Publications by authors named "Kristy Nguyen"

17 Publications

  • Page 1 of 1

Robotic microsurgical spermatic cord denervation for chronic orchialgia: a case series.

J Osteopath Med 2021 Jan;121(1):29-34

Department of Urology , University of Louisville School of Medicine , 501 E. Broadway, Suite 270 , 40202-2040 Louisville , KY , USA.

Context: Chronic orchialgia is a frustrating urologic condition that is commonly refractory to conservative modes of therapy. Microscopic spermatic cord denervation is a proven solution for patients who do not achieve relief from nonsurgical treatments. However, current widely used techniques require additional training in microsurgery.

Objective: To describe an adaptation and improvement of spermatic cord microdenervation technique that leveraged the robotic surgical training common for new urologists and is also accessible for urologists not specifically trained in microsurgery.

Methods: Robotic-assisted microdenervation of the spermatic cord was performed in three patients using a fluorescence vascular imaging tool to improve visualization of vascular structures (Firefly™; Innovative Surgical, Sunnyvale, CA, USA), along with a tissue matrix allograft to allow for better healing (AminoFix™; MiMedx®, Marietta, GA, USA).

Results: All three patients (100%) experienced postoperative resolution of their chronic orchialgia, and none reported any new pain.

Conclusion: Utilization of robotic-assisted surgery offers more urologists the ability to use familiar techniques to treat chronic orchialgia when conservative measures are unsuccessful.
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http://dx.doi.org/10.1515/jom-2020-0176DOI Listing
January 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

Diagnostic molecular markers predicting aggressive potential in low-grade prostate cancer.

Transl Res 2021 05 3;231:92-101. Epub 2020 Dec 3.

Department of Urology, University of Louisville, Louisville, KY. Electronic address:

Currently, clinicians rely on clinical nomograms to stratify progression risk at the time of diagnosis in patients with prostate cancer (CaP). However, these tools may not accurately distinguish aggressive potential in low-grade CaP. The current study determined the diagnostic potential of 3 molecular markers (ROCK1, RUNX3, and miR-301a) in terms of their ability to identify which low-grade tumors are likely to progress. Real-time PCR and immunohistochemical analysis were used to assess ROCK1, RUNX3, and miR-301a expression profiles in 118 serum and needle biopsy specimens. Expressions of ROCK1 and miR-301a were found to be significantly higher in Gleason 6 and 7 CaP as compared to BPH, while an inverse trend was observed with RUNX3. Further, incorporation of all 3 molecular markers significantly improved clinical nomograms' diagnostic accuracy and correlated with disease progression. Hence, in conclusion, the inclusion of these 3 molecular markers identified aggressive phenotype and predicted disease progression in low-grade CaP tumors at the time of diagnosis.
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http://dx.doi.org/10.1016/j.trsl.2020.11.014DOI Listing
May 2021

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

Cancer 2021 03 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

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

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

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

Attitudes and Beliefs About Medical Usefulness and Legalization of Marijuana among Cancer Patients in a Legalized and a Nonlegalized State.

J Palliat Med 2019 10 6;22(10):1213-1220. Epub 2019 Aug 6.

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

There is a growing preference for the use of marijuana for medical purposes, despite limited evidence regarding its benefits and potential safety risks. Legalization status may play a role in the attitudes and preferences toward medical marijuana (MM). The attitudes and beliefs of cancer patients in a legalized (Arizona) versus nonlegalized state (Texas) regarding medical and recreational legalization and medical usefulness of marijuana were compared. Two hundred adult cancer patients were enrolled from outpatient Palliative Care centers at Banner MD Anderson Cancer Center in Gilbert, AZ ( = 100) and The University of Texas MD Anderson Cancer Center in Houston, TX ( = 100). Adult cancer patients seen by the Palliative Care teams in the outpatient centers were evaluated. Various physical and psychosocial assessments were conducted, including a survey of attitudes and beliefs toward marijuana. The majority of individuals support legalization of marijuana for medical use (Arizona 92% [85-97%] vs. Texas 90% [82-95%];  = 0.81) and belief in its medical usefulness (Arizona 97% [92-99%] vs. Texas 93% [86-97%];  = 0.33) in both states. Overall, 181 (91%) patients supported legalization for medical purposes whereas 80 (40%) supported it for recreational purposes ( < 0.0001). Patients preferred marijuana over current standard treatments for anxiety (60% [51-68%];  = 0.003). Patients found to favor legalizing MM were younger ( = 0.027), had worse fatigue ( = 0.015), appetite ( = 0.004), anxiety ( = 0.017), and were Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs (CAGE-AID) positive for alcohol/drugs ( < 0.0001). Cancer patients from both legalized and nonlegalized states supported legalization of marijuana for medical purposes and believed in its medical use. The support for legalization for medical use was significantly higher than for recreational use in both states.
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http://dx.doi.org/10.1089/jpm.2019.0218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364300PMC
October 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

