O51 BIOSYNTHETIC MESH VERSUS NON-ABSORBABLE SYNTHETIC MESH IN COMPLEX ABDOMINAL WALL REPAIR (CAWR): A UK NHS COST-CONSEQUENCE ANALYSIS OF MANAGEMENT STRATEGIES

Abstract Aim CAWR is marked by high complication and hernia recurrence rates. Different management strategies of CAWR may result in a significant reduction in quality of life and increased financial burden. The use of certain non-absorbable synthetic meshes in CAWR may be associated with an increased risk of adverse events for certain patients. Recent evidence suggests that biosynthetic meshes may contribute to lower complications and may be more cost-effective. Material and Methods To compare the cost between a synthetic mesh, and a bio-synthetic mesh in the management of patients undergoing CAWR. A cost-consequence model was developed to simulate clinical pathways for patients undergoing CAWR with different management strategies. Clinical parameters were informed by literature review and expert opinion. Adverse events associated with the use of a mesh, resource utilisation and re-admissions were compared between patient management strategies over a period of two years. Costing information were gathered from national tariffs using NICE methodology. Results Use of a biosynthetic mesh was associated with a significant reduction in total costs (£15,489 / €17,953) compared to a synthetic mesh at two years. Cost-savings were driven by a lower rate adverse events (hernia recurrence [2% vs.8%] and sepsis [5% vs. 12%] respectively), and resource utilisation after the initial procedure in the management of complications. There was no difference in the intra-procedural time and complications. Conclusions The use of a certain biosynthetic mesh is likely to be highly cost saving compared to a certain synthetic mesh in high-risk patients undergoing CAWR. Well conducted comparative clinical studies are needed to inform robust economic modelling.

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Risk Stratification and Management of Arterial Hypertension and Cardiovascular Adverse Events Related to Cancer Treatments: An Oncology Network from Piedmont and Aosta Valley (North-Western Italy) Consensus Document

Hearts ◽

10.3390/hearts2010006 ◽

2021 ◽

Vol 2 (1) ◽

pp. 61-73

Author(s):

Giulia Mingrone ◽

Elena Coletti Moia ◽

Erica Delsignore ◽

Gloria Demicheli ◽

Paola Destefanis ◽

...

Keyword(s):

Adverse Events ◽

Arterial Hypertension ◽

Cancer Patients ◽

Management Strategies ◽

Risk Groups ◽

Cancer Treatments ◽

Risk Class ◽

Increased Risk ◽

The Impact ◽

North Western

Cancer patients receiving a potentially cardiotoxic oncologic therapy have an increased risk of cardiovascular adverse events (CVAEs), especially in presence of concomitant arterial hypertension (AH). Therefore, cancer patients should be evaluated before, during and after cardiotoxic treatments, to early identify new-onset or worsening AH or CVAEs. An expert panel of oncology networks from Piedmont and Aosta Valley (North-Western Italy) aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk–benefit ratio of diagnostic/therapeutic tools. We proposed an useful document for evaluating and managing AH related to cancer treatments. Patients should be divided into 4 cardiovascular (CV) risk groups before starting potentially cardiotoxic therapies: patients with low/moderate risk who should be entirely evaluated by oncologists and patients with high/very high risk who should be referred to a cardiologist or arterial hypertension specialist. According to the CV risk class, every patient should be followed up during cancer treatment to monitor any possible CV complications. Adequate control of AH related to antineoplastic treatments is crucial to prevent severe CVAEs. In the presence of high-profile risk or lack of response to anti-hypertensive therapy, the patients should be managed with a cardiovascular-oncology expert center.

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O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Rheumatology ◽

10.1093/rheumatology/keab246.005 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Ahmad A Sherbini ◽

James M Gwinnutt ◽

Kimme L Hyrich ◽

Suzanne M M Verstappen ◽

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Health Assessment ◽

Prevalence Rates ◽

Clinical Predictors ◽

Research Support ◽

Related Data ◽

Increased Risk ◽

One Year

Abstract Background/Aims Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (> upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT >1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

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OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3213 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 54.1-54

Author(s):

S. Benamar ◽

C. Lukas ◽

C. Daien ◽

C. Gaujoux-Viala ◽

L. Gossec ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Treatment Response ◽

Univariate Analysis ◽

Group Versus ◽

Biological Database ◽

Lower Probability ◽

Research Support ◽

Early Ra ◽

Increased Risk

Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer

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Treatment of attention deficit/hyperactivity disorder in children with CHD

