arm was allowed. Data on patient demographics, radiographic features, and final pathologic or radiographic follow-up were collected. Statistical comparisons were made by Fisher exact test, χ
test, and Student t test. Bivariate and multivariate analyses were performed to determine predictors of diagnostic yield.
One hundred and ninety-seven patients were included in the final analyses. There was no difference in demographics, lesion size, or location between study arms. The average lesion size was 31.2 mm (SD, 10.8 mm). Bronchoscopy was diagnostic in 87 patients (44%). Although the diagnostic yield was higher in the TB-EBUS arm compared with the SB-F arm (49% vs 37%), this difference was not statistically significant (P = .11). Among those with nondiagnostic bronchoscopic findings in the standard arm, 87% (n = 46) crossed over to TB-EBUS, resulting in a diagnosis in seven additional patients (15% of 46).
Bronchoscopy with or without a thin scope and R-EBUS had a poor diagnostic yield for pulmonary lesions. Future work should focus on improvements in technique and technology advances that ensure a higher likelihood of obtaining a diagnosis.
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