scholarly journals Fabry disease and COVID-19: international expert recommendations for management based on real-world experience

2020 ◽  
Vol 13 (6) ◽  
pp. 913-925
Author(s):  
Dawn A Laney ◽  
Dominique P Germain ◽  
João Paulo Oliveira ◽  
Alessandro P Burlina ◽  
Gustavo Horacio Cabrera ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Real World ◽  
Tissue Injury ◽  
Healthcare Providers ◽  
Outcome Data ◽  
Organ Support ◽  
Real World Data ◽  
Enzyme Replacement ◽  
Susceptibility To Infection ◽  
Rapid Spread

Abstract The rapid spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has raised questions about Fabry disease (FD) as an independent risk factor for severe COVID-19 symptoms. Available real-world data on 22 patients from an international group of healthcare providers reveals that most patients with FD experience mild-to-moderate COVID-19 symptoms with an additional complication of Fabry pain crises and transient worsening of kidney function in some cases; however, two patients over the age of 55 years with renal or cardiac disease experienced critical COVID-19 complications. These outcomes support the theory that pre-existent tissue injury and inflammation may predispose patients with more advanced FD to a more severe course of COVID-19, while less advanced FD patients do not appear to be more susceptible than the general population. Given these observed risk factors, it is best to reinforce all recommended safety precautions for individuals with advanced FD. Diagnosis of FD should not preclude providing full therapeutic and organ support as needed for patients with FD and severe or critical COVID-19, although a FD-specific safety profile review should always be conducted prior to initiating COVID-19-specific therapies. Continued specific FD therapy with enzyme replacement therapy, chaperone therapy, dialysis, renin–angiotensin blockers or participation to clinical trials during the pandemic is recommended as FD progression will only increase susceptibility to infection. In order to compile outcome data and inform best practices, an international registry for patients affected by Fabry and infected by COVID-19 should be established.

scholarly journals Considerations for Home-Based Treatment of Fabry Disease in Poland during the COVID-19 Pandemic and Beyond

2021 ◽  
Vol 18 (16) ◽  
pp. 8242
Author(s):  
Michał Nowicki ◽  
Stanisława Bazan-Socha ◽  
Mariusz Kłopotowski ◽  
Beata Błażejewska-Hyżorek ◽  
Mariusz Kusztal ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Genetic Diseases ◽  
Healthcare Providers ◽  
Treatment Programs ◽  
Current Therapy ◽  
Term Care ◽  
Pharmacological Chaperone ◽  
Enzyme Replacement ◽  
Home Based ◽  
Rare Genetic Diseases

Current therapy for Anderson–Fabry disease in Poland includes hospital or clinic-based intravenous enzyme replacement therapy with recombinant agalsidase alpha or beta, or oral pharmacological chaperone therapy with migalastat. Some countries around the world offer such treatment to patients in the comfort of their own homes. The 2020–2021 COVID-19 pandemic has pushed global healthcare providers to evolve their services so as to minimize the risk of COVID-19 exposure to both patients and providers; this has led to advances in telemedicine services and the increasing availability of at-home treatment for various procedures including parenteral drug administration. A total of 80% of surveyed Anderson–Fabry disease patients in Poland would prefer home-based treatment, which would be a safe and convenient alternative to clinic-based treatment if patient selection is based on our proposed algorithm. Our recommendations for home-based treatments appear feasible for the long term care of Anderson–Fabry disease patients during the COVID-19 pandemic and beyond. This may also serve as a basis for home-based treatment programs in other rare and ultra-rare genetic diseases.

Defensive Medicine

2021 ◽  
pp. 99-124
Author(s):  
Michael J. Saks ◽  
Stephan Landsman
Keyword(s):  
Medical Practice ◽  
Real World ◽  
Healthcare Providers ◽  
Defensive Medicine ◽  
Self Report ◽  
Healthcare Industry ◽  
Clinical Scenario ◽  
Real World Data ◽  
Considerable Uncertainty ◽  
Legal Response

“Defensive Medicine: A Response to the Legal Response?” discusses the origins, meaning, purposes, and uncertain existence of defensive medicine. The concept has been most useful for those promoting changes in the law to economically benefit the healthcare industry. In the span of several decades, healthcare providers reversed their stance on whether or not they practice defensively. Why would providers commit defensive medicine? Why would they admit to practices that are universally seen as unethical, illegal (fraud), and unsound medical practice? Different types of empirical research have tried to determine whether defensive medicine occurs and, if so, its extent, cost, and effects on patients: physician self-report surveys, clinical scenario surveys, and multivariate analyses of real-world data. The chapter explores the possibility that defensive practices mostly occur in those situations where considerable uncertainty about diagnosis exists and the risk of serious harm is great if the patient is not treated correctly.

