Publications by authors named "Joseph Arthur"

58 Publications

A retrospective review of the use of oxymorphone immediate release for long term pain control in cancer patients with gastrostomy tubes.

Ann Palliat Med 2021 Mar 27;10(3):2662-2667. Epub 2021 Jan 27.

Department of Palliative, Rehabilitation, and Integrative Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.

Background: Cancer patients often require feeding or venting gastrostomy-tubes (G-tubes) for enteral nutrition or symptom palliation. The administration of most extended-release (ER) opioids via the G-tube or orally followed by clamping of the venting G-tube is contraindicated. Oxymorphone immediate release (IR) may be useful because of its longer half-life compared to other IR opioids. We examined the use of oxymorphone IR administered every 8 hours in patients with G-tubes.

Methods: This was a retrospective chart review of 40 consecutive cancer patients with G-tubes who underwent opioid rotation (OR) to oxymorphone. Demographics, symptoms, morphine equivalent daily dose (MEDD), and oxymorphone dose were collected. Successful OR was defined as a 2-point or 30% reduction in pain score and continued use of oxymorphone at follow-up in outpatient setting, or discharge in inpatient setting. Opioid rotation ration (ORR) between MEDD and oxymorphone in patients with successful OR was calculated as MEDD before the OR divided by total oxymorphone dose/day at follow-up or discharge.

Results: The median age was 56 years, 57.5% were white, 68% male, 47.5% (n=19) had head and neck cancer, 90% had advanced disease, 67.5% (n=27) were inpatient, and 15% (n=6) had venting G-tubes. 25/40 (62.5%) patients had successful OR to oxymorphone. The median ORR from MEDD to oxymorphone was 3.5 (IQR, 3.1-4). There were no independent predictors for successful OR, and ORR did not significantly differ among various groups.

Conclusions: Oxymorphone IR can be used successfully in cancer patients with G-tubes using an ORR of 3.5 to calculate dose from MEDD.
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http://dx.doi.org/10.21037/apm-20-969DOI Listing
March 2021

Rapid Transition to Virtual Care during the COVID-19 Epidemic: Experience of a Supportive Care Clinic at a Tertiary Care Cancer Center.

J Palliat Med 2021 Feb 2. Epub 2021 Feb 2.

Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

COVID-19 pandemic necessitated rapid adoption of telemedicine at our supportive care center (SCC) to ensure continuity of care while maintaining social distancing. To document the process of transition from in-person to virtual care. The charts of 1744 consecutive patients in our SCC located in the United States were retrospectively reviewed during the four weeks before transition (February 14-March 12), four weeks after transition (March 20-April 16), and transition week (March 13-March 19). Patient demographics, vital aspects of a supportive care visit such as assessments (Edmonton Symptom Assessment Scale-Financial and Spiritual [ESAS-FS], Cut-down, Annoyed, Guilty, Eye-opener Screen-Adapted to Include Drugs [CAGE-AID], and Memorial Delirium Assessment Scale [MDAS]), interdisciplinary team involvement, and visit type were recorded. In total 763 patients were seen before transition, 168 during the transition week, and 813 after transitioning to virtual care. Patient characteristics, ESAS-FS, CAGE-AID, and nurse assessment did not significantly differ among the three groups. The after-transition group had a small reduction in counseling intervention compared with before (20.2% vs. 26.2%;  = 0.0068). MDAS completion was higher after transition (99.6% vs. 98%;  = 0.007). In-person visits decreased from 100% before to 12.7% after transition ( < 0.0001) and virtual visits increased to 49.3% (video) and 38% (telephone). In-person visits decreased to 49% in the week one, 3% in week two, and <2% in week four after transition ( < 0.0001). Our supportive care team transitioned from in-person care to virtual visits within weeks while maintaining a high patient volume, continuity of care, and adherence to social distancing. Our transition can serve as a model for other centers.
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http://dx.doi.org/10.1089/jpm.2020.0737DOI Listing
February 2021

Managing Nonmedical Opioid Use Among Patients With Cancer Pain During the COVID-19 Pandemic Using the CHAT Model and Telehealth.

J Pain Symptom Manage 2021 07 27;62(1):192-196. Epub 2021 Jan 27.

Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA.

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http://dx.doi.org/10.1016/j.jpainsymman.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274019PMC
July 2021

Frequency of and Factors Associated With Nonmedical Opioid Use Behavior Among Patients With Cancer Receiving Opioids for Cancer Pain.

JAMA Oncol 2021 Mar;7(3):404-411

Department of Palliative Care, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston.

Importance: One of the main aims of research on nonmedical opioid use (NMOU) is to reduce the frequency of NMOU behaviors through interventions such as universal screening, reduced opioid exposure, and more intense follow-up of patients with elevated risk. The absence of data on the frequency of NMOU behavior is the major barrier to conducting research on NMOU.

Objective: To determine the overall frequency of and the independent predictors for NMOU behavior.

Design, Setting, And Participants: In this prognostic study, 3615 patients with cancer were referred to the supportive care center at MD Anderson Cancer Center from March 18, 2016, to June 6, 2018. Patients were eligible for inclusion if they had cancer and were taking opioids for cancer pain for at least 1 week. Patients were excluded if they had no follow-up within 3 months of initial consultation, did not complete the appropriate questionnaire, or did not have scheduled opioid treatments. After exclusion, a total of 1554 consecutive patients were assessed for NMOU behavior using established diagnostic criteria. All patients were assessed using the Edmonton Symptom Assessment Scale, the Screener and Opioid Assessment for Patients with Pain (SOAPP), and the Cut Down, Annoyed, Guilty, Eye Opener-Adapted to Include Drugs (CAGE-AID) survey. Data were analyzed from January 6 to September 25, 2020.

