scholarly journals Safety of benzodiazepines and opioids in interstitial lung disease: a national prospective study

2018 ◽  
Vol 52 (6) ◽  
pp. 1801278 ◽  
Author(s):  
Sabrina Bajwah ◽  
Joanna M. Davies ◽  
Hanan Tanash ◽  
David C. Currow ◽  
Adejoke O. Oluyase ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Low Dose ◽  
Cox Regression ◽  
Oral Morphine ◽  
High Dose ◽  
Opioid Use ◽  
Respiratory Compromise ◽  
Oral Morphine Equivalent ◽  
Morphine Equivalent

Safety concerns are a barrier to prescribing benzodiazepines (BDZs) and opioids in interstitial lung disease (ILD). We therefore examined the association of BDZs and opioids on risk of admission to hospital and death.We conducted a population-based longitudinal cohort study of fibrotic ILD patients starting long-term oxygen therapy in Sweden between October 2005 and December 2014. Effects of BDZs and opioids on rates of admission to hospital and mortality were analysed using Fine–Gray and Cox regression while adjusting for potential confounders.We included 1603 patients (61% females). BDZs were used by 196 (12%) patients and opioids were used by 254 (15%) patients. There was no association between BDZs and increased admission. Treatment with high- versus low-dose BDZs was associated with increased mortality (subdistribution hazard ratio (SHR) 1.46, 95% CI 1.08–1.98 versus 1.13, 95% CI 0.92–1.38). Opioids showed no association with increased admission. Neither low-dose opioids (≤30 mg·day−1 oral morphine equivalent) (SHR 1.18, 95% CI 0.96–1.45) nor high-dose opioids (>30 mg·day−1 oral morphine equivalent) (SHR 1.11, 95% CI 0.89–1.39) showed association with increased mortality.This first ever study to examine associations between BDZ and opioid use and harm in ILD supports the use of opioids and low-dose BDZs in severely ill patients with respiratory compromise.

scholarly journals β-blocker Use is Associated with a Reduction in Opioid Use 30 Days After Total Knee Arthroplasty

2019 ◽  
Vol 5 (22;5) ◽  
pp. E395-E406
Author(s):  
Jordan Starr
Keyword(s):  
Total Knee Arthroplasty ◽  
Oral Morphine ◽  
Veterans Affairs ◽  
Prescription Opioid ◽  
Opioid Use ◽  
Total Knee ◽  
Β Blocker ◽  
Β Blockers ◽  
Oral Morphine Equivalent ◽  
Morphine Equivalent

Background: Total knee arthroplasty (TKA) can lead to chronic pain and prolonged postoperative opioid use. There are few evidence-based interventions to prevent these outcomes. Recently, β-blockers have emerged as possible novel analgesics. Objectives: The objective of this study was to determine whether perioperative β-blocker use is associated with reduced prolonged postoperative opioid use after TKA. Study Design: This study used a retrospective cohort design. Setting: The research took place within Department of Veterans Affairs hospitals in the United States between April 2012 and April 2016. Methods: Patients: IRB approval was obtained to examine the records of Veterans Affairs (VA) patients undergoing TKA. Patients using opioids 60 days before surgery were excluded. Intervention: The intervention being investigated was perioperative β-blocker use, overall and by class. Measurement: Oral morphine equivalent usage through postoperative day 1 and prescription opioid refills through 30, 90, and 365 days after TKA were recorded. Adjusted models were created controlling for relevant demographic and comorbidity covariates. A secondary analysis examined the same outcomes separated by β-blocker class. Results: The cohort was 93.8% male with a mean age of 66 years. Among the 11,614 TKAs that comprised the cohort, 2,604 (22.4%) were performed on patients using β-blockers. After adjustment, β-blocker use was associated with reduced opioid use through 30 days after surgery (odds ratio [OR] 0.89 [95% confidence interval (CI), 0.80-0.99], P = .026). Selective β-blockers were associated with reduced opioid use at 30 days (OR 0.88 [95% CI, 0.78-0.98], P = .021), and nonselective β-blockers were associated with reduced oral morphine equivalent usage through postoperative day 1 (β = -17.9 [95% CI, -29.9 to -5.8], P = .004). Limitations: Generalizability of these findings is uncertain, because this study was performed on a cohort of predominantly white, male VA patients. This study also measured opioid use, but opioid use is not a perfect surrogate for pain. Nevertheless, opioid use offers value as an objective measure of pain persistence in a national cohort for which patient-reported outcomes are otherwise unavailable. Conclusions: Perioperative β-blocker use was associated with reduced prescription opioid use at 30 days after surgery. Both selective and nonselective β-blockers were associated with reduced opioid use when analyzed individually. Key words: Analgesics, opioid, arthroplasty, replacement, knee, adrenergic beta-antagonists, pain management

scholarly journals Corticosteroid responsiveness in patients with acute exacerbation of interstitial lung disease admitted to the emergency department

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hye Jin Jang ◽  
Seung Hyun Yong ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Song Yee Kim ◽  
...  
Keyword(s):  
Emergency Department ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Acute Exacerbation ◽  
Cox Regression ◽  
High Dose ◽  
Cox Regression Analysis ◽  
Prednisolone Dose ◽  
Single Center Study ◽  
Independent Risk Factors

AbstractInterstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102–0.408, P < 0.001), initial P/F ratio (HR:0.995, CI:0.992–0.999, P = 0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059–8.589, P < 0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (> 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.

scholarly journals Corticosteroid Responsiveness in Patients With Acute Exacerbation of Interstitial Lung Disease Admitted to the Emergency Department

2020 ◽  
Author(s):  
Hye Jin Jang ◽  
Seung Hyun Yong ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Song Yee Kim ◽  
...  
Keyword(s):  
Emergency Department ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Acute Exacerbation ◽  
Cox Regression ◽  
High Dose ◽  
Cox Regression Analysis ◽  
Prednisolone Dose ◽  
Single Center Study ◽  
Independent Risk Factors

Abstract Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (>1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n=117) and non-IPF (n=65). Multivariate Cox regression analysis showed that corticosteroid dose (HR:0.221, CI:0.102–0.408, P<0.001), initial P/F ratio (HR:0.995, CI:0.992–0.999, P=0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059–8.589, P<0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (>1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.

scholarly journals POS0331 LUNG TARGETED DELIVERY OF EVEROLIMUS AS A NEW TREATMENT OF SCLERODERMA-RELATED INTERSTITIAL LUNG DISEASE (SSc-ILD) DEVELOPED BY PSGL-1 KO MICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 393.1-393
Author(s):  
E. González Sánchez ◽  
J. Gómez-Román ◽  
A. Muñoz-Callejas ◽  
A. Marengo ◽  
N. Tsapis ◽  
...  
Keyword(s):  
T Cells ◽  
Hyaluronic Acid ◽  
Interstitial Lung Disease ◽  
Observational Study ◽  
Lung Disease ◽  
High Dose ◽  
Lung Pathology ◽  
Intratracheal Administration ◽  
Interstitial Inflammation ◽  
Autoimmune Syndrome

Background:Interstitial lung disease (ILD), the main cause of mortality in scleroderma (SSc) patients (1), has no treatment (2). P-selectin glycoprotein ligand 1 (PSGL-1), the main ligand for P-Selectin, is expressed on leukocytes and responsible for the initial steps of extravasation (3). The absence of PSGL-1 in mice spontaneously develops an autoimmune syndrome similar to human SSc with fibrosis, vascular damage, autoantibodies and pulmonary arterial hypertension in females, and almost 60% of animals older than 12 months develop ILD with aging (4). In this work, the therapeutic action of everolimus-loaded nanomedicine given by local administration as a treatment for ILD was evaluated. The intratracheal administration of everolimus loaded into in liposomes decorated with hyaluronic acid (HA) is studied as an administration strategy to reach the inflammatory and fibrotic cells, targeting these cells and avoiding systemic effects and possible toxicity on epithelial cellsObjectives:1) To study the effect of everolimus on bronchoalveolar lavage (BAL) cell populations and in lung pathology in SSc-ILD PSGL-1 KO mice2) To analyze the intratracheal application of everolimus included in empty liposomes (Lip+Ev) vs. liposomes decorated with hyaluronic acid (Lip-HA+Ev) as an administration strategy to decrease drug toxicity and increase drug effectivityMethods:In an observational study, PSGL-1−/− C57BL/6 males older than 12 months (n=4) were treated intratracheally with 4 doses of Lip or Lip-HA (with or without everolimus included), once a week (Lip+Ev 295.67µg/mL; Lip+Ev 82.73µg/mL; Lip-HA+Ev 82.73µg/mL). Then, animals were euthanatized and BAL and lungs were obtained. BAL cells were stained for flow cytometry analysis. Lungs were embedded in paraffin blocks for blind histological analysis by a pathologist and evaluated for interstitial inflammation and fibrosis degree. Lip-HA was selected as the treatment of choice for a second experiment (n=8) following the same experimental design (86.22µg/mL)Results:The observational study showed an increase in CD45+, alveolar macrophages (AM), eosinophils (Eos), granulocytes (Gr1+) and T cells in the BAL of untreated PSGL-1-/- mice compared with WT mice. Everolimus reduced these populations to WT levels in all casesLip-HA+Ev administration was chosen for further experiments because a lower dose of the drug gave a better result than the high dose in undecorated liposomes. Reduction of CD45+, AM, eosinophils, and CD45- cells populations by Lip-HA+Ev was confirmed. Lip-HA treatment increased the number of neutrophils and T cells, but this effect is controlled by the everolimus administrationHistological lung analysis showed an increase in interstitial inflammation and fibrosis in untreated PSGL-1-/- and empty Lip-HA experimental groups. Treatment with everolimus included in Lip-HA reduced the fibrotic and inflammatory interstitial lung lesions, reaching values similar to those observed in WT miceConclusion:PSGL-1 KO mice present ILD associated with scleroderma (SSc-ILD) with an increase of CD45+, Gr1+, Eos, T cells and AM populations in the BAL. Intratracheal treatment with everolimus included in liposomes decorated with hyaluronic acid reduces immune cell infiltration and fibrosis once SSc-ILD is establishedReferences:[1]Solomon JJ, Olson AL, Fischer A, Bull T, Brown KK, Raghu G (2013). Scleroderma lung disease[2]Singh D, Parihar AK, Patel S, Srivastava S, Diwan P, Singh MR (2019). Scleroderma: An insight into causes, pathogenesis and treatment strategies. Pathophysiology, 26(2)[3]Zarbock A, McEver RP, Hidalgo A (2011). Leukocyte Ligands for Endothelial Selectins: Specialized Glycoconjugates That Mediate Rolling and Signaling Under Flow. BLOOD[4]Pérez-Frías A, Núñez-Andrade N, et al. (2014). Development of an autoimmune syndrome affecting the skin and internal organs in P-selectin glycoprotein ligand 1 leukocyte receptor-deficient mice. Arthritis RheumatolDisclosure of Interests:None declared

scholarly journals THU0305 PREVALENCE AND CLINICAL OUTCOME OF INTERSTITIAL LUNG DISEASE IN ANCA ASSOCIATED VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 381.2-381
Author(s):  
J. Fernandes Serodio ◽  
J. Hernández-Rodríguez ◽  
G. Espígol-Frigolé ◽  
M. Alba ◽  
J. Marco-Hernández ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Cox Regression ◽  
Clinical Course ◽  
Usual Interstitial Pneumonia ◽  
Classification Criteria ◽  
Lung Involvement ◽  
Anca Associated Vasculitis ◽  
Inflammatory Infiltrates

Background:Lung involvement is frequent in ANCA-associated vasculitis (AAV). Classical lung manifestations consist of capillaritis with lung haemorrhage, inflammatory infiltrates and nodules. Interstitial lung disease (ILD) is increasingly recognized among patients with AAV. However, little is known concerning risk factors and clinical course of these patients.Objectives:The aim of our study was to characterize the prevalence and clinical course of ILD in patients with AAV.Methods:We have performed a clinical retrospective single-centre observational analysis (1990-2019) of all patients with the diagnosis of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) diagnosed according to 2018 Draft Classification Criteria for GPA and MPA1. Demographic, clinical and immunologic data were reviewed. Radiologic pattern of ILD were assessed by high-resolution-CT. Main outcome evaluated was overall-all survival.Results:The study population consisted of 123 patients, 56% female, aged 59.3±18.2 years old at the time of diagnosis. Clinical diagnosis was of MPA in 54% of patients and GPA in 46%. While 108 (88%) ANCA positive patients had PR3 (n=25) or MPO (n=83), 15 (12%) patients had negative or atypical ANCA. Any lung involvement was present in 82 (71%) and ILD was identified in 24 (20%) of all patients. ILD pattern was of usual interstitial pneumonia (UIP) in 12 patients, non-specified interstitial pneumonia (NSIP) in 9 and chronic organizing pneumonia (OP) in 3. There was an association between the presence of ILD and ANCA specificity: MPO were present in 100% of patients with UIP and in 75% of patients with NSIP/OP (p=0.017). Bronchiectasis were more prevalent among patients with ILD (19/24; p<0.001). During the median follow-up time period of 68 (23-126) months, mortality was of 42% among patients with ILD-AAV compared with 11% in no ILD-AAV (log-rank p=0.0001). On the multivariate Cox regression model, ILD was an independent predictor of mortality HR 2.95 (95%CI 1.09-7.96; p=0.033).Conclusion:ILD is a frequent manifestation of MPA and GPA patients. The presence of ILD, particularly UIP, is associated with ANCA-MPO and is a predictor of mortality. Therefore, a better management of fibrotic lung involvement in AAV is warranted.References:[1]Robson JC, Grayson PC, Ponte C, et al. Draft classification criteria for the ANCA associated vasculitides. Ann Rheum Dis 2018;77 (suppl 2):60-1.Disclosure of Interests:João Fernandes Serodio: None declared, José Hernández-Rodríguez: None declared, Georgina Espígol-Frigolé: None declared, Marco Alba: None declared, Javier Marco-Hernández: None declared, Marcelo Sánchez: None declared, Fernanda Hernández-González: None declared, Jacobo Sellarés: None declared, Maria C. Cid Grant/research support from: Kiniksa Pharmaceuticals, Consultant of: Janssen, Abbvie, Roche, GSK, Speakers bureau: Vifor, Sergio Prieto-González: None declared

scholarly journals OP0088 INITIATING TNF INHIBITORS IN INFLAMMATORY ARTHRITIS DOES NOT DECREASE THE AVERAGE OPIOID ANALGESIC CONSUMPTION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 58.2-59
Author(s):  
O. Palsson ◽  
T. Love ◽  
J. K. Wallman ◽  
M. C. Kapetanovic ◽  
P. S. Gunnarsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Inflammatory Arthritis ◽  
Opioid Analgesic ◽  
Oral Morphine ◽  
Undifferentiated Arthritis ◽  
First Line ◽  
The Mean ◽  
Oral Morphine Equivalent ◽  
Morphine Equivalent

Background:TNFα-inhibitor (TNFi) therapy is effective in controlling several rheumatic diseases and has been shown to reduce pain in patients with arthritis. Opioids are often prescribed for chronic pain, a common issue in inflammatory joint disease.Objectives:To explore the impact of the initiation of TNFi therapy as a first-line biologic disease-modifying anti-rheumatic drug (DMARD) on the prescription rates of opioids in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and undifferentiated arthritis (UA) in Iceland.Methods:All patients receiving biologic DMARD therapy for rheumatic diseases in Iceland are registered in a nationwide database (ICEBIO). The Icelandic Directorate of Health operates a Prescription Medicines Register that includes over 90% of all drug prescriptions in Iceland. The study group included patients with RA, PsA, AS, and UA registered in ICEBIO and for each of them five randomly selected comparators from the general population matched on age, sex, and calendar time. On February 1st2016 we extracted data on all filled opioid analgesic prescriptions two years before and two years after the date of TNFi initiation.Results:Data from 359 RA, 217 AS, 251 PsA and 113 UA patients and 4700 comparators were collected. In total, 75% of patients compared to 43% of comparators received ≥1 opiate prescription during the study period. The proportion of patients using opioids (regardless of dose) two years prior to TNFi initiation was 41%, increasing to 49% the following year. After TNFi initiation the proportion returned to 40% (Figure 1). Despite this, the mean yearly opiate dose used by the patients followed a rising trajectory throughout the study period (Figure 2). In total, patients were prescribed nearly 6 times more opioids than the comparators, corresponding to a bootstrapped mean (95% CI) dose of 818 (601-1073) mg MED per patient and year compared to 139 (111-171) mg for comparators.Figure 1.Percental distributions of opioid analgesic use by dose (according to dispensed prescriptions) among patients with inflammatory arthritis (A) and matched comparators (B). All doses are oral morphine equivalent dose (MED) in milligrams.Figure 2.Bootstrapped mean oral morphine equivalent dose per person per year for patients with inflammatory arthritis (above) and age and sex matched comparators (below). Box edges represent 25-75thpercentiles and whiskers 95% confidence intervals.Conclusion:Three out of four patients with inflammatory arthritis in Iceland use opioid analgesics in the two years prior to and/or after the initiation of TNFi therapy and the mean doses were significantly higher than in matched comparators. The proportion of patients receiving opioids increased before TNFi therapy and then decreased again to the previous level. The initiation of the first-line TNFi did not reduce opioid consumption by dose at the group level. On the contrary, there was a trend towards increasing doses over time in both patients and comparators, possibly reflecting the development of opiate tolerance.Table 1.Baseline demographic data. Mean ± SD unless specified. * defined from diagnosis to baselAll patientsRheumatoid arthritisPsoriatic arthritisAnkylosing spondylitisUndifferentiated arthritisTotal n (%)940 (100)359 (38)251 (27)217 (23)113 (12)Age (years)49 ± 1453 ± 1449 ± 1343 ± 1344 ± 15Disease duration (years)*7.8 ± 8.58.2 ± 8.27.4 ± 7.88.3 ± 10.26.3 ± 6.6Female58%73%59%34%52%Disclosure of Interests:Olafur Palsson: None declared, Thorvardur Love: None declared, Johan K Wallman Consultant of: Consultant for AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma., Meliha C Kapetanovic: None declared, Petur S Gunnarsson: None declared, Björn Gudbjornsson Speakers bureau: Novartis and Amgen

The conversion ratio from intravenous (IV) hydromorphone to oral (PO) opioids in patients with cancer.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 197-197
Author(s):  
Akhila Sunkepally Reddy ◽  
Sara Dost ◽  
Marieberta Vidal ◽  
Saneese Stephen ◽  
Karen Baumgartner ◽  
...  
Keyword(s):  
Palliative Care ◽  
Linear Regression Analysis ◽  
Oral Morphine ◽  
Patient Characteristics ◽  
Conversion Ratio ◽  
Opioid Rotation ◽  
Patients With Cancer ◽  
Daily Dose ◽  
Oral Morphine Equivalent ◽  
Morphine Equivalent

197 Background: Inpatients with cancer frequently undergo conversions from IV to PO hydromorphone (HM) or opioid rotation (OR) from IV HM to another PO opioid prior to discharge. Currently used conversion ratios (CR) between IV and PO HM range from 2-5 and opioid rotation ratios (ORR) between IV HM and oral morphine equivalent daily dose (MEDD) range from 10-20. This large variation in ratios may lead to uncontrolled pain or overdosing. Our aim was to determine the accurate CR from IV to PO HM and ORR from IV HM to PO morphine and oxycodone (measured as MEDD). Methods: We reviewed records of 4745 consecutive inpatient palliative care consults in our institute during 2010-14 for patients who underwent conversion from IV to PO HM or OR from IV HM to PO morphine or oxycodone. Patient characteristics, symptoms and opioid doses were determined in patients successfully discharged on oral opioids without readmission within 1 week. Linear regression analysis was used to estimate the CR or ORR between the 24 hour IV HM mg dose prior to conversion to PO and the oral opioid mg dose used in the 24 hours prior to discharge. Results: Among 394 eligible patients on IV HM, 147 underwent conversion to PO HM and 247 underwent OR to oral morphine (163) or oxycodone (84). Mean age was 54 years, 39% were male, and 95% had advanced cancer. Median time between conversion to PO and discharge was 2 days. In 147 patients the median CR (IQR) from IV to PO HM was 2.5 (2.1-2.7) and correlation of IV to PO dose of HM was .95 (P < .0001). The median CR was 2.5 in patients receiving < 30mg of IV HM/day and 2.1 in patients receiving ≥ 30mg of HM/day (P = .004). In 247 patients the median ORR (IQR) from IV HM to MEDD was 11.5 (10-13) and correlation of IV HM to MEDD was .93 (P < .0001). The median ORR was 11.5 in patients receiving < 30mg of IV HM/day and 9.9 in patients receiving ≥ 30mg of HM/day (P = .0004). ORR from IV HM to MEDDs obtained from morphine (11) and oxycodone (12.1) were significantly different (P = .0023). The CR and ORR were not significantly impacted by other variables. Conclusions: The median CR from IV to PO HM is 2.5 and ORR from IV HM to MEDD is 11.5. This implies that 1 mg IV HM is equivalent to 2.5 mg PO HM and 11.5 mg MEDD. HM may cause hyperalgesia at doses ≥ 30 mg/day and thereby requires a lower ORR to other opioids.

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