P101 SARCOPENIA IS ASSOCIATED WITH INCREASED RISK OF INFECTION IN IBD PATIENTS OLDER THAN 50 YEARS STARTING BIOLOGIC MEDICATIONS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S3-S3
Author(s):  
James Campbell ◽  
Levi Teigen ◽  
Ghislaine Feussom ◽  
Kathleen Price ◽  
Rebecca Cogswell ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Response ◽  
Clinical Outcomes ◽  
Disease Severity ◽  
Response To Therapy ◽  
Secondary Outcome ◽  
Risk Of Infection ◽  
Skeletal Muscle Index ◽  
Increased Risk ◽  
One Year

Abstract Background The relationship between sarcopenia and clinical outcomes outside of the post-operative setting has not been well-studied in IBD patients. We aimed to characterize the prevalence of sarcopenia and its association with adverse events and clinical response in IBD patients starting on new biologic medications. Methods We identified a retrospective cohort of adult (≥18 years old) IBD patients at the University of Minnesota with an abdominal CT or MRI within 6 months prior to or one month after starting a new biologic medication. Baseline demographics, disease severity (based on Physician’s Global Assessment from GI encounters), laboratory values and clinical outcomes for one year after the start of medications were obtained from chart review. The primary endpoint was incidence of adverse events (defined as infection, need for surgery, or hospitalization) within one year after medication start. The secondary outcome was clinical response as assessed based on clinical, endoscopic, and radiographic follow-up. Skeletal muscle index (SMI) measures were obtained from CT/MRI images at the L3 vertebral level. Published cut-offs (SMI of 38.5 cm2/m2 for women and 52.4 cm2/m2 for men) were used to determine the presence of sarcopenia. Associations between sarcopenia and outcomes were analyzed using logistic regression and age stratification was performed. Results Ninety-four patients (74 CD, 20 UC, 47% male, mean age 38 years) were included in the analysis. The majority of patients had moderate disease severity or worse (83%) at the time of medication start, and 75% were started on anti-TNF medications. Overall prevalence of sarcopenia was 57% (57% CD, 60% UC). In the entire cohort, sarcopenia was not associated with increased rates of adverse events (OR = 0.516, 95% CI 0.217–1.225; p= 0.1334). However, in patients ≥ 50 years of age (n=23), those with sarcopenia had higher risk of infection at 1 year compared to those without sarcopenia (85% vs. 20%; OR = 21.99, 95% CI 3.086–262.515; p = 0.0051). The majority of infections were those that required antibiotics or antivirals, but not hospitalization. Examples included sinusitis, upper respiratory infections, periodontitis, urinary tract infection, herpes simplex, and two cases of C. difficile. Furthermore, when controlling for disease duration and concomitant steroid use, the association between sarcopenia and infection remained significant. In this age subgroup, there was no association between sarcopenia and clinical response to therapy. Conclusions In our cohort, sarcopenia was present in the majority of adult IBD patients starting new biologic medications. In patients ≥ 50 years old, sarcopenia was associated with an increased risk of infections. Further work is needed to validate these findings and to understand which patients may benefit from sarcopenia assessment prior to biologic start.

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

Rheumatology ◽  
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.

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

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.

Treatment practices, response to therapy and adverse events in ANCA-associated vasculitis patients in Europe: top-line findings from a retrospective observational study

2019 ◽  
Author(s):  
Peter Rutherford ◽  
Dieter Goette
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Real World ◽  
Response To Therapy ◽  
Remission Induction ◽  
Induction Treatment ◽  
Symptom Duration ◽  
Similar Distribution ◽  
Presenting Symptoms ◽  
Anca Associated Vasculitis

Abstract Background ANCA-associated vasculitis patient outcome data in the real world setting is scarce. This study measures key clinical outcomes and adverse effects over the first 12 months of remission induction therapy.Methods This was a retrospective study of 929 newly diagnosed [ND] and 268 relapsing patients [RP] conducted online by 399 clinicians. Each clinician completed a survey for 3 patients meeting the following criteria: initiated remission induction treatment for new or relapsing disease between Nov 2014 and Feb 2017, ≥ 6 months of therapy including ≥ 1 course of induction therapy, under continuous care for ≥12 months. Data were collected relating to baseline presentation and at 1, 3, 6, and 12 months.Results 58% were >55 years old with more granulomatosis with polyangiitis (GPA, 54%) versus microscopic polyangiitis (MPA, 46%), and <20% of patients had Birmingham Vasculitis Activity Scoring (BVAS) performed. Median symptom duration prior to diagnosis was 6 to 7 weeks. Presenting symptoms were similar between ND and RP, noted differences (≥ 5%) were more fever, rash, and neuropathy, and less renal disease in RP. The majority (68% ND and 84% RP) had at least one comorbidity at diagnosis, with a similar distribution. Glucocorticoids (GC) were used by 83% ND and 76% RP; >50% were still receiving GC at 12 months. Most common treatments were cyclophosphamide+GC for ND (59%) and rituximab+GC for RP (44%). Many patients had slow and/or partial response to therapy, by 12 months >60% had a full response. 81% of patients with response by month 1 maintained full response through month 12. Adverse events and infections were common, especially during the first 3 months when GC use is highest.Conclusions Real world data show that both ND and RP ANCA-associated vasculitis patients respond variably to induction remission treatment and many experience adverse events and infections over the first 12 months of treatment. The presence of comorbidities at treatment initiation in most patients compounded the adverse impacts of disease and treatment. This study improves our understanding of the reality of clinical outcomes in ANCA-associated vasculitis and the need for targeted therapeutic approaches.