Results: A total of 1554 patients (median [interquartile range (IQR)] age, 61 [IQR, 52-69] years; 816 women [52.5%]; 1124 White patients [72.3%]) were evaluable for the study, and 299 patients (19.2%) had 1 or more NMOU behaviors. The median (IQR) number of NMOU behaviors per patient was 1 (IQR, 1-3). A total of 576 of 745 NMOU behaviors (77%) occurred by the first 2 follow-up visits. The most frequent NMOU behavior was unscheduled clinic visits for inappropriate refills (218 of 745 [29%]). Eighty-eight of 299 patients (29.4%) scored 7 or higher on SOAPP, and 48 (16.6%) scored at least 2 out of 4 points on the CAGE-AID survey. Results from the multivariate model suggest that marital status (single, hazard ratio [HR], 1.58; 95% CI, 1.15-2.18; P = .005; divorced, HR, 1.43; 95% CI, 1.01-2.03; P = .04), SOAPP score (positive vs negative, HR, 1.35; 95% CI, 1.04-1.74; P = .02), morphine equivalent daily dose (MEDD) (HR, 1.003; 95% CI, 1.002-1.004; P < .001), and Edmonton Symptom Assessment Scale pain level (HR, 1.11; 95% CI, 1.06-1.16; P < .001) were independently associated with the presence of NMOU behavior. In recursive partition analysis, single marital status, MEDD greater than 50 mg, and SOAPP scores greater than 7 were associated with a higher risk (56%) for the presence of NMOU behavior.

Conclusions And Relevance: This prognostic study of patients with cancer taking opioids for cancer pain found that 19% of patients developed NMOU behavior within a median duration of 8 weeks after initial supportive care clinic consultation. Marital status (single or divorced), SOAPP score greater than 7, higher levels of pain severity, and MEDD level were independently associated with NMOU behavior. This information will assist clinicians and investigators designing clinical and research programs in this important field.
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http://dx.doi.org/10.1001/jamaoncol.2020.6789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791402PMC
March 2021

Deficiencies with the Use of Prescription Drug Monitoring Program in Cancer Pain Management: A Report of Two Cases.

J Palliat Med 2021 05 22;24(5):751-754. Epub 2020 Dec 22.

Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Prescription drug monitoring programs (PDMPs) help maintain electronic records of controlled substances and are a resource to help direct patient care. As the use of these electronic programs expands, limitations of their use are becoming more apparent. We present two cases that illustrate the effects and the need to interpret the PDMPs with caution. Case 1: A male in his 60s presented with metastatic lung cancer who was being managed by our team for pain management along with oncology for cancer directed care. The PDMP erroneously reported that he had filled methadone, thereby impacting the provider-patient relationship. The second case was a female patient in her 40s who had metastatic lung cancer currently receiving cancer directed therapy and also followed with the Supportive Care Clinic for the management of cancer associated pain. The patient had demonstrated nonmedical opioid use behaviors in past visits so a careful monitoring approach had been implemented by the clinic to help safely prescribe opioids. The patient was wearing a fentanyl patch that was found only on physical examination during a clinic visit, because it was not noted in the PDMP. The PDMP has been found to assist physicians in decision making but there are limitations with its use. Enhanced real-time reporting of opioid prescribing information, increased integration into electronic health systems, and universal interstate sharing of prescribing data are some of the ways to improve their effectiveness. More research is needed to further examine the deficiencies and improve on its utility in routine chronic opioid therapy.
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http://dx.doi.org/10.1089/jpm.2020.0537DOI Listing
May 2021

Random urine drug testing among patients receiving opioid therapy for cancer pain.

Cancer 2021 Mar 24;127(6):968-975. Epub 2020 Nov 24.

Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: There is limited information regarding the true frequency of nonmedical opioid use (NMOU) among patients receiving opioid therapy for cancer pain. Data to guide patient selection for urine drug testing (UDT) as well as the timing and frequency of ordering UDT are insufficient. This study examined the frequency of abnormal UDT among patients with cancer who underwent random UDT and their characteristics.

Methods: Demographic and clinical information for patients with cancer who underwent random UDT were retrospectively reviewed and compared with a historical cohort that underwent targeted UDT. Random UDT was ordered regardless of a patient's risk potential for NMOU. Targeted UDT was ordered on the basis of a physician's estimation of a patient's risk for NMOU.

Results: In all, 552 of 573 eligible patients (96%) underwent random UDT. Among these patients, 130 (24%) had 1 or more abnormal results; 38 of the 88 patients (43%) who underwent targeted UDT had 1 or more abnormal results. When marijuana was excluded, 15% of the random group and 37% of the targeted group had abnormal UDT findings (P < .001). It took a shorter time from the initial consultation to detect 1 or more abnormalities with the random test than the targeted test (median, 130 vs 274 days; P = .02). Abnormal random UDT was independently associated with younger age (P < .0001), male sex (P = .03), Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs positivity (P = .001), and higher Edmonton Symptom Assessment System anxiety (P = .01).

Conclusions: Approximately 1 in 4 patients receiving opioids for cancer pain at a supportive care clinic who underwent random UDT had 1 or more abnormalities. Random UDT detected abnormalities earlier than the targeted test. These findings suggest that random UDT is justified among patients with cancer pain.
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http://dx.doi.org/10.1002/cncr.33326DOI Listing
March 2021

The development of a nomogram to determine the frequency of elevated risk for non-medical opioid use in cancer patients.

Palliat Support Care 2021 02;19(1):3-10

Department of Palliative Care, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Objective: Non-medical opioid use (NMOU) is a growing crisis. Cancer patients at elevated risk of NMOU (+risk) are frequently underdiagnosed. The aim of this paper was to develop a nomogram to predict the probability of +risk among cancer patients receiving outpatient supportive care consultation at a comprehensive cancer center.

