Association between adverse events and prognosis in postoperative adjuvant chemotherapy for colorectal cancer
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ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2740981 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Primary outcome(s): overall survival relapse-free survival disease-free survival Time-to-treatment-failure Compliance Relative Dose Intensity Percentage of drug treatment discontinuation, dose reduction and drug suspension
| 2725003 | ecrin-mdr-crc
Project description:BackgroundSide effects of immune checkpoint inhibitors (ICIs), called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. We aimed to understand the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs.Patients and methodsPatients without pre-existing autoimmune disease (pAID) who had cancer treated with ICI(s) treatment from 1/1/2011 to 12/21/2020 and a rhAb checked were retrospectively identified. Logistic regression assessed associations between autoantibodies and irAEs, cancer outcome, and survival. Specificity, sensitivity, and positive/negative predictive values (PPV, NPV) were estimated for key rhAbs and ICI-arthritis. Kaplan-Meier analyzed objective response rate (ORR) and overall survival (OS).ResultsA total of 2662 patients were treated with≥1 ICIs. One hundred and thirty-five without pAID had ≥ 1 rhAb tested. Of which 70/135(52%) were female; median age at cancer diagnosis was 62 years with most common cancers: melanoma (23%) or non-small cell lung cancer (21%), 96/135 (75%) were anti-PD1/PDL1 treated. Eighty had a rhAb ordered before ICI, 96 after ICI, and 12 before and after. Eighty-two (61%) experienced an irAE, 33 (24%) with rheumatic-irAE. Pre-ICI RF showed significant association with rheumatic-irAEs (OR = 25, 95% CI, 1.52-410.86, P = .024). Pre- and post-ICI RF yielded high specificity for ICI-arthritis (93% and 78%), as did pre- and post-ICI CCP (100% and 91%). Pre-ICI RF carried 93% NPV and pre-ICI CCP had 89% PPV for ICI-arthritis. No variables were significantly correlated with ORR. Any-type irAE, rheumatic-irAE and ICI-arthritis were all associated with better OS (P = .000, P = .028, P = .019).ConclusionsPre-ICI RF was associated with higher odds of rheumatic-irAEs. IrAEs had better OS; therefore, clinical contextualization for rhAbs is critical to prevent unnecessary withholding of lifesaving ICI for fear of irAEs.
| S-EPMC10166164 | biostudies-literature
Project description:Primary outcome(s): The incidence of Grade >=2 hand-foot syndrome (Relapse-Free survival(RFS))
| 104238 | ecrin-mdr-crc
Project description:OBJECTIVE:To compare different blood pressure (BP) levels in their association with the risk of renal outcomes in type 1 diabetes and to determine whether an intensive glycemic control strategy modifies this association. RESEARCH DESIGN AND METHODS:We included 1,441 participants with type 1 diabetes between the ages of 13 and 39 years who had previously been randomized to receive intensive versus conventional glycemic control in the Diabetes Control and Complications Trial (DCCT). The exposures of interest were time-updated systolic BP (SBP) and diastolic BP (DBP) categories. Outcomes included macroalbuminuria (>300 mg/24 h) or stage III chronic kidney disease (CKD) (sustained estimated glomerular filtration rate <60 mL/min/1.73 m2). RESULTS:During a median follow-up time of 24 years, there were 84 cases of stage III CKD and 169 cases of macroalbuminuria. In adjusted models, SBP in the <120 mmHg range was associated with a 0.59 times higher risk of macroalbuminuria (95% CI 0.37-0.95) and a 0.32 times higher risk of stage III CKD (95% CI 0.14-0.75) compared with SBPs between 130 and 140 mmHg. DBP in the <70 mmHg range were associated with a 0.73 times higher risk of macroalbuminuria (95% CI 0.44-1.18) and a 0.47 times higher risk of stage III CKD (95% CI 0.21-1.05) compared with DBPs between 80 and 90 mmHg. No interaction was noted between BP and prior DCCT-assigned glycemic control strategy (all P > 0.05). CONCLUSIONS:A lower BP (<120/70 mmHg) was associated with a substantially lower risk of adverse renal outcomes, regardless of the prior assigned glycemic control strategy. Interventional trials may be useful to help determine whether the currently recommended BP target of 140/90 mmHg may be too high for optimal renal protection in type 1 diabetes.
