Methods for pragmatic randomized clinical trials of pain therapies: IMMPACT statement.

ABSTRACT: Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the appropriate level of flexibility in treatment delivery, integrating information on concomitant treatments and adherence, and choosing comparator conditions and outcome measures. Ensuring data quality in real-world clinical settings is another challenging goal. Furthermore, current trials in the field would benefit from analysis methods that allow for a differentiated understanding of effects across patient subgroups and improved reporting of methods and context, which is required to assess the generalizability of findings. At the same time, a range of novel methodological approaches provide opportunities for enhanced efficiency and relevance of pragmatic trials to stakeholders and clinical decision making. In this study, best-practice considerations for these and other concerns in pragmatic trials of pain treatments are offered and a number of promising solutions discussed. The basis of these recommendations was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks.

Primary care barriers and facilitators to nonpharmacologic treatments for low back pain: A qualitative pilot study.

BACKGROUND: Clinical practice guidelines encourage primary care providers (PCPs) to recommend nonpharmacologic treatment as first-line therapy for low back pain (LBP). However, the determinants of nonpharmacologic treatment use for LBP in primary care remain unclear, particularly in low-income settings. OBJECTIVE: To pilot a framework-informed interview guide and codebook to explore determinants of nonpharmacologic treatment use in primary care. METHODS: In this qualitative interview study, we enrolled PCPs and community health workers (CHWs) from four primary care clinics at a safety net hospital. A semistructured interview guide informed by the Consolidated Framework for Implementation Research (CFIR) guided inquiry on barriers/facilitators to nonpharmacologic treatments for LBP (eg, acupuncture, chiropractic care, physical therapy). We included questions on whether current CHW roles may address barriers to nonpharmacologic treatment use. Interviews were audio-recorded, transcribed verbatim, and independently coded by four investigators. An a priori codebook composed of CFIR determinants and known CHW roles guided deductive content analysis to identify major themes. RESULTS: Eight individuals (six PCPs, two CHWs; age range: 32-51 years, five female) participated in hour-long interviews. Half had worked at the hospital for ≥15 years and all reported seeing patients with LBP (range: 2-20 patients per week). All participants identified the following CFIR factors as barriers/facilitators: nonpharmacologic treatment characteristics (perceived cost, relative advantage compared to other treatments); outer setting (patient needs/resources, limited connections with community-based nonpharmacologic treatment) and PCP characteristics (attitudes/beliefs about nonpharmacologic treatments). Although participants indicated several CHW roles could be adapted to address barriers (eg, care coordination, resource linking, case management), other roles seemed less feasible (eg, targeted health education) in our health care system. CONCLUSIONS: Preliminary insight on key determinants of nonpharmacologic treatments for LBP should be further examined in large multisite studies. Future studies may also determine whether a CHW-led strategy can improve nonpharmacologic treatment access and clinical outcomes in primary care.

Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations.

ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.

Trends in Chiropractic Care and Physical Rehabilitation Use Among Adults with Low Back Pain in the United States, 2002 to 2018.

BACKGROUND: While nonpharmacologic treatments are increasingly endorsed as first-line therapy for low back pain (LBP) in clinical practice guidelines, it is unclear if use of these treatments is increasing or equitable. OBJECTIVE: Examine national trends in chiropractic care and physical rehabilitation (occupational/physical therapy (OT/PT)) use among adults with LBP. DESIGN/SETTING: Serial cross-sectional analysis of the National Health Interview Survey, 2002 to 2018. PARTICIPANTS: 146,087 adults reporting LBP in prior 3 months. METHODS: We evaluated the association of survey year with chiropractic care or OT/PT use in prior 12 months. Logistic regression with multilevel linear splines was used to determine if chiropractic care or OT/PT use increased after the introduction of clinical guidelines. We also examined trends in use by age, sex, race, and ethnicity. When trends were similar over time, we present differences by these demographic characteristics as unadjusted ORs using data from all respondents. RESULTS: Between 2002 and 2018, less than one-third of adults with LBP reported use of either chiropractic care or OT/PT. Rates did not change until 2016 when uptake increased with the introduction of clinical guidelines (2016-2018 vs 2002-2015, OR = 1.15; 95% CI: 1.10-1.19). Trends did not differ significantly by sex, race, or ethnicity (p for interactions > 0.05). Racial and ethnic disparities in chiropractic care or OT/PT use were identified and persisted over time. For example, compared to non-Hispanic adults, either chiropractic care or OT/PT use was lower among Hispanic adults (combined OR = 0.62, 95% CI: 0.65-0.73). By contrast, compared to White adults, Black adults had similar OT/PT use (OR = 0.98; 95% CI: 0.94-1.03) but lower for chiropractic care use (OR = 0.50; 95% CI: 0.47-0.53). CONCLUSIONS: Although use of chiropractic care or OT/PT for LBP increased after the introduction of clinical guidelines in 2016, only about a third of US adults with LBP reported using these services between 2016 and 2018 and disparities in use have not improved.

