Improving cancer pain control: Potential impact of CYP2D6 pharmacogenomic (PGx) testing in oncology (Onc) patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12089-12089
Author(s):  
Natalie Reizine ◽  
Keith Danahey ◽  
Emily Schierer ◽  
Tien Truong ◽  
Mark J. Ratain ◽  
...  

12089 Background: Several opioid analgesics have well-known germline PGx associations which may predict either inefficacy or exaggerated (toxic) responses, depending on the patient’s genotype. Despite this, germline PGx testing has not been routinely incorporated into oncology care. We hypothesized that CYP2D6 germline PGx profiling offers the potential to improve oncology patients’ pain control by identifying individuals at increased risk for inadequate analgesia with standard opioid dosing. Methods: We retrospectively analyzed the medication histories of over 81,000 adult oncology patients treated at the University of Chicago from 2012-2018 for exposure to opioids. CYP2D6 genotype (permitting assignment of metabolizer phenotype: normal metabolizer [NM], intermediate metabolizer [IM], or poor metabolizer [PM]) was determined post-hoc for 127 patients who were genotyped for other reasons unrelated to pain prescribing. The primary endpoint was the number of opioids required for pain control over the course of longitudinal care, comparing PM/IMs with NMs. The secondary endpoint was the number of hospitalizations for pain control. Results: Over 47,000 oncology patients were exposed to opioids, with an average of 2.67±1.6 different opioid medication exposures per patient. Thirteen percent of genotyped patients were IM/PM, who were at risk for inadequate analgesia. IM/PM patients demonstrated an increased number of different opioid exposures (4.5±2.1) compared to NM (2.7±2.1, P value = 0.002). IM/PM patients were also more likely to have a pain related hospitalization (OR 4.17, CI 1.3-13.2, P = 0.016). Conclusions: Based on population prevalence, we estimate that > 6000 oncology patients (1000 patients/year) who received opioids at our center were IM/PM and thus at risk for inadequate analgesia due to genetic predisposition. CYP2D6 germline PGx profiling offers the potential to improve oncology patients’ pain management.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Michelle C Odden ◽  
Carmen A Peralta ◽  
Mary N Haan ◽  
Kenneth E Covinsky

Introduction: The association between high blood pressure (BP) and risk of death varies by age and appears to be attenuated in some elderly adults. Walking speed is an excellent measure of functional status and may identify which elders may be most at risk for the adverse consequences of hypertension. Hypothesis: We hypothesized that elevated BP would be associated with greater risk of mortality in faster walkers, but not in slower walkers. Methods: The study population included 2,340 persons ≥ 65 years, with measured BP, in the National Health and Nutrition Examination Survey (NHANES) waves 1999-2000 and 2001-2002. Mortality data was linked to death certificate data in the National Death Index. Walking speed was measured over a 20-foot walk; 243 (8%) did not complete the walk for various safety and logistical reasons. Participants with walking speed above the mean (2.7 ft/sec) were classified as faster walkers. Potential confouders included age, sex, race, survey year, lifestyle and physiologic factors, chronic health conditions, and antihypertensive use. Results: There were 589 deaths recorded through December 31 st , 2006. Among faster walkers, those with elevated systolic BP (≥140 mmHg) had a higher mortality rate compared to those with systolic BP <140 mmHg (236 vs. 161 per 100,000 person-years). Among slower walkers, mortality rates did not appear to differ by the presence of elevated systolic BP (586 vs. 563 per 100,000 person-years). This pattern remained after multivariable adjustment; there was an association between elevated systolic BP and mortality in faster, but not slower walkers (Table). Elevated diastolic BP was not independently associated with an increased risk of mortality. Conclusions: If confirmed in other studies, walking speed could be a simple measure to identify elderly adults who are most at risk for poor outcomes related to high blood pressure. Table Association of elevated blood pressure and mortality, stratified by walking speed Hazard Ratio (HR) of Death Faster Walking Speed >2.7 ft/sec (n = 1,279) Slower Walking Speed ≤ 2.7 ft/sec (n = 818) p-value for interaction HR (95% CI) p-value HR (95% CI) p-value Elevated Systolic BP (≥140 mmHg) 1.44 (1.04, 1.99) 0.03 1.08 (0.82, 1.42) 0.56 0.11 Elevated Diastolic BP (≥90 mmHg) 1.09 (0.52, 2.27) 0.82 0.65 (0.30, 1.45) 0.28 0.28 Funding (This research has received full or partial funding support from the American Heart Association, Western States Affiliate (California, Nevada&Utah))


