Association of co-medication quality with chemotherapy-related adverse drug reactions and survival in older colorectal cancer patients

Author(s):  
Li-Ju Chen ◽  
Thi Ngoc Mai Nguyen ◽  
Dana Clarissa Laetsch ◽  
Jenny Chang-Claude ◽  
Michael Hoffmeister ◽  
...  

Abstract Background Evidence about the clinical relevance of appropriate co-medication among older colorectal cancer (CRC) patients is sparse. Methods A cohort study was conducted with 3,239 CRC patients aged 65 years and older. To assess co-medication quality, we calculated the total Fit fOR The Aged (FORTA) score and its sub-scores for medication overuse, underuse, and potentially inappropriate medication use. Multivariable Cox proportional hazards or logistic regression models were performed to evaluate the association of co-medication quality with up to 5-year overall survival, CRC-specific survival, and chemotherapy-related adverse drug reactions (ADRs). Results Overall, 3,239 and 1,209 participants were included in analyses on survival and ADRs, respectively. The hazard ratios [95%-confidence intervals] for the total FORTA score ≥ 7 vs. 0-1 points were 1.83 [1.40-2.40] and 1.76 [1.22-2.52] for up to 5-year overall and CRC-specific survival, respectively. Worse up to 5-year OS and CSS was also evident for FORTA sub-scores for PIM use and overuse whereas no association was observed for underuse. Although results for the total FORTA and potentially inappropriate medication score were much stronger among patients receiving chemotherapy, no significant associations with chemotherapy-related ADRs were observed. Moreover, associations were particularly strong among men and rectal cancer patients as compared to women and colon cancer patients. Conclusions Poor total co-medication quality was significantly associated with worse up to 5-year overall and CRC-specific survival. Randomized controlled trials are needed to test whether improved cancer co-medication management in older CRC patients prolongs survival.

2021 ◽  
Vol 147 (5) ◽  
pp. 1407-1419
Author(s):  
Manuela Limam ◽  
Katarina Luise Matthes ◽  
Giulia Pestoni ◽  
Eleftheria Michalopoulou ◽  
Leonhard Held ◽  
...  

Abstract Background Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland. Methods Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis. Results Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival. Conclusion The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.


2021 ◽  
Author(s):  
Suehyun Lee ◽  
Jaehun Cha ◽  
Jong-Yeup Kim ◽  
Gil Myeong Son ◽  
Dong-Kyu Kim

Abstract Ototoxic medications can lead to significant morbidity. Thus, pre-marketing clinical trials have assessed new drugs that have ototoxic potential. Nevertheless, several ototoxic side effects of drugs may remain undetected. Hence, we sought to retrospectively investigate the potential risk of ototoxic adverse drug reactions among commonly used drugs via a longitudinal cohort study. An electronic health records-based data analysis with a propensity-matched comparator group was carried out. This study was conducted using the MetaNurse algorithm for standard nursing statements on electronic healthcare records and the National Sample Cohort obtained from the South Korea National Health Insurance Service. Five target drugs capable of causing ototoxic adverse drug reactions were identified using MetaNurse; two drugs were excluded after database-based analysis because of the absence of bilateral hearing loss events in patients. Survival analysis, log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio of bilateral hearing loss among patients who were prescribed candidate ototoxic drugs. The adjusted hazard ratio of bilateral hearing loss was 1.31 (1.03–1.68), 2.20 (1.05–4.60), and 2.26 (1.18–4.33) in cimetidine, hydroxyzine, and sucralfate users, respectively. Our results indicated that hydroxyzine and sucralfate may cause ototoxic adverse drug reactions in patients. Thus, clinicians should consider the risk of ototoxicity when prescribing these drugs.


2006 ◽  
Vol 24 (7) ◽  
pp. 1112-1118 ◽  
Author(s):  
Allison Alcalay ◽  
Ted Wun ◽  
Vijay Khatri ◽  
Helen K. Chew ◽  
Danielle Harvey ◽  
...  

