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Eliglustat, an oral substrate reduction therapy, is approved for eligible adults with Gaucher disease type 1. In the Phase 3 ENGAGE trial of previously untreated adults with Gaucher disease type 1, eliglustat-treated patients had statistically significant improvements in organ volumes and hematologic parameters compared with placebo in the 9-month primary analysis. We report final outcomes by time on eliglustat among all patients who participated in the ENGAGE trial and extension. No patient deteriorated clinically or withdrew due to adverse events; 39/40 patients entered the open-label extension period and 34/40 (85%) remained in the trial until completion or switching to commercial eliglustat after its approval (2.3-6 years). Clinically meaningful improvements in Gaucher disease manifestations were seen in all patients concomitant with reductions in pathological lipid substrate levels (glucosylceramide and glucosylsphingosine). Among patients with 4.5 years of eliglustat exposure, mean spleen volume decreased by 66% (from 17.1 to 5.8 multiples of normal [MN], n = 13), mean liver volume decreased by 23% (from 1.5 to 1.1 MN, n = 13), mean hemoglobin increased 1.4 g/dl (from 11.9 to 13.4 g/dl, n = 12), mean platelet count increased by 87% (from 67.6 to 122.6 × 109 /L, n = 12), median chitotriosidase decreased by 82% (from 13 394 to 2312 nmol/h/ml, n = 11), median glucosylceramide decreased by 79% (from 11.5 to 2.4 μg/ml, n = 11), median glucosylsphingosine decreased by 84% (from 518.5 to 72.1 ng/ml, n = 10), and mean spine T-score increased from -1.07 (osteopenia) to -0.53 (normal) (n = 9). The magnitude of improvement in Gaucher disease manifestations and biomarkers over time was similar among the full trial cohort. Eliglustat was well-tolerated and led to clinically significant improvements in previously untreated patients with Gaucher disease type 1 during 4.5 years of treatment.

Byline: Prince. Ntiamoah, Michelle. Biehl, Victoria. Ruesch, Atul. Mehta, Samar. Farha BACKGROUND: Systemic corticosteroids have been shown to improve outcomes in severe coronavirus disease 2019 (COVID-19) pneumonia; however, their role [...]

BackgroundTransbronchial lung biopsies are commonly performed for a variety of indications. Although generally well tolerated, complications such as bleeding do occur. Description of bleeding severity is crucial both clinically and in research trials; to date, there is no validated scale that is widely accepted for this purpose. Can a simple, reproducible tool for categorizing the severity of bleeding after transbronchial biopsy be created?MethodsUsing the modified Delphi method, an international group of bronchoscopists sought to create a new scale tailored to assess bleeding severity among patients undergoing flexible bronchoscopy with transbronchial lung biopsies. Cessation criteria were specified a priori and included reaching > 80% consensus among the experts or three rounds, whichever occurred first.ResultsThirty-six expert bronchoscopists from eight countries, both in academic and community practice settings, participated in the creation of the scale. After the live meeting, two iterations were made. The second and final scale was vetted by all 36 participants, with a weighted average of 4.47/5; 53% were satisfied, and 47% were very satisfied. The panel reached a consensus and proposes the Nashville Bleeding Scale.ConclusionsThe use of a simplified airway bleeding scale that can be applied at bedside is an important, necessary tool for categorizing the severity of bleeding. Uniformity in reporting clinically significant airway bleeding during bronchoscopic procedures will improve the quality of the information derived and could lead to standardization of management. In addition to transbronchial biopsies, this scale could also be applied to other bronchoscopic procedures, such as endobronchial biopsy or endobronchial ultrasound-guided needle aspiration.