Method: 3,588 consecutive patients referred to a supportive care clinic were reviewed. All patients had a diagnosis of cancer and were on opioids for pain. All patients were assessed using the Edmonton Symptom Assessment Scale (ESAS), Screener and Opioid Assessment for Patients with Pain (SOAPP-14), and CAGE-AID (Cut Down-Annoyed-Guilty-Eye Opener) questionnaires. "+risk" was defined as an SOAPP-14 score of ≥7. A nomogram was devised based on the risk factors determined by the multivariate logistic regression model to estimate the probability of +risk.

Results: 731/3,588 consults were +risk. +risk was significantly associated with gender, race, marital status, smoking status, depression, anxiety, financial distress, MEDD (morphine equivalent daily dose), and CAGE-AID score. The C-index was 0.8. A nomogram was developed and can be accessed at https://is.gd/soappnomogram. For example, for a male Hispanic patient, married, never smoked, with ESAS scores for depression = 3, anxiety = 3, financial distress = 7, a CAGE score of 0, and an MEDD score of 20, the total score is 9 + 9+0 + 0+6 + 10 + 23 + 0+1 = 58. A nomogram score of 58 indicates the probability of +risk of 0.1.

Significance Of Results: We established a practical nomogram to assess the +risk. The application of a nomogram based on routinely collected clinical data can help clinicians establish patients with +risk and positively impact care planning.
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http://dx.doi.org/10.1017/S1478951520000322DOI Listing
February 2021

Health Care Provider Attitudes, Beliefs, and Perceived Confidence in Managing Patients With Cancer Pain and Nonmedical Opioid Use.

J Pain Symptom Manage 2021 01 6;61(1):128-135.e6. Epub 2020 Jul 6.

Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA.

Context: Health care provider education is an effective strategy to improve knowledge and competencies in opioid-prescribing practices. However, there are very few studies regarding this among providers of patients with cancer pain and nonmedical opioid use (NMOU). The aim of our study was to assess participants' attitudes, beliefs, and self-perceived confidence in caring for patients with cancer pain and NMOU before and after attending an opioid educational seminar on the use and nonmedical use of opioids in patients with cancer.

Methods: An anonymous cross-sectional survey was conducted among health care providers who attended an opioid educational event in April 2018 and May 2019.

Results: The overall response rate was 63% (129 of 206). Approximately 72% of participants had concerns about NMOU in patients with cancer, 69% felt that such patients are frequently underdetected, and 63% felt that cancer pain is frequently undertreated. At baseline, only 23% reported adequate knowledge and 35% reported confidence in caring for patients with cancer with NMOU-related issues. Among those who completed both the preseminar and postseminar surveys, these numbers improved significantly at the end of the seminar (26% vs. 71% and 43% vs. 84%, respectively; all P < 0.001).

Conclusion: Most health care providers expressed concerns about underdetection of NMOU and undertreatment of pain among patients with cancer. Many self-reported knowledge and confidence deficits in caring for patients with cancer with NMOU. Seminar participation was associated with an increase in the number of participants with self-perceived knowledge and confidence. Future studies are needed to ascertain the impact of such opioid educational events on patient care practices.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.06.040DOI Listing
January 2021

Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial.

Lancet Oncol 2020 07 29;21(7):989-998. Epub 2020 May 29.

Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium.

Methods: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486.

Findings: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [-4·4 to -2·2]), and combination group (n=10, -3·0 [-4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths.

Interpretation: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group.

Funding: National Institute of Nursing Research.
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http://dx.doi.org/10.1016/S1470-2045(20)30307-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433183PMC
July 2020

Combinatorial single-cell CRISPR screens by direct guide RNA capture and targeted sequencing.

Nat Biotechnol 2020 08 30;38(8):954-961. Epub 2020 Mar 30.

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.

Single-cell CRISPR screens enable the exploration of mammalian gene function and genetic regulatory networks. However, use of this technology has been limited by reliance on indirect indexing of single-guide RNAs (sgRNAs). Here we present direct-capture Perturb-seq, a versatile screening approach in which expressed sgRNAs are sequenced alongside single-cell transcriptomes. Direct-capture Perturb-seq enables detection of multiple distinct sgRNA sequences from individual cells and thus allows pooled single-cell CRISPR screens to be easily paired with combinatorial perturbation libraries that contain dual-guide expression vectors. We demonstrate the utility of this approach for high-throughput investigations of genetic interactions and, leveraging this ability, dissect epistatic interactions between cholesterol biogenesis and DNA repair. Using direct capture Perturb-seq, we also show that targeting individual genes with multiple sgRNAs per cell improves efficacy of CRISPR interference and activation, facilitating the use of compact, highly active CRISPR libraries for single-cell screens. Last, we show that hybridization-based target enrichment permits sensitive, specific sequencing of informative transcripts from single-cell RNA-seq experiments.
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http://dx.doi.org/10.1038/s41587-020-0470-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416462PMC
August 2020

Urine Drug Testing in Cancer Pain Management.

Authors:
Joseph A Arthur

Oncologist 2020 02 11;25(2):99-104. Epub 2019 Oct 11.

Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA.

