The Opioid Epidemic
The Complicated Case of Pain Management and Cancer
Weighing the benefits of using opioids to treat cancer-related pain against the risk of abuse is an ongoing challenge in the hematology / oncology community . Douglas E . Brandoff , MD , director of opioid safety and compliance at Dana- Farber Cancer Institute , helps to manage challenging pain-management cases . Together with a host of fellow physicians , he spoke to Massachusetts legislators in 2016 about the topic .
“ We strive to find a balance when caring for our patients with pain . On the one hand , we want to ensure that access to opioid medications is preserved for when clinically appropriate and necessary for treating cancer-related pain ,” he said . “[ But ] we need to be thoughtful about how much we prescribe , and , when appropriate , to try non-opioid pain medications first without automatically turning to opioid therapy .”
To help clinicians limit the opportunities for opioid misuse and abuse when treating patients with cancer-related pain , Dr . Brandoff offers the following advice :
• Use opioid medication agreements : These agreements between providers and patients allow clinicians to request urine samples and conduct other monitoring measures in patients who are prescribed opioids . This is a universal precaution taken whether or not there is evidence of misuse .
• Check prescription monitoring programs : Clinicians should thoroughly review their state ’ s prescription drug monitoring program when prescribing opioids . Such reviews provide valuable information on who is writing a patient ’ s opioid prescriptions and dispensing medications .
• Consider non-opioid pain management : Patients may benefit from non-opioid pain-management methods such as palliative radiation , interventional pain management with nerve block or epidural-based steroid injections , neuropathic pain medications , massage therapy , physical therapy , general exercise , Reiki therapy , or acupuncture .
• Use multidisciplinary care : Clinicians can consult other oncologists or palliative pharmacists to ensure that pain medication will not cause adverse reactions and side effects when combined with certain cancer treatment protocols .
“ Ultimately , our goal is to craft a mosaic of therapeutic options : to call upon nonopioid therapies to the fullest extent possible , to safely prescribe opioids when clinically appropriate , to advocate for preserved access to opioids for cancer pain management , and to identify opportunities to taper medication doses when clinically feasible ,” Dr . Brandoff said .
Source : Dana-Farber Cancer Institute , Pain Management and Cancer : What You Need to Know .
legislation and work continue to evolve and address the opioid crisis , it will be important to keep at the forefront the patients who rely on these drugs to decrease their suffering and promote their function .” — By Leah Lawrence ●
REFERENCES
1 . Centers for Disease Control and Prevention . Opioid Overdose : Understanding the Epidemic . Accessed August 14 , 2017 , from www . cdc . gov / drugoverdose / epidemic / index . html .
2 . Porter J , Jick H . Addiction rare in patients treated with narcotics . N Engl J Med . 1980 ; 302:123 .
3 . U . S . Food and Drug Administration ’ s Center for Drug Evaluation and Research . Memorandum from the FDA Center for Drug Evaluation and Research ’ s Division of Anesthesia , Analgesia , and Rheumatology Products . November 10 , 2008 . Accessed August 28 , 2017 , from www . fda . gov / ohrms / dockets / ac / 08 / briefing / 2008-4395b1-01-FDA . pdf .
4 . The Joint Commission on Accreditation of Healthcare Organizations . Pain assessment and management standards for hospitals , August 1999 .
5 . Leung PTM , Macdonald EM , Dhalla IA , Juurlink DN . A 1980 letter on the risk of opioid addiction . N Engl J Med . 2017 ; 376:2194-5 .