Physical function in older adults with and without a cancer history: Findings from the National Health and Aging Trends Study.

BACKGROUND: Previous studies identified physical function limitations in older cancer survivors, but few have included objective measures and most focused on breast and prostate cancer survivors. The current study compared patient-reported and objective physical function measures between older adults with and without a cancer history. METHODS: Our cross-sectional study used a nationally representative sample of community-dwelling, Medicare beneficiaries from the 2015 National Health and Aging Trends Study (n = 7495). Data collected included patient-reported physical function, including a composite physical capacity score and limitations in strength, mobility, and balance, and objectively measured physical performance metrics, including gait speed, five time sit-to-stand, tandem stand, and grip strength. All analyses were weighted to account for the complex sampling design. RESULTS: Thirteen percent of participants (n = 829) reported a history of cancer, of which more than half (51%) reported a diagnosis other than breast or prostate cancer. In models adjusted for demographics and health history, older cancer survivors had lower Short Physical Performance Battery scores (unstandardized beta [B] = -0.36; 95% CI: -0.64, -0.08), slower gait speed (B = -0.03; 95% CI: -0.05, -0.01), reduced grip strength (B = -0.86; 95% CI: -1.44, -0.27), worse patient-reported composite physical capacity (B = -0.43; 95% CI: -0.67, -0.18) and patient-reported upper extremity strength (B = 1.27; 95% CI: 1.07, 1.50) compared to older adults without cancer. Additionally, the burden of physical function limitations was greater in women than in men, which may be explained by cancer type. CONCLUSIONS: Our results extend studies in breast and prostate cancer to show worse objective and patient-reported physical function outcomes in older adults with a range of cancer types compared to those without a cancer history. Moreover, these burdens seem to disproportionately affect older adult women, underscoring the need for interventions to address functional limitations and prevent further health consequences of cancer and its treatment.

Exercise Intensity Among Older Adults Participating From Home in Remotely Delivered EnhanceFitness.

We aimed to examine exercise intensity among older adults participating from home in remotely delivered EnhanceFitness (Tele-EF). Exercise intensity was assessed through Fitbit-measured heart rate and the Borg 10-point rating of perceived exertion over 1 week of a 16-week exercise program. Outcomes included mean minutes spent at or above the heart rate reserve calculated threshold for moderate intensity and mean rating of perceived exertion. Pearson and Spearman rank correlations were used to examine associations between baseline characteristics with exercise intensity. During the 60-min classes, the 55 participants achieved moderate intensity for a mean of 21.0 min (SD = 13.5) and had a mean rating of perceived exertion of 4.9 (SD = 1.2). There were no significant associations between baseline characteristics and exercise intensity. Older adults can achieve sustained moderate-intensity exercise during Tele-EF supervised classes. Baseline physical function, physical activity, and other health characteristics did not limit ability to exercise at a moderate intensity, though further investigation is warranted.

Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement.