Urine drug test (UDT) is an effective tool used in chronic opioid therapy to ensure patient adherence to treatment and detect nonmedical opioid use. The two main types of UDT used in routine clinical practice are the screening tests or immunoassays and the confirmatory tests or laboratory-based specific drug identification tests such as gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, or tandem mass spectrometry. UDT produces objective data on some nonmedical opioid use that may otherwise go undetected, such as the use of undisclosed medications, the nonuse of prescribed medications, and the use of illegal drugs. It allows clinicians to initiate an open and effective conversation about nonmedical opioid use with their patients. However, the test has certain limitations that sometimes compromise its use. Its interpretation can be challenging to clinicians because of the complexity of the opioid metabolic pathways. Clear guidelines or recommendations regarding the use of UDT in cancer pain is limited. As a result, UDT appears to be underused among patients with cancer pain receiving opioid therapy. More studies are needed to help standardize the integration and use of UDT in routine cancer pain management. IMPLICATIONS FOR PRACTICE: Despite its potential benefits, urine drug testing (UDT) appears to be underused among patients with cancer pain receiving opioid therapy. This is partly because its interpretation can be challenging owing to the complexity of the opioid metabolic pathways. Information regarding the use of UDT in opioid therapy among patients with cancer is limited. This review article will improve clinician proficiency in UDT interpretation and assist oncologists in developing appropriate treatment plans during chronic opioid therapy.
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http://dx.doi.org/10.1634/theoncologist.2019-0525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011652PMC
February 2020

Random vs Targeted Urine Drug Testing Among Patients Undergoing Long-term Opioid Treatment for Cancer Pain.

JAMA Oncol 2020 04;6(4):580-581

Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston.

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http://dx.doi.org/10.1001/jamaoncol.2019.6756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042919PMC
April 2020

Chronic Non-Malignant Pain in Patients with Cancer Seen at a Timely Outpatient Palliative Care Clinic.

Cancers (Basel) 2020 Jan 15;12(1). Epub 2020 Jan 15.

Department of Palliative Care, Rehabilitation and Integrative Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.

Palliative care is seeing cancer patients earlier in the disease trajectory with a multitude of chronic issues. Chronic non-malignant pain (CNMP) in cancer patients is under-studied. In this prospective study, we examined the prevalence and management of CNMP in cancer patients seen at our supportive care clinic for consultation. We systematically characterized each pain type with the Brief Pain Inventory (BPI) and documented current treatments. The attending physician made the pain diagnoses according to the International Association for the Study of Pain (IASP) task force classification. Among 200 patients (mean age 60 years, 69% metastatic disease, 1-year survival of 77%), the median number of pain diagnosis was 2 (IQR 1-2); 67 (34%, 95% CI 28-41%) had a diagnosis of CNMP; 133 (67%) had cancer-related pain; and 52 (26%) had treatment-related pain. In total, 12/31 (39%) patients with only CNMP and 21/36 (58%) patients with CNMP and other pain diagnoses were on opioids. There was a total of 94 CNMP diagnoses among 67 patients, including 37 (39%) osteoarthritis and 20 (21%) lower back pain; 30 (32%) were treated with opioids. In summary, CNMP was common in the timely palliative care setting and many patients were on opioids. Our findings highlight the need to develop clinical guidelines for CNMP in cancer patients to standardize its management.
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http://dx.doi.org/10.3390/cancers12010214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016539PMC
January 2020

Factors Associated with Improvement in Uncontrolled Cancer Pain without Increasing the Opioid Daily Dose among Patients Seen by an Inpatient Palliative Care Team.

J Palliat Med 2020 04 5;23(4):483-488. Epub 2019 Nov 5.

Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Increasing the total opioid dose is the standard approach for managing uncontrolled cancer pain. Other than simply increasing the opioid dose, palliative care interventions are multidimensional and may improve pain control in the absence of opioid dose increase. The purpose of this study was to determine the proportion of patients referred to our inpatient palliative care (IPC) team who achieved clinically improved pain (CIP) without opioid dose increase. We reviewed consecutive patients referred to our IPC team. Eligibility criteria included (1) taking opioid medication; (2) having ≥2 consecutive visits with the IPC team; and (3) an Edmonton Symptom Assessment Scale (ESAS) pain score ≥4 at consultation. We assessed patient demographics and clinical variables, including cancer type, opioid prescription data (type, route, and oral morphine equivalent daily dose [MEDD]), presence of opioid rotation, psychological consultation, changes in adjuvant medications (e.g., corticosteroids; antiepileptics-gabapentin and pregabalin; benzodiazepines; and neuroleptics), and achievement of CIP. Of the 300 patients enrolled, CIP was achieved in 196 (65%) patients. Of CIP patients, 85 (43%) achieved CIP without an increase in MEDD. CIP without MEDD increase was associated with more adjuvant medication changes ( = 0.003), less opioid rotation ( = 0.005), and lower symptom distress scale of ESAS ( = 0.04). Nearly half of the patients achieved CIP without MEDD increase, suggesting that the multidimensional palliative care intervention is effective in improving pain control in many opioid-tolerant patients without the need to increase the opioid dose.
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http://dx.doi.org/10.1089/jpm.2019.0243DOI Listing
April 2020

Urine Drug Testing in Cancer Pain Management.

Authors:
Joseph A Arthur

Oncologist 2019 Oct 11. Epub 2019 Oct 11.

Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA

Urine drug test (UDT) is an effective tool used in chronic opioid therapy to ensure patient adherence to treatment and detect nonmedical opioid use. The two main types of UDT used in routine clinical practice are the screening tests or immunoassays and the confirmatory tests or laboratory-based specific drug identification tests such as gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, or tandem mass spectrometry. UDT produces objective data on some nonmedical opioid use that may otherwise go undetected, such as the use of undisclosed medications, the nonuse of prescribed medications, and the use of illegal drugs. It allows clinicians to initiate an open and effective conversation about nonmedical opioid use with their patients. However, the test has certain limitations that sometimes compromise its use. Its interpretation can be challenging to clinicians because of the complexity of the opioid metabolic pathways. Clear guidelines or recommendations regarding the use of UDT in cancer pain is limited. As a result, UDT appears to be underused among patients with cancer pain receiving opioid therapy. More studies are needed to help standardize the integration and use of UDT in routine cancer pain management. IMPLICATIONS FOR PRACTICE: Despite its potential benefits, urine drug testing (UDT) appears to be underused among patients with cancer pain receiving opioid therapy. This is partly because its interpretation can be challenging owing to the complexity of the opioid metabolic pathways. Information regarding the use of UDT in opioid therapy among patients with cancer is limited. This review article will improve clinician proficiency in UDT interpretation and assist oncologists in developing appropriate treatment plans during chronic opioid therapy.
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http://dx.doi.org/10.1634/theoncologist.2019-0525DOI Listing
October 2019

Concurrent use of opioids with benzodiazepines or nonbenzodiazepine sedatives among patients with cancer referred to an outpatient palliative care clinic.