scholarly journals P600 Vedolizumab dose optimisation: Findings from a Belgian registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S501-S502
Author(s):  
E Louis ◽  
V Muls ◽  
P Bossuyt ◽  
A Colard ◽  
A Nakad ◽  
...  
Keyword(s):  
Clinical Response ◽  
Median Duration ◽  
Real World ◽  
Clinical Remission ◽  
Outcome Data ◽  
Real World Data ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Starting Point ◽  
Dose Optimisation

Abstract Background Vedolizumab (VDZ) dose optimisation (DO), by interval shortening from 8-weekly (Q8W) to 4-weekly (Q4W) dosing, is used for patients with secondary loss of response. This report presents outcome data on patients receiving DO in real-world clinical practice in Belgium. Methods The Belgian VDZ Registry (ENcePP EUPAS6469) enrolled 202 VDZ-treated ulcerative colitis (UC) or Crohn’s disease (CD) adult patients (26% with no prior use of anti-TNF therapy) from 19 centres. The median length of VDZ therapy prior to enrolment was 11 months. Patients were followed-up every 6 months with the assessment of IBD features, use of biologics, and disease activity. Clinical remission was defined as Harvey–Bradshaw Index (HBI) <5 or partial Mayo Score (pMS) <2, and clinical response as a 2+ point improvement in pMS or a 3+ improvement in HBI. Results During a median follow-up of 19 months from enrolment, 57 (28%) patients (41 CD and 16 UC) received VDZ Q4W due to secondary loss of response. Q4W was mostly used in patients with CD or with prior anti-TNF therapy failure. The median starting point for Q4W dosing was 16 months after the start of VDZ (interquartile range (IQR) 8–27 months) and median duration of Q4W dosing was 4 months (IQR 2–8 months). After changing to Q4W dosing 44% achieved clinical remission, 3% clinical response, and 53% showed no improvement (Table 1). Among the 17 patients with clinical remission/response on Q4W dosing, 53% de-escalated back to Q8W, and continued with Q8W for a median duration of 12 months, 23.5% remained on Q4W with clinical remission, and 23.5% eventually stopped VDZ due to loss of response. A limitation of this study is that it did not systematically collect data on DO prior to recruitment, hence the proportion of patients receiving DO may be higher than reported here. Conclusion These real-world data show DO plays an important role in management of UC and CD. In this study, 28% of patients received DO following the secondary loss of response to Q8W therapy. Forty-seven per cent of patients receiving Q4W subsequently returned to clinical remission or had a clinical response, and half of these patients successfully returned to Q8W VDZ therapy. Controlled studies are warranted, ideally blinded, using more objective endpoint to reveal the true success rate of dose-optimisation.

Retrospective comparison of neoadjuvant chemoradiation (nCRT) +/- surgery using the CROSS trial regimen and definitive chemoradiation (dCRT) with carboplatin (C) and paclitaxel (P) in esophageal (EC), and gastroesophageal junction cancer (GEJC) in Canada.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 313-313
Author(s):  
Sidra Khalid ◽  
Wilma M. Hopman ◽  
Kiran Virik
Keyword(s):  
Real World ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Outcome Data ◽  
World Population ◽  
Trial Protocol ◽  
Real World Data ◽  
Eligibility Criteria ◽  
Trimodality Therapy ◽  
The Cross

313 Background: Trimodality therapy using the CROSS trial protocol is an accepted standard of care for locally advanced EC and GEJC. For medically inoperable patients (pts), CRT has been a standard. CRT with C and P is an option in the definitive setting. This single institution review aims to assess the application and outcomes of the CROSS trial protocol in our real world population. Methods: From June 2012 until June 2018, a retrospective review was undertaken of 83 pts who underwent CRT with C and P with trimodaility or upfront definitive intent. 65 pts underwent nCRT; 40 proceeded to surgery. 18 had upfront dCRT. Pt demographics, clinical, pathological, treatment and surgical characteristics were assessed. These factors and outcomes were analyzed in exploratory analyses. Results: Of the 83 pts: median (m) age was 69 yrs (range 48-82), 34% were ≥ 75 yrs, 80% were male, 21% had CAD, 43% GERD, 23% Barrett’s, 77% adenocarcinoma, m tumor length was 5 cm, 36% had BMI > 30 and 80% were Siewert I tumors. The m RT dose was 50.4 Gy, m chemo doses were 5, m time to CRT was 69 days and m time from CRT to surgery was 66 days. 23% nCRT pts and 72% dCRT pts were ≥ 75 yrs and 49% and 33% of these respectively had no interruptions to CRT. Pts who underwent surgery were younger (p = 0.04) and weighed more (p = 0.05). Pts ≥75 yrs were likely to have dCRT (p = 0.001). For nCRT and surgery, nCRT only and dCRT respectively, median overall survival (mOS) was 35.5, 12.1 and 17.1 months (M) (log rank p = 0.08), PFS was 32.2, 10 and 9.6M (log rank p = 0.01). Compared to the other 2 groups, pts who underwent surgery had: no COPD (p = 0.004), less CAD (p = 0.003), less renal impairment (p = 0.023) and had lower esophageal tumors (p = 0.027). mOS for pts who had nCRT was 28.9M and 17.1M for dCRT (log rank p = 0.70). Further correlative outcome data will be presented. Conclusions: Despite the broadening of CROSS trial eligibility criteria in our real world data, there appears to be a survival benefit with trimodality therapy. The use of C and P in dCRT may be of value especially in the elderly, and requires further study.