ABSTRACT: Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care. This article summarizes methodological considerations for pragmatic trials, mainly concerning methods of fundamental importance to the internal validity of trials. The relationship between these methods and common pragmatic trials methods and goals is considered, recognizing that the resulting trial designs are highly dependent on the specific research question under investigation. The basis of this statement was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) systematic review of methods and a consensus meeting. The meeting was organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The consensus process was informed by expert presentations, panel and consensus discussions, and a preparatory systematic review. In the context of pragmatic trials of pain treatments, we present fundamental considerations for the planning phase of pragmatic trials, including the specification of trial objectives, the selection of adequate designs, and methods to enhance internal validity while maintaining the ability to answer pragmatic research questions.

Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations.

Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, "precision pain medicine"). Precision pain medicine, currently an aspirational goal, would consist of empirically based algorithms that determine the optimal treatments, or treatment combinations, for specific patients (ie, targeting the right treatment, in the right dose, to the right patient, at the right time). Answering this question of "what works for whom" will certainly improve the clinical care of patients with pain. It may also support the success of novel drug development in pain, making it easier to identify novel treatments that work for certain patients and more accurately identify the magnitude of the treatment effect for those subgroups. Significant preliminary work has been done in this area, and analgesic trials are beginning to utilize precision pain medicine approaches such as stratified allocation on the basis of prespecified patient phenotypes using assessment methodologies such as quantitative sensory testing. Current major challenges within the field include: 1) identifying optimal measurement approaches to assessing patient characteristics that are most robustly and consistently predictive of inter-patient variation in specific analgesic treatment outcomes, 2) designing clinical trials that can identify treatment-by-phenotype interactions, and 3) selecting the most promising therapeutics to be tested in this way. This review surveys the current state of precision pain medicine, with a focus on drug treatments (which have been most-studied in a precision pain medicine context). It further presents a set of evidence-based recommendations for accelerating the application of precision pain methods in chronic pain research. PERSPECTIVE: Given the considerable variability in treatment outcomes for chronic pain, progress in precision pain treatment is critical for the field. An array of phenotypes and mechanisms contribute to chronic pain; this review summarizes current knowledge regarding which treatments are most effective for patients with specific biopsychosocial characteristics.

Remotely delivered exercise to older rural cancer survivors: a randomized controlled pilot trial.

PURPOSE: The study aimed to determine the feasibility of remotely delivered exercise (tele-exercise) for older, rural cancer survivors and to explore the effects of tele-exercise on physical function, physical activity, and patient-reported outcomes. METHODS: Participants were rural cancer survivors age ≥ 60 years (79% female; mean age 70.4 ± 5.7) randomly assigned to the remotely delivered EnhanceFitness (tele-EF) exercise program, inclusive of aerobic, strength, and balance training and led by American Council on Exercise certified instructors for 1 h, 3 days/week for 16 weeks (n = 20) or to a waitlist control group (n = 19). We assessed feasibility, physical function, accelerometer-measured physical activity, and patient-reported outcomes at baseline and post intervention. RESULTS: Among those screened as eligible, 44 (64%) consented to participate with 39 randomized after completing baseline measures. Attrition was equivalent between groups (n = 1, each) with 95% completing the study. The median class attendance rate was 86.9% (interquartile range: 79-94%). Compared to controls, tele-EF participants had statistically significant improvement in the five-time sit-to-stand test (- 3.4 vs. - 1.1 s, p = 0.03, effect size = 0.44), mean daily light physical activity (+ 38.5 vs 0.5 min, p = 0.03, effect size = 0.72) and step counts (+ 1977 vs. 33, p = 0.01, effect size = 0.96). There were no changes in self-efficacy for exercise, fatigue, or sleep disturbance between groups. CONCLUSIONS: Findings indicate that tele-EF is feasible in older, rural cancer survivors and results in positive changes in physical function and physical activity. IMPLICATIONS FOR CANCER SURVIVORS: Tele-EF addresses common barriers to exercise for older, rural cancer survivors, including limited accessible opportunities for professional instruction and supervision.

Provider perceptions of severe pediatric traumatic brain injury care priorities across hospitals in South America before and during the COVID-19 pandemic.

BACKGROUND: To understand provider perceptions of the COVID-19 pandemic on priorities of severe pediatric traumatic brain injury (TBI) care across hospitals in South America. METHODS: Site principal investigators (PIs) from 17 hospitals in South America enrolled in the PEGASUS-Argentina randomized controlled trial completed questionnaires regarding order of tasks performed in the care of a typical pediatric patient with severe TBI before (2019) and during (2021) the COVID-19 pandemic. Acute care processes were examined by quintiles to identify early, mid, and late actions and were categorized and compared. Associations of hospital volume and subspecialty resource availability with prioritization of key process actions were examined. FINDING: Site PIs from 15 and 16 hospitals completed the surveys in 2019 and 2021, respectively, including 14 who completed both. Action category order was stable between 2019 and 2021 and were ranked in priorities as: initial encounter, primary survey, interventions and invasive monitors, diagnostics, medications, staff communication, then disposition (in 2019) or nutrition (in 2021). There was variation in specific action order between hospitals at both timepoints, with only a few initial encounter and disposition actions limited to a single quintile. There was no reported association between hospital volume or subspecialty resource availability with prioritization of key process actions. INTERPRETATION: Despite novel healthcare challenges presented by the COVID-19 pandemic, providers in South America perceived maintaining standard severe pediatric TBI care consistent with BTF guidelines. There was large variability in specific action order between individual hospitals reported.

Remotely Delivered Exercise to Rural Older Adults With Knee Osteoarthritis: A Pilot Study.

OBJECTIVE: EnhanceFitness (EF) is an evidence-based exercise program recommended for management of osteoarthritis (OA). However, access to EF is limited in rural areas. Accordingly, we evaluated the feasibility and acceptability of remotely delivered EF (tele-EF) in rural, community-dwelling older adults with symptomatic knee OA. METHODS: A single-arm pilot trial of tele-EF classes was conducted. Videoconferencing was used to livestream the instructor-led, 1-hour EF classes 3 days/week for 12 weeks. Outcomes were assessed at baseline and immediately post intervention. RESULTS: A total of 15 of 27 potential participants (55%) were screen eligible and enrolled into the trial. Participants had a median age of 70 years (interquartile range: 67-75), and 14 (93%) were women. The median EF class attendance rate was 91% (interquartile range: 85%-94%). Knee pain, as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS), improved significantly from baseline to the 12-week end point (mean difference = -11.4 [95% confidence interval (CI): -20.9 to -2.0]; P = 0.02). In addition, participants' self-reported knee function improved significantly (mean difference in KOOS function score = -11.8 [95% CI: -18.4 to -5.2]; P < 0.01) as well as their physical capacity (mean difference in Timed Up and Go test time = 1.8 seconds [95% CI: 0.2-3.4]; P = 0.03). All participants (100%) were very satisfied with tele-EF classes, and 12 participants (86%) reported that their condition had much improved or very much improved since beginning the EF exercise program. Lastly, there were no serious adverse events. CONCLUSION: Findings from this pilot trial indicate that tele-EF is feasible and acceptable in rural older adults with knee OA.

Trajectories of physical capacity among community-dwelling older adults in the United States.

OBJECTIVE: Although the prognostic value of physical capacity is well-established, less is known about longitudinal patterns of physical capacity among community-dwelling older adults. We sought to describe long-term trajectories of physical capacity in a nationally representative sample of Medicare beneficiaries. DESIGN: Cohort study SETTING AND PARTICIPANTS: Annually collected data on 6,783 community-dwelling participants in the National Health and Aging Trends Study from 2011 to 2016 were analyzed. METHODS: Performance-based physical capacity was measured using the Short Physical Performance Battery [(SPPB) range: 0-12, higher is better]. Self-reported physical capacity was measured using six pairs of activities with composite scores from 0 to 12 (higher is better). We then used group-based trajectory modeling to identify longitudinal patterns of each physical capacity measure over 6 years. Associations of baseline characteristics with trajectories were examined using multinomial logistic regression. RESULTS: The cohort was 57% female, 68% white, and 58% were ≥75 years. Six distinct trajectories of SPPB scores were identified. Two "high" groups (n = 2192, 43%) maintained high average SPPB scores. Two "moderate decline" groups (n = 1459, 29%) had a mid-range SPPB score at baseline and demonstrated gradual decline. A "low decline" group (n = 811, 16%) started with a low SPPB score and experienced a greater decline. A "very low" group (n = 590, 12%) had very low SPPB scores in all years. Six trajectories for self-reported physical capacity were also identified. Older age, worse health, lower income and education, and being Black or Hispanic were associated with lower and declining physical capacity.

Benefit-risk assessment and reporting in clinical trials of chronic pain treatments: IMMPACT recommendations.

ABSTRACT: Chronic pain clinical trials have historically assessed benefit and risk outcomes separately. However, a growing body of research suggests that a composite metric that accounts for benefit and risk in relation to each other can provide valuable insights into the effects of different treatments. Researchers and regulators have developed a variety of benefit-risk composite metrics, although the extent to which these methods apply to randomized clinical trials (RCTs) of chronic pain has not been evaluated in the published literature. This article was motivated by an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting and is based on the expert opinion of those who attended. In addition, a review of the benefit-risk assessment tools used in published chronic pain RCTs or highlighted by key professional organizations (ie, Cochrane, European Medicines Agency, Outcome Measures in Rheumatology, and U.S. Food and Drug Administration) was completed. Overall, the review found that benefit-risk metrics are not commonly used in RCTs of chronic pain despite the availability of published methods. A primary recommendation is that composite metrics of benefit-risk should be combined at the level of the individual patient, when possible, in addition to the benefit-risk assessment at the treatment group level. Both levels of analysis (individual and group) can provide valuable insights into the relationship between benefits and risks associated with specific treatments across different patient subpopulations. The systematic assessment of benefit-risk in clinical trials has the potential to enhance the clinical meaningfulness of RCT results.

Use of regional analgesia and risk of delirium in older adults with multiple rib fractures: An Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: Single-center data demonstrates that regional analgesia (RA) techniques are associated with reduced risk of delirium in older patients with multiple rib fractures. We hypothesized that a similar effect between RA and delirium would be identified in a larger cohort of patients from multiple level I trauma centers. METHODS: Retrospective data from seven level I trauma centers were collected for intensive care unit (ICU) patients 65 years or older with ≥3 rib fractures from January 2012 to December 2016. Those with a head and/or spine injury Abbreviated Injury Scale (AIS) score of ≥ 3 or a history of dementia were excluded. Delirium was defined as one positive Confusion Assessment Method for the Intensive Care Unit score in the first 7 days of ICU care. Poisson regression with robust standard errors was used to determine the association of RA (thoracic epidural or paravertebral catheter) with delirium incidence. RESULTS: Data of 574 patients with a median age of 75 years (interquartile range [IQR], 69-83), Injury Severity Score of 14 (IQR, 11-18), and ICU length of stay of 3 days (IQR, 2-6 days) were analyzed. Among the patients, 38.9% were women, 15.3% were non-White, and 31.4% required a chest tube. Regional analgesia was used in 19.3% patients. Patient characteristics did not differ by RA use; however, patients with RA had more severe chest injury (chest AIS, flail segment, hemopneumothorax, thoracostomy tube). In univariate analysis, there was no difference in the likelihood of delirium between the RA and no RA groups (18.9% vs. 23.8% p = 0.28). After adjusting for age, sex, Injury Severity Score, maximum chest AIS, thoracostomy tube, ICU length of stay, and trauma center, RA was associated with reduced risk of delirium (incident rate ratio [IRR], 0.65; 95% confidence interval [CI], 0.44-0.94) but not with in-hospital mortality (IRR, 0.42; 95% CI, 0.14-1.26) or respiratory complications (IRR, 0.70; 95% CI, 0.42-1.16). CONCLUSION: In this multicenter cohort of injured older adults with multiple rib fractures, RA use was associated with a 35% lower risk of delirium. Further studies are needed to standardize protocols for optimal pain management and prevention of delirium in older adults with severe thoracic injury. LEVEL OF EVIDENCE: Therapeutic, level IV; Epidemiologic, level III.