6 . U . S . Food and Drug Administration . Califf , FDA top officials call for
The Challenge of Cytomegalovirus
CMV seropositivity is common in the United States
Cytomegalovirus ( CMV ) is a highly transmissible and prevalent herpesvirus that remains in the body after primary infection . 1 Data from the National Health and Nutrition Examination Survey ( NHANES ) III ( 1988 – 1994 ), a population-based survey meant to be representative of the US population , established that 66.7 % of the adult population aged ≥25 years were CMV seropositive . 1 CMV seroprevalence increases with age , as a study representative of the US population ( 1999 – 2004 ) revealed a CMV seroprevalence of 49.5 % among 20- to 29-year-old patients and 58.0 % among 40- to 49-year-old patients . 2
Hematopoietic stem cell transplant ( HSCT ), solid organ transplant ( SOT ), intensive care unit ( ICU ), and human immunodeficiency virus ( HIV ) - infected patient populations are most frequently affected by CMV infection . The risk of CMV infection and reactivation varies among these patients , with a 50 % to 90 % incidence in HSCT patients , 30 % to 75 % in SOT patients , 25.7 % in HIV-infected patients with a diagnosis of AIDS , and 15 % to 20 % in ICU patients . 3 – 6
The relationship between CMV and the immune response
A bidirectional relationship exists between CMV and the immune system . Impaired immune defenses allow CMV replication and could lead to CMV disease and associated complications . 6 On the other hand , CMV infection can also alter immune defenses against infections and could increase the likelihood of secondary infections , including bacterial and fungal infections , as well as potentially enhance the proinflammatory response . 6 , 7
Risk factors for CMV infection and reactivation
CMV serostatus is a significant risk factor for CMV infection and reactivation and poor prognosis , especially in immunosuppressed patients . In addition , there are multiple risk factors , such as high-dose corticosteroids , acute and chronic GVHD , ICU admission , mechanical ventilation , and sepsis . These risk factors contribute to the overall state of immunosuppression , which can lead to CMV infection and reactivation . 6 , 8 – 12
CMV disease has serious clinical consequences
The development of CMV disease can have serious consequences , including end-organ damage , increased risk of secondary infections ,
6 , 7 , 13 – 16 and mortality .
The clinical impact of CMV can vary significantly by patient type . HSCT patients most commonly manifest CMV disease as pneumonia or gastrointestinal disease . 8 For SOT patients , the transplanted allograft is typically involved if end-organ damage occurs . This has serious clinical consequences as CMV disease has been associated with an increased
ADVERTISEMENT sweeping review of agency opioids policies . Accessed August 14 , 2017 , from www . fda . gov / NewsEvents / Newsroom / PressAnnouncements / ucm484765 . htm .
7 . U . S . Food and Drug Administration . FDA requests removal of Opana ER for risks related to abuse . Accessed August 15 , 2017 , from www . fda . gov / NewsEvents / Newsroom / PressAnnouncements / ucm562401 . htm .
8 . Dowell D , Haegerich TM , Chou R . CDC Guideline for Prescribing Opioids for Chronic Pain — United States , 2016 . MMWR Recomm Rep . 2016 ; 65 ( No . RR-1 ): 1-49 .
9 . Sutradhar R , Lokku A , Barbera L . Cancer survivorship and opioid prescribing rates : a population-based matched cohort study among individuals with and without a prior history of cancer . Cancer . 2017 August 7 . [ Epub ahead of print ]
risk of acute allograft rejection and mortality . 17 In HIV-infected patients with advanced immunosuppression ( CD4 +, < 50 cells / μL ), CMV retinitis is the most common CMV end-organ disease , but since the advance of HAART , CMV end-organ disease has declined by ≥95 %. 14
In addition to end-organ damage , there is an increased risk of secondary opportunistic infections , including bacterial and fungal infections . 7 ICU patients with CMV infection , specifically , were observed to have an increased risk for nosocomial infections . 6 Secondary infections can also have serious clinical consequences , even contributing toward mortality . 16