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4740-4740
Author(s):  
Frederick R Rickles ◽  
Gregory A Maynard ◽  
Richard J Friedman ◽  
Alan P Brownstein ◽  
Elizabeth A Varga ◽  
...  

Abstract Abstract 4740 Deep vein thrombosis (DVT) and pulmonary embolism (PE) affect up to 600,000 individuals and account for ~100,000 deaths in the United States each year, according to The Surgeon General's Call to Action (CTA) To Prevent Deep Vein Thrombosis and Pulmonary Embolism (2008). Oncology patients, particularly those who are hospitalized or undergo chemotherapy, are at increased risk for DVT/PE. Mortality is greater among patients with cancer and venous thromboembolism (VTE) than among those with cancer alone. In response to the Surgeon General's CTA, the National Blood Clot Alliance (NBCA), a national, community-based, non-profit organization dedicated to the prevention, diagnosis, and treatment of thrombosis and thrombophilia, conducted a survey to benchmark DVT/PE awareness among the general public and several at-risk patient groups, including oncology patients. The literature contains little information about at-risk patient knowledge, and almost no information about general public knowledge of VTE, making this the first, large survey of both public and at-risk patient awareness of DVT/PE. The survey was conducted in November 2009, among a representative cross-section of 500 adults, >20 years, participating in online research panels. For comparison, the identical survey was conducted among a sample of 500 adults, >20 years, screened from an online research panel, who had received a cancer diagnosis or experienced recurrence of cancer within the past 6 months, or who were on active cancer treatment. Evaluations comparing survey responses provided by oncology patients who, in connection with their treatment, did require a hospital stay versus those who did not require a hospital stay showed no statistically significant differences in DVT/PE awareness between the two subgroups. Among all oncology patients surveyed, 24% said that they had heard of a medical condition called DVT, compared to 21% of the general public. Among all respondents who said that they knew what a DVT was (unaided) or who were able to correctly identify DVT on an aided checklist, 61% of oncology and 53% of national respondents said they could name DVT risk factors. The most frequently mentioned DVT risk factor was “sitting for a long time” among both the oncology (45%) and national (28%) samples. Among oncology patients who could name DVT risk factors (n=155), 8% named surgery, 1% named cancer treatment. Among national respondents who could name DVT risk factors (n=109), significantly more (79%) said they could name DVT signs/symptoms compared to oncology respondents (63%) who said the same. While not statistically significant, the national sample did show greater recognition of certain DVT signs/symptoms: skin redness/discoloration, 41% national, 21% oncology; leg swelling, 50% national, 31% oncology; and, leg pain, 37% national, 27% oncology. PE awareness was low among both groups, with 15% of all oncology and 16% of all national respondents saying that they had heard of PE. Of those who what said they knew what a PE was (unaided) or identified it correctly from an aided checklist, about one-third of both groups said they could name PE signs/symptoms, with “breathing difficulties” cited most frequently by oncology (69%) and national (73%) respondents. Significantly fewer oncology patients (28%) mentioned chest pain/tightness as a PE sign/symptom, compared to the national sample (57%). About 8 in 10 oncology and national respondents said that they did know what a blood clot is, and virtually all respondents (98%) recognized blood clots as life threatening. DVT/PE awareness/knowledge was low. Despite increased risk, oncology patients demonstrated no greater awareness of DVT/PE than the general public. DVT/PE education, utilizing interventions identified in the Surgeon General's DVT/PE CTA, should target the general public, with special emphasis on at-risk oncology patients to fill gaps relative to increased DVT/PE risks and signs/symptoms. Terms should be further simplified for future public awareness and patient education initiatives. Disclosures: Brownstein: Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.: Data reported from project supported by Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Ansell:Bayer, Inc: Consultancy; Bristol Myers Squibb: Consultancy, Data Safety Monitoring Boards; Daiichi Sankyo: Consultancy; Boehringer Ingleheim: Consultancy; Ortho McNeil: Consultancy; Sanofi Aventis: Speakers Bureau.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii25-ii25
Author(s):  
Melissa Gardner ◽  
Farah Aslanzadeh ◽  
Giuliana Zarrella ◽  
Sarah Braun ◽  
Ashlee Loughan ◽  
...  

