Pain Management in Older Adults Before and During the First Year of COVID-19 Pandemic: Prevalence, Trends, and Correlates.

BACKGROUND: There is limited knowledge on whether and how health care access restrictions imposed by the coronavirus disease of 2019 pandemic have affected utilization of both opioid and nonpharmacological treatments among US older adults living with chronic pain. METHODS: We compared prevalence of chronic pain and high impact chronic pain (ie, chronic pain limiting life or work activities on most days or every day in the past 6 months) between 2019 (pre-pandemic) and 2020 (first year of pandemic) and utilization of opioids and nonpharmacological pain treatments among adults aged ≥65 years enrolled in the National Health Interview Survey, a nationally representative sample of noninstitutionalized civilian U.S. adults. RESULTS: Of 12 027 survey participants aged ≥65 (representing 32.6 million noninstitutionalized older adults nationally), the prevalence of chronic pain was not significantly different from 2019 (30.8%; 95% confidence interval [CI], 29.7%-32.0%) to 2020 (32.1%; 95% CI, 31.0%-33.3%; p = .06). Among older adults with chronic pain, the prevalence of high impact chronic pain was also unchanged (38.3%; 95% CI, 36.1%-40.6% in 2019 versus 37.8%; 95% CI, 34.9%-40.8% in 2020; p = .79). Use of any nonpharmacological interventions for pain management decreased significantly from 61.2% (95 CI, 58.8%-63.5%) in 2019 to 42.1% (95% CI, 40.5%-43.8%) in 2020 (p < .001) among those with chronic pain, as did opioid use in the past 12 months from 20.2% (95% CI, 18.9%-21.6%) in 2019 to 17.9% (95% CI, 16.7%-19.1%) in 2020 (p = .006). Predictors of treatment utilization were similar in both chronic pain and high-impact chronic pain. CONCLUSION: Use of pain treatments among older adults with chronic pain declined in the first year of coronavirus disease of 2019 pandemic. Future research is needed to assess long-term effects of coronavirus disease of 2019 pandemic on pain management in older adults.

Assessment of Hypothetical Out-of-Pocket Costs of Guideline-Recommended Medications for the Treatment of Older Adults With Multiple Chronic Conditions, 2009 and 2019.

IMPORTANCE: Most adults 65 years or older have multiple chronic conditions. Managing these conditions with prescription drugs can be costly, particularly for older adults with limited incomes. OBJECTIVE: To estimate hypothetical out-of-pocket costs associated with guideline-recommended outpatient medications for the initial treatment of 8 common chronic diseases among older adults with Medicare prescription drug plans (PDPs). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study used 2009 and 2019 Medicare prescription drug plan formulary files to estimate annual out-of-pocket costs among hypothetical patients enrolled in Medicare Advantage or stand-alone Medicare Part D plans. A total of 3599 PDPs in 2009 and 3618 PDPs in 2019 were included after inclusion and exclusion criteria were applied. Costs associated with guideline-recommended medications for 8 of the most common chronic diseases (atrial fibrillation, chronic obstructive pulmonary disease [COPD], heart failure with reduced ejection fraction, hypercholesterolemia, hypertension, osteoarthritis, osteoporosis, and type 2 diabetes), alone and in 2 clusters of commonly comorbid conditions, were examined. MAIN OUTCOMES AND MEASURES: Annual out-of-pocket costs for each chronic condition, inflation adjusted to 2019 dollars. RESULTS: Among 3599 Medicare PDPs in 2009, 1998 were Medicare Advantage plans and 1601 were stand-alone plans; among 3618 Medicare PDPs in 2019, 2719 were Medicare Advantage plans and 899 were stand-alone plans. For an older adult enrolled in any Medicare PDP in 2019, the median annual out-of-pocket costs for individual conditions varied, from a minimum of $32 (IQR, $6-$48) for guideline-recommended management of osteoporosis (a decrease from $128 [IQR, $102-$183] in 2009) to a maximum of $1579 (IQR, $1524-$2229) for guideline-recommended management of atrial fibrillation (an increase from $91 [IQR, $73-$124] in 2009). For an older adult with a cluster of 5 commonly comorbid conditions (COPD, hypertension, osteoarthritis, osteoporosis, and type 2 diabetes) enrolled in any PDP, the median out-of-pocket cost in 2019 was $1999 (IQR, $1630-$2564), a 12% decrease from $2284 (IQR, $1920-$3107) in 2009. For an older adult with all 8 chronic conditions (atrial fibrillation, COPD, diabetes, hypercholesterolemia, heart failure, hypertension, osteoarthritis, and osteoporosis) enrolled in any PDP, the median out-of-pocket cost in 2019 was $3630 (IQR, $3234-$5197), a 41% increase from $2571 (IQR, $2185-$3719) in 2009. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, out-of-pocket costs for guideline-recommended outpatient medications for the initial treatment of 8 common chronic diseases varied by condition. Although costs generally decreased between 2009 and 2019, particularly with regard to conditions for which generic drugs were available, out-of-pocket costs remained high and may have presented a substantial financial burden for Medicare beneficiaries, especially older adults with conditions for which brand-name drugs were guideline recommended.