The number of farm suicides in India is alarming. While the official data on farm suicides released by National Crime Records Bureau (NCRB) shows a rising trend till 2015, the figure went slightly down from 12,590 in 2015 to 10,338 in 2018. Any increase in the farm suicide cases in India is worrisome because of majority of population's dependence on agriculture. The report also mentions about the various reasons for farmers committing suicide with bankruptcy being a major cause of suicide among farmers. Considering the dismal state of farm suicides in the Maharashtra state of India, the present study attempts to analyze the debt behavior of the farm households for two time periods viz. 2004-05 and 2011-12. The study uses information on debt behavior of farm households in Maharashtra collected through two rounds of India Human Development Survey (IHDS) survey, which is a nationally representative, multi-topic survey across India. The first round of interviews was completed in 2004-05 and the second round of IHDS re-interviewed most of these households in 2011-12. The sample consists of a total of 1543 households in 2004-05 and 1685 households in 2011-12 in the Maharashtra state. The state of Maharashtra has been divided into 5 divisions viz. Konkan, Vidarbha, Nashik, Pune, and Marathwada. The sample households in the state have been divided based on land ownership and size of land into Agri wage laborer, small and marginal, medium, and large farm households. The debt profile of the households is analyzed using information on the share of indebted households, number of loans taken in the past 5 years, average loan size, outstanding debt, interest rate on the largest loan, debt-servicing capacity, debt-to-income ratio, consumption-income ratio, etc. The study also attempts to identify the key factors that are likely to have contributed to the highest number of farm suicides in Maharashtra and also provides policy suggestions for the government. The comparison between the two time periods not only helps understand what went wrong with the finances of farmers during the study period but also helps us identify the factors which may result in farmers taking such extreme steps in the future. JEL Classifications: G5, I3, O1, and R5 Keywords: Farmer Suicide, Maharashtra, Debt Behavior, IHDS, Bankruptcy. Corresponding Author's Email Address: f11atulm@iimidr.ac.in, INTRODUCTION The number of farm suicides in India is alarming. While the official data on farm suicides released by National Crime Records Bureau (NCRB) shows a rising trend till 2015, [...]

Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double-blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double-blind period, eliglustat treatment during the 9-month, open-label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double-blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment-naïve patients. Eliglustat was well-tolerated, and there were no new safety concerns with longer-term exposure.

Diaphragmatic palsy after lung transplantation has been reported infrequently. Given the role of the diaphragm in respiration, the palsy may play a significant role in the post-surgical recovery as well as morbidity and mortality. This review summarises the current literature to better understand diaphragmatic palsy in the post lung-transplant setting among adults. A thorough literature search was conducted through multiple databases and 91 publications were identified that fit the research question. The review aimed to report the burden of this problem, explore different modalities of diagnosis reported, the effect of various clinical factors and treatment modalities, as well as their effects on outcomes. Additionally, it aimed to highlight the variability, limitations of reported data, and the absence of a standardised approach. This review emphasises the crucial need for more dedicated research to better address this clinical challenge. [ABSTRACT FROM AUTHOR]

ImportanceGaucher disease type 1 is characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. A safe, effective oral therapy is needed.ObjectiveTo determine whether eliglustat, a novel oral substrate reduction therapy, safely reverses clinical manifestations in untreated adults with Gaucher disease type 1.Design, setting, and participantsPhase 3, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 12 countries from November 2009 to July 2012 among eligible patients with splenomegaly plus thrombocytopenia and/or anemia. Of 72 patients screened, 40 were enrolled.InterventionsPatients were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100 mg twice daily; n = 20) or placebo (n = 20) for 9 months.Main outcomes and measuresThe primary efficacy end point was percentage change in spleen volume in multiples of normal from baseline to 9 months; secondary efficacy end points were change in hemoglobin level and percentage changes in liver volume and platelet count.ResultsAll patients had baseline splenomegaly and thrombocytopenia (mostly moderate or severe), most had mild or moderate hepatomegaly, and 20% had mild anemia. Least-square mean spleen volume decreased by 27.77% (95% CI, -32.57% to -22.97%) in the eliglustat group (from 13.89 to 10.17 multiples of normal) vs an increase of 2.26% (95% CI, -2.54% to 7.06%) in the placebo group (from 12.50 to 12.84 multiples of normal) for an absolute treatment difference of -30.03% (95% CI, -36.82% to -23.24%; P