Cancer 2019 Dec 28;125(24):4525-4531. Epub 2019 Aug 28.

Department of Palliative Care, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The concurrent use of opioids with benzodiazepines (BZD) or nonbenzodiazepine sedatives (S) recently was found to be associated with an increased risk of overdose death compared with the use of opioids alone. In the current study, the authors examined the frequency and trend of concurrent opioid/BZD-S use and its associated risk factors among patients with cancer.

Methods: Data regarding the frequency and trend of concurrent opioid/BZD-S use were extracted for 1500 randomly selected patients referred to the outpatient palliative care clinic at The University of Texas MD Anderson Cancer Center between the calendar years of 2011 and 2016. To explore associated risk factors, the authors compared the demographic and clinical predictors of 418 patients each in the concurrent opioid/BZD-S group and opioids-only group.

Results: In 2011, at the time of referral to the palliative care clinic, 96 of 221 patients with cancer (43%) were prescribed concurrent opioids/BZD-S. This rate progressively declined to 67 of 217 patients (31%) by 2016 (P = .0008). Patients in the concurrent opioid/BZD-S group had a higher percentage of females (233 individuals; 55% [P = .007]) and whites (323 individuals; 77% [P = .002]), and patients reported higher scores regarding depression (P = .0001), anxiety (P ≤ .0001), drowsiness (P = .048), and worst feeling of well-being (P = .001). The morphine equivalent daily dose was significantly higher in concurrent opioid/BZD-S group (median of 67.5 mg/day [interquartile range (IQR), 30-135 mg/day] vs 60 mg/day [IQR, 30-105 mg/day]; P = .034). Multivariate analysis demonstrated that anxiety (P ≤ .0001), white race (P = .0092), and poor Eastern Cooperative Oncology Group performance status (P = .0017) were significantly associated with concurrent use.

Conclusions: The concurrent use of opioids with BZD-S has declined but continues to be frequent among patients with cancer. Anxiety, white race, and poor Eastern Cooperative Oncology Group performance status were associated with its use. More research is needed to explore which medications can replace these agents.
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http://dx.doi.org/10.1002/cncr.32484DOI Listing
December 2019

Extension for Community Healthcare Outcomes-Palliative Care in Africa Program: Improving Access to Quality Palliative Care.

J Glob Oncol 2019 07;5:1-8

University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: There is limited access to quality palliative care (PC) for patients with advanced cancer in sub-Saharan Africa. Our aim was to describe the development of the Project Extension for Community Healthcare Outcomes-Palliative Care in Africa (ECHO-PACA) program and describe a preliminary evaluation of attitudes and knowledge of participants regarding the ability of the program to deliver quality PC.

Methods: An interdisciplinary team at the MD Anderson Cancer Center, guided by experts in PC in sub-Saharan Africa, adapted a standardized curriculum based on PC needs in the region. Participants were then recruited, and monthly telementoring sessions were held for 16 months. The monthly telementoring sessions consisted of case presentations, discussions, and didactic lectures. Program participants came from 14 clinics and teaching hospitals in Ghana, Kenya, Nigeria, South Africa, and Zambia. Participants were surveyed at the beginning, midpoint, and end of the 16-month program to evaluate changes in attitudes and knowledge of PC.

Results: The median number of participants per session was 30. Thirty-three (83%) of 40 initial participants completed the feedback survey. Health care providers' self-reported confidence in providing PC increased with participation in the Project ECHO-PACA clinic. There was significant improvement in the participants' attitudes and knowledge, especially in titrating opioids for pain control ( = .042), appropriate use of non-opioid analgesics ( = .012), and identifying and addressing communication issues related to end-of-life care ( = .014).

Conclusion: Project ECHO-PACA was a successful approach for disseminating knowledge about PC. The participants were adherent to ECHO PACA clinics and the completion of feedback surveys. Future studies should evaluate the impact of Project ECHO-PACA on changes in provider practice as well as patient outcomes.
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http://dx.doi.org/10.1200/JGO.19.00128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776016PMC
July 2019

Practices and perceptions regarding intravenous opioid infusion and cancer pain management.

Cancer 2019 11 10;125(21):3882-3889. Epub 2019 Jul 10.

Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer, Houston, Texas.

Background: In view of the recent opioid crisis, ways to promote safe and effective opioid-related practices are needed. Faster intravenous (iv) opioid infusion rates can result in increased adverse effects and risk for nonmedical opioid use. Data on best practices regarding safe iv opioid administration for cancer pain are limited. This study examined iv opioid bolus infusion practices and perceptions about opioids in cancer pain among 4 groups of inpatient oncology nurses.

Methods: An anonymous cross-sectional survey was conducted among oncology nurses working in medical, surgical, intensive care unit (ICU), and emergency department (ED) settings. An iv opioid bolus infusion speed less than 120 seconds was considered too fast.