Associations of Multiple Chronic Conditions With Physical Performance and Falls Among Older Adults With Back Pain: A Longitudinal, Population-based Study.

OBJECTIVE: To determine the association of chronic conditions measured at baseline with physical performance and falls over time among older adults with back pain. We examined both number and type (depression, anxiety, arthritis) of chronic conditions. DESIGN: Retrospective cohort study. SETTING: National Health and Aging Trends Study. PARTICIPANTS: A total of 2438 community-dwelling Medicare beneficiaries aged ≥65 years with bothersome back pain (N=2438). The sample was mostly female (62%; 95% confidence interval [CI], 59%-64%) and aged 65-74 years (56%; 95% CI, 53%-58%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Short Physical Performance Battery (SPPB) (range, 0-12, lower indicates worse function) and recurrent falls measured annually over 6 years. RESULTS: Multiple chronic conditions were highly prevalent (82%; 95% CI, 79%-84%) among those reporting back pain. Adjusted regressions using survey weights with Taylor series linearization method and containing interaction terms for comorbidity and time showed having 2-3 chronic conditions vs 0-1 was associated with lower SPPB scores, and differences grew over time (for example 0.61 points lower [95% CI, -0.88 to -0.34] and 1.22 points lower [95% CI, -1.76 to -0.67] in rounds 3 and 6, respectively). Having ≥4 chronic conditions was associated with lower SPPB scores at all time points vs 0-1 (point estimate range, -1.72 to -2.31). Arthritis alone; the combination of arthritis with depression; and the triad of arthritis, depression, and anxiety were associated with lower SPPB scores at all time points. Logistic regression models showed presence of 2-3 and ≥4 chronic conditions was associated with increased odds of recurrent falls in any given year (odds ratio, 1.91; 95% CI, 1.35-2.69 and odds ratio, 3.92; 95% CI, 2.81-5.46, respectively). Those with the triad of arthritis, depression, and anxiety had greater odds of recurrent falls vs none or 1 condition. CONCLUSIONS: Among older adults with back pain, those with multiple chronic conditions, including co-occurrence of arthritis, depression, and anxiety, have greater risk for poor physical functioning and falls over time.

Clinical outcome assessment in clinical trials of chronic pain treatments.

Clinical outcome assessments (COAs) measure outcomes that are meaningful to patients in clinical trials and are critical for determining whether a treatment is effective. The objectives of this study are to (1) describe the different types of COAs and provide an overview of key considerations for evaluating COAs, (2) review COAs and other outcome measures for chronic pain treatments that are recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) or other expert groups, and (3) review advances in understanding pain-related COAs that are relevant to clinical trials. The authors reviewed relevant articles, chapters, and guidance documents from the European Medicines Agency and U.S. Food and Drug Administration. Since the original core set of outcome measures were recommended by IMMPACT 14 years ago, several new advancements and publications relevant to the measurement or interpretation of COAs for chronic pain trials have emerged, presenting new research opportunities. Despite progress in the quality of measurement of several outcome domains for clinical trials of chronic pain, there remain some measurement challenges that require further methodological investigation.

Impact of COVID-19 'Stay Home, Stay Healthy' Orders on Function among Older Adults Participating in a Community-Based, Behavioral Intervention Study.

Background: Early mitigation orders for COVID-19 halted participation in community-based programs. We examined the early impact of "Stay Home, Stay Healthy" orders on functioning in older adults participating in a behavioral intervention study involving community-based exercise. Methods: A quasi-natural experiment, using mixed methods (n = 39). Participants completed interviews and questionnaires after 3-4 weeks of the Stay Home, Stay Healthy directive. PROMIS-29 outcomes were compared to pre-COVID-19 responses. Results: Participants had a mean age of 74.1 (6.5) years, 79.5% were women, and 20.5% were racial/ethnic minorities. Compared to pre-COVID-19, there was a significant increase in anxiety and decrease in fatigue and social participation. Thematic analysis revealed five main themes related to disruption of daily life, the emotional and physical impact of stay-at-home orders, unexpected positive outcomes, and perspectives on messaging surrounding the pandemic. Conclusions: Efforts to curb the spread of COVID-19 have substantially impacted the lives of older adults participating in community-based exercise.