Purpose To describe the incidence and outcomes associated with venous thromboembolism (VTE) among patients with colorectal cancer. Methods This was a retrospective analysis of all colorectal cancer patients diagnosed in California between 1993 and 1995 and 1997 to 1999. Principal outcomes were incident symptomatic VTE events and death. Associations between specific risk factors and principal outcomes were analyzed using Cox proportional hazards models. Results Among 68,142 colorectal cancer patients, 50% were women, mean age was 70 ± 15 years, and approximately 70% underwent a major operation. The 2-year cumulative incidence of VTE was 2,100 patients (3.1%), with an incidence rate that decreased significantly over time from 5.0% (events/100 patient-years) in months 0 to 6 to 1.4% during months 7 to 12 to 0.6% during the second year. Significant predictors of VTE included metastatic stage (hazard ratio [HR] = 3.2; 95% CI, 2.8 to 3.8) and three or more comorbid conditions (HR = 2.0; 95% CI, 1.7 to 2.3). The risk of VTE was significantly reduced among Asians/Pacific Islanders (HR = 0.4; 95% CI, 0.3 to 0.5.) and patients who underwent an abdominal operation (HR = 0.4; 95% CI, 0.3 to 0.4). In risk-adjusted models, VTE was a significant predictor of death within 1 year of cancer diagnosis among patients with local- (HR = 1.8; 95% CI, 1.4 to 2.3) or regional-stage disease (HR = 1.5; 95% CI, 1.3 to 1.8) but not among patients with metastatic disease (HR = 1.1; 95% CI, 1.0 to 1.2). Conclusion The incidence of VTE among colorectal cancer patients was highest in the first 6 months after diagnosis and decreased rapidly thereafter. Metastatic disease and the number of medical comorbidities were the strongest predictors of VTE. Incident VTE reduced survival among patients with local or regional disease, suggesting that, in these patients, VTE may reflect the presence of a biologically more aggressive cancer.


2021 ◽  
pp. 1-9
Author(s):  
Christian Gessner ◽  
Karin Potthoff ◽  
Nikolaj Frost

<b><i>Background/Aim:</i></b> Chemotherapy-induced neutropenia is a common and serious complication in cancer patients receiving myelosuppressive chemotherapy. This analysis was undertaken to evaluate the effectiveness and safety of prophylaxis with lipegfilgrastim, a glycoPEGylated granulocyte colony-stimulating factor, in lung cancer patients undergoing chemotherapy in real-world clinical practice. <b><i>Methods:</i></b> Data from two European non-interventional studies (NIS NADIR and NIS LEOS) investigating lipegfilgrastim for primary and secondary prophylaxis were pooled. Outcomes included the incidence of chemotherapy-induced neutropenia and febrile neutropenia (FN), use of anti-infectives and antimycotics, and adverse events and their relationship to lipegfilgrastim. <b><i>Results:</i></b> The safety population included 361 patients with lung cancer (median age, 66 years [range, 36–88]), of whom 322 had received 2 or more consecutive cycles of lipegfilgrastim (efficacy population [primary prophylaxis, 75.5%; secondary prophylaxis, 16.5%]). Almost 40% of the patients were considered to have a high risk (&#x3e;20%) of FN, and around 60% had an intermediate risk (10–20%). For all cycles, FN was reported in 3 patients (0.9%), neutropenia in 14 (4.3%), and grade 4 neutropenia in 9 (2.8%). Anti-infectives were used in 27 patients (8.4%) and antimycotics in 6 (1.9%). The incidence rates were lower for the patients’ first cycle (FN, 0.4%; neutropenia, 0.8%; grade 4 neutropenia, 0.8%; anti-infectives, 0.6%; antimycotics, 0.6%). Adverse drug reactions considered lipegfilgrastim related were reported in 35 patients (9.7%), and serious adverse drug reactions in 10 (2.8%). None of the fatal events reported in 28 patients (7.8%) were lipegfilgrastim related. <b><i>Conclusion:</i></b> Lipegfilgrastim administered to patients with lung cancer undergoing chemotherapy in real-world clinical practice showed similar effectiveness and safety to that reported in published pivotal trials.