Real-world evidence of male breast cancer (BC) patients treated with palbociclib (PAL) in combination with endocrine therapy (ET).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1055-1055 ◽  
Author(s):  
Cynthia Huang Bartlett ◽  
Jack Mardekian ◽  
Michelle Yu-Kite ◽  
Matthew James Cotter ◽  
Sindy Kim ◽  
...  
Keyword(s):  
Real World ◽  
Randomized Clinical Trials ◽  
Treatment Guidelines ◽  
Healthcare Providers ◽  
First Line ◽  
Duration Of Treatment ◽  
Real World Data ◽  
The Real ◽  
Real World Evidence ◽  
Line Setting

1055 Background: The rarity of BC in men limits the feasibility of randomized clinical studies in this population. Treatment guidelines recommend that men with BC be treated similarly to postmenopausal women. PAL, a cyclin-dependent kinase 4/6 inhibitor, is used in men with metastatic BC (mBC) in real-world clinical practice, presenting an opportunity to utilize real-world evidence to enable healthcare providers to assess novel agents in this space. Methods: Two parallel approaches were taken. In the first approach, pharmacy and medical claims data from IQVIA Inc were retrospectively analyzed to describe the treatment patterns and duration of PAL + ET (aromatase inhibitor or fulvestrant) compared to ET in men with mBC. The second approach was a retrospective analysis of data derived from electronic health records in the Flatiron Health database to understand real-world clinical response to PAL + ET vs ET alone. Median duration of treatment (mDOT) was estimated by the Kaplan-Meier method. Results: Between Feb 2015 and Apr 2017, 12.9% (147/1139 [IQVIA dataset]) of men receiving treatment for mBC were prescribed PAL + ET for any line of therapy. The mDOT in the first-line setting was numerically longer in the PAL cohort (n=37) compared with the non-PAL cohort (n=214; 8.5 vs 4.3 mo, respectively). In particular, mDOT in the first-line setting was longer with PAL + letrozole (LET; n=26) than with LET alone (n=63; 9.4 vs 3.0 mo, respectively). In the Flatiron Health dataset between Feb 2015 and July 2017, the real-world maximum response rate in the PAL + ET cohort across all lines of therapy in the mBC setting (n=12) was 33.3% (2 complete responses [CR], 2 partial responses [PR]) vs 12.5% (0 CR, 1 PR) for the ET alone cohort (n=8). Conclusions: The real-world data sources used in this study support that men with mBC derive clinical benefit from the addition of PAL to ET. Given the challenges of conducting randomized clinical trials in men with mBC, noninterventional, real-world evidence data appear to be useful to delineate the benefit of such therapies in this setting. Funding: Pfizer.

Direct Oral Anticoagulants Plasma Levels Measurement: Clinical Usefulness from Trials and Real-World Data

2021 ◽  
Vol 47 (02) ◽  
pp. 150-160
Author(s):  
Francesca Renon ◽  
Anna Rago ◽  
Biagio Liccardo ◽  
Antonello D'Andrea ◽  
Lucia Riegler ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Plasma Levels ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Outcome Data ◽  
Bleeding Events ◽  
Real World Data ◽  
World Data ◽  
Emergency Situations

AbstractMeasurement of direct oral anticoagulants (DOACs) activity is not routinely necessary. Indeed, evaluation of DOACs plasmatic concentration is discouraged for the majority of patients, due to the lack of outcome data supporting this approach. Nevertheless, DOAC measurements may be useful in emergency situations such as serious bleeding events, need for urgent invasive procedures, and acute ischemic stroke or in managing anticoagulation in “special populations” not adequately studied in clinical trials, for example the very elderly or those at the extremes of body weight. The aim of this review is to describe and summarize the methods for DOACs activity evaluation and the settings in which their plasma level measurement may be indicated, analyzing indications from scientific societies and evidence from clinical trials, as well as real world data on the usefulness of DOACs plasma levels “monitoring.”