Cardiology in the Young ◽

10.1017/s1047951120004965 ◽

2021 ◽

pp. 1-4

Author(s):

Alyson R. Pierick ◽

Melodie Lynn ◽

Courtney M. McCracken ◽

Matthew E. Oster ◽

Glen J. Iannucci

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

General Population ◽

Adverse Events ◽

Supraventricular Tachycardia ◽

Medical Therapy ◽

Attention Deficit ◽

Case Reports ◽

Single Centre ◽

Hyperactivity Disorder ◽

Increased Risk

Abstract Introduction: The prevalence of attention deficit/hyperactivity disorder in the general population is common and is now diagnosed in 4%–12% of children. Children with CHD have been shown to be at increased risk for attention deficit/hyperactivity disorder. Case reports have led to concern regarding the use of attention deficit/hyperactivity disorder medications in children with underlying CHD. We hypothesised that medical therapy for patients with CHD and attention deficit/hyperactivity disorder is safe. Methods: A single-centre, retrospective chart review was performed evaluating for adverse events in patients aged 4–21 years with CHD who received attention deficit/hyperactivity disorder therapy over a 5-year span. Inclusion criteria were a diagnosis of CHD and concomitant medical therapy with amphetamines, methylphenidate, or atomoxetine. Patients with trivial or spontaneously resolved CHD were excluded from analysis. Results: In 831 patients with CHD who received stimulants with a mean age of 12.9 years, there was only one adverse cardiovascular event identified. Using sensitivity analysis, our median follow-up time was 686 days and a prevalence rate of 0.21% of adverse events. This episode consisted of increased frequency of supraventricular tachycardia in a patient who had this condition prior to initiation of medical therapy; the condition improved with discontinuation of attention deficit/hyperactivity disorder therapy. Conclusion: The incidence of significant adverse cardiovascular events in our population was similar to the prevalence of supraventricular tachycardia in the general population. Our single-centre experience demonstrated no increased risk in adverse events related to medical therapy for children with attention deficit/hyperactivity disorder and underlying CHD. Further population-based studies are indicated to validate these findings.

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AB1158 VACCINATION BARRIERS IN PATIENTS WITH RHEUMATIC DISEASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5521 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1869.2-1870

Author(s):

G. Figueroa-Parra ◽

A. Moreno-Salinas ◽

L. Santoyo-Fexas ◽

C. M. Gamboa-Alonso ◽

A. L. De-Leon-Ibarra ◽

...

Keyword(s):

Human Papillomavirus ◽

Herpes Zoster ◽

Hepatitis B ◽

Adverse Events ◽

Rheumatic Diseases ◽

Demographic Characteristics ◽

Specific Patient ◽

Increased Risk ◽

Rheumatic Patients ◽

Vaccination Barriers

Background:Patients with rheumatic diseases (RD) are at increased risk of infections, attributed to the underlying RD, comorbidities and immunosuppressive therapy, including glucocorticoids, disease-modifying antirheumatic drugs, etc. (1). While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal (2). Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs (3).Objectives:To describe the main causes of non-vaccination in patients with RD.Methods:A self-questionnaire was applied to a sample of patients with RD in the rheumatology clinic of the university hospital “Dr. Jose Eleuterio Gonzalez” in Monterrey, Mexico between September and December 2019. The questionnaire evaluated demographic characteristics (age, gender, diagnosis) and the vaccination status for Influenza (last year), pneumococcal (last 5 years), Herpes zoster (ever), Human papillomavirus (any dose) and Hepatitis B (any dose). It also includes a question asking: If you didn’t receive any of the previous vaccines, what was the reason? (multiple-choice are shown in Table 2). Results are shown in frequencies and percentages.Table 2.Vaccination barriersN=82If you didn’t receive any of the previous vaccines,what was the reason? n (%)1)Did not was recommended22 (26.8)2) Lack of availability21 (25.6)3) Vaccines don’t work13 (15.8)4) Fear of adverse events8 (9.7)5) Previous adverse event3 (3.6)6) Other reason- Own decision8 (9.7)- Disinformation7 (8.5)Results:102 patients were evaluated: Mean age was 51.27 (SD 14.68) years; 84 (82.4%) were females; 71 (69.6%) had rheumatoid arthritis, 13 (12.7%) had systemic lupus erythematosus, 6 (5.8%) had other autoimmune diseases and 12 (11.8%) had osteoarthritis. The rate of vaccination for Influenza was 49 (48%), for pneumococcal 25 (24.5%), for Herpes zoster 5 (4.9%), for Human papillomavirus 9 (8.8%), for Hepatitis B 14 (13.7%) (Table 1). 82 (80.3%) patients reported some barriers in vaccination, from these: 22 (26.8%) did not get the recommendation from the rheumatologist, 21 (25.6%) did not found available the vaccine, 13 (15.8%) believes that vaccines don’t work, 8 (9.7%) had fear of adverse events, 3 (3.6%) reported previous adverse events, and 15 (18.2%) reported other reasons, that we classified as own decision 8 (9.7%) and disinformation 7 (8.5%) (Table 2).Table 1.Demographic characteristicsN= 102Age, years, mean (SD)51.27 (14.68)Female, n (%)84 (82.4)Diagnosis, n (%)-RA71 (69.6)-SLE13 (12.7)-OA12 (11.8)-Other AID6 (5.8)Conclusion:The main barriers in vaccination of rheumatic patients reported were the lack of availability of the indicated vaccines and the medical and patient disinformation. This problem must be combated to ensure the complete vaccination of rheumatic patients.References:[1]Ann Rheum Dis. 2020;79:39-52.[2]J Rheumatol. 2019;46(7):751-754[3]Hum Vaccin Immunother. 2013;9(8):1763-73.Disclosure of Interests:None declared

