An Adaptive Pragmatic Randomized Controlled Trial of Emergency Department Acupuncture for Acute Musculoskeletal Pain Management.

STUDY OBJECTIVE: Acute musculoskeletal pain in emergency department (ED) patients is frequently severe and challenging to treat with medications alone. The purpose of this study was to determine the feasibility, acceptability, and effectiveness of adding ED acupuncture to treat acute episodes of musculoskeletal pain in the neck, back, and extremities. METHODS: In this pragmatic 2-stage adaptive open-label randomized clinical trial, Stage 1 identified whether auricular acupuncture (AA; based on the battlefield acupuncture protocol) or peripheral acupuncture (PA; needles in head, neck, and extremities only), when added to usual care was more feasible, acceptable, and efficacious in the ED. Stage 2 assessed effectiveness of the selected acupuncture intervention(s) on pain reduction compared to usual care only (UC). Licensed acupuncturists delivered AA and PA. They saw and evaluated but did not deliver acupuncture to the UC group as an attention control. All participants received UC from blinded ED providers. Primary outcome was 1-hour change in 11-point pain numeric rating scale. RESULTS: Stage 1 interim analysis found both acupuncture styles similar, so Stage 2 continued all 3 treatment arms. Among 236 participants randomized, demographics and baseline pain were comparable across groups. When compared to UC alone, reduction in pain was 1.6 (95% confidence interval [CI]: 0.7 to 2.6) points greater for AA+UC and 1.2 (95% CI: 0.3 to 2.1) points greater for PA+UC patients. Participants in both treatment arms reported high satisfaction with acupuncture. CONCLUSION: ED acupuncture is feasible and acceptable and can reduce acute musculoskeletal pain better than UC alone.

Phenotypic characteristics of F64L, I68L, I107V, and S77Y ATTRv genotypes from the Transthyretin Amyloidosis Outcomes Survey (THAOS).

Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multi-systemic disease with wild-type (ATTRwt) and hereditary (ATTRv) forms. Over 130 variants associated with ATTRv amyloidosis have been identified, although little is known about the majority of these genotypes. This analysis examined phenotypic characteristics of symptomatic patients with ATTRv amyloidosis enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) with four less frequently reported pathogenic genotypes: F64L (c.250T>C, p.F84L), I68L (c.262A>T, p.I88L), I107V (c.379A>G; p.I127V), and S77Y (c.290C>A; p.S97Y). THAOS is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both ATTRwt and ATTRv amyloidosis. This analysis describes the baseline demographic and clinical characteristics of untreated symptomatic patients with the F64L, I68L, I107V, or S77Y genotypes at enrollment in THAOS (data cutoff date: January 4, 2022). There were 141 symptomatic patients with F64L (n = 46), I68L (n = 45), I107V (n = 21), or S77Y (n = 29) variants at the data cutoff. Most patients were male and median age at enrollment was in the sixth decade for S77Y patients and the seventh decade for the others. A predominantly neurologic phenotype was associated with F64L, I107V, and S77Y genotypes, whereas patients with the I68L genotype presented with more pronounced cardiac involvement. However, a mixed phenotype was also reported in a considerable proportion of patients in each variant subgroup. This analysis from THAOS represents the largest study of ATTRv symptomatic patients with the F64L, I68L, I107V, and S77Y genotypes. These data add to the limited knowledge on the clinical profile of patients with specific ATTRv variants and emphasize the importance of comprehensive assessment of all patients. Trial registration ClinicalTrials.gov: NCT00628745.

Electroconvulsive Therapy in Heart Transplant Patients: To Avoid or Embrace?