scholarly journals Genetic Variations in the PI3K/PTEN/AKT/mTOR Pathway Are Associated With Clinical Outcomes in Esophageal Cancer Patients Treated With Chemoradiotherapy

2009 ◽  
Vol 27 (6) ◽  
pp. 857-871 ◽  
Author(s):  
Michelle A.T. Hildebrandt ◽  
Hushan Yang ◽  
Mien-Chie Hung ◽  
Julie G. Izzo ◽  
Maosheng Huang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Genetic Variations ◽  
Chemotherapeutic Agents ◽  
Response To Therapy ◽  
Nucleotide Polymorphisms ◽  
Chemotherapeutic Regimen ◽  
Risk Of Death ◽  
Increased Risk

Purpose The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. Patients and Methods Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. Results We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes—AKT2 and FRAP1—were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). Conclusion These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen.

Preoperative muscle strength as a predictor of complications after esophagectomy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 454-454
Author(s):  
Madison Colcord ◽  
Michael D Watson ◽  
Nicole Lee Gower ◽  
Jennifer H Benbow ◽  
Sally Jeanne Trufan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Mass ◽  
Clinical Care ◽  
Cost Effective ◽  
Skeletal Muscle Index ◽  
Intramuscular Adipose Tissue ◽  
Operative Outcomes ◽  
Increased Risk ◽  
One Year

454 Background: Sarcopenia has been associated with post-operative complications and length of stay (LOS) in patients undergoing esophagectomy. A variety of methods exist to measure muscle mass and strength, with few comparisons between methods. We compared hand-grip strength (HGS), muscle mass and intramuscular adipose tissue as predictors of post-operative outcomes. Methods: Patients with esophageal cancer undergoing esophagectomy were identified between January 2015 – June 2019 at Levine Cancer Institute. Skeletal muscle index (SMI) and skeletal muscle density (SMD), a measure of intramuscular adipose tissue, were derived from CT. HGS was measured using a dynamometer. Uni- and multivariable GLM analyses were performed. Results: 115 patients (100 male, 15 female) underwent esophagectomy with an average age of 64.3 +/- 9.8. The analysis was stratified by sex due to significant differences in HGS, SMI, and SMD. Among men, univariable analysis revealed a significant association between pre-operative HGS <25 kg and increased risk of post-operative pneumonia ( p=0.02), ventilation >48hrs ( p=0.02), LOS ( p=0.002), discharge to home ( p=0.001), and one-year mortality ( p=0.005). All associations except discharge home remained significant in multivariable analyses (Table). Among women, no factors analyzed were significantly associated with postoperative outcomes. Conclusions: HGS is a more powerful predictor of postoperative complications and LOS than either muscle mass or intramuscular adipose tissue among men undergoing esophagectomy. HGS is cost-effective and easily incorporated into routine clinical care, allowing for preoperative intervention to optimize patients for esophagectomy. To better understand the implications in women, additional research with a larger cohort is needed. [Table: see text]

scholarly journals Increased Postoperative Fasting Glucose Is Associated With Unfavorable Outcomes in Patients Treated With Mechanical Thrombectomy Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Zongjie Shi ◽  
Shunyuan Guo ◽  
Jie Pan ◽  
Chao Xu ◽  
Yu Geng ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Primary Outcome ◽  
Mechanical Thrombectomy ◽  
Fasting Glucose ◽  
Independent Predictor ◽  
Secondary Outcome ◽  
Vessel Occlusion ◽  
Glucose Levels ◽  
Increased Risk ◽  
Symptomatic Intracranial Hemorrhage