Age differences in cognitive-affective processes in adults with chronic pain.

BACKGROUND: Chronic pain is associated with significant physical and psychological impairments across the adult lifespan. However, there is a relative gap in knowledge on individual differences that predict pain-related functioning. The current study highlights one important source of individual variation: age. METHODS: We used cross-sectional data from a large treatment-seeking cohort of 2,905 adults (M age = 46.6 [13.1]; 71.8% women) presenting to a tertiary pain centre in the United Kingdom to determine age differences in cognitive-affective processes (catastrophizing, acceptance, self-efficacy), including their differential patterns and effects on disability and depression. RESULTS: Older adults (ages 65-75) were found to experience higher pain acceptance and pain self-efficacy compared to both middle-aged (ages 40-64) and young adult (ages 18-39) age groups. Older adults also experienced lower levels of catasophizing compared to middle-age adults. Testing age as a moderator, we found that the relationships of pain self-efficacy and acceptance with depression as well as the relationship between pain self-efficacy and disability were comparatively weakest among older adults and strongest among young adults. Similarly, the relationship between pain catastrophizing and depression was relatively stronger for young and middle-aged adults compared to older adults. CONCLUSIONS: Age-related differences in psychological mechanisms that influence pain-related functioning present unique challenges and opportunities for scientists and clinicians to improve our understanding and treatment of pain across the lifespan. Additional work is needed to refine our knowledge of age-related differences in cognitive-affective, biopsychosocial dimensions of chronic pain and to develop and test the efficacy of age-tailored interventions. SIGNIFICANCE: Our cross-sectional analysis of 2,905 treatment-seeking adults with chronic pain presenting to a tertiary care center in the United Kingdom revealed distinct age differences in cognitive-affective linked to disability and depression. This study contributes to the limited knowledge on age-related variance in psychological mechanisms underlying adjustment to chronic pain. Promising avenues for future research include refining our understanding of age-related differences in cognitive-affective, biopsychosocial dimensions of chronic pain and elucidating the most salient treatment targets among different age groups.

Psychosocial Correlates of Objective, Performance-Based, and Patient-Reported Physical Function Among Patients with Heterogeneous Chronic Pain.

BACKGROUND: Improving all aspects of physical function is an important goal of chronic pain management. Few studies follow recent guidelines to comprehensively assess physical function via patient-reported, performance-based, and objective/ambulatory measures. PURPOSE: To test 1) the interrelation between the 3 types of physical function measurement and 2) the association between psychosocial factors and each type of physical function measurement. METHODS: Patients with chronic pain (N=79) completed measures of: 1) physical function (patient-reported disability; performance-based 6-minute walk-test; objective accelerometer step count); 2) pain and non-adaptive coping (pain during rest and activity, pain-catastrophizing, kinesiophobia); 3) adaptive coping (mindfulness, general coping, pain-resilience); and 4) social-emotional dysfunction (anxiety, depression, social isolation and emotional support). First, we tested the interrelation among the 3 aspects of physical function. Second, we used structural equation modeling to test associations between psychosocial factors (pain and non-adaptive coping, adaptive coping, and social-emotional dysfunction) and each measurement of physical function. RESULTS: Performance-based and objective physical function were significantly interrelated (r=0.48, p<0.001) but did not correlate with patient-reported disability. Pain and non-adaptive coping (ß=0.68, p<0.001), adaptive coping (ß=-0.65, p<0.001) and social-emotional dysfunction (ß=0.65, p<0.001) were associated with patient-reported disability but not to performance-based or objective physical function (ps>0.1). CONCLUSION: Results suggest that patient-reported physical function may provide limited information about patients' physical capacity or ambulatory activity. While pain and non-adaptive reactions to it, adaptive coping, and social-emotional dysfunction may potentially improve patient-reported physical function, additional targets may be needed to improve functional capacity and ambulatory activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03412916.