Results: The participant response rate was 59% (731 of 1234). Approximately 58%, 54%, and 58% of all nurses administered morphine, hydromorphone, and fentanyl, respectively, in less than 120 seconds. The median morphine infusion speeds were 55, 60, 60, and 85 seconds for ICU, surgical, ED, and medical unit nurses, respectively (P = .0002). The odds ratios for infusing too fast were 2.04 and 2.52 for ED (P = .039) and ICU nurses (P = .003), respectively, in comparison with medical unit nurses, and they were 0.27 and 0.18 with frequent (P = .003) and very frequent use of a timing device (P = .0001), respectively, in comparison with no use.

Conclusions: More than half the nurses working in the inpatient setting reported administering iv opioids too fast. ICU nurses administered opioids the fastest. Nurses who frequently used a timing device were less likely to infuse too fast. Further research is needed to standardize and improve the safe intermittent administration of iv opioids to patients with cancer.
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http://dx.doi.org/10.1002/cncr.32380DOI Listing
November 2019

Transjugular Portosystemic Shunt Reductions: A Retrospective Single-Center Experience.

J Vasc Interv Radiol 2019 Jun;30(6):876-884

Department of Interventional Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.

Purpose: To report the results of transjugular intrahepatic portosystemic shunt (TIPS) reductions for hepatic encephalopathy (HE), acute liver failure (ALF), and pulmonary hypertension (PH).

Materials And Methods: A single-institution retrospective review analysis was performed between 2007 and 2017 on patients undergoing TIPS reduction at single tertiary liver transplant center. A total of 27 patients (14 males and 13 females) underwent TIPS reduction for refractory HE (n = 18), ALF (n = 7), and PH (n = 2). The average age at time of reduction was 59 years (range, 23-73; standard deviation [SD], 8). Mean prereduction Model of End-State Liver Disease-Na and portosystemic pressure gradient were 19 (range, 11-29; SD, 6) and 9.4 mm Hg (range, -2 to 19; SD, 4.8), respectively. Comparison between responders and nonresponders was performed for multiple variables using a 2-tailed t test. Methods of reduction were compared in cases of HE.

Results: Technical success, defined as a decrease of at least 50% of the caliber of the shunt, was 100%. Clinical success rates in improving HE, ALF, and PH were calculated at 89%, 71%, and 100%, respectively. Eight patients had major and 10 had minor complications after the reductions. There were 3 shunt thrombosis. Pre- and postreduction Model of End-State Liver Disease-Na, portosystemic pressure gradient change, duration of indwelling TIPS, and reduction method were not significantly different between responders and nonresponders. Six-month survival rates were 80%, 20%, and 100% for HE, ALF, and PH, respectively.

Conclusions: TIPS reduction is effective in reversing refractory HE, ALF, and PH after TIPS creation. TIPS reduction is associated with a high rate of complications and should be reserved for severe refractory overshunting complications.
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http://dx.doi.org/10.1016/j.jvir.2019.01.031DOI Listing
June 2019

Opioid Prescribing in an Opioid Crisis: What Basic Skills Should an Oncologist Have Regarding Opioid Therapy?

Curr Treat Options Oncol 2019 04 1;20(5):39. Epub 2019 Apr 1.

Department of Palliative, Rehabilitation, & Integrative Medicine, The University of Texas MD Anderson Cancer, Unit 1414, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.

Opinion Statement: Although clinical evidence supports the use of opioids for cancer-related pain, doing so amidst the current opioid crisis remains a challenge. A proportion of opioid-related deaths in the USA are attributable to prescription opioids, which implicates health care providers as one of the major contributors. It is therefore even more important now for all clinicians to follow safe and effective opioid prescribing practices. Oncologists are often in the frontline of cancer pain management. They are encouraged to use validated tools to screen all patients receiving opioids for high risk behaviors. Those identified as high risk for potential abuse of opioids should be monitored closely. When aberrant behavior is detected, the clinician will need to openly discuss the issue and its possible implications. Oncologists may then implement measures such as limiting the dose and quantity of opioids prescribed, shortening interval between follow-ups for refills to allow for increased monitoring, setting boundaries/limitations, weaning off opioid analgesics, or/and referring to a pain or palliative medicine or drug addiction expert for co-management when necessary. These efforts may aid oncologists in safely managing cancer pain in the environment of national opioid crisis.
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http://dx.doi.org/10.1007/s11864-019-0636-3DOI Listing
April 2019

Implications of the Parenteral Opioid Shortage for Prescription Patterns and Pain Control Among Hospitalized Patients With Cancer Referred to Palliative Care.

JAMA Oncol 2019 Jun;5(6):841-846

Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston.

Importance: The recent parenteral opioid shortage (POS) has potential implications for cancer-related pain management in hospitalized patients.

Objective: This study compared changes in opioid prescriptions and clinically improved pain (CIP) among patients treated by an inpatient palliative care (PC) team before and after our institution first reported the POS.

Design, Setting, And Participants: A cohort study of 386 eligible patients with cancer treated at a comprehensive cancer center 1 month before and after the announcement of the POS. We reviewed data from electronic health records, including patient demographics, opioid type, route of administration, and dose. Board-certified palliative care specialists assessed CIP at follow-up day 1.

Exposures: The announcement of the POS by the institution's pharmacy and therapeutics committee on February 8, 2018.

Main Outcomes And Measures: The primary outcome was to measure the change in opioid prescription patterns of physicians, and the secondary outcome was to measure the proportion of patients who achieved CIP before and after announcement of the POS.

Results: Of 386 eligible patients, 196 were men (51%), 270 were white (70%), and the median age was 58 years (interquartile range, 46-67 years). Parenteral opioids were prescribed less frequently by the referring oncology teams after the POS (56 of 314 [18%]) vs before the POS (109 of 311 [35%]) (P < .001). The PC team also prescribed fewer parenteral opioids after the POS (96 of 336 [29%]) vs before the POS (159 of 338 [47%]) (P < .001). After the POS (vs before the POS), significantly fewer patients achieved CIP on follow-up day 1 (119 [62%] vs 144 [75%] of 193; P = .01). Multivariate analysis showed that before the POS, patients had an 89% higher chance of achieving CIP on follow-up day 1 (odds ratio, 1.89; 95% CI, 1.22-2.94; P = .005).