Background and objective: Hyperglycemia on admission was associated with worse clinical outcomes after mechanical thrombectomy (MT) of acute ischemic stroke (AIS). We evaluated whether increased postoperative fasting glucose (PFG) was also related to poor clinical outcomes in patients who underwent MT treatment.Methods: Consecutive patients with large vessel occlusion underwent MT in our center were included. Admission glucose and fasting glucose levels after MT treatment were evaluated. Primary outcome was 90-day unfavorable outcomes (modified Rankin Scale score of 3–6). Secondary outcome was the rate of symptomatic intracranial hemorrhage (sICH) after MT treatment. The association of PFG and 90-day clinical outcome after MT treatment was determined using logistic regression analyses.Results: One hundred twenty seven patients were collected. The median postoperative fasting glucose level was 6.27 mmol/L (IQR 5.59–7.62). Fourteen patients (11.02%) had sICH, and fifty-eight patients (45.67%) had unfavorable outcomes at 90-day after MT. After adjustment for potential confounding factors, PFG level was an independent predictor of 90-day unfavorable outcome (OR 1.265; 95% CI 1.017–1.575; p = 0.035) and sICH (OR 1.523; 95% CI 1.056–2.195; p = 0.024) after MT. In addition, older age, higher baseline NIHSS score, and higher postoperative NLR were also associated with unfavorable outcomes at 90-day after MT treatment.Conclusions: Increased PFG is associated with unfavorable outcomes at 90-day and an increased risk of sICH in patients underwent MT treatment.

scholarly journals Anxiety and clinical outcomes of patients with acute coronary syndrome: a meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034135 ◽  
Author(s):  
Jie Li ◽  
Feng Ji ◽  
Junxian Song ◽  
Xiangyang Gao ◽  
Deguo Jiang ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Clinical Outcomes ◽  
Mortality Risk ◽  
Meta Analysis ◽  
Secondary Outcome ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Follow Up Studies ◽  
Poor Outcomes

ObjectivesAnxiety has been suggested to be associated with poor outcomes in patients with acute coronary syndrome (ACS). However, results of previous follow-up studies were inconsistent. The aim of this meta-analysis was to evaluate the association between anxiety and clinical outcomes in patients with ACS, and to investigate the potential role of depression underlying the above association.DesignA meta-analysis of prospective follow-up studies.SettingHospitals.ParticipantsPatients with ACS.InterventionsWe included related prospective follow-up studies up through 20 July 2019 that were identified by searching PubMed and Embase databases. A random-effect model was used for the meta-analysis. Anxiety was evaluated by validated instruments at baseline.Primary and secondary outcome measuresWe determined the association between anxiety and risks of mortality and adverse cardiovascular events (MACEs) in patients with ACS.ResultsOur analysis included 17 studies involving 39 038 patients wqith ACS. Anxiety was independently associated with increased mortality risk (adjusted risk ratio (RR) 1.21, 95% CI 1.07 to 1.37, p=0.002) and MACEs (adjusted RR 1.47, 95% CI 1.24 to 1.74, p<0.001) in patients with ACS. Subgroup analyses showed that depression may at least partly confound the association between anxiety and poor outcomes in patients with ACS. Adjustment of depression significantly attenuated the association between anxiety and MACEs (adjusted RR 1.25, 95% CI 1.04 to 1.52, p=0.02). Moreover, anxiety was not significantly associated with mortality risk after adjusting for depression (adjusted RR 0.88, 95% CI 0.66 to 1.17, p=0.37).ConclusionsAnxiety is associated with increased risk of mortality and MACEs in patients with ACS. However, at least part of the association may be confounded by concurrent depressive symptoms in these patients.

scholarly journals Influence of Implant Thread Morphology on Primary Stability: A Prospective Clinical Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Maria Menini ◽  
Francesco Bagnasco ◽  
Ivan Calimodio ◽  
Nicolò Di Tullio ◽  
Francesca Delucchi ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Outcome Measures ◽  
Primary Stability ◽  
Secondary Outcome ◽  
Prospective Clinical Study ◽  
Insertion Torque ◽  
Significant Difference ◽  
Group 5 ◽  
One Year ◽  
Torque Values

Objectives. The purpose of this study was to evaluate the primary stability of two implants with the same macro- and micromorphology but different thread design and analyze their clinical outcomes over a one-year period. Materials and Methods. 14 patients needing a partial rehabilitation with a delayed loading approach (DEL group: 9 patients) or a full-arch rehabilitation treated with immediately loaded fixed prostheses supported by 4 implants following the Columbus Bridge Protocol (CBP) (IL group: 5 patients) were included. In each patient, at least one SY (implant with standard threads) and one SL implant (implant with an augmented depth of the threads) were randomly inserted. Primary outcome measures were the number of threads exposed at a torque of 30 Ncm and 50 Ncm and final insertion torque. Secondary outcome measures were implant and prosthetic failure, peri-implant bone resorption, and periodontal parameters: bleeding on probing (BoP), plaque index (PI), and probing depth (PD) evaluated at 3, 6, and 12 months of healing. Results. Nineteen SY and 19 SL implants were inserted in 14 patients. Twenty implants (10 SL and 10 SY) were inserted in the IL group, while 18 (9 SL and 9 SY) were inserted in the DEL group and followed-up for 12 months. No patients dropped out. No implants and prostheses failed. No biological complications were identified. No significant differences were found between SY and SL implants comparing the number of exposed threads when inserting the implant with a torque insertion of 30 N (T student test p=.142 and U test p=.164). At 50 N, no threads were visible in either groups. Final torque insertion values were higher for SL (mean: 48.42 Ncm) compared to SY implants (mean: 43.42 Ncm) without a statistically significant difference. All the implants showed good clinical outcomes at the 1-year-in-function visit. Conclusions. After 12 months of function, both implant types provided good clinical outcomes without statistically significant differences between the two groups. A difference in insertion torque (even if not statistically significant) was found with higher insertion torque values for SL implants with a larger thread depth.

Abstract 13009: The Significance of ATP Therapy Failure During Appropriate ICD-Delivered Therapy in Patients With Ventricular Tachycardia

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Dalia Giedrimiene ◽  
Craig Coleman ◽  
Danette Guertin ◽  
Jeffrey Kluger
Keyword(s):  
Ventricular Tachycardia ◽  
Clinical Outcomes ◽  
Sudden Cardiac Arrest ◽  
Shock Therapy ◽  
Successful Termination ◽  
Increased Risk ◽  
Patients At Risk ◽  
Icd Shock ◽  
Gender Based ◽  
One Year

Prospective clinical trials have demonstrated that ICD-delivered therapy reduces mortality in patients at risk for sudden cardiac arrest due to ventricular tachycardia (VT). ICDs through anti-tachycardia pacing (ATP) modalities are able to terminate spontaneous VT. Although ATP is highly effective in terminating VT in ICD patients, 5 - 30% of these events ultimately need shocks. Unsuccessful ATP attempts, as well as shocks, prolong the duration of the episode and are associated with poor clinical outcomes. Methods: Our study focused on 1873 ICD-delivered therapies in pts who received ICD implants from 2008 to 2012 and completed one year follow up. Only patients who received ATP therapy for the first time for a ventricular tachycardia (VT) event were included. All therapy zones contained ATP therapy followed by shock therapy. Results: 806 pts with ICD implants for primary or secondary prevention were analyzed. Study population consisted of 636 (78.9%) males and 170 (21.1%) females with average age of 72.8±29.8y (range: 29 - 98y). 622 (77.2%) of these patients had successful termination of VT with ICD-delivered ATP therapy. In 184 (22.8%) patients with unsuccessful ATP, appropriate ICD shocks were delivered. Only 66.8% of patients with failed ATP had successful VT termination after 1st ICD shock. More than 33% of patients required 2 or more ICD-delivered shocks, of which 13% required four or more. No gender based difference was found regarding success for VT termination after first, second or multiple ICD delivered shocks. Conclusions: 1) ATP therapy is successful in the majority of patients. 2) After ATP failure only 66.8% of pts respond to first ICD shock. 33.2% require multiple ICD shocks that delay VT termination and may lead to worse clinical outcomes. 3) ATP failure for VT termination may identify patients who are at increased risk for failure to respond to ICD shocks. A careful observation and further clinical correlation is warranted in this group.

scholarly journals Identifying frailty in trials: an analysis of individual participant data from trials of novel pharmacological interventions

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Peter Hanlon ◽  
Elaine Butterly ◽  
Jim Lewsey ◽  
Stefan Siebert ◽  
Frances S. Mair ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Disease Severity ◽  
Negative Binomial ◽  
Frailty Index ◽  
Chronic Obstructive ◽  
Pharmacological Interventions ◽  
Phase 3 ◽  
Serious Adverse Events ◽  
Increased Risk

Abstract Background 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. The 99th centile of the FI ranged between 0.35 and 0.45. Female sex was associated with higher FI in all trials. Increased disease severity was associated with higher FI in RA and COPD, but not T2DM. 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 The upper limit of frailty in trials is lower than has been described in the general population. However, mild to moderate frailty was common, suggesting trial data may be harnessed to inform disease management in people living with frailty. Participants with higher FI experienced more serious adverse events, suggesting screening for frailty in trial participants would enable identification of those that merit closer monitoring. Frailty is identifiable and prevalent among middle-aged and older participants in phase 3/4 drug trials and has clinically important safety implications.

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