2020 ◽  
Vol 5 (4) ◽  
pp. 598-616 ◽  
Author(s):  
Austin C Doctor

Abstract Why do rebel organizations splinter into competing factions during civil war? To explain this outcome, I leverage variation in rebel leadership. I argue that rebel leaders draw on their pre-war experiences—i.e., their military and political experiences—to manage their organizations during conflict. These experiences bear unique patterns of rebel management and, thus, corresponding risks of fragmentation. Empirical evidence comes from a two-stage research design and original data featuring over 200 rebel leaders from 1989 to 2014. In the first stage, I estimate the probability of group fragmentation with a series of logistic regression models. In the second stage, I use Cox proportional-hazards models to estimate leadership effects on the rate of group fragmentation. Results indicate that variation in rebel leadership corresponds with unique risks of fragmentation. In particular, the results suggest that leaders with real military experience are best equipped to maintain group cohesion. This study offers insight into the processes by which rebel groups splinter into armed factions. In addition, it makes an important contribution to the broader discussion on the roles of structure and agency in shaping the dynamics of civil war.


2014 ◽  
Vol 23 (4) ◽  
pp. 1091-1097 ◽  
Author(s):  
Naomi Iihara ◽  
Takayuki Nishio ◽  
Tetsuko Goda ◽  
Hideaki Anzai ◽  
Masatoshi Kagawa ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 453
Author(s):  
Yu-Han Wang ◽  
Shih-Ching Chang ◽  
Muhamad Ansar ◽  
Chin-Sheng Hung ◽  
Ruo-Kai Lin

Colorectal cancer (CRC) arises from chromosomal instability, resulting from aberrant hypermethylation in tumor suppressor genes. This study identified hypermethylated genes in CRC and investigated how they affect clinical outcomes. Methylation levels of specific genes were analyzed from The Cancer Genome Atlas dataset and 20 breast cancer, 16 esophageal cancer, 33 lung cancer, 15 uterine cancer, 504 CRC, and 9 colon polyp tissues and 102 CRC plasma samples from a Taiwanese cohort. In the Asian cohort, Eps15 homology domain-containing protein 3 (EHD3) had twofold higher methylation in 44.4% of patients with colonic polyps, 37.3% of plasma from CRC patients, and 72.6% of CRC tissues, which was connected to vascular invasion and high microsatellite instability. Furthermore, EHD3 hypermethylation was detected in other gastrointestinal cancers. In the Asian CRC cohort, low EHD3 mRNA expression was found in 45.1% of patients and was connected to lymph node metastasis. Multivariate Cox proportional-hazards survival analysis revealed that hypermethylation in women and low mRNA expression were associated with overall survival. In the Western CRC cohort, EHD3 hypermethylation was also connected to overall survival and lower chemotherapy and antimetabolite response rates. In conclusion, EHD3 hypermethylation contributes to the development of CRC in both Asian and Western populations.


Author(s):  
Joshua R Ehrlich ◽  
Bonnielin K Swenor ◽  
Yunshu Zhou ◽  
Kenneth M Langa

Abstract Background Vision impairment (VI) is associated with incident cognitive decline and dementia. However, it is not known whether VI is associated only with the transition to cognitive impairment, or whether it is also associated with later transitions to dementia. Methods We used data from the population-based Aging, Demographics and Memory Study (ADAMS) to investigate the association of visual acuity impairment (VI; defined as binocular presenting visual acuity &lt;20/40) with transitions from cognitively normal (CN) to cognitive impairment no dementia (CIND) and from CIND to dementia. Multivariable Cox proportional hazards models and logistic regression were used to model the association of VI with cognitive transitions, adjusted for covariates. Results There were 351 participants included in this study (weighted percentages: 45% male, 64% age 70-79 years) with a mean follow-up time of 4.1 years. In a multivariable model, the hazard of dementia was elevated among those with VI (HR=1.63, 95%CI=1.04-2.58). Participants with VI had a greater hazard of transitioning from CN to CIND (HR=1.86, 95%CI=1.09-3.18). However, among those with CIND and VI a similar percentage transitioned to dementia (48%) and remained CIND (52%); there was no significant association between VI and transitioning from CIND to dementia (HR=0.94, 95%CI=0.56-1.55). Using logistic regression models, the same associations between VI and cognitive transitions were identified. Conclusions Poor vision is associated with the development of CIND. The association of VI and dementia appears to be due to the higher risk of dementia among individuals with CIND. Findings may inform the design of future interventional studies.


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