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416 - Risk of Mortality Associated with Antipsychotics in Alzheimer's Disease

International Psychogeriatrics ◽

10.1017/s1041610220002690 ◽

2020 ◽

Vol 32 (S1) ◽

pp. 132-132

Author(s):

Liliana P. Ferreira ◽

Núria Santos ◽

Nuno Fernandes ◽

Carla Ferreira

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Adverse Events ◽

Mortality Risk ◽

Antipsychotic Treatment ◽

Serious Adverse Events ◽

Risk Of Death ◽

Mesh Terms ◽

Risk Of Mortality ◽

Increased Risk

Objectives: Alzheimer's disease (AD) is the most common cause of dementia and it is associated with increased mortality. The use of antipsychotics is common among the elderly, especially in those with dementia. Evidence suggests an increased risk of mortality associated with antipsychotic use. Despite the short-term benefit of antipsychotic treatment to reduce the behavioral and psychological symptoms of dementia, it increases the risk of mortality in patients with AD. Our aim is to discuss the findings from the literature about risk of mortality associated with the use of antipsychotics in AD.Methods: We searched Internet databases indexed at MEDLINE using following MeSH terms: "Antipsychotic Agents" AND "Alzheimer Disease" OR "Dementia" AND "Mortality" and selected articles published in the last 5 years.Results: Antipsychotics are widely used in the pharmacological treatment of agitation and aggression in elderly patients with AD, but their benefit is limited. Serious adverse events associated with antipsychotics include increased risk of death. The risk of mortality is associated with both typical and atypical antipsychotics. Antipsychotic polypharmacy is associated with a higher mortality risk than monotherapy and should be avoided. The mortality risk increases after the first few days of treatment, gradually reducing but continues to increase after two years of treatment. Haloperidol is associated with a higher mortality risk and quetiapine with a lower risk than risperidone.Conclusions: If the use of antipsychotics is considered necessary, the lowest effective dose should be chosen and the duration should be limited because the mortality risk remains high with long-term use. The risk / benefit should be considered when choosing the antipsychotic. Further studies on the efficacy and risk of adverse events with antipsychotics are needed for a better choice of treatment and adequate monitoring with risk reduction.

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The CoPrescription of Contraindicated Drugs With Statins: Continuing Potential for Increased Risk of Adverse Events

American Journal of Therapeutics ◽

10.1097/01.mjt.0000208875.61480.c8 ◽

2007 ◽

Vol 14 (1) ◽

pp. 30-40 ◽

Cited By ~ 10

Author(s):

Paul Stang ◽

Lisa Morris ◽

Judy Kempf ◽

Scott Henderson ◽

Marianne Ulcickas Yood ◽

...

Keyword(s):

Adverse Events ◽

Increased Risk

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Investigating whether adverse prenatal and perinatal events are associated with non-clinical psychotic symptoms at age 12 years in the ALSPAC birth cohort

Psychological Medicine ◽

10.1017/s0033291708005126 ◽

2009 ◽

Vol 39 (9) ◽

pp. 1457-1467 ◽

Cited By ~ 73

Author(s):

S. Zammit ◽

D. Odd ◽

J. Horwood ◽

A. Thompson ◽

K. Thomas ◽

...