Clinical outcomes of metastatic renal carcinoma following disease progression to programmed death (PD)-1 or PD-L1 inhibitors (I-O): A Meet-URO group real-world study (Meet-Uro 7).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 691-691
Author(s):  
Daniele Santini ◽  
Marco Stellato ◽  
Ugo De Giorgi ◽  
Sandro Pignata ◽  
Francesco Pantano ◽  
...  
Keyword(s):  
Adverse Events ◽  
Real World ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Outcome Data ◽  
First Line ◽  
Real World Data ◽  
Best Response ◽  
Ecog Ps ◽  
Immune Oncology

691 Background: In metastatic renal cell carcinoma (mRCC), immune-oncology (IO), alone or in combination, (IO-IO or IO-TKI) has changed the therapeutic scenario. Few real-world data are available about safety and outcome after IO progression. Methods: Baseline characteristics, outcome data including progression-free survival (PFS) and toxicities were retrospectively collected from 162 eligible pts treated in 16 Italian referral centers adhering to the Meet-Uro group and progressing to IO. Results: 111 pts (68,5%) were treated after progression to IO. 142 (87.6%) pts received IO as second line, 5 pts as first line and 16 pts as further line. Subsequent therapy included cabozantinib (n = 79, 48.0%), everolimus (n = 11, 6.7%), sunitinib (n = 6, 3.7%) and others (n = 15, 9.25%). Median IO-PFS was 4 months (95%CI 3.1-4.8) with no difference in pts pretreated with pazopanib or sunitinib (4 months (95%CI 2.4-5.5) vs 3,9 months (95%CI 2.9-4.9) p = 0.5). PFS tends to be longer in pts reporting adverse events of any grade (5.03 (95%CI 3.8-6.1) vs 2,99 (95%CI 2.4-3.5) months p = 0.004) or without nephrectomy (4.1 vs 2.9 months p = 0.071). Median PFS, in pts treated post-IO, was 6.5 months (95%CI 5.1-7.8). In term of best response, 55 pts (49%) had stability of disease/partial response and 29 pts (26%) had progressive disease, for the other pts treatment is still ongoing. Pts with ECOG PS 0 at progression to IO, had longer PFS, 11 months (95%CI 5.7-17.5) as well as those treated with cabozantinib (7.6 months, 95%CI 5.2-10.1) compared to everolimus, (3.2 months, 95%CI 1.8-4.5) or other drugs (4.3 months, 95%CI 1.3-7.4) p = 0.001. All grade adverse events were reported in 83 pts (74%) with G3-G4 adverse events in 39 pts (35%). Median overall survival, from first line, was 41,1 months (95%CI 30.4-51.8). Conclusions: In our real world experience after progression to IO, most pts received VEGF-TKI and mTOR inhibitors that showed to be active and safe choices. Cabozantinib was associated with a longer mPFS.

scholarly journals Assessing the Effectiveness of Pirfenidone in Idiopathic Pulmonary Fibrosis: Long-Term, Real-World Data from European IPF Registry (eurIPFreg)

2020 ◽  
Vol 9 (11) ◽  
pp. 3763
Author(s):  
Ekaterina Krauss ◽  
Silke Tello ◽  
Jochen Wilhelm ◽  
Johanna Schmidt ◽  
Mark Stoehr ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Real World ◽  
Global Analysis ◽  
Pulmonary Function Tests ◽  
Outcome Data ◽  
Longitudinal Change ◽  
Walking Distance ◽  
Rapid Progression ◽  
Real World Data

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic pulmonary disease with rising incidence. In this study the effectiveness of pirfenidone, as measured by longitudinal change in individual slope of forced vital capacity (FVC) prior to and after initiating pirfenidone treatment, was evaluated in IPF patients recruited into the European registry for idiopathic pulmonary fibrosis (eurIPFreg). Secondary variables were the evaluation of the change in individual slope of diffusion capacity of the lungs for carbon monoxide (DLco), the Borg dyspnea scale, and six-minute walking distance (6MWD), as well as survival analyses. Results: Data of 122 eurIPFreg patients, who had at least two pulmonary function tests (PFTs) prior to or under treatment with pirfenidone, were analyzed by calculating slope-changes. The global analysis revealed an average slope change of +1.48 ± 0.28 (% per annum (p.a)) after start of treatment (p < 0.001), reflecting a reduction in annual FVC decline of approx. 50% under pirfenidone; it also showed a reduction in DLco, and increase in 6MWD (both p < 0.0001), as well as a flattening of the Borg dyspnea scale (p = 0.02). The median survival under treatment was 4.82 years. Patients with a more restrictive disease (FVC < 80% pred.), with a rapid progression (FVC decline >10% pred. p.a.), previous smokers and patients > 60 years of age seemed to profit more from pirfenidone treatment. Conclusions: We report the effectiveness of pirfenidone in a European “real world” IPF cohort with outcome data extending up to 9 years. Global analyses demonstrated a positive effect of pirfenidone on the decline of the lung function over time. Survival was dependent on Gender–Age–Physiology (GAP) score and age prior to therapy.

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