| S-EPMC5127223 | biostudies-other
Project description:Musculoskeletal symptoms including arthralgia and myalgia occur frequently in aging women, particularly during the transition to menopause, when plasma estrogens precipitously decline. In postmenopausal women (PMW) with breast cancer, third-generation aromatase inhibitors (AIs) as adjuvant hormonal therapy have proven to be more effective, and to have a more predictable side effect profile, than tamoxifen. However, AIs further reduce plasma estrogens in PMW, exacerbating musculoskeletal symptoms. Clinical trial data have shown significantly higher incidences of arthralgia and myalgia with AIs compared with women on tamoxifen or placebo. Symptoms may be severe enough to significantly affect quality of life; musculoskeletal symptoms are a frequent reason for discontinuing therapy. In many cases, symptoms can be effectively managed with oral analgesics or other strategies. Early recognition and effective management of musculoskeletal symptoms can help maximize treatment compliance, enabling patients to derive optimal benefit from therapy in terms of preventing recurrence.
| S-EPMC2943085 | biostudies-literature
Project description:Metaphase karyotyping is an established diagnostic standard in acute myeloid leukemia (AML) for risk stratification. One of the cytogenetic findings in AML are structurally highly abnormal marker chromosomes. In this study, we have assessed frequency, cytogenetic characteristics, prognostic impact and underlying biological origin of marker chromosomes. Given their inherent gross structural chromosomal damage, we speculated that they may arise from chromothripsis, a recently described phenomenon of chromosome fragmentation in a single catastrophic event. In 2 large consecutive prospective, randomized, multicenter, intensive chemotherapy trials (AML96, AML2003) from the Study Alliance Leukemia (SAL), marker chromosomes were detectable in 165/1026 (16.1%) of aberrant non-core-binding-factor (CBF) karyotype patients. Adverse-risk karyotypes displayed a higher frequency of marker chromosomes (26.5% in adverse-risk, 40.3% in complex aberrant and 41.2% in abnormality(17p) karyotypes, p<.0001 each). Marker chromosomes were associated with a poorer prognosis compared to other non-CBF aberrant karyotypes and led to lower remission rates (CR+CRi), inferior event-free survival as well as overall survival in both trials. In multivariate analysis, marker chromosomes independently predicted poor prognosis in the AML96 trial ≤60 years. As detected by array-CGH, about one third of marker chromosomes (18/49) had arisen from chromothripsis, whereas this phenomenon was virtually undetectable in a control group of marker chromosome-negative complex aberrant karyotypes (1/34). The chromothripsis-positive cases were characterized by a particularly high degree of karyotype complexity and dismal prognosis. In conclusion, marker chromosomes are indicative of chromothripsis and associated with poor prognosis per se and not merely by association with other adverse cytogenetic features.
2017-03-29 | GSE93886 | GEO
Project description:Polymorphisms thiopurine-S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) can increase the risk of azathioprine myelotoxicity, but little is known about other genetic factors that increase risk for azathioprine-associated side effects. PrediXcan is a gene-based association method that estimates the expression of individuals' genes and examines their correlation to specified phenotypes. As proof of concept for using PrediXcan as a tool to define the association between genetic factors and azathioprine side effects, we aimed to determine whether the genetically predicted expression of TPMT or NUDT15 was associated with leukopenia or other known side effects. In a retrospective cohort of 1364 new users of azathioprine with EHR-reported White race, we used PrediXcan to impute expression in liver tissue, tested its association with pre-specified phecodes representing known side effects (e.g., skin cancer), and completed chart review to confirm cases. Among confirmed cases, patients in the lowest tertile (i.e., lowest predicted) of TPMT expression had significantly higher odds of developing leukopenia (OR=3.30, 95%CI: 1.07-10.20, p=0.04) versus those in the highest tertile; no other side effects were significant. The results suggest that this methodology could be deployed on a larger scale to uncover associations between genetic factors and drug side effects for more personalized care.