Adverse Effects of Pharmacologic Treatments of Major Depression in Older Adults.

OBJECTIVES: To assess adverse effects of pharmacologic antidepressants for treatment of major depressive disorder (MDD) in adults 65 years of age or older. DESIGN: Systematic review and meta-analysis. SETTING: Specialist or generalist outpatient setting, rehabilitation facility, and nursing facilities. PARTICIPANTS: Persons 65 years and older with MDD. INTERVENTION: Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone, or vortioxetine compared with another antidepressant, placebo, or nonpharmacologic therapy. MEASUREMENTS: Adverse events, arrhythmias, cognitive impairment, falls, fractures, hospitalization, mortality, QTc prolongation, serious adverse events, and withdrawals due to adverse events. RESULTS: Nineteen randomized controlled trials and two observational studies were included. Most studies evaluated treatment of the acute phase (<12 wk) of MDD of moderate severity. SSRIs led to a statistically similar frequency of overall adverse events vs placebo (moderate strength of evidence [SOE]), but SNRIs caused more overall adverse events vs placebo (high SOE) during the acute treatment phase. Both SSRIs and SNRIs led to more study withdrawals due to adverse events vs placebo (SSRIs low SOE; SNRIs moderate SOE). Duloxetine led to a more falls vs placebo (moderate SOE) during 24 weeks of acute and continuation treatment of MDD. CONCLUSION: In patients 65 years of age or older with MDD, treatment of the acute phase of MDD with SNRIs, but not SSRIs, was associated with a statistically greater number of overall adverse events vs placebo. SSRIs and SNRIs led to a greater number of study withdrawals due to adverse events vs placebo. Duloxetine increased the risk of falls that as an outcome was underreported in the literature. Few studies examined head-to-head comparisons, most trials were not powered to evaluate adverse events, and results of observational studies may be confounded. Comparative long-term studies reporting specific adverse events are needed to inform clinical decision making regarding choice of antidepressants in this population. J Am Geriatr Soc 67:1571-1581, 2019.

The interaction of active substance use, depression, and antiretroviral adherence in methadone maintenance.

BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) remains crucial in successfully treating HIV. While active substance use and depression are both associated with each other and with HAART nonadherence, little is known about their interaction. An understanding of the interaction of substance use and depressive symptoms on HAART adherence can inform adherence-enhancing interventions as well as interventions that target substance use and depression. PURPOSE: We tested an interaction between substance use and depression on HAART adherence among methadone maintenance patients. METHOD: We assessed substance use, depressive symptoms, and HAART adherence among 100 HIV-infected individuals receiving methadone maintenance in The Bronx, New York. Regressions were performed on adherence using an interaction term comprised of substance use and depressive symptoms. MODPROBE was used to assess significant interactions. RESULTS: Any use of illicit substances was associated with HAART nonadherence (p = 0.043). Cannabis was the single substance of abuse most strongly associated with nonadherence (p = 0.003). Depressive symptoms approached significance in bivariate analysis (p = 0.066). In regression analysis, a significant interaction was found between illicit substance use and depressive symptoms [OR (95% CI) 1.23 (1.06-1.44), p = 0.007], where illicit substance use was associated with nonadherence in individuals with lower depressive symptoms, but not among those with depressive symptoms at higher levels. No individual substances interacted with depressive symptoms on adherence. CONCLUSION: Though substance use and depressive symptoms interacted on HAART adherence, they did not have a synergistic effect. Continued substance use (51% of the sample) suggests an unmet need for treatment, even in methadone maintenance. Further examinations of the interplay of substance use and depression on HAART adherence are warranted.

Differential medication nonadherence and illness beliefs in co-morbid HIV and type 2 diabetes.