Keyword(s):

Longitudinal Study ◽

Adverse Events ◽

Birth Cohort ◽

Early Development ◽

Gestational Age ◽

Apgar Score ◽

Psychotic Symptoms ◽

Maternal Infection ◽

Increased Risk ◽

Clinical Disorders

BackgroundNon-clinical psychosis-like symptoms (PLIKS) occur in about 15% of the population. It is not clear whether adverse events during early development alter the risk of developing PLIKS. We aimed to examine whether maternal infection, diabetes or pre-eclampsia during pregnancy, gestational age, perinatal cardiopulmonary resuscitation or 5-min Apgar score were associated with development of psychotic symptoms during early adolescence.MethodA longitudinal study of 6356 12-year-old adolescents who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Prenatal and perinatal data were obtained from obstetric records and maternal questionnaires completed during pregnancy.ResultsThe presence of definite psychotic symptoms was associated with maternal infection during pregnancy [adjusted odds ratio (OR) 1.44, 95% confidence interval (CI) 1.11–1.86, p=0.006], maternal diabetes (adjusted OR 3.43, 95% CI 1.14–10.36, p=0.029), need for resuscitation (adjusted OR 1.50, 95% CI 0.97–2.31, p=0.065) and 5-min Apgar score (adjusted OR per unit decrease 1.30, 95% CI 1.12–1.50, p<0.001). None of these associations were mediated by childhood IQ score. Most associations persisted, but were less strong, when including suspected symptoms as part of the outcome. There was no association between PLIKS and gestational age or pre-eclampsia.ConclusionsAdverse events during early development may lead to an increased risk of developing PLIKS. Although the status of PLIKS in relation to clinical disorders such as schizophrenia is not clear, the similarity between these results and findings reported for schizophrenia indicates that future studies of PLIKS may help us to understand how psychotic experiences and clinical disorders develop throughout the life-course.

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Management of Oral Anti-Coagulation in Patients with Heart Failure—Insights from the ThrombEVAL Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1673380 ◽

2018 ◽

Vol 118 (11) ◽

pp. 1930-1939

Author(s):

Sebastian Göbel ◽

Jürgen Prochaska ◽

Lisa Eggebrecht ◽

Ronja Schmitz ◽

Claus Jünger ◽

...

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Vitamin K Antagonists ◽

Plasma Concentrations ◽

Regular Care ◽

Increased Risk ◽

Patients With Heart Failure ◽

Specialized Care ◽

The Impact

AbstractPatients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.

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32 Quantifying the Prevalence of Frailty in Drug Trials and the Relationship with Serious Adverse Events

Age and Ageing ◽

10.1093/ageing/afab029.11 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

pp. i7-i11

Author(s):

P Hanlon ◽

E Butterly ◽

J Lewsey ◽

S Siebert ◽

F S Mair ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Disease Severity ◽

Negative Binomial ◽

Frailty Index ◽

Chronic Obstructive ◽

Drug Trials ◽

Phase 3 ◽

Serious Adverse Events ◽

Increased Risk

Abstract Introduction Frailty is common in clinical practice, but trials rarely report on participant frailty. Consequently, clinicians and guideline-developers assume frailty is largely absent from trials and have questioned the relevance of trial findings to frail people. Therefore, we examined frailty in phase 3/4 industry-sponsored clinical trials of pharmacological interventions for three exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD). Methods We constructed a 40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 42–65 years) using individual-level participant data. Participants with a FI >0.24 were considered “frail”. Baseline disease severity was assessed using HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 for COPD. Using generalised gamma regression, we modelled FI on age, sex and disease severity. In negative binomial regression we modelled serious adverse event rates on FI, and combined results for each index condition in a random-effects meta-analysis. Results All trials included frail participants: prevalence 7–21% in T2DM trials, 33–73% in RA trials, and 15–22% in COPD trials. Increased disease severity and female sex were associated with higher FI in all trials. Frailty was associated with age in T2DM and RA trials, but not in COPD. Across all trials, and after adjusting for age, sex, and disease severity, higher FI predicted increased risk of serious adverse events; the pooled incidence rate ratios (per 0.1-point increase in FI scale) were 1.46 (95% CI 1.21–1.75), 1.45 (1.13–1.87) and 1.99 (1.43–2.76) for T2DM, RA and COPD, respectively. Conclusion Frailty is identifiable and prevalent among middle aged and older participants in phase 3/4 drug trials and has clinically important safety implications. Trial data may be harnessed to better understand chronic disease management in people living with frailty.

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