| S-EPMC9882694 | biostudies-literature
Project description:ObjectiveTo examine the association between antihypertensive treatment and specific adverse events.DesignSystematic review and meta-analysis.Eligibility criteriaRandomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up.Information sourcesSearches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020.Main outcome measuresThe primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (?2).ResultsOf 15?023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280?638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, ?2=0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, ?2=0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, ?2=0.122, n=26), hypotension (1.97, 1.67 to 2.32, ?2=0.132, n=35), and syncope (1.28, 1.03 to 1.59, ?2=0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction.ConclusionsThis meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function.RegistrationPROSPERO CRD42018116860.
| S-EPMC7873715 | biostudies-literature
Project description:ImportanceChildren of parents expressing limited comfort with English (LCE) or limited English proficiency may be at increased risk of adverse events (harms due to medical care). No prior studies have examined, in a multicenter fashion, the association between language comfort or language proficiency and systematically, actively collected adverse events that include family safety reporting.ObjectiveTo examine the association between parent LCE and adverse events in a cohort of hospitalized children.Design, setting, and participantsThis multicenter prospective cohort study was conducted from December 2014 to January 2017, concurrent with data collection from the Patient and Family Centered I-PASS Study, a clinician-family communication and patient safety intervention study. The study included 1666 Arabic-, Chinese-, English-, and Spanish-speaking parents of general pediatric and subspecialty patients 17 years and younger in the pediatric units of 7 North American hospitals. Data were analyzed from January 2018 to May 2020.ExposuresLanguage-comfort data were collected through parent self-reporting. LCE was defined as reporting any language besides English as the language in which parents were most comfortable speaking to physicians or nurses.Main outcomes and measuresThe primary outcome was adverse events; the secondary outcome was preventable adverse events. Adverse events were collected using a systematic 2-step methodology. First, clinician abstractors reviewed patient medical records, solicited clinician reports, hospital incident reports, and family safety interviews. Then, review and consensus classification were completed by physician pairs. To examine the association of LCE with adverse events, a multivariable logistic regression was conducted with random intercepts to adjust for clustering by site.ResultsOf 1666 parents providing language-comfort data, 1341 (80.5%) were female, and the mean (SD) age of parents was 35.4 (10.0) years. A total of 147 parents (8.8%) expressed LCE, most of whom (105 [71.4%]) preferred Spanish. Children of parents who expressed LCE had higher odds of having 1 or more adverse events compared with children whose parents expressed comfort with English (26 of 147 [17.7%] vs 146 of 1519 [9.6%]; adjusted odds ratio, 2.1; 95% CI, 1.2-3.7), after adjustment for parent race and education, complex chronic conditions, length of stay, site, and the intervention period. Similarly, children whose parents expressed LCE were more likely to experience 1 or more preventable adverse events (adjusted odds ratio, 2.3; 95% CI, 1.2-4.2).Conclusions and relevanceHospitalized children of parents expressing LCE were twice as likely to experience harms due to medical care. Targeted strategies are needed to improve communication and safety for this vulnerable group of children.
| S-EPMC7573792 | biostudies-literature
Project description:Gene expression profiles were compared between diagnosis and relapse specimens of paediatric patients with acute lymphoblastic leukaemia (ALL) to identify mechanisms and pathways of therapy failure. The following descriptions provide further information on the annotations applied in this submission: Day 7 MRD- Minimal residual disease (MRD) measured at Day 7 after treatment initiation. Day 14 MRD- MRD measured at day 14 after treatment initiation. End of Induction MRD- MRD at the end of remission induction therapy. Event- Clinical event that is used to interpret patient outcome and used to determine relapse status. Relapse status- The relapse status of the patient which is used to model kaplan-meier survival curves in the related manuscript. Status 0 indicates non-relapse status (patient didn't relapse within time monitored), and 1 indicates relapse. Relapse-Free Survival- The length of time that the patients were relapse-free, or the length of time they were studied for, if they did not relapse. Paired Specimen- Many of the specimens in this study were diagnosis and relapse specimens from the same patient (i.e. Specimens taken at different times). This factor indicates which of the specimens were matched to each other in this way i.e. Which came from the same patient.
2012-07-13 | E-MTAB-1216 | biostudies-arrayexpress