Increased antiretroviral availability has decreased mortality and increased rates of comorbid chronic illnesses, including type 2 diabetes, among people living with HIV. Little work has compared within-person adherence rates for HIV and comorbid conditions. Sixty-two adults with HIV and type 2 diabetes reported adherence rates, illness representations, beliefs about medications, symptoms, side-effects, and negative mood states. Adherence to antiretrovirals was better than diabetes medication (95 vs. 90 %, z = -2.05, p = 0.04). Participants reported better control over diabetes compared to HIV (t = 1.98, p = 0.05) while antiretrovirals were considered more necessary than diabetes medication (t = -2.79, p < 0.05). In adjusted analyses, antiretroviral nonadherence was associated with antiretroviral concerns (OR = 0.24, 95 % CI 0.08-0.67) and diabetes medication nonadherence with diabetes-related symptom burden (OR = 0.69, 95 % CI 0.53-0.89). Results indicate that medication nonadherence varies within individuals across comorbid illnesses and suggest this variation may depend on symptom attribution and medication concerns.

Social support networks and primary care use by HIV-infected drug users.

HIV-infected current and former drug users utilize primary care and preventive health services at suboptimal rates, but little is known about how social support networks are associated with health services use. We investigated the relationship between social support networks and the use of specific types of health services by HIV-infected drug users receiving methadone maintenance. We found that persons with greater social support, in particular more social network members or more network members aware of their HIV status, were more likely to use primary care services. In contrast, social support networks were not related to emergency room or inpatient hospital use. Interventions that build social support might improve coordinated and continuous health services utilization by HIV-infected persons in outpatient drug treatment.

Impact of adherence counseling dose on antiretroviral adherence and HIV viral load among HIV-infected methadone maintained drug users.

Adherence counseling can improve antiretroviral adherence and related health outcomes in HIV-infected individuals. However, little is known about how much counseling is necessary to achieve clinically significant effects. We investigated antiretroviral adherence and HIV viral load relative to the number of hours of adherence counseling received by 60 HIV-infected drug users participating in a trial of directly observed antiretroviral therapy delivered in methadone clinics. Our adherence counseling intervention combined motivational interviewing and cognitive-behavioral counseling, was designed to include six 30 minute individual counseling sessions with unlimited "booster" sessions, and was offered to all participants in the parent trial. We found that, among those who participated in adherence counseling, dose of counseling had a significant positive relationship with antiretroviral adherence measured after the conclusion of counseling. Specifically, a liner mixed-effects model revealed that each additional hour of counseling was significantly associated with a 20% increase in post-counseling adherence. However, the number of cumulative adherence counseling hours was not significantly associated with HIV viral load, also measured after the conclusion of counseling. Our findings suggest that more intensive adherence counseling interventions may have a greater impact on antiretroviral adherence than less intensive interventions; however, it remains unknown how much counseling is required to impact HIV viral load.

Directly observed antiretroviral therapy eliminates adverse effects of active drug use on adherence.

BACKGROUND: The impact of adherence enhancing interventions on the relationship between active drug use and adherence is largely unknown. METHODS: We conducted a 24-week randomized controlled trial of antiretroviral directly observed therapy (DOT) vs. treatment as usual (TAU) among HIV-infected methadone patients. Our outcome measure was pill count antiretroviral adherence, and our major independent variables were treatment arm (DOT vs. TAU) and active drug use (opiates, cocaine, or both opiates and cocaine). We defined any drug use as ≥ 1 positive urine toxicology result, and frequent drug use as ≥ 50% tested urines positive. We used mixed-effects linear models to evaluate associations between adherence and drug use, and included a treatment arm-by-drug use interaction term to evaluate whether DOT moderates associations between drug use and adherence. RESULTS: 39 participants were randomized to DOT and 38 to TAU. We observed significant associations between adherence and active drug use, but these were limited to TAU participants. Adherence was worse in TAU participants with any opiate use than in TAU participants without (63% vs. 75%, p<0.01); and worse among those with any polysubstance (both opiate and cocaine) use than without (60% vs. 73%, p=0.01). We also observed significant decreases in adherence among TAU participants with frequent opiate or frequent polysubstance use, compared to no drug use. Among DOT participants, active drug use was not associated with worse adherence. CONCLUSIONS: Active opiate or polysubstance use decreases antiretroviral adherence, but the negative impact of drug use on adherence is eliminated by antiretroviral DOT.

Comparison of antiretroviral adherence questions.

Our objective was to compare antiretroviral adherence questions to better understand concordance between measures. Among 53 methadone maintained HIV-infected drug users, we compared five measures, including two single item measures using qualitative Likert-type responses, one measure of percent adherence, one visual analog scale, and one multi-item measure that averaged responses across antiretrovirals. Responses were termed inconsistent if respondents endorsed the highest adherence level on at least one measure but middle levels on others. We examined ceiling effects, concordance, and correlations with VL. Response distributions differed markedly between measures. A ceiling effect was less pronounced for the single-item measures than for the measure that averaged responses for each antiretroviral: the proportion with 100% adherence varied from 22% (single item measure) to 58% (multi-item measure). Overall agreement between measures ranged from fair to good; 49% of participants had inconsistent responses. Though responses correlated with VL, single-item measures had higher correlations. Future studies should compare single-item questions to objective measures.

Social networks of substance users with HIV infection: application of the Norbeck Social Support Scale.

The role of social support networks in medication adherence among HIV-infected substance users remains understudied. In this secondary data analysis, the authors sought to determine the relationship between social support networks and antiretroviral adherence among HIV-infected substance abusers receiving methadone. They analyzed data collected in a 24-week study of 76 methadone-maintained, HIV-infected substance abusers randomized to directly observed antiretroviral therapy or treatment as usual. The authors used logistic regression to examine the relationship between social support networks and self-reported antiretroviral adherence. Their results showed that study participants had an average of 1.36 social network members (SD = 1.4); 34% of participants had at least one drug user and 25% had at least one HIV-infected person in their network. The presence of network drug users and HIV-infected network members was associated with less antiretroviral medication adherence (p < .05). The authors conclude that both social network density and characteristics of network members have implications for medication adherence.

Responding to surrogate requests that seem inconsistent with a patient's living will.

Clinicians may feel conflicted when a patient's legal decision maker is making decisions that seem inconsistent with a patient's living will. We provide evidence-based information to help clinicians consider whether a surrogate's inconsistent decisions are ethically appropriate. Surrogates are not flawless translators of their loved one's preferences; they are influenced by their own hopes and the current clinical context. Patients may be aware of this, are often concerned about burdening their loved ones, and often grant their surrogates leeway in interpreting their wishes. When appropriate, clinicians should respect surrogates' interpretations of patient values and take steps to decrease surrogate stress during the decision-making process. Finally, if clinicians are cognizant of their own values and preferences, they may recognize how these may affect their responses to certain clinical cases.

Rationale and design of a randomized controlled trial of directly observed hepatitis C treatment delivered in methadone clinics.

BACKGROUND: Most methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment. Physicians may be reluctant to treat HCV in IDUs because of concerns about treatment adherence, psychiatric comorbidity, or ongoing drug use. Optimal HCV management approaches for IDUs remain unknown. We are conducting a randomized controlled trial in a network of nine methadone clinics with onsite HCV care to determine whether modified directly observed therapy (mDOT), compared to treatment as usual (TAU), improves adherence and virologic outcomes among opioid users. METHODS/DESIGN: We plan to enroll 80 HCV-infected adults initiating care with pegylated interferon alfa-2a (IFN) plus ribavirin, and randomize them to mDOT (directly observed daily ribavirin plus provider-administered weekly IFN) or TAU (self-administered ribavirin plus provider-administered weekly IFN). Our outcome measures are: 1) self-reported and pill count adherence, and 2) end of treatment response (ETR) or sustained viral response (SVR). We will use mixed effects linear models to assess differences in pill count adherence between treatment arms (mDOT v. TAU), and we will assess differences between treatment arms in the proportion of subjects with ETR or SVR with chi square tests. Of the first 40 subjects enrolled: 21 have been randomized to mDOT and 19 to TAU. To date, the sample is 77% Latino, 60% HCV genotype-1, 38% active drug users, and 27% HIV-infected. Our overall retention rate at 24 weeks is 92%, 93% in the mDOT arm and 92% in the TAU arm. DISCUSSION: This paper describes the design and rationale of a randomized clinical trial comparing modified directly observed HCV therapy delivered in a methadone program to on-site treatment as usual. Our trial will allow rigorous evaluation of the efficacy of directly observed HCV therapy (both pegylated interferon and ribavirin) for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs, and can also guide protocols for studies among HCV-infected drug users receiving methadone for opiate dependence.

Lack of sustained improvement in adherence or viral load following a directly observed antiretroviral therapy intervention.

BACKGROUND: Methadone clinic-based directly observed antiretroviral therapy (DOT) has been shown to be more efficacious for improving adherence and suppressing human immunodeficiency virus (HIV) load than antiretroviral self-administration. We sought to determine whether the beneficial effects of DOT remain after DOT is discontinued. METHODS: We conducted a post-trial cohort study of 65 HIV-infected opioid-dependent adults who had completed a 24-week randomized controlled trial of methadone clinic-based DOT versus treatment as usual (TAU). For 12 months after DOT discontinuation, we assessed antiretroviral adherence using monthly pill counts and electronic monitors. We also assessed viral load at 3, 6, and 12 months after DOT ended. We examined differences between DOT and TAU in (1) adherence, (2) viral load, and (3) proportion of participants with viral load of <75 copies/mL. RESULTS: At trial end, adherence was higher among DOT participants than among TAU participants (86% and 54%, respectively; P < .001), and more DOT participants than TAU participants had viral loads of <75 copies/mL (71% and 44%, respectively; P = .03). However, after DOT ended, differences in adherence diminished by 1 month (55% for DOT vs 48% for TAU; P = .33) and extinguished completely by 3 months (49% for DOT vs 50% for TAU; P = .94). Differences in viral load between DOT and TAU disappeared by 3 months after the intervention, and the proportion of DOT participants with undetectable viral load decreased steadily after DOT was stopped until there was no difference (36% for DOT and 34% for TAU; P = .92). CONCLUSIONS: Because the benefits of DOT for adherence and viral load among HIV-infected methadone patients cease after DOT is stopped, methadone-based DOT should be considered a long-term intervention.

Strategies to improve access to and utilization of health care services and adherence to antiretroviral therapy among HIV-infected drug users.

We review five innovative strategies to improve access, utilization, and adherence for HIV-infected drug users and suggest areas that need further attention. In addition, we highlight two innovative programs. The first increases access and utilization through integrated HIV and opioid addiction treatment with buprenorphine in a community health center, and the second incorporates adherence counseling for antiretroviral therapy in methadone programs. Preliminary evaluations demonstrated that these strategies may improve both HIV and opioid addiction outcomes and may be appropriate for wider dissemination. Further refinement and expansion of strategies to improve outcomes of HIV-infected drug users is warranted.

Directly observed antiretroviral therapy in substance abusers receiving methadone maintenance therapy does not cause increased drug resistance.

Direct observation of antiretroviral therapy (DOT) can increase adherence rates in HIV-infected substance users, but whether this affects the development of antiretroviral drug resistance has not been fully explored. We conducted a 24-week randomized controlled trial of methadone clinic-based antiretroviral DOT compared with treatment as usual (TAU) among antiretroviral-experienced substance users. To examine the development of new resistance mutations, we identified all participants with an amplifiable resistance test at both baseline and either week 8 or week 24. We compared the development of new drug resistance mutations between participants in the two arms of the trial. Among the 77 participants enrolled in the parent trial, antiretroviral DOT was efficacious for improving adherence and decreasing HIV viral load. Twenty-one participants had a detectable HIV viral load at both baseline and a second time point. Of these, nine developed new drug resistance mutations not seen at baseline (three in the DOT arm and six in the TAU arm; p = 0.27). Overall, five subjects in the TAU arm developed major mutations correlating with their current antiretroviral regimen, while no subjects in the DOT arm developed such mutations. Direct observation of antiretroviral therapy was associated with improved adherence and viral suppression among methadone maintained HIV-infected substance users, but was not associated with an increase in the development of antiretroviral drug resistance. DOT should be considered for substance users attending methadone maintenance clinics who are at high risk of nonadherence.

Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: a randomized controlled trial.

OBJECTIVE: To determine if directly observed antiretroviral therapy (DOT) is more efficacious than self-administered therapy for improving adherence and reducing HIV viral load (VL) among methadone-maintained opioid users. DESIGN: Two-group randomized trial. SETTING: Twelve methadone maintenance clinics with on-site HIV care in the Bronx, New York. PARTICIPANTS: HIV-infected adults prescribed combination antiretroviral therapy. MAIN OUTCOMES MEASURES: Between group differences at four assessment points from baseline to week 24 in: (1) antiretroviral adherence measured by pill count, (2) VL, and (3) proportion with undetectable VL (< 75 copies/ml). RESULTS: Between June 2004 and August 2007, we enrolled 77 participants. Adherence in the DOT group was higher than in the control group at all post-baseline assessment points; by week 24 mean DOT adherence was 86% compared to 56% in the control group (p < 0.0001). Group differences in mean adherence remained significant after stratifying by baseline VL (detectable versus undetectable). In addition, during the 24-week intervention, the proportion of DOT participants with undetectable VL increased from 51% to 71%. CONCLUSIONS: Among HIV-infected opioid users, antiretroviral DOT administered in methadone clinics was efficacious for improving adherence and decreasing VL, and these improvements were maintained over a 24-week period. DOT should be more widely available to methadone patients.