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Online Unsupervised Tai Chi Intervention for Knee Pain and Function in People With Knee Osteoarthritis: The RETREAT Randomized Clinical Trial

Author/s: 
Shiyi Julia Zhu, Rana S Hinman, Rachel K Nelligan, Peixuan Li, Anurika P De Silva, Jenny Harrison, Alexander J Kimp, Kim L Bennell

Importance: Tai chi is a type of exercise recommended for knee osteoarthritis, but access to in-person tai chi can be limited.

Objective: To evaluate the effects of an unsupervised multimodal online tai chi intervention on knee pain and function for people with knee osteoarthritis.

Design, setting, and participants: The RETREAT study was a 2-group superiority randomized clinical trial enrolling participants who met clinical criteria for knee osteoarthritis in Australian communities from August 2023 and November 2024.

Interventions: Participants in the control group received access to a purpose-built website containing information about osteoarthritis and exercise benefits. Participants in the intervention group received the My Joint Tai Chi intervention comprising access to the same website plus tai chi information, a 12-week unsupervised video-based Yang-style tai chi program, and encouragement to use an app to facilitate program adherence.

Main outcomes and measures: Changes in knee pain during walking (Numeric Rating Scale; range 0-10 with higher scores indicating greater pain) and difficulty with physical function (Western Ontario and McMaster Universities Osteoarthritis Index; range 0-68 with higher scores indicating greater dysfunction) during 12 weeks. Secondary outcomes included another knee pain measure, sport and recreation function, quality of life, physical and mental well-being, fear of movement, self-efficacy, balance confidence, positive activated affect, sleep quality, global improvement, and oral medication use.

Results: Of 2106 patients screened, 178 met inclusion criteria and were randomized, 89 (mean [SD] age, 61.0 [8.7] years; 66 female [74%] and 23 [26%] male participants) to the control group and 89 (mean [SD] age, 62.1 [7.3] years; 59 [66%] female and 30 male [34%] participants) to the tai chi intervention. Of the total, 170 (96%) completed both of the primary outcomes at 12 weeks. The tai chi group reported greater improvements in knee pain (control, -1.3; tai chi, -2.7; mean difference, -1.4 [95% CI, -2.1 to -0.7] units; P < .001) and function (control, -6.9; tai chi, -12.0; mean difference, -5.6 [95% CI, -9.0 to -2.3] units; P < .001) compared to the control group. More participants in the tai chi than in the control group achieved a minimal clinically important difference in pain (73% vs 47%; risk difference, 0.3; 95% CI, 0.1 to 0.4; P < .001) and function (72% vs 52%; risk difference, 0.2; 95% CI, 0.1 to 0.3; P = .007). Between-group differences for most secondary outcomes favored tai chi, including another knee pain measure, sport and recreation function, quality of life, physical and mental well-being, global improvement, pain self-efficacy, and balance confidence. No associated serious adverse events were reported.

Conclusions and relevance: This randomized clinical trial found that this unsupervised multimodal online tai chi intervention improved knee pain and function compared with the control at 12 weeks. This free-to-access web-based intervention offers an effective, safe, accessible, and scalable option for guideline-recommended osteoarthritis exercise.

Keywords 
Knee osteoarthritis kinesiophobia Tai Chi

Comparative efficacy and safety of exercise modalities in knee osteoarthritis: systematic review and network meta-analysis

Author/s: 
Lei Yan, Dijun Li, Dan Xing, Zijuan Fan, Guangyuan Du, Jingwei Jiu, Xiaoke Li, Janne Estill, Qi Wang, Ahmed Atef Belal, Chen Tian, Jiao Jiao Li, Songyan Li, Haifeng Liu, Xuanbo Liu, Yijia Ren, Yiqi Yang, Jinxiu Chen, Yihe Hu, Long Ge, Bin Wang

Objective: To assess the efficacy and safety of various exercise modalities as therapeutic interventions for managing knee osteoarthritis.

Design: Systematic review with network meta-analysis.

Data sources: PubMed, Embase, Cochrane Library, Web of Science, CINAHL, PsycINFO, AMED, PEDro, Scopus, ClinicalTrials.gov, ICTRP, and ClinicalTrialsRegister.eu from database inception to August 2024.

Eligibility criteria for selecting studies: Randomised controlled trials comparing different exercise modalities, including aerobic exercise, flexibility exercise, mind-body exercise, neuromotor exercise, strengthening exercise, mixed exercise, and control group for patients with knee osteoarthritis.

Main outcome measures: Primary outcomes included pain, function, gait performance, and quality of life, assessed at short term (four weeks), mid-term (12 weeks), and long term (24 weeks) follow-up. When exact time points were unavailable, data from adjacent time windows were used.

Results: 217 randomised controlled trials involving 15 684 participants were included. Moderate certainty evidence showed that, compared with the control group, aerobic exercise probably results in large improvements in pain at short term (standardised mean difference -1.10, 95% confidence interval -1.68 to -0.52) and mid-term follow-up (-1.19, -1.59 to -0.79), function at mid-term (1.78, 1.05 to 2.51), gait performance at mid-term (0.85, 0.55 to 1.14), and quality of life at short term (1.53, 0.47 to 2.59). Mind-body exercise probably results in a large increase in function at short term follow-up (0.88, 0.03 to 1.73; moderate certainty), while neuromotor exercise probably results in a large increase in gait performance at short term follow-up (1.04, 0.51 to 1.57; moderate certainty). Strengthening (0.86, 0.53 to 1.18) and mixed exercise (1.07, 0.68 to 1.46) probably result in a large increase in function at mid-term follow-up, all with moderate certainty evidence. Regarding long term follow-up, flexibility exercise may result in a large reduction in pain (-0.99, -1.63 to -0.36; low certainty); aerobic exercise may result in a large increase in function (0.87, 0.02 to 1.72, low certainty); and mixed exercise may increase function (0.56, 0.26 to 0.86; low certainty) and probably increases gait performance (0.57, 0.21 to 0.92, moderate certainty). Overall, aerobic exercise consistently showed the highest probability of being the best treatment, as reflected by surface under the cumulative ranking curve values (mean 0.72) across outcomes. The safety outcome was reported in a small proportion of studies (40 studies, 18%), and no clear differences were observed between exercise interventions and control.

Conclusions: In patients with knee osteoarthritis, aerobic exercise is likely the most beneficial exercise modality for improving pain, function, gait performance, and quality of life, with moderate certainty.

Systematic review registration: PROSPERO CRD42023469762.

Keywords 
exercise exercise therapy Knee osteoarthritis

The effectiveness and safety of methotrexate in the intervention of osteoarthritis: A systematic review and meta-analysis of randomized controlled trials

Author/s: 
Wan, Lifei, Yang, Qianyue, Yang, Kailin, Zeng, Liuting, Sun, Lingyun

Background:
Osteoarthritis (OA) is a prevalent chronic joint disorder among middle-aged and older adults, characterized by progressive cartilage degeneration, subchondral bone remodeling, and osteophyte formation, leading to joint pain, stiffness, dysfunction, and reduced quality of life. With the global aging population, OA imposes a growing socioeconomic burden, yet no disease-modifying therapy is currently available—particularly for moderate-to-severe stages. Emerging evidence implicates synovial inflammation as a central contributor to OA symptoms and progression, raising interest in methotrexate (MTX), a well-established, low-dose anti-inflammatory agent used safely in rheumatoid arthritis. Preliminary studies suggest MTX may alleviate OA-related pain, but findings from randomized controlled trials (RCTs) have been inconsistent and limited in number. Given recent new RCTs and the heterogeneity of existing outcomes, an updated systematic review and meta-analysis is urgently needed to clarify the efficacy and safety of MTX in OA and inform future clinical trial design.

Methods:
PubMed, ClinicalTrials, Web of Science, Cochrane Library and other databases were searched to find randomized controlled trials (RCT) of MTX treatment of OA. Methodological quality was assessed using the Cochrane "risk of bias" assessment tool, and the meta-analysis was conducted using Review Manager (RevMan) version 5.3 (The Cochrane Collaboration, London, UK).

Results:
Fifteen RCTs involving 1591 participants were included in this review. The meta-analysis results showed that the ineffective rate in the experimental group was lower [RR: 0.40 (0.24, 0.67), P = .004]; the VAS in the experimental group was lower [WMD: −0.66 (−1.08, −0.24), P = .002]; the WOMAC score-stiffness in the experimental group was lower [WMD: −0.72 (−1.04, −0.41), P < .00001]; the WOMAC score-function in the experimental group was lower [WMD: −7.72 (−13.56, −1.87), P = .01]. The adverse events in the experimental group were not statistically significant compared with the control group [RR: 1.04 (0.77, 1.42), P = .78].

Conclusion:
MTX demonstrates potential in effectively alleviating pain, improving joint function, and slowing disease progression in patients with OA. Its safety profile is comparable to that of control treatments, making it a viable and reliable therapeutic option worthy of broader clinical application.

Keywords 
methotrexate osteoarthritis meta-analysis systematic review

Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity

Author/s: 
Sean Wharton, Ildiko Lingvay, Pawel Bogdanski, Ruben Duque do Vale, Stephan Jacob, Tobias Karlsson, Chaithra Shaji, Domenica Rubino, W. Timothy Garvey

Background
Oral semaglutide at a dose of 25 mg may provide an alternative treatment option to injectable semaglutide (2.4 mg) and higher-dose oral semaglutide (50 mg) for persons with overweight or obesity.

Methods
In a 71-week, double-blind, randomized, placebo-controlled trial conducted at 22 sites in four countries, we enrolled persons without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. The participants were randomly assigned in a 2:1 ratio to receive oral semaglutide (25 mg) or placebo once daily, plus lifestyle interventions. The coprimary end points at week 64 were the percent change in body weight and a reduction of 5% or more in body weight; confirmatory secondary end points included reductions in body weight of 10% or more, 15% or more, and 20% or more and the change in the Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score.

Results
A total of 205 participants were randomly assigned to receive oral semaglutide, and 102 to receive placebo. The estimated mean change in body weight from baseline to week 64 was −13.6% in the oral semaglutide group and −2.2% in the placebo group (estimated difference, −11.4 percentage points; 95% confidence interval, −13.9 to −9.0; P<0.001). Participants in the oral semaglutide group were significantly more likely than those in the placebo group to have body-weight reductions of 5% or more, 10% or more, 15% or more, and 20% or more (P<0.001 for all comparisons) and to have an improved IWQOL-Lite-CT Physical Function score (P<0.001). Gastrointestinal adverse events were more common with oral semaglutide than with placebo (74.0% vs. 42.2%).

Conclusions
Oral semaglutide at a dose of 25 mg once daily resulted in a greater mean reduction in body weight than placebo in participants with overweight or obesity. (Funded by Novo Nordisk; OASIS 4 ClinicalTrials.gov number, NCT05564117.)

Keywords 
Semaglutide overweight

Cognitive Behavioral Therapy for Insomnia in People With Chronic Disease: A Systematic Review and Meta-Analysis

Author/s: 
Amelia J. Scott, Ashleigh B. Correa, Madelyne A. Bisby

Importance: Insomnia is highly prevalent among individuals with chronic disease (eg, chronic pain, cardiovascular disease, and cancer) and results in poorer disease outcomes and quality of life. Cognitive behavioral therapy for insomnia (CBT-I) is recommended as first-line treatment for insomnia. However, concerns remain about its applicability and efficacy in people with chronic disease.

Objective: To evaluate the nature, efficacy, and acceptability of CBT-I in adults with chronic disease, and to identify moderators of treatment outcomes.

Data sources: Systematic searches were conducted in PsycINFO, Medline, Embase, and CENTRAL from database inception to June 5, 2025. Additional records were identified from reference lists of relevant reviews and studies.

Study selection: Eligible studies were randomized clinical trials (RCTs) involving adults (aged ≥18 years) with chronic disease and insomnia. Studies using CBT-I with measured sleep outcomes were included.

Data extraction and synthesis: Two assessors extracted data from RCTs. Hedges g was used to calculate effect sizes, and random effects meta-analyses were conducted. Heterogeneity was assessed via I2. Subgroup analyses examined whether outcomes varied by delivery format, chronic condition type, or control group.

Main outcomes and measures: Primary outcomes included insomnia severity, sleep efficiency, and sleep onset latency. Secondary outcomes included treatment acceptability and adverse effects.

Results: Sixty-seven RCTs (5232 participants) met inclusion criteria, including chronic diseases such as cancer, chronic pain, irritable bowel syndrome, and stroke. CBT-I was associated with significantly improved outcomes for insomnia severity (g = 0.98; 95% CI, 0.81-1.16) and moderate effect sizes regarding sleep efficiency (g = 0.77; 95% CI, 0.63-0.91) and sleep onset latency (g = 0.64; 95% CI, 0.50-0.78). Subgroup analyses revealed some sample, treatment, and methodological moderators (eg, longer treatment yielded better outcomes for sleep efficiency and sleep onset latency). Satisfaction with CBT-I was high, with a mean dropout rate of 13.3%. Treatment-related adverse effects were rare.

Conclusions and relevance: This systematic review and meta-analysis showed that CBT-I demonstrated strong efficacy and acceptability in chronic disease populations, with moderate to large effect sizes that appear comparable to those in non-chronic disease populations. Efficacy of CBT-I was similar across a range of disease subgroups. Future research should explore the role and nature of treatment adaptations for specific populations and increase access to CBT-I in medical settings.

Keywords 
sleep medicine Geriatrics psychotherapy neurology

Canadian guideline for Parkinson disease

Author/s: 
David Grimes, Megan Fitzpatrick, Joyce Gordon, Janis Miyasaki, Edward A Fon, Michael Schlossmacher, Oksana Suchowersky, Alexander Rajput, Anne Louise Lafontaine, Tiago Mestre, Silke Appel-Cresswell, Suneil K Kalia, Kerrie Schoffer, Mateusz Zurowski, Ronald B Postuma, Sean Udow, Susan Fox, Pauline Barbeau, Brian Hutton

KEY POINTS

This guideline update reflects substantial changes in the literature on diagnosis and treatment of Parkinson disease, and adds information on palliative care.

Impulse control disorders can develop in a person with Parkinson disease who is on any dopaminergic therapy at any stage in the disease course, especially for those taking dopamine agonists.

Advanced therapies like deep brain stimulation and intrajejunal levodopa-carbidopa gel infusion are now routinely used in Parkinson disease to manage motor symptoms and fluctuations.

Evidence exists to support early institution of exercise at the time of diagnosis of Parkinson disease, in addition to the clear benefit now shown in those with well-established disease.

Palliative care requirements of people with Parkinson disease should be considered throughout all phases of the disease, which includes an option of medical assistance in dying.

Parkinson disease is chronic and progressive in nature, decreasing the quality of life for both patients with the disease and their caregivers and placing an onerous economic burden on society.1

The first Canadian guideline on Parkinson disease was published in 2012.2 Since that guideline, there have been substantial advances in the literature on the disease, particularly with respect to diagnostic criteria and treatment options. Parkinson Canada undertook to update the existing guideline to reflect these advances, as well as to add information on palliative care.

With the aim of enhancing care for all Canadians with Parkinson disease, this guideline is based on the best published evidence, involves expert consensus when there is a lack of evidence, offers practical clinical advice, takes patient choice and informed decision-making into account and is relevant to the Canadian health care system. The guideline has been divided into 5 main sections to improve the ease of use: communication, diagnosis and progression, treatment, nonmotor features and palliative care. The full guideline is available in Appendix 1, at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.181504/-/DC1.

Keywords 
Disease Progression Dopamine Agonists exercise therapy palliative care Parkinson Disease quality of life

Hidradenitis suppurativa

Author/s: 
Robert Sabat, Afsaneh Alavi, Kerstin Wolk, Ximena Wortsman, Barry McGrath, Amit Garg, Jacek C Szepietowski

Hidradenitis suppurativa is a chronic inflammatory disease characterised by painful, deep-seated nodules, abscesses, and draining tunnels in the skin of axillary, inguinal, genitoanal, or inframammary areas. In recent years, the body of knowledge in hidradenitis suppurativa has advanced greatly. This disorder typically starts in the second or third decade of life. The average worldwide prevalence is 1% but varies geographically. Hidradenitis suppurativa has a profound negative effect on patients' quality of life and on the gross value added to society. Comorbidities (eg, metabolic syