Lung function and side effects of Aspirin desensitization: a real world study

Introduction: Multiple Myeloma (MM) is a disease of the elderly; with approximately two-thirds of cases diagnosed at ages older than 65 years. However, this population has been underrepresented in clinical trials. Hence, there are no evidence-based guidelines to select the most appropriate treatment that would balance effectiveness against risk for side effects in the real world. Currently, guidelines advise that doublet regimens should be considered for frail, elderly patients; but more detailed recommendations are lacking. This study aims to describe treatment patterns in older patients with MM and compare treatment response and side effects between doublet and triplet regimens. Methods: Patients diagnosed with MM at 70 years or older and treated at Montefiore Medical Center between 2000 and 2017 were identified using Clinical Looking Glass, an institutional software tool. Recipients of autologous stem cell transplant were excluded. We collected demographic data and calculated comorbidity burden based on the age-adjusted Charlson Comorbidity Index (CCI). Laboratory parameters included cell blood counts, renal function, serum-protein electrophoresis and free kappa/lambda ratio pre and post first-line treatment. Treatment was categorized into doublet [bortezomib/dexamethasone (VD) and lenalidomide/dexamethasone (RD)] or triplet regimens [lenalidomide/bortezomib/dexamethasone (RVD) and cyclophosphamide/bortezomib/dexamethasone (CyborD)]. Disease response was reported as VGPR, PR, SD or PD using pre-established criteria. Side effects included cytopenias, diarrhea, thrombosis and peripheral neuropathy. Clinical and laboratory data were obtained by manual chart review. Event-free survival was defined as time to treatment change, death or disease progression. Data were analyzed by treatment group using Stata 14.1 Results: A total of 97 patients were included, of whom 46 (47.4%) were males, 47 (48.5%) were Non-Hispanic Black and 23 (23.7%) were Hispanic. Median age at diagnosis was 77 years (range: 70-90). Median baseline hemoglobin was 9.4 (8.5-10.5) and 14 (16.1%) had grade 3/4 anemia. Baseline thrombocytopenia and neutropenia of any grade were less common (18.4% and 17.7%, respectively) and 11 patients (20%) had GFR ≤30. Treatment regimens included VD (51, 52.6%), CyborD (18, 18.6%), RD (15, 15.5%) and RVD (13, 13.4%). Overall, doublets were more commonly used than triplets (66, 68% vs 31, 32%). Baseline characteristics were similar among treatment regimen groups. There was no difference in treatment selection among patients with baseline anemia or baseline neutropenia; however, doublets were preferred for those with underlying thrombocytopenia compared to triplets (93.8% vs 6.2%, p<0.01). Median first-line treatment duration was 4.1 months and did not differ among treatment groups (3.9 vs. 4.3 months; p=0.88 for doublets and triplets, respectively). At least a partial response was achieved in 47 cases (63.5%) and it did not differ between doublets and triplets (61.7% vs 66.7%). In general, first line treatment was changed in 50 (51.5%) patients and the change frequency was higher for triplets than doublets (71% vs 42.4%, p<0.01). Among patients that changed treatment, 17(34.7%) switched from a doublet to a triplet; 15 (30.6%) from a triplet to a doublet and 17 (34.7%) changed the regimen remaining as doublet or triplet, respectively. There was no difference in frequency of cytopenias, diarrhea, thrombosis or peripheral neuropathy among groups. Median event-free survival was longer in patients receiving doublet vs. triplet therapy, although the difference was not statistically significant (7.3 vs 4.3 months; p=0.06). Conclusions: We show a real-world experience of an inner city, elderly MM cohort, ineligible for autologous transplantation. A doublet combination and specifically the VD regimen was the treatment of choice in the majority of cases. In this cohort, triplet regimens did not show better response rates and led to treatment change more often than doublets. Among patients requiring treatment, approximately a third switched from doublet to triplet or viceversa which suggest that current evaluation of patient frailty at diagnosis is suboptimal. Despite similar frequency of side effects among groups, there was a trend towards longer event-free survival in patients receiving doublets. Larger retrospective studies are needed to confirm these results. Disclosures Verma: Janssen: Research Funding; BMS: Research Funding; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria.

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Reasoning with linguistic preferences using NPN logic

Computer Science and Information Systems ◽

10.2298/csis090223003d ◽

2010 ◽

Vol 7 (3) ◽

pp. 511-528 ◽

Cited By ~ 3

Author(s):

Goran Devedzic ◽

Danijela Milosevic ◽

Lozica Ivanovic ◽

Dragan Adamovic ◽

Miodrag Manic

Keyword(s):

Side Effects ◽

Decision Analysis ◽

Decision Maker ◽

Real World ◽

Cognitive Maps ◽

Fuzzy Cognitive Maps ◽

Basic Notion ◽

The Real ◽

Alternative Framework ◽

Linguistic Models

Negative-positive-neutral logic provides an alternative framework for fuzzy cognitive maps development and decision analysis. This paper reviews basic notion of NPN logic and NPN relations and proposes adaptive approach to causality weights assessment. It employs linguistic models of causality weights activated by measurement-based fuzzy cognitive maps? concepts values. These models allow for quasi-dynamical adaptation to the change of concepts values, providing deeper understanding of possible side effects. Since in the real-world environments almost every decision has its consequences, presenting very valuable portion of information upon which we also make our decisions, the knowledge about the side effects enables more reliable decision analysis and directs actions of decision maker.

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Long-Term Inhalative Sedation in Children With Pulmonary Diseases

Journal of Intensive Care Medicine ◽

10.1177/0885066620953395 ◽

2020 ◽

pp. 088506662095339

Author(s):

Jochen Meyburg ◽

David Frommhold ◽

Johann Motsch ◽

Navina Kuss

Keyword(s):

Side Effects ◽

Lung Function ◽

Medical Center ◽

Academic Medical Center ◽

Tertiary Care ◽

Prospective Trial ◽

Pediatric Intensive Care ◽

Normal Lung ◽

Beneficial Effects

Objectives: To describe safety and feasibility of long-term inhalative sedation (LTIS) in children with severe respiratory diseases compared to patients with normal lung function with respect to recent studies that showed beneficial effects in adult patients with acute respiratory distress syndrome (ARDS). Design: Single-center retrospective study. Setting: 12-bed pediatric intensive care unit (PICU) in a tertiary-care academic medical center in Germany. Patients: All patients treated in our PICU with LTIS using the AnaConDa® device between July 2011 and July 2019. Measurements and Main Results: Thirty-seven courses of LTIS in 29 patients were analyzed. LTIS was feasible in both groups, but concomitant intravenous sedatives could be reduced more rapidly in children with lung diseases. Cardiocirculatory depression requiring vasopressors was observed in all patients. However, severe side effects only rarely occured. Conclusions: In this largest cohort of children treated with LTIS reported so far, LTIS was feasible even in children with severely impaired lung function. From our data, a prospective trial on the use of LTIS in children with ARDS seems justified. However, a thorough monitoring of cardiocirculatory side effects is mandatory.

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N15 A ‘real-world’ observational multi-centre study comparing the side effects and patient acceptability of budesonide MMX with prednisolone in patients with mild to moderate ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.998 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S664-S665

Author(s):

J Kearns ◽

L Scullion ◽

C Masterson ◽

N Kennedy ◽

C Butcher

Keyword(s):

Ulcerative Colitis ◽

Side Effects ◽

Real World ◽

Additional Data ◽

Patient Acceptability ◽

Multi Centre Study ◽

Real World Evidence ◽

Randomised Controlled ◽

The Impact

Abstract Background Budesonide MMX is indicated for the induction of remission in mild to moderate Ulcerative Colitis (UC) patients when 5-ASA treatment is not sufficient. Unlike traditional first-generation glucocorticoid steroids such as prednisolone, budesonide MMX has demonstrated a robust safety profile, comparable to placebo in several randomised controlled trials1,2,3. There is however limited real-world evidence to substantiate this safety claim in clinical practice. The aim of this observational analysis is to evaluate the tolerability and ease of administration of budesonide MMX in the real-world setting using prednisolone as a benchmark. Methods Patients receiving treatment for mild to moderate UC were identified in 3 treatment centres between April and October 2019. After providing privacy and data consent, patients completed a detailed nurse-led questionnaire regarding their experiences with prednisolone treatment. Following 6 weeks of therapy with budesonide MMX, patients were sent a follow-up questionnaire. Data from both the initial and subsequent questionnaires were entered by the nurse into a database for assimilation and analysis. Results Twenty-eight patients completed initial and follow-up questionnaires. Of these, 78.6% (n = 22) had experienced ≥1 prednisolone-related side effects. In comparison, following treatment with budesonide MMX, 21.4% (n = 6) reported ≥1 side effects. Instances of these side effects are shown in Figure 1. 46.4% of patients (n = 13) reported the impact of prednisolone-related side effects on daily life as moderate or severe vs. 7.1% (n = 2) following treatment with budesonide MMX. By week 2 of treatment with budesonide MMX, rectal bleeding was resolved in 32.1% of patients (n = 9) and stool frequency in 35.7% (n = 10). 93.1% (n = 27) found the instructions to take budesonide MMX given by the health care professional very easy to understand and of those expressing a preference, 71.1% of patients (n = 19) would take budesonide MMX again if prescribed. Additional data will be presented. Conclusion Data from this ‘real-world’ observational study appear to support the safely profile of budesonide MMX reported in clinical trials. The incidence of patients who experienced > 1 side-effect was nearly 4 times lower for budesonide vs. prednisolone. In addition, budesonide MMX therapy was acceptable to the majority of patients and accompanying instructions easy to understand. Additional data will be presented. References

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P232 Effectiveness of adalimumab biosimilar switching: real world data from a London rheumatology centre

Rheumatology ◽

10.1093/rheumatology/keaa111.226 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Shivanee Vigneswaran ◽

Megan Galloway ◽

Samuel Hanlon ◽

Aoife Tynan ◽

Animesh Singh

Keyword(s):

Side Effects ◽

Disease Activity ◽

Real World ◽

Biologic Therapy ◽

Underlying Disease ◽

Real World Data ◽

Biologic Drugs ◽

Control Activity ◽

World Data ◽

Long Term Treatment

Abstract Background Biologic drugs have revolutionised the management of many rheumatological diseases with remission or low disease activity now the realistic targets for treatment. However, given the chronic nature of most rheumatological disease and the need for long term treatment, there has been a significant increase in the cost associated with disease treatment. The advent of biosimilars offers an attractive target in reducing drug costs for payers. Biosimilar medications are thought to be equally efficacious as originator drugs. Real world data in adalimumab biosimilar switching is limited. In this audit we aim to examine the real-world outcomes from switching from originator Humira to biosimilar Amgevita in a London teaching hospital. Methods A list of all adult rheumatology patients on Amgevita was obtained through pharmacy records. All patients had been switched from Humira to Amgevita from February 2019. Using clinic letters and an in-house biologics database, data was collected on the underlying disease and the date of switch. Outcomes reviewed were disease activity scores pre and post switch, documented side effects and flare of disease activity following switch including decision to revert to originator Humira or change treatment. Results There was a total of 289 adult patients on Humira who switched to Amgevita. Of these patients, 28 in total discontinued treatment - 13 with rheumatoid arthritis, 10 with psoriatic arthritis and 5 with ankylosing spondylitis. 22 had to be switched back to Humira, with a further 4 patients approved to switchback and awaiting to restart. Two additional patients were switched to alternative biologic therapy due to inefficacy. A further 3 patients refused to switch onto Amgevita. Sixteen patients had documented flares, with one requiring admission and ten requiring local or systemic corticosteroid therapy to control activity. Seven patients had documented side effects which included chest pain, headache, rash and site reactions and one patient developed shingles post switch. Conclusion A total of 9.6% of patients switched to Amgevita had disease flare or side effects resulting in a switchback to Humira or alternative biologic therapy. For a biosimilar to be approved, efficacy and safety profiles needs to be comparable to the originator biological therapy and usually looks at two treatment naïve groups, rather than direct switch. Thereby, data on switches in therapy is limited. One systematic review looking at 11,053 patients with inflammatory arthritis treated with Etanercept and switched to Benepali, found 768 reverting to original therapy giving a lower total of 6.9%. We find that although no previous data of Amgevita, our figure of 9.6% appears high in the context of previously controlled inflammatory disease with Humira. Disclosures S. Vigneswaran None. M. Galloway None. S. Hanlon None. A. Tynan None. A. Singh None.

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Effect of intranasal mometasone furoate administered in children with coexisting allergic rhinitis and asthma towards asthma attacks and lung function

Paediatrica Indonesiana ◽

10.14238/pi49.6.2009.359-64 ◽

2009 ◽

Vol 49 (6) ◽

pp. 359

Author(s):

Ellen P. Gandaputra ◽

Zakiudin Munasir ◽

Bambang Supriyatno ◽

Jose R. L. Batubara

Keyword(s):

Allergic Rhinitis ◽

Side Effects ◽

Lung Function ◽

Persistent Asthma ◽

Mometasone Furoate ◽

Lower Airway ◽

Asthma Attack ◽

Persistent Allergic Rhinitis ◽

Before And After ◽

Term Administration

Background Allergic rhinitis and asthma are allergic manifestations in respiratory tract, which related each other. Intranasal corticosteroid is effective in allergic rhinitis and has benefits in decreasing lower airway reactivity.Objectives To evaluate effectiveness of intranasal mometasonefuroate towards asthma in children aged 6-18 years with coexisting allergic rhinitis and asthma.Methods A one group pretest-posttest ("before and after") study was conducted in Cipto Mangunkusumo Hospital from May to December 2008. Subjects were children aged 6-18 years, with moderate-severe intermittent or persistent allergic rhinitis with coexisting frequent episodic asthma or persistent asthma, and visited outpatient clinic of allergy immunology division or respirology division. Subjects were administered intranasal mometasone furoate 100 J-ig daily only for 8 weeks, without long term administration of oral and inhaled corticosteroid. Improvements in allergic rhinitis and asthma were evaluated using questionnaires and lung function tests.Results There were 35 subjects and four of them dropped outduring the study. There was >50% improvement in allergic rhinitis symptoms after 4 weeks of treatment (P<0.001). This improvement was associated with decreasing in frequency of asthma attack >50% after 8 weeks of treatment (P< 0.001). There was an insignificant improvement in FEY 1 (P=0.51). However, the evaluation of sinusitis was not performed in all subjects, thus may influence the results. During study, there were no side effects observed.Conclusions Intranasal mometasone furoate improves allergicrhinitis and decrease >50% of asthma symptoms, however it is not followed with significant improvement in lung function. No side effects are reported during 8 weeks use of intranasal mometasone furoate.

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The utility ofHLA-DQB302as a genetic marker to predict the effect of aspirin desensitization on lung function of patients with aspirin exacerbated respiratory disease

10.1183/13993003.congress-2015.pa3611 ◽

2015 ◽

Author(s):

Zahra Aryan ◽

Hossein Esmaeilzadeh ◽

Ali Akbar Amirzargar ◽

Mohammad Nabavi

Keyword(s):

Lung Function ◽

Genetic Marker ◽

Respiratory Disease ◽

Aspirin Desensitization ◽

Aspirin Exacerbated Respiratory Disease

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Real world experience of palbociclib in hormone receptor-positive metastatic breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18094 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18094-e18094 ◽

Cited By ~ 2

Author(s):

Faizan Malik ◽

Naveed Ali ◽

Syed Imran Mustafa Jafri ◽

Mark L. Sundermeyer ◽

Michael Jeffrey Seidman ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Side Effects ◽

Real World ◽

Hormone Receptor ◽

Objective Response ◽

Metastatic Breast ◽

Hormone Receptor Positive ◽

Her 2 ◽

Grade 3

e18094 Background: Palbociclib has been approved as a first line therapy in hormone-receptor positive (HR+) and HER-2 negative metastatic breast cancer(MBC) manifesting significant improvement in progression free survival (PFS). We studied this drug in a community setting. The endpoints were estimated PFS, objective response, toxicities and patient outcomes. Methods: This was a single-center, retrospective study of HR+MBC patients receiving palbociclib after its FDA approval. 22 patients were selected Results: A total of 22 patients were included (Male = 2, Female = 20). Median age was 60-years (range, 49-84). About 90% patients had received at least one previous therapy and the median number was 1.5. 13% patients were on fulvestrant, 86% on letrozole and 4.5% on exemestane. About 64% of patients had ECOG status of ≥ 1. Median duration of palbociclib treatment was 5-months, therefore, an estimated PFS at 18-months was 50%. 4.5% patients attained complete response. 22% patients achieved partial response, 22% had stable disease and 50% patients demonstrated disease progression. 72% patients had neutropenia, of which 45% were grade ≥ 3. Thrombocytopenia and anemia were common (63% and 58%, respectively) but grade ≥ 3 thrombocytopenia or anemia was not observed. 50% patients required dose reductions and 18% required drug cessation owing to side effects. Conclusions: PFS was much lower as compared to actual trials in our real-world experience. Despite, several interesting observations were good objective response rates in males and HER-2+ patients underscoring its potential clinical efficacy in these subsets. Furthermore, apart from myelosuppressive side effects, pneumonitis was observed in one patient necessitating vigilance in clinical practice

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Treatment Patterns and Bleeding Events Among Patients with Immune Thrombocytopenia Based on Duration of Corticosteroid Treatment

Blood ◽

10.1182/blood-2020-141457 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 40-41

Author(s):

Mark D. Hatfield ◽

Janna Manjelievskaia ◽

Kristin A. Evans ◽

Philip K. Chan ◽

Neel Shah ◽

...

Keyword(s):

Side Effects ◽

Real World ◽

Immune Thrombocytopenia ◽

Bleeding Event ◽

Corticosteroid Treatment ◽

Treatment Patterns ◽

Second Line ◽

Bleeding Events ◽

Ibm Watson

Background: Oral corticosteroids (CS) are often the first line of therapy for immune thrombocytopenia (ITP). Recent guidelines recommend against prolonged CS use (>6 weeks) for adults with ITP and suggest switching to second-line treatments for non-responsive or CS-dependent patients. The duration and potential overuse of CS among newly treated with CS adult ITP patients has yet to be described in a real-world setting. This study quantified the real-world duration of CS use among adult ITP patients newly treated with CS and assessed the clinical and economic consequences of prolonged CS use. Objectives: 1) To describe treatment patterns, bleeding events, and side effects of CS among patients with ITP; 2) To describe healthcare resource utilization (HRU) and costs among patients with ITP treated with CS. Methods: A retrospective observational cohort study was conducted using claims contained in the IBM® MarketScan® Commercial and Medicare Databases. Adult patients with an ITP diagnosis between January 1, 2013 and June 30, 2018 were selected for the study. Patients were required to be newly treated with CS (prednisone, dexamethasone, methylprednisolone) (first CS claim=index date) with at least 12 months of continuous enrollment prior to and 12 months following index. Patients with a diagnosis for any other thrombocytopenia and evidence of causes of secondary thrombocytopenia were excluded. Patients were categorized into cohorts based on CS duration during the follow-up period: CS days' supply ≤6 weeks, >6 weeks to 8 weeks, or >8 weeks. Discontinuation was defined as a gap of >30 days of the index CS following the run-off date of the last observed claim. Bleeding events, incidence of CS side effects (defined as new events occurring during the follow-up period only), HRU and costs (2018 USD), and treatment patterns were described during the follow-up period. Results: Among 1,720 patients who met study inclusion criteria, 65% had ≤6 weeks of CS use, 6% had >6-8 weeks, and 29% had >8 weeks. Median age among all patients was 48 years and majority were female (61%). About three quarters (71%) of patients started on prednisone as the index CS treatment, 16% on methylprednisolone, and 13% on dexamethasone. Patients with higher CS duration of use (>6-8 and >8 week) had a shorter time to CS treatment start following ITP diagnosis (mean 69 and 92 days, respectively; median 5 days for both) compared to the ≤6 week cohort (mean 306, median 152 days). All but one patient discontinued their index CS therapy. Patients with >8 weeks of CS had higher CS restart rates following discontinuation (49%) compared to patients with ≤6 weeks (23%). Among patients who switched therapies following CS discontinuation, those in the ≤6 week cohort had higher utilization of second line ITP agents compared to the >8 week cohort, including eltrombopag (16% vs. 11%) and romiplostim (23% vs. 11%). Patients in the >8 week cohort had higher rates of switching to splenectomy (15%) and rituximab (33%) following CS discontinuation compared to the ≤6 cohort (6% and 26%). About a fifth (19%) of patients experienced a bleeding event during the follow-up period. Bleeding event rates were higher for those with >8 weeks of CS than those with ≤6 weeks (23% vs. 17%). Nearly 40% of all patients experienced a CS side effect and rates were similar among the three cohorts. Patients with greater use of CS (>8 weeks) had higher rates of inpatient admissions (34%) compared to the ≤6 week (22%) and >6-8 week (32%) cohorts. Mean annual all-cause costs were $24,800, $42,706, and $51,896 for the ≤6 week, >6-8 week, and >8 week cohorts, respectively. Conclusions: Patients with ≤6 weeks of CS had the shortest switch time to a non-CS ITP treatment, with higher utilization of thrombopoietin receptor agonists, as compared to patients with greater CS use. Patients with a higher duration of CS use had significantly higher inpatient and outpatient HRU and more than double the healthcare costs compared to patients with ≤6 weeks of CS. The rate of bleeding events was lowest among patients with ≤6 weeks of CS use. Approximately 35% of patients in this study were treated with >6 weeks of CS, indicating a need for earlier intervention with more effective ITP therapies that may reduce CS use and risk of bleeding events, and subsequently decrease the economic burden incurred by patients with prolonged CS exposure. Further study is needed to assess the clinical and economic outcomes related to duration of CS use. Figure Disclosures Hatfield: Amgen Inc.: Current Employment. Manjelievskaia:Amgen Inc.: Consultancy; IBM Watson Health: Current Employment. Evans:Amgen Inc.: Consultancy; IBM Watson Health: Current Employment. Chan:Amgen Inc.: Consultancy; IBM Watson Health: Current Employment. Shah:Amgen Inc.: Current Employment. Saad:Amgen Inc: Current Employment.

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