Abstract BACKGROUND The COVID-19 pandemic altered the delivery of healthcare services globally with a rapid adoption of telemedicine to meet patient’s needs. Telemedicine is critical for neuro-oncology patients who may be at an increased risk of infection, yet require continuity of care. An important aspect of neuro-oncology care includes neuropsychological assessment, which can be challenging to complete outside of a structured testing environment. Teleneuropsychology (TNP) has been explored under proctored conditions and proven feasible and reliable. Conducting TNP visits directly to the patients’ home (DTH-TNP) had minimal study prior to the pandemic, but was implemented to reduce COVID-19 exposure. METHODS We used surveys to examine patient acceptance and clinician feasibility of DTH-TNP at two regionally diverse medical institutions routinely providing neuropsychological assessments services to neuro-oncology patients from April to August 2020, Massachusetts General Hospital (MGH) and Virginia Commonwealth University (VCU). RESULTS 45 patients voluntarily responded (MGH=30, VCU=15) and 98 percent (MGH=100%, VCU=93%) of respondents were satisfied with the DTH-TNP experience. Nine percent (MGH=7%, VCU=13%) reported challenges (e.g., technological issues) during the appointment. Eighty-nine percent (MGH=90%, VCU=87%) would recommend the virtual visit to others. Patients perceived reduced risk of infection (MGH=77%, VCU=87%) and time traveling to clinic (MGH=87%, VCU=80%) as favorable aspects of DTH-TNP. 43 clinician surveys collected at MGH indicated that clinicians were able to achieve the goal of their appointment in 91% of clinical encounters. Common issues reported by clinicians included trouble connecting (7%) to the telemedicine platform and environmental disruptions (12%). DISCUSSION This preliminary data suggests neuro-oncology patients and clinicians find DTH-TNP to be an acceptable and feasible practice, while also recognizing its limitations. This study is limited in that voluntary patient surveys are subject to bias. These results suggest that further study of DTH-TNP (e.g., reliability, validity, and limitations) for neuro-oncology patients is warranted. Future directions are discussed.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18234-e18234
Author(s):  
Ian Matthew Allen ◽  
Yonina Robbie Murciano-Goroff ◽  
Leyre Zubiri ◽  
Qun Li ◽  
Michael Sang Hughes ◽  
...  