Patterns of Opioid Prescription, Use, and Costs Among Patients With Advanced Cancer and Inpatient Palliative Care Between 2008 and 2014.

J Oncol Pract 2019 01 29;15(1):e74-e83. Epub 2018 Nov 29.

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

Purpose: An understanding of opioid prescription and cost patterns is important to optimize pain management for patients with advanced cancer. This study aimed to determine opioid prescription and cost patterns and to identify opioid prescription predictors in patients with advanced cancer who received inpatient palliative care (IPC).

Materials And Methods: We reviewed data from 807 consecutive patients with cancer who received IPC in each October from 2008 through 2014. Patient characteristics; opioid types; morphine equivalent daily dose (MEDD) in milligrams per day of scheduled opioids before, during, and after hospitalization; and in-admission opioid cost per patient were assessed. We determined symptom changes between baseline and follow-up palliative care visits and the in-admission opioid prescription predictors.

Results: A total of 714 (88%) of the 807 patients were evaluable. The median MEDD per patient decreased from 150 mg/d in 2008 to 83 mg/d in 2014 ( P < .001). The median opioid cost per patient decreased and then increased from $22.97 to $40.35 over the 7 years ( P = .03). The median MEDDs increased from IPC to discharge by 67% ( P < .001). The median Edmonton Symptom Assessment Scale pain improvement at follow-up was 1 ( P < .001). Younger patients with advanced cancer (odds ratio [OR[, 0.95; P < . 001) were prescribed higher preadmission MEDDs (OR, 1.01; P < .001) more often in the earlier study years (2014 v 2009: OR, 0.18 [ P = .004] v 0.30 [ P = .02]) and tended to use high MEDDs (> 75 mg/d) during hospitalization.

Conclusion: The MEDD per person decreased from 2008 to 2014. The opioid cost per patient decreased from 2008 to 2011 and then increased from 2012 to 2014. Age, prescription year, and preadmission opioid doses were significantly associated with opioid doses prescribed to patients with advanced cancer who received IPC.
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http://dx.doi.org/10.1200/JOP.18.00205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333384PMC
January 2019

Predicting the risk for aberrant opioid use behavior in patients receiving outpatient supportive care consultation at a comprehensive cancer center.

Cancer 2018 10 7;124(19):3942-3949. Epub 2018 Sep 7.

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

Background: Opioid misuse is a growing crisis. Patients with cancer who are at risk of aberrant drug behaviors are frequently underdiagnosed. The primary objective of this study was to determine the frequency and factors predicting a risk for aberrant opioid and drug use behaviors (ADB) among patients who received an outpatient supportive care consultation at a comprehensive cancer center. In addition, the screening performance of the Cut Down-Annoyed-Guilty-Eye Opener (CAGE) questionnaire adapted to include drug use (CAGE-AID) was compared with that of the 14-item Screener and Opioid Assessment for Patients With Pain (SOAPP-14) tool as instruments for identifying patients at risk for ADB.

Methods: In total, 751 consecutive patients with cancer who were referred to a supportive care clinic were reviewed. Patients were eligible if they had diagnosis of cancer and had received opioids for pain for at least 1 week. All patients were assessed using the Edmonton Symptom Assessment Scale (ESAS), the SOAPP-14, and the CAGE-AID. SOAPP scores ≥7 (SOAPP-positive) were used to identify patients who were at risk of ADB.

Results: Among the 729 of 751 (97%) evaluable consults, 143 (19.6%) were SOAPP-positive, and 73 (10.5%) were CAGE-AID-positive. Multivariate analysis revealed that the odds ratio of a positive SOAPP score was 2.3 for patients who had positive CAGE-AID scores (P < .0001), 2.08 for men (P = .0013), 1.10 per point for ESAS pain (P = .014), 1.13 per point for ESAS anxiety (P = .0015), and 1.09 per point for ESAS financial distress (P = .012). A CAGE-AID cutoff score of 1 in 4 had 43.3% sensitivity and 90.93% specificity for screening patients with a high risk of ADB.

Conclusions: The current results indicate a high frequency of an elevated risk of ADB among patients with cancer. Men and patients who have anxiety, financial distress, and a prior history of alcoholism/illicit drug use are at increased risk of ADB.
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http://dx.doi.org/10.1002/cncr.31670DOI Listing
October 2018

Effects of primary care physician density, urologist presence, and insurance status on stage of diagnosis for urologic malignancies.

Cancer Epidemiol 2018 02 13;52:10-14. Epub 2017 Nov 13.

Department of Urology, University of Oklahoma HSC, Oklahoma City, OK, United States. Electronic address:

Objective: To evaluate effects of PCP density, insurance status, and urologist presence on stage of diagnosis for urologic malignancies. Cancer stage at diagnosis is an important outcome predictor. Studies have shown an inverse relationship to primary care physician (PCP) density and insurance coverage with stage of cancer diagnosis.

Methods: Data was obtained from OK2Share, an Oklahoma Central Cancer Registry, for bladder, kidney, and prostate cancer from 2000 to 2010. Physician data was obtained through the State Licensing Board. The 2010 national census was used for population data. High PCP density was defined as greater than or equal to the median value: 3.17 PCP/10,000 persons. Chi-square and multivariate logistic regressions were used to analyze effects of PCP density, insurance status, and urologist presence on advanced stage diagnosis.

Results: 27,086 patients were identified across 77 counties. As PCP density increased by 1 PCP/10,000 persons, the odds ratios (OR) of an advanced stage at diagnosis were 0.383, 0.468, 0.543 for bladder, kidney, and prostate cancer respectively. Compared to private insurance, being uninsured had OR of 1.61 and 2.45 respectively for kidney and prostate cancers. The OR of an advanced stage diagnosis for bladder and prostate cancer were 3.77 and 1.73, respectively, in counties with a urologist.

Conclusions: Increased PCP density and insurance coverage reduced the odds of an advanced diagnosis. Implementation of policies to improve access to healthcare including through increasing PCP density and reducing the number of uninsured patients should result in diagnosis at an earlier stage, which will likely improved cancer-related outcomes.
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http://dx.doi.org/10.1016/j.canep.2017.10.012DOI Listing
February 2018

Outcomes of a Specialized Interdisciplinary Approach for Patients with Cancer with Aberrant Opioid-Related Behavior.

Oncologist 2018 02 11;23(2):263-270. Epub 2017 Oct 11.

Department of Palliative Care and Rehabilitation Medicine, Houston, Texas, USA.

Background: Data on the development and outcomes of effective interventions to address aberrant opioid-related behavior (AB) in patients with cancer are lacking. Our outpatient supportive care clinic developed and implemented a specialized interdisciplinary team approach to manage patients with AB. The purpose of this study was to report clinical outcomes of this novel intervention.

Materials And Methods: The medical records of 30 consecutive patients with evidence of AB who received the intervention and a random control group of 70 patients without evidence of AB between January 1, 2015, and August 31, 2016, were reviewed.

Results: At baseline, pain intensity ( = .002) and opioid dose ( = .001) were significantly higher among patients with AB. During the course of the study, the median number of ABs per month significantly decreased from three preintervention to 0.4 postintervention ( < .0001). The median morphine equivalent daily dose decreased from 165 mg/day at the first intervention visit to 112 mg/day at the last follow-up ( = .018), although pain intensity did not significantly change ( = .984). "Request for opioid medication refills in the clinic earlier than the expected time" was the AB with the highest frequency prior to the intervention and the greatest improvement during the study period. Younger age ( < .0001) and higher Edmonton Symptom Assessment System anxiety score ( = .005) were independent predictors of the presence of AB.

Conclusion: The intervention was associated with a reduction in the frequency of AB and opioid utilization among patients with cancer receiving chronic opioid therapy. More research is needed to further characterize the clinical effectiveness of this intervention.

Implications For Practice: There are currently no well-defined and evidence-based strategies to manage cancer patients on chronic opioid therapy who demonstrate aberrant opioid-related behavior. The findings of this study offer a promising starting point for the creation of a standardized strategy for clinicians and provides valuable information to guide their practice regarding these patients. The study results will also help clinicians to better understand the types and frequencies of the most common aberrant behaviors observed among patients with cancer who are receiving chronic opioid therapy. This will enhance the process of timely patient identification, management, or referral to the appropriate specialist teams.
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http://dx.doi.org/10.1634/theoncologist.2017-0248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813743PMC
February 2018

Functional constraints on SoxE proteins in neural crest development: The importance of differential expression for evolution of protein activity.

Dev Biol 2016 10 5;418(1):166-178. Epub 2016 Aug 5.

Department of Biology, University of Oklahoma, 730 Van Vleet Oval, Norman, OK, USA. Electronic address:

Vertebrate SoxE genes (Sox8, 9, and 10) are key regulators of neural crest cell (NCC) development. These genes arose by duplication from a single SoxE gene in the vertebrate ancestor. Although SoxE paralogs are coexpressed early in NCC development, later, Sox9 is restricted to skeletogenic lineages in the head, and Sox10 to non-skeletogenic NCC in the trunk and head. When this subfunctionalization evolved and its possible role in the evolution of the neural crest are unknown. Sea lampreys are basal vertebrates that also possess three SoxE genes, while only a single SoxE is present in the cephalochordate amphioxus. In order to address the functional divergence of SoxE genes, and to determine if differences in their biochemical functions may be linked to changes in neural crest developmental potential, we examined the ability of lamprey and amphioxus SoxE genes to regulate differentiation of NCC derivatives in zebrafish colourless (cls) mutants lacking expression of sox10. Our findings suggest that the proto-vertebrate SoxE gene possessed both melanogenic and neurogenic capabilities prior to SoxE gene duplication. Following the agnathan-gnathostome split, lamprey SoxE1 and SoxE3 largely lost their melanogenic and/or enteric neurogenic properties, while gnathostome SoxE paralogs have retained functional conservation. We posit that this difference in protein subfunctionalization is a direct consequence of the independent regulation of SoxE paralog expression between the two lineages. Specifically, we propose that the overlapping expression of gnathostome SoxE paralogs in early neural crest largely constrained the function of gnathostome SoxE proteins. In contrast, the largely non-overlapping expression of lamprey SoxE paralogs allowed them to specialize with regard to their DNA-binding and/or protein interaction properties. Restriction of developmental potential among cranial and trunk neural crest in lampreys may be related to constraints on SoxE activity among duplicates, but such specialization does not appear to have occurred in gnathostomes. This highlights an important difference in the evolution of SoxE activity between these two divergent vertebrate lineages and provides insights for understanding how cell fate restriction in different NCC populations may be dependent on subfunctionalization among SoxE duplicates.
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http://dx.doi.org/10.1016/j.ydbio.2016.07.022DOI Listing
October 2016

A theoretical and empirical framework for constructing culture-specific stigma instruments for Chile.

Cad Saude Colet 2013 ;21(1):71-79

Assistant Professor at Department of Epidemiology, Columbia University - New York, NY, USA.

Different cultural contexts contribute to substantial variation in the stigma faced by people with psychosis globally. We propose a new formulation of how culture affects stigma to create psychometrically-validated tools to assess stigma's culture-specific effects. We propose to construct culture-specific stigma measures for the Chilean context via: 1) open-ended administration of 'universal' stigma scales to a sample of individuals with psychosis, relatives, and community respondents; 2) qualitative analyses to identify how culture shapes stigma and to derive initial 'culture-specific' stigma items; 3) construction and pilot-testing of final 'culture-specific' stigma measures; 4) initial psychometric validation among a sample of individuals with psychosis. We identify initial hypotheses for how stigma might threaten the capacities to participate in fundamental activities that 'matter most' in the Chilean context. These include mental illness stigma threatening the man's ability to protect the honor of the family, and the woman's ability to be a 'holy and pure' mother. Mental illness stigma may further endanger the ability of the family to uphold reciprocal obligations within their social network. Developing such measures promises to aid efforts to address culture-specific forms of stigma, and to facilitate implementation of community mental health services, in Chile and other Latin American contexts.
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http://dx.doi.org/10.1590/s1414-462x2013000100011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753780PMC
January 2013

GRK2 and Beta-Arrestins in Cardiovascular Disease: Established and Emerging Possibilities for Therapeutic Targeting.

Curr Mol Pharmacol 2011 Jun 15. Epub 2011 Jun 15.

Department of Pharmaceutical, Sciences, Nova Southeastern University College of Pharmacy, 3200 S., University Dr., HPD (Terry) Bldg/Room 1338, Ft. Lauderdale, FL, 33328, USA.

Heptahelical G protein-coupled receptors, such as the -adrenergic and the angiotensin II type 1 receptors, are the most diverse and therapeutically important family of receptors in the human genome, playing major roles in the physiology of various organs/tissues including the heart and blood vessels. Ligand binding activates heterotrimeric G proteins that transmit intracellular signals by regulating effector enzymes or ion channels. G protein signaling is terminated, in large part, by phosphorylation of the agonist-bound receptor by the family of G-protein coupled receptor kinases (GRKs), with GRK2 being its most prominent member, followed by barrestin binding, which uncouples the phosphorylated receptor and G protein and subsequently targets the receptor for internalization. As the receptor-barrestin complex enters the cell, barrestins serve as ligand-regulated scaffolds that recruit a host of intracellular proteins and signal transducers, thus promoting their own wave of signal transduction independently of G-proteins. A large number of preclinical studies in small and large animals over the past several years have pinpointed specific pathophysiologic roles played by these two families of receptor-regulating proteins in various cardiovascular diseases, directly implicating them in disease pathology and suggesting them as potential therapeutic targets. The present review gives an account of what is currently known about the benefits of cardiac and adrenal GRK2 inhibition for cardiovascular disease treatment, and also discusses the exciting new therapeutic possibilities emerging from uncovering the physiological roles of arrestin-mediated signaling in vivo in the cardiovascular system.
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June 2011

Impaired desensitization of a human polymorphic α2B-adrenergic receptor variant enhances its sympatho-inhibitory activity in chromaffin cells.

Cell Commun Signal 2011 Feb 7;9(1). Epub 2011 Feb 7.

Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

Background: α2-adrenergic receptors (ARs) mediate many cellular actions of epinephrine and norepinephrine and inhibit their secretion from adrenal chromaffin cells. Like many other G-protein coupled receptors (GPCRs), they undergo agonist-dependent phopshorylation and desensitization by GPCR Kinases (GRKs), a phenomenon recently shown to play a major role in the sympathetic overdrive that accompanies and aggravates chronic heart failure. A deletion polymorphism in the human α2B-AR gene (Glu301-303) causes impaired agonist-promoted receptor phosphorylation and desensitization in heterologous cell lines. Given the importance of α2-ARs in regulation of catecholamine secretion from chromaffin cells, we sought to investigate, in the present study, the desensitization properties and the sympatho-inhibitory activity of this variant in a chromaffin cell line. For this purpose, we expressed this variant and its wild type counterpart in the well-established chromaffin cell line PC12, and performed receptor phosphorylation and desensitization studies, as well as in vitro catecholamine secretion assays.

Results: Both the agonist-induced phosphorylation and agonist-dependent desensitization of the human Glu301-303 deletion polymorphic α2B-AR are significantly impaired in PC12 cells, resulting in enhanced signaling to inhibition of cholinergic-induced catecholamine secretion in vitro.

Conclusion: This α2B-AR gene polymorphism (Glu301-303 deletion) might confer better protection against conditions characterized and aggravated by sympathetic/catecholaminergic overstimulation in vivo.
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http://dx.doi.org/10.1186/1478-811X-9-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041786PMC
February 2011
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