ABSTRACT: Patients with heart disease are at an increased risk of depression. Electroconvulsive therapy (ECT) is a highly effective treatment for severe depressive episodes. However, ECT may increase the risk for adverse outcomes in certain patients because of changes in blood pressure and heart rate secondary to an initial parasympathetic surge followed by a sympathetic surge and peripheral catecholamine release. In post-cardiac transplant patients, these acute hemodynamic changes on a denervated heart may bring clinical challenges. The available data on ECT in heart transplant patients are limited. The authors of this article present a summary of the available literature relating to ECT in heart transplant patients.The authors performed a literature search of 6 online databases yielding 6 English-language case reports of ECT in cardiac transplant patients. All patients experienced changes in hemodynamic variables during and immediately after ECT, ranging from moderate decrease in blood pressure to extreme hypertension. The cases did not report any serious cardiac complications during the course of ECT. In the 5 patients whose psychiatric responses to treatment were detailed, all had improvement in their depressive symptoms. Electroconvulsive therapy may be considered for severe cases of depression in patients with a history of cardiac transplant, but the potential benefit of ECT needs to be weighed against risks. In the limited number of cases reported in the literature, ECT seems to have been relatively safe and effective.

Clinical and Genotype Characteristics and Symptom Migration in Patients With Mixed Phenotype Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey.

INTRODUCTION: Transthyretin amyloidosis (ATTR amyloidosis) is primarily associated with a cardiac or neurologic phenotype, but a mixed phenotype is increasingly described. METHODS: This study describes the mixed phenotype cohort in the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, longitudinal, observational survey of patients with ATTR amyloidosis, including both hereditary (ATTRv) and wild-type disease, and asymptomatic carriers of pathogenic transthyretin variants. Baseline characteristics of patients with a mixed phenotype (at enrollment or reclassified during follow-up) are described (data cutoff: January 4, 2022). RESULTS: Approximately one-third of symptomatic patients (n = 1185/3542; 33.5%) were classified at enrollment or follow-up as mixed phenotype (median age, 66.5 years). Of those, 344 (29.0%) were reclassified to mixed phenotype within a median 1-2 years of follow-up. Most patients with mixed phenotype had ATTRv amyloidosis (75.7%). The most frequent genotypes were V30M (38.9%) and wild type (24.3%). CONCLUSIONS: These THAOS data represent the largest analysis of a real-world mixed phenotype ATTR amyloidosis population to date and suggest that a mixed phenotype may be more prevalent than previously thought. Patients may also migrate from a primarily neurologic or cardiologic presentation to a mixed phenotype over time. These data reinforce the need for multidisciplinary evaluation at initial assessment and follow-up of all patients with ATTR amyloidosis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00628745.

A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS).

BACKGROUND: Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs. METHODS: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry. RESULTS: This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5). CONCLUSIONS: This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00628745.

Acupuncture for acute musculoskeletal pain management in the emergency department and continuity clinic: a protocol for an adaptive pragmatic randomised controlled trial.

INTRODUCTION: Chronic musculoskeletal pain causes a significant burden on health and quality of life and may result from inadequate treatment of acute musculoskeletal pain. The emergency department (ED) represents a novel setting in which to test non-pharmacological interventions early in the pain trajectory to prevent the transition from acute to chronic pain. Acupuncture is increasingly recognised as a safe, affordable and effective treatment for pain and anxiety in the clinic setting, but it has yet to be established as a primary treatment option in the ED. METHODS AND ANALYSIS: This pragmatic clinical trial uses a two-stage adaptive randomised design to determine the feasibility, acceptability and effectiveness of acupuncture initiated in the ED and continued in outpatient clinic for treating acute musculoskeletal pain. The objective of the first (treatment selection) stage is to determine the more effective style of ED-based acupuncture, auricular acupuncture or peripheral acupuncture, as compared with no acupuncture. All arms will receive usual care at the discretion of the ED provider blinded to treatment arm. The objective of the second (effectiveness confirmation) stage is to confirm the impact of the selected acupuncture arm on pain reduction. An interim analysis is planned at the end of stage 1 based on probability of being the best treatment, after which adaptations will be considered including dropping the less effective arm, sample size re-estimation and unequal treatment allocation ratio (eg, 1:2) for stage 2. Acupuncture treatments will be delivered by licensed acupuncturists in the ED and twice weekly for 1 month afterward in an outpatient clinic. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Duke University Health System Institutional Review Board. Informed consent will be obtained from all participants. Results will be disseminated through peer-review publications and public and conference presentations. TRIAL REGISTRATION NUMBER: NCT04290741.

Perceptions of Exercise and Its Challenges in Patients With Nonalcoholic Fatty Liver Disease: A Survey-Based Study.

Exercise is a foundational treatment for nonalcoholic fatty liver disease (NAFLD); however, the majority of patients are unable to initiate and maintain effective exercise habits and remain at increased risk for progressive liver disease. Barriers and limitations to exercise in patients with NAFLD have not been fully identified. We performed a single survey of 94 patients with biopsy-proven NAFLD to understand baseline physical activity and sedentary behavior, self-perceived fitness, limitations to exercise, potential solutions to increase physical activity behavior, and perception of exercise as a foundational treatment for NAFLD. For exploratory analyses, we evaluated differences in responses to the survey by grouping severity of hepatic fibrosis as follows: nonalcoholic fatty liver (NAFL); early stage (nonalcoholic steatohepatitis [NASH] F0, NASH F1, NASH F2); and late stage (NASH F3, NASH F4). Zero weekly total physical activity was reported by 29% of patients with NAFLD. Late-stage NASH had significantly lower vigorous (P = 0.024), walking (P = 0.029), total weekly activity (P = 0.043), and current fitness level (P = 0.022) compared to early stage NASH. Overall, 72% of patients with NAFLD reported limitations to exercise, with the greatest proportion citing lack of energy (62%), fatigue (61%), prior/current Injury (50%), and shortness of breath (49%). A preference for personal training to increase their physical activity was indicated by 66% of patients with NAFLD, and 63% preferred exercise over medication to treat NAFLD. Conclusion: The majority of patients with NAFLD have limitations to exercise but prefer exercise as a treatment option for NAFLD in the form of personal training. Patients with NAFLD may have unique physiologic limitations to exercise that worsen with fibrosis severity. Exercise interventions or services that are personalized and scalable may improve sustainability of exercise habits in the long term.

Feasibility, acceptability, and potential effectiveness of an online expressive writing intervention for COVID-19 resilience.

BACKGROUND & PURPOSE: The COVID-19 pandemic has negatively impacted mental health in the general population. In this trial, our objective was to assess whether a 6-week expressive writing intervention improves resilience in a sample from the general population in the midst of the COVID-19 pandemic. MATERIALS & METHODS: This 6-week trial was conducted online. Eligible participants (n=63) were a sample of adults who self-identified as having been significantly affected by the COVID-19 pandemic. PRIMARY OUTCOME: Connor-Davidson Resilience Scale (CD-RISC). SECONDARY OUTCOMES: Perceived Stress Scale - 10-Item (PSS-10); Center for Epidemiologic Studies Depression Scale - Revised (CESD-R); Post-Traumatic Growth Inventory (PTGI). RESULTS: Resilience measures (CD-RISC) increased from baseline (66.6 ± 14.9) to immediately post-intervention (73.0 ± 12.4; p=0.014; Cohen's d =0.31), and at a 1- month follow-up (72.9 ± 13.6; p=0.024; Cohen's d =0.28). Across the same timepoints, perceived stress scores (PSS-10) decreased from baseline (21.8 ± 6.6) to immediately post-intervention (18.3 ± 7.0; p=0.008; Cohen's d =0.41), and at the 1- month follow-up to (16.8 ± 6.7; p=0.0002; Cohen's d =0.56). Depression symptoms (CESD-R) decreased from baseline (23.3 ± 15.3) at 6 weeks (17.8 ± 15.4; p=0.058; Cohen's d =0.22), and 10 weeks (15.5 ± 12.7; p=0.004; Cohen's d =0.38). Posttraumatic growth (PTGI) increased from baseline (41.7 ± 23.4) at 6 weeks (55.8 ± 26.4; p=0.004; Cohen's d =0.44), and at the 1-month follow-up (55.9 ± 29.3; p=0.008; Cohen's d =0.49). CONCLUSION: An online expressive writing intervention was effective at improving resilience in the midst of the COVID-19 pandemic. NCT#: NCT04589104.

Standardisation of diet and exercise in clinical trials of NAFLD-NASH: Recommendations from the Liver Forum.

Lifestyle modification is the foundation of treatment recommendations for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The design of clinical trials in NASH may be impeded by the lack of a systematic approach to identify and evaluate how lifestyle changes and/or modifications influence clinical trial outcomes and associated endpoints. Furthermore, there are additional uncertainties regarding the methods that can be utilised to better characterise and quantify lifestyle variables - which can influence disease activity and alter trial endpoints - to allow for comparisons of trial outcomes across different phases of research and/or within drug-classes. This summary by the Liver Forum's Standard of Care Working Group reviews currently available clinical data, identifies the barriers and challenges associated with the standard of care in NAFLD/NASH clinical trials, defines available assessments of lifestyle changes, and proposes approaches to better understand and define the influence of diet and exercise on NASH treatment in the context of different pharmacologic interventions. The ultimate objective is to propose tangible solutions which enable investigators, sponsors, and regulatory authorities to meaningfully interpret clinical trial outcomes and the impact of lifestyle modification on such outcomes as they pertain to phase I-IV clinical trials.

Considerations and Current Trends in the Management of the Geriatric Patient on a Consultation-Liaison Service.

PURPOSE OF REVIEW: To provide consultation-liaison psychiatrists with an updated resource that can assist in the treatment and management of geriatric patients. RECENT FINDINGS: The current available literature has not shown any differences in efficacy between haloperidol and second-generation antipsychotics in patients with delirium. When considering relative advantages of forms of antipsychotic administration, there is no support for a superior safety profile of oral compared to intramuscular or intravenous administration. A recent meta-analysis of four randomized controlled trials concluded that when melatonin was administered to older age patients on medical wards, it significantly prevented the incidence of delirium when compared with the control group. While suvorexant administered nightly to elderly patients in acute care settings may lower the incidence of delirium, larger studies are needed to confirm this finding. Despite the black box warning of increased mortality risk in older patients with dementia, antipsychotics may be used with caution by the consultation-liaison (CL) psychiatrist to treat the neuropsychologic symptoms of dementia including hallucinations and psychosis in the hospital setting. While antidepressant studies have focused primarily on citalopram and escitalopram in the treatment of agitation in the setting of dementia, these two medications have not been adequately compared directly to other SSRIs for this condition. It is therefore not clear whether citalopram and escitalopram are more efficacious in treating agitation in the setting of dementia when compared to other SSRIs. While the evidence supporting trazodone's use is limited, it is generally well tolerated and is an option as a PRN for irritability and agitation in patients with Alzheimer's and mixed dementia. While there is some evidence to support the use of acetylcholinesterase inhibitors for treating cognitive impairments and hallucinations in Lewy body dementia, the usefulness of these agents in other forms of dementia is not well studied, and those studies did not show any benefit in the management of acute agitation. It is important to note that memantine can cause or exacerbate agitation and may be the cause of behavioral dysregulation. There is no evidence to support the routine use of benzodiazepines for behavioral improvement in patients with dementia. Escitalopram and citalopram do have a unique pharmacokinetic properties in the sense that they have been found to have 50-56% plasma protein binding, compared to sertraline, fluoxetine, and paroxetine (95% or more). Pooled analyses suggest that antidepressants are more effective than placebo in reducing the symptoms of post-stroke depression. SSRIs are considered first-line antidepressants in stroke patients, who are often elderly with underlying cardiovascular problems. Although treatment with SSRIs is recommended for post-stroke depression, there are no studies providing conclusive data on the superiority of a specific drug. Older age is associated with a better outcome from ECT, with remission rates of approximately 73% to 90% in patients over 65 years. ECT is the treatment of choice for patients with psychotic depression, and elderly patients with psychotic depression have been shown to have a higher remission rate and faster time to response than depressed patients without psychotic symptoms. With the average life expectancy increase, it is projected that 19 million people will reach the age of 85 or higher, an increase from 5.5 million in 2010. With an increasing older population, psychiatric consultation in the management of geriatric patients is becoming more necessary. Psychiatrists must be aware of the unique considerations in elderly patients. In this article, we provide evidence-based guidance to the CL psychiatrist on major issues relating to the older age patient, highlighting recent trends in treatment. First, we provide background on the evaluation of the medically hospitalized geriatric patient. As rates of medical and psychiatric illnesses increase with advancing age, elderly patients are more likely to be taking a higher number of medications as compared to younger patients, and physicians must pay special attention to polypharmacy, including side effects and drug interactions in this group. Next, we focus on the diagnosis, management, and unique needs of the geriatric patient presenting with common clinical syndromes of delirium, dementia, and depression. Delirium and dementia are among the most common causes of cognitive impairment in clinical settings yet are often either unrecognized or misdiagnosed as they may have similar signs and symptoms. In addition, depression is prevalent in older adults, especially in those with comorbid medical illness. Depression can be fatal as the rates of suicide are higher in later life than in any other age group. Consultation can improve the management of elderly patients and prevent unnecessary nursing home placement.

Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia (BPSD): A Retrospective Chart Review.

OBJECTIVE: Much of the functional disturbance in patients with dementia reflects the presence of noncognitive behavioral and psychological symptoms of dementia (BPSD). Agitation is among the most distressing symptoms for patients, clinicians, and caregivers. Currently no pharmacotherapy has clearly been shown to be of value for this condition. This study used a chart review method to examine the safety and efficacy of electroconvulsive therapy (ECT) for patients with dementia receiving ECT for agitation. METHODS: A retrospective chart review was conducted of patients with dementia presenting with symptoms of aggression or agitation and who received ECT treatments. Aggression and agitation were measured by pre- and post-ECT Pittsburg Agitation Scale (PAS) scores. Detailed history of the use of psychotropic medications as well as other clinically relevant variables was analyzed. FINDINGS: Sixty elderly patients (45 women and 15 men, 75% female, mean age 77.5 ± 8.0 years) were included in the analysis. Most patients were treatment resistant to multiple psychotropic medications prior to ECT (mean number 6.1±1.5). The baseline PAS total was 9.3 ± 3.7 and it decreased significantly after three (2.5±2.8) and six (1.5±2.3) ECT treatments. No significant ECT-related medical complications were observed except transient confusion. A decrease in the number of psychotropics prescribed along with an increase in the GAF score was observed after the ECT treatment course. CONCLUSION: ECT was safe in this sample of patients who had co-morbid medical conditions. ECT was associated with the following observations: 1) a reduction in agitation; 2) a reduction in psychotropic polypharmacy; and 3) an improvement in global functioning level. Further research evaluating the effects of ECT in the setting of dementia is warranted.

Expressive writing to improve resilience to trauma: A clinical feasibility trial.

BACKGROUND AND PURPOSE: Trauma is highly prevalent, with estimates that up to 90% of the U.S. population have been exposed to a traumatic event. The adverse health consequences of trauma exposure are diverse and often long-lasting. While expressive writing has been shown to improve emotional and physical health in numerous populations, the feasibility and potential effectiveness of a novel expressive writing program provided in a clinical setting to improve resilience is unknown. Our objective was to determine the feasibility and potential effectiveness of a 6-week expressive writing course provided in a clinical setting to improve resilience in individuals with a history of trauma. MATERIALS AND METHODS: This prospective, observational trial of a 6-week expressive writing intervention (Transform Your Life: Write to Heal) was conducted in an academic outpatient integrative clinic. Eligible participants were a self-referred sample of 39 English-speaking adults who identified as having had a trauma, or significant emotional/physical upheaval, within the past year. Main outcome measures included: Feasibility: Enrollment, Retention in Program and Trial, Adherence. Acceptability: Adverse Events; Participant Ratings. Primary Psychological Outcome: Connor-Davidson Resilience Scale (CD-RISC). Secondary Psychological Outcomes: Perceived Stress Scale - 10 item (PSS-10); Center for Epidemiologic Studies Depression Scale (CES-D); Rumination Response Scale (RRS). RESULTS: All measures of feasibility including those related to enrollment, retention, and adherence support feasibility. All measures of acceptability including adverse events and participant ratings support the intervention as being safe, well-received and personally valuable. Resilience scores increased from baseline (64.3 ±â€¯14.40) to post-intervention (74.2 ±â€¯13.15), t(37) = 4.61, p < 0.0005; Cohen's d = 0.75. In addition, across the same period, Perceived Stress scores decreased close to a standard deviation (20.5 ±â€¯7.43 to 14.3 ±â€¯6.64), t(37) = -4.71, p < 0.0005, Cohen's d = 0.76; depression symptoms decreased (from 19.0 ±â€¯13.48 to 12.7 ±â€¯11.68), t(37) = -3.21, p = 0.003, Cohen's d = 0.52; and rumination scores decreased from 48.5 ±â€¯12.56 to 39.8 ±â€¯10.07), t(37) = -5.03, p < 0.0005, Cohen's d = 0.82. Effect sizes ranged from medium to large. CONCLUSION: The Transform Your Life: Write to Heal program is feasible to offer in a clinical setting, was well-received by participants, and demonstrated preliminary findings of effectiveness. Our study suggests that this novel 6-week writing intervention including expressive, transactional, poetic, affirmative, legacy, and mindful writing prompts increases resilience, and decreases depressive symptoms, perceived stress, and rumination in an outpatient sample of those reporting trauma in the past year. The program appears suitable to be evaluated in a larger randomized controlled trial.

Efficacy and Safety of Massage for Osteoarthritis of the Knee: a Randomized Clinical Trial.

BACKGROUND: Current treatment options for knee osteoarthritis have limited effectiveness and potentially adverse side effects. Massage may offer a safe and effective complement to the management of knee osteoarthritis. OBJECTIVE: Examine effects of whole-body massage on knee osteoarthritis, compared to active control (light-touch) and usual care. DESIGN: Multisite RCT assessing the efficacy of massage compared to light-touch and usual care in adults with knee osteoarthritis, with assessments at baseline and weeks 8, 16, 24, 36, and 52. Subjects in massage or light-touch groups received eight weekly treatments, then were randomized to biweekly intervention or usual care to week 52. The original usual care group continued to week 24. Analysis was performed on an intention-to-treat basis. PARTICIPANTS: Five hundred fifty-one screened for eligibility, 222 adults with knee osteoarthritis enrolled, 200 completed 8-week assessments, and 175 completed 52-week assessments. INTERVENTION: Sixty minutes of protocolized full-body massage or light-touch. MAIN MEASURES: Primary: Western Ontario and McMaster Universities Arthritis Index. Secondary: visual analog pain scale, PROMIS Pain Interference, knee range of motion, and timed 50-ft walk. KEY RESULTS: At 8 weeks, massage significantly improved WOMAC Global scores compared to light-touch (- 8.16, 95% CI = - 13.50 to - 2.81) and usual care (- 9.55, 95% CI = - 14.66 to - 4.45). Additionally, massage improved pain, stiffness, and physical function WOMAC subscale scores compared to light-touch (p < 0.001; p = 0.04; p = 0.02, respectively) and usual care (p < 0.001; p = 0.002; p = 0.002; respectively). At 52 weeks, the omnibus test of any group difference in the change in WOMAC Global from baseline to 52 weeks was not significant (p = 0.707, df = 3), indicating no significant difference in change across groups. Adverse events were minimal. CONCLUSIONS: Efficacy of symptom relief and safety of weekly massage make it an attractive short-term treatment option for knee osteoarthritis. Longer-term biweekly dose maintained improvement, but did not provide additional benefit beyond usual care post 8-week treatment. TRIAL REGISTRATION: clinicaltrials.gov NCT01537484.