CMV viremia has also been identified as an independent risk factor for mortality . This was established in a study of 14,153 subjects aged ≥25 years who were tested for CMV and eligible for mortality follow-up on December 31 , 2006 , after being interviewed in NHANES III ( 1988 – 1994 ). CMV seropositivity was associated with all-cause mortality even after adjusting for age , gender , race / ethnicity , country of origin , education level , BMI , smoking status , and diabetes status . 1
Challenges of monitoring CMV
CMV viral load threshold for CMV reactivation or viremia has been difficult to establish due to variability in assay performance with respect to quantitative measurement . 7 , 8 The typical testing methods of DNA PCR , pp65 antigenemia assay , and pp67 mRNA assay perform well , but assay variability is concerning in immunocompromised patients where the viral load can increase rapidly . 8
The optimal strategy for CMV surveillance in posttransplant and severely immunocompromised patients is not well defined . 18 This is particularly important as the significance and role of monitoring varies depending on preventative measures typically used across patient populations . Different CMV monitoring practices are used depending on the current standard of care or guideline recommendations for various patient types . CMV in HSCT and some SOT patients may rely heavily on monitoring for CMV viremia to determine whether preventative measures should be initiated . Weekly monitoring is recommended for HSCT and SOT recipients with either quantitative PCR or detection of CMV RNA . Recommended monitoring is even more rigorous and should continue beyond day 100 posttransplant for HSCT patients who develop acute or chronic GVHD , had an earlier CMV reactivation , or were mismatched or unrelated donor transplants . 7 , 8 , 19 , 20 HIV-infected patients should maintain their CD4 + count in order to prevent CMV disease . 18 Finally , only ICU patients considered at high risk , meaning those with impaired immune systems , are monitored for CMV reactivation . 6
References : 1 . Simanek AM et al . PLoS One . 2011 ; 6 ( 2 ): e16103 . doi : 10.1371 / journal . pone . 0016103 . 2 . Bate SL et al . Clin Infect Dis . 2010 ; 50 ( 11 ): 1439 – 1447 . 3 . Peres RMB et al . BMC Infect Dis . 2010 ; 10:147 . doi : 10.1186 / 1471-2334-10-147 . 4 . van der Bij W , Speich R . Clin Infect Dis . 2001 ; 33 ( suppl 1 ): S32 – S37 . 5 . Wohl DA et al . J Acquir Immune Defic Syndr . 2005 ; 38 ( 5 ): 538 – 544 . 6 . Papazian L et al . Intensive Care Med . 2016 ; 42 ( 1 ): 28 – 37 . 7 . Kotton CN et al . Transplantation . 2013 ; 96 ( 4 ): 333 – 360 . 8 . Boeckh M et al . Biol Blood Marrow Transplant . 2003 ; 9 ( 9 ): 543 – 558 . 9 . Piñana JL et al . Bone Marrow Transplant . 2010 ; 45 ( 3 ): 534 – 542 . 10 . Cohen L et al . Transpl Infect Dis . 2015 ; 17 ( 4 ): 510 – 517 . 11 . Razonable RR , Humar A . Am J Transplant . 2013 ; 13 ( suppl 4 ): 93 – 106 . 12 . Schwarcz L et al . AIDS . 2013 ; 27 ( 4 ): 597 – 605 . 13 . Ljungman P et al . Clin Infect Dis . 2017 ; 64 ( 1 ): 87 – 91 . 14 . Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents . Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents : recommendations from the Centers for Disease Control and Prevention , the National Institutes of Health , and the HIV Medicine Association of the Infectious Diseases Society of America . AIDSinfo website . http :// aidsinfo . nih . gov / contentfiles / lvguidelines / adult _ oi . pdf . Revised November 10 , 2016 . Accessed February 16 , 2017 . 15 . Jabs DA et al . Ophthalmology . 2005 ; 112 ( 5 ): 771 – 779 . 16 . Nichols WG et al . J Infect Dis . 2002 ; 185 ( 3 ): 273 – 282 . 17 . Beam E , Razonable RR . Curr Infect Dis Rep . 2012 ; 14 ( 6 ): 633 – 641 . 18 . Bieniek R et al . Lab Med . 2011 ; 42 ( 6 ): 339 – 343 . 19 . NCCN clinical practical guidelines on oncology ( NCCN Guidelines ® ). https :// www . nccn . org / professionals / physician _ gls / PDF / infections . pdf . Accessed February 16 , 2017 . 20 . Ljungman P et al . https :// www . ebmt . org / Contents / Resources / Library / ECIL / Documents / ECIL % 204 % 20 % 20Update % 202011 % 20CMV . pdf . Accessed February 16 , 2017 .
Learn more about CMV at www . aboutcmv . com .
60 ASH Clinical News
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