e18234 Background: Infection with influenza in adults with cancer carries an increased risk of morbidity and mortality. Vaccination against seasonal influenza (Flu-V) can decrease the incidence of influenza, shorten its course, and reduce influenza-associated morbidity. Recent data has suggested that the administration of the Flu-V to patients on an ICI leads to an exaggerated inflammatory response and an increased risk of irAE. However, this trend was demonstrated in a small cohort of patients with lung cancer. Current recommendation for annual Flu-V in patients treated with ICI is unclear and literature about safety is limited. We compared rates of Flu-V for patients on ICI admitted with severe toxicity vs those patients on ICI who were admitted for reasons other than toxicity. We also evaluated rate of Flu-V among oncology patients who had received non-immunotherapy modalities. Methods: We retrospectively evaluated patients treated with ICI who were admitted to Massachusetts General Hospital from February 5, 2011- June 12, 2017. Patients received ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or a combination in treatment of an advanced solid tumor malignancies including melanoma, NSCLC, SCCHN. Admissions due to irAE were confirmed by review of clinical, radiologic, and pathologic features. Flu-V status was determined by rigorous chart review. Nearest neighbor matching was used to create a control group of cancer patients treated with non-ICI modalities. Descriptive statistics compared rates and timing of Flu-V relative to admission. Statistical significance was determined using Fischer’s Exact Test, p < 0.05. Results: Of 540 patients on ICI, 28% were admitted for irAE, 72% had a non-irAE reason for admission. The rate of Flu-V in the flu season prior to admission for irAE group was lower than for non-irAE (18.5% vs 29.6%; p value = 0.01). There were no differences in vaccination rates within ≤30 days (2.7% vs 3.6%, p = 0.80), ≤90 days (4.0% vs 9.3%, p = 0.05), or ≤180 days of admission (11.9% vs 18.5%, p = 0.07). Flu-V rate overall in patients on ICI was 26.5%. In comparison, Flu-V rate in the nearest neighbor non-immunotherapy oncology patients was 67% (n = 101). Conclusions: Flu-V rates were much lower in patients treated with ICI compared to patients treated with non-ICI modalities. We did not see a higher rate of Flu-V in patients admitted with irAE compared to non-irAE which suggests that Flu-V and severe irAE may not be linked in clinical practice. Additional studies are needed, but Flu-V in patients on ICI holds potential to improve care.


2021 ◽  
Author(s):  
Melissa M Gardner ◽  
Farah J Aslanzadeh ◽  
Giuliana V Zarrella ◽  
Sarah E Braun ◽  
Ashlee R Loughan ◽  
...  

Abstract Background The COVID-19 pandemic induced rapid adoption of telemedicine services for neuro-oncology patients at an increased risk of infection. Neuropsychological assessment is important to neuro-oncology care yet challenging to complete outside of a structured testing environment. Teleneuropsychology (TNP) has been explored in limited populations and proven feasible and reliable. Conducting TNP visits directly to patients' home (DTH) had minimal prior study. Methods We used two voluntary surveys to examine acceptance (patients) and feasibility (providers) of DTH-TNP at two regionally diverse medical institutions providing neuropsychological services to neuro-oncology patients from April to September 2020. Results A total of 119 patients were scheduled during the study period, 79 of whom completed neuropsychological testing via DTH-TNP. Neuropsychology providers completed surveys on 68 of these encounters (86%). In 98% of cases, neuropsychologists were able to achieve or partially achieve the individually defined goals of their assessment. Common problems reported included patient dysregulation (16%) and slow/unreliable internet (15%). Of the 52 patients who responded, 98% were satisfied with the DTH-TNP experience and 92% would recommend the virtual visit to others. All respondents felt understood by the examiner (100%) and the majority denied technical difficulties (90%), communication challenges (94%), or privacy concerns (98%). Patients reported reduced risk of infection and saved travel time as favorable aspects of DTH-TNP. Conclusions These preliminary results suggest neuro-oncology patients find DTH-TNP acceptable and neuropsychologists find it a feasible practice, while also recognizing its limitations. Results suggest that further study of DTH-TNP (e.g., reliability, validity) for neuro-oncology patients is warranted.


2021 ◽  
Vol 10 (9) ◽  
pp. 1835
Author(s):  
Stephen Contag ◽  
Silvia Visentin ◽  
Katherine Goetzinger ◽  
Erich Cosmi

Objective: To measure the sensitivity and positive predictive value (PPV) for an adverse neonatal outcome among growth-restricted fetuses (FGR) comparing the cerebral–placental ratio (CPR) with the cerebral–renal ratio (CRR). Methods: Retrospective analysis of 92 women who underwent prenatal ultrasound at the University of Maryland and the University of Padua. Renal, middle cerebral and umbilical artery Doppler waveforms were recorded for all scans during the third trimester. The last scan prior to delivery was included for analysis. We calculated the test characteristics of the pulsatility indices (PI) of the umbilical and renal arteries in addition to the derived CPR and CRR to detect a composite adverse neonatal outcome. Results: The test characteristics of the four Doppler ratios to detect increased risk for the composite neonatal outcome demonstrated that the umbilical artery pulsatility index had the best test performance (sensitivity 64% (95% CI: 47–82%), PPV 24% (95% CI: 21–27), and positive likelihood ratio 2.7 (95% CI: 1.4–5.2)). There was no benefit to using the CRR compared with the CPR. The agreement between tests was moderate to poor (Kappa value CPR compared with CRR: 0.5 (95%CI 0.4–0.70), renal artery PI:−0.1 (95% CI −0.2–0.0), umbilical artery PI: 0.5 (95% CI 0.4–0.7)). Only the umbilical artery had an area under the receiver operating curve that was significantly better compared with the CPR as a reference (p-value < 0.01). Conclusions: The data that we present do not support the use of renal artery Doppler as a useful clinical test to identify a fetus at risk for an adverse neonatal outcome. Within the various indices applied to this population, umbilical artery Doppler performed the best in identifying the fetuses at risk for an adverse perinatal outcome.


2016 ◽  
Vol 42 (5-6) ◽  
pp. 361-369 ◽  
Author(s):  
Jan-Dirk Vermeij ◽  
Willeke F. Westendorp ◽  
Yvo B. Roos ◽  
Matthijs C. Brouwer ◽  
Diederik van de Beek ◽  
...  

Background: The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients who received intravenous thrombolysis (IVT), patients who received ceftriaxone had a significantly better outcome as compared with the control group. This study aimed to gain more insight into the characteristics of these patients. Methods: In PASS, 2,550 patients were randomly assigned to preventive antibiotic treatment with ceftriaxone or standard care. In current post-hoc analysis, 836 patients who received IVT were included. Primary outcome included functional status on the modified Rankin Scale, analyzed with adjusted ordinal regression. Secondary outcomes included infection rate and symptomatic intracerebral hemorrhage (sICH) rate. Results: For all patients in PASS, the p value for the interaction between IVT and preventive ceftriaxone regarding functional outcome was 0.03. Of the 836 IVT-treated patients, 437 were administered ceftriaxone and 399 were allocated to the control group. Baseline characteristics were similar. In the IVT subgroup, preventive ceftriaxone was associated with a significant reduction in unfavorable outcome (adjusted common OR 0.77; 95% CI 0.61-0.99; p = 0.04). Mortality at 3 months was similar (OR 0.75; 95% CI 0.48-1.18). Preventive ceftriaxone was associated with a reduction in infections (OR 0.43; 95% CI 0.28-0.66), and a trend towards an increased risk for sICH (OR 3.09; 95% CI 0.85-11.31). Timing of ceftriaxone administration did not influence the outcome (aOR 1.00; 95% CI 0.98-1.03; p = 0.85). Conclusions: According to the post-hoc analysis of PASS, preventive ceftriaxone may improve the functional outcome in IVT-treated patients with acute stroke, despite a trend towards an increased rate of post-IVT-sICH.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Raphaela Ulrich ◽  
Thomas D. Meyer ◽  
Sylke Andreas ◽  
Claudia Lex

Background There is still a lack of knowledge about attitudes and cognitions that are related to bipolar disorder. Theoretically, it was proposed that exaggerated beliefs about the self, relationships, the need for excitement, and goal-related activities might lead to mania in vulnerable individuals, however, the few studies that examined this hypothesis provided mixed results. One of the unresolved issues is if such a cognitive style is associated with current mood symptoms or with different stages of the illness, i.e. at-risk versus diagnosed bipolar disorder. Therefore, the present study aimed at evaluating depression and mania-related cognitive style in individuals at-risk for mania. Method In an online survey, we collected data of 255 students of the University of Klagenfurt, Austria. All participants completed the Hypomanic Personality Scale (HPS), the Cognition Checklist for Mania – Revised (CCL-M-R), the Dysfunctional Attitude Scale (DAS), the Beck Depression Inventory (BDI), and the Internal State Scale (ISS). Results In a hierarchical regression, HPS was positively related to scores of all subscales of the CCL-M-R. The HPS did not significantly predict scores of the DAS. Current manic and depressive symptoms significantly contributed to the models. Conclusion The present results suggest that a trait-like risk for mania is associated with mania-related but not depression-related cognitions.


2021 ◽  
Vol 8 ◽  
pp. 204993612110273
Author(s):  
Samuel Windham ◽  
Melissa P. Wilson ◽  
Connor Fling ◽  
David Sheneman ◽  
Taylor Wand ◽  
...  

Background: Several studies have explored hospitalization risk factors with the novel coronavirus disease 2019 (COVID-19) infection. Our goal was to identify clinical characteristics outside of laboratory or radiologic data associated with intubation or death within 7 days of admission. Methods: The first 436 patients admitted to the University of Colorado Hospital (Denver metropolitan area) with confirmed COVID-19 were included. Demographics, comorbidities, and select medications were collected by chart abstraction. Missing height for calculating body mass index (BMI) was imputed using the median height for patients’ sex and race/ethnicity. Adjusted odds ratios (aOR) were estimated using multivariable logistic regression and a minimax concave penalty (MCP) regularized logistic regression explored prediction. Results: Participants had a mean [standard deviation (SD)] age 55 (17), BMI 30.9 (8.2), 55% were male and 80% were ethnic/racial minorities. Increasing age [aOR: 1.24 (1.07, 1.45) per 10 years], higher BMI (aOR 1.03 (1.00, 1.06), and poorly controlled diabetes [hemoglobin A1C (HbA1c) ⩾ 8] (aOR 2.26 (1.24, 4.12) were significantly ( p < 0.05) associated with greater odds of intubation or death. Female sex [aOR: 0.63, 95% CI (0.40, 0.98); p value = 0.043] was associated with lesser odds of intubation or death. The odds of death and/or intubation increased 19% for every 1 unit increase in HbA1c value [OR: 1.19 (1.01, 1.43); p = 0.04]. Our final MCP model included indicators of A1C ⩾ 8, age > 65, sex, and minority status, but predicted intubation/death only slightly better than random chance [area under the receiver operating characteristic curve (AUC) = 0.61 (0.56, 0.67)]. Conclusion: In a hospitalized patient cohort with COVID-19, worsening control of diabetes as evidenced by higher HbA1c was associated with increased risk of intubation or death within 7 days of admission. These results complement and help clarify previous associations found between diabetes and acute disease in COVID-19. Importantly, our analysis is missing some known predictors of severity in COVID-19. Our predictive model had limited success, suggesting unmeasured factors contribute to disease severity differences.


Crisis ◽  
2017 ◽  
Vol 38 (6) ◽  
pp. 433-442 ◽  
Author(s):  
Kim Gryglewicz ◽  
Melanie Bozzay ◽  
Brittany Arthur-Jordon ◽  
Gabriela D. Romero ◽  
Melissa Witmeier ◽  
...  

Abstract. Background: Given challenges that exceed the normal developmental requirements of adolescence, deaf and hard-of-hearing (DHH) youth are believed to be at elevated risk for engaging in suicide-related behavior (SRB). Unfortunately, little is known about the mechanisms that put these youth potentially at risk. Aims: To determine whether peer relationship difficulties are related to increased risk of SRB in DHH youth. Method: Student records (n = 74) were retrieved from an accredited educational center for deaf and blind students in the United States. Results: Peer relationship difficulties were found to be significantly associated with engagement in SRB but not when accounting for depressive symptomatology. Limitations: The restricted sample limits generalizability. Conclusions regarding risk causation cannot be made due to the cross-sectional nature of the study. Conclusion: These results suggest the need for future research that examines the mechanisms of the relationship between peer relationship difficulties, depression, and suicide risk in DHH youth and potential preventive interventions to ameliorate the risks for these at-risk youth.


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