Conclusions And Relevance: There was a significant change in opioid prescription patterns associated with the POS. Furthermore, after the POS, fewer patients achieved CIP. These factors have potential implications for patient satisfaction and hospital length of stay.
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http://dx.doi.org/10.1001/jamaoncol.2019.0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567824PMC
June 2019

Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2.

Nucleic Acids Res 2019 05;47(8):3846-3861

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.

HepG2 is one of the most widely used human cancer cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher order genomic structural features are largely unknown. The high degree of aneuploidy in HepG2 renders traditional genome variant analysis methods challenging and partially ineffective. Correct and complete interpretation of the extensive functional genomics data from HepG2 requires an understanding of the cell line's genome sequence and genome structure. Using a variety of sequencing and analysis methods, we identified a wide spectrum of genome characteristics in HepG2: copy numbers of chromosomal segments at high resolution, SNVs and Indels (corrected for aneuploidy), regions with loss of heterozygosity, phased haplotypes extending to entire chromosome arms, retrotransposon insertions and structural variants (SVs) including complex and somatic genomic rearrangements. A large number of SVs were phased, sequence assembled and experimentally validated. We re-analyzed published HepG2 datasets for allele-specific expression and DNA methylation and assembled an allele-specific CRISPR/Cas9 targeting map. We demonstrate how deeper insights into genomic regulatory complexity are gained by adopting a genome-integrated framework.
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http://dx.doi.org/10.1093/nar/gkz169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486628PMC
May 2019

Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562.

Genome Res 2019 03 8;29(3):472-484. Epub 2019 Feb 8.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.

K562 is widely used in biomedical research. It is one of three tier-one cell lines of ENCODE and also most commonly used for large-scale CRISPR/Cas9 screens. Although its functional genomic and epigenomic characteristics have been extensively studied, its genome sequence and genomic structural features have never been comprehensively analyzed. Such information is essential for the correct interpretation and understanding of the vast troves of existing functional genomics and epigenomics data for K562. We performed and integrated deep-coverage whole-genome (short-insert), mate-pair, and linked-read sequencing as well as karyotyping and array CGH analysis to identify a wide spectrum of genome characteristics in K562: copy numbers (CN) of aneuploid chromosome segments at high-resolution, SNVs and indels (both corrected for CN in aneuploid regions), loss of heterozygosity, megabase-scale phased haplotypes often spanning entire chromosome arms, structural variants (SVs), including small and large-scale complex SVs and nonreference retrotransposon insertions. Many SVs were phased, assembled, and experimentally validated. We identified multiple allele-specific deletions and duplications within the tumor suppressor gene Taking aneuploidy into account, we reanalyzed K562 RNA-seq and whole-genome bisulfite sequencing data for allele-specific expression and allele-specific DNA methylation. We also show examples of how deeper insights into regulatory complexity are gained by integrating genomic variant information and structural context with functional genomics and epigenomics data. Furthermore, using K562 haplotype information, we produced an allele-specific CRISPR targeting map. This comprehensive whole-genome analysis serves as a resource for future studies that utilize K562 as well as a framework for the analysis of other cancer genomes.
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http://dx.doi.org/10.1101/gr.234948.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396411PMC
March 2019

Palliative Care for Patients With Opioid Misuse.

JAMA 2019 02;321(5):511

Department of Palliative Care, Rehabilitation, and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston.

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http://dx.doi.org/10.1001/jama.2018.18640DOI Listing
February 2019

A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis.

Nat Genet 2019 02 14;51(2):267-276. Epub 2019 Jan 14.

deCODE genetics/Amgen Inc., Reykjavik, Iceland.

Nasal polyps (NP) are lesions on the nasal and paranasal sinus mucosa and are a risk factor for chronic rhinosinusitis (CRS). We performed genome-wide association studies on NP and CRS in Iceland and the UK (using UK Biobank data) with 4,366 NP cases, 5,608 CRS cases, and >700,000 controls. We found 10 markers associated with NP and 2 with CRS. We also tested 210 markers reported to associate with eosinophil count, yielding 17 additional NP associations. Of the 27 NP signals, 7 associate with CRS and 13 with asthma. Most notably, a missense variant in ALOX15 that causes a p.Thr560Met alteration in arachidonate 15-lipoxygenase (15-LO) confers large genome-wide significant protection against NP (P = 8.0 × 10, odds ratio = 0.32; 95% confidence interval = 0.26, 0.39) and CRS (P = 1.1 × 10, odds ratio = 0.64; 95% confidence interval = 0.55, 0.75). p.Thr560Met, carried by around 1 in 20 Europeans, was previously shown to cause near total loss of 15-LO enzymatic activity. Our findings identify 15-LO as a potential target for therapeutic intervention in NP and CRS.
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http://dx.doi.org/10.1038/s41588-018-0314-6DOI Listing
February 2019

Extensive and deep sequencing of the Venter/HuRef genome for developing and benchmarking genome analysis tools.

Sci Data 2018 12 18;5:180261. Epub 2018 Dec 18.

Department of Psychiatry and Behavioral Sciences, Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.

We produced an extensive collection of deep re-sequencing datasets for the Venter/HuRef genome using the Illumina massively-parallel DNA sequencing platform. The original Venter genome sequence is a very-high quality phased assembly based on Sanger sequencing. Therefore, researchers developing novel computational tools for the analysis of human genome sequence variation for the dominant Illumina sequencing technology can test and hone their algorithms by making variant calls from these Venter/HuRef datasets and then immediately confirm the detected variants in the Sanger assembly, freeing them of the need for further experimental validation. This process also applies to implementing and benchmarking existing genome analysis pipelines. We prepared and sequenced 200 bp and 350 bp short-insert whole-genome sequencing libraries (sequenced to 100x and 40x genomic coverages respectively) as well as 2 kb, 5 kb, and 12 kb mate-pair libraries (49x, 122x, and 145x physical coverages respectively). Lastly, we produced a linked-read library (128x physical coverage) from which we also performed haplotype phasing.
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http://dx.doi.org/10.1038/sdata.2018.261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298255PMC
December 2018

Balancing opioid analgesia with the risk of nonmedical opioid use in patients with cancer.

Nat Rev Clin Oncol 2019 04;16(4):213-226

Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer, Houston, TX, USA.

The current opioid crisis has brought renewed attention and scrutiny to opioid prescriptions. When patients receiving opioid therapy for pain engage in nonmedical opioid use (NMOU) or diversion, untoward consequences can occur. New evidence suggests that patients with cancer might be at a higher risk of NMOU than was previously thought, but clinical evidence still supports the use of opioid analgesics as the gold standard to treat cancer-related pain, creating a dilemma in patient management. Clinicians are encouraged to adopt a universal precautions approach to patients with cancer receiving opioids, which includes screening all patients; discussing the risks, benefits, adverse effects and alternatives of opioid therapy; and providing education on safe use, storage and disposal. Use of urine drug tests, prescription drug monitoring programmes and close observation of behaviours related to opioid use help to ensure treatment adherence, detect NMOU and support therapeutic decision-making. These measures can optimize the risk-benefit ratio while supporting safe opioid use. In this Review, we examine the role of opioids in cancer pain, the risk of substance use disorder and methods to achieve the right balance between the two in order to ensure safe opioid use.
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http://dx.doi.org/10.1038/s41571-018-0143-7DOI Listing
April 2019

Frequency and characteristics of drowsiness, somnolence, or daytime sleepiness in patients with advanced cancer.

Palliat Support Care 2019 08;17(4):459-463

Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Introduction: Cancer-related drowsiness (CRD) is a distressing symptom in advanced cancer patients (ACP). The aim of this study was to determine the frequency and factors associated with severity of CRD. We also evaluated the screening performance of Edmonton Symptom Assessment Scale-drowsiness (ESAS-D) item against the Epworth Sedation Scale (ESS).

Method: We prospectively assessed 180 consecutive ACP at a tertiary cancer hospital. Patients were surveyed using ESAS, ESS, Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Hospital Anxiety Depression Scale.

Result: Ninety of 150 evaluable patients had clinically significant CRD (ESS); median (interquartile ratio): ESS. 11 (7-14); ESAS-D. 5 (2-6); Pittsburgh Sleep Quality Index. 8 (5-11); Insomnia Severity Index. 13 (5-19); Stop Bang Scoring 3 (2-4), and Hospital Anxiety Depression Scale-D 6 (3-10). ESAS-D was associated with ESAS (r, p) sleep (0.38, <0.0001); pain (0.3, <0.0001); fatigue (0.51, <0.0001); depression (0.39, <0.0001); anxiety (0.44, <0.0001); shortness of breath (0.32, <0.0001); anorexia (0.36, <0.0001), feeling of well-being [(0.41, <0.0001), ESS (0.24, 0.001), and opioid daily dose (0.19, 0.01). Multivariate-analysis showed ESAS-D was associated with fatigue (odds ratio [OR] = 9.08, p < 0.0001), anxiety (3.0, p = 0.009); feeling of well-being (OR = 2.27, p = 0.04), and insomnia (OR = 2.35; p = 0.036). Insomnia (OR = 2.35; p = 0.036) cutoff score ≥3 (of 10) resulted in a sensitivity of 81% and 32% and specificity of 70% and 44% in the training and validation samples, respectively.

Significance Of Results: Clinically significant CRD is frequent and seen in 50% of ACP. CRD was associated with severity of insomnia, fatigue, anxiety, and worse feeling of well-being. An ESAS-D score of ≥3 is likely to identify most of the ACP with significant CRD.
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http://dx.doi.org/10.1017/S1478951518000779DOI Listing
August 2019

Sequence variants associating with urinary biomarkers.

Hum Mol Genet 2019 04;28(7):1199-1211

Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Urine dipstick tests are widely used in routine medical care to diagnose kidney and urinary tract and metabolic diseases. Several environmental factors are known to affect the test results, whereas the effects of genetic diversity are largely unknown. We tested 32.5 million sequence variants for association with urinary biomarkers in a set of 150 274 Icelanders with urine dipstick measurements. We detected 20 association signals, of which 14 are novel, associating with at least one of five clinical entities defined by the urine dipstick: glucosuria, ketonuria, proteinuria, hematuria and urine pH. These include three independent glucosuria variants at SLC5A2, the gene encoding the sodium-dependent glucose transporter (SGLT2), a protein targeted pharmacologically to increase urinary glucose excretion in the treatment of diabetes. Two variants associating with proteinuria are in LRP2 and CUBN, encoding the co-transporters megalin and cubilin, respectively, that mediate proximal tubule protein uptake. One of the hematuria-associated variants is a rare, previously unreported 2.5 kb exonic deletion in COL4A3. Of the four signals associated with urine pH, we note that the pH-increasing alleles of two variants (POU2AF1, WDR72) associate significantly with increased risk of kidney stones. Our results reveal that genetic factors affect variability in urinary biomarkers, in both a disease dependent and independent context.
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http://dx.doi.org/10.1093/hmg/ddy409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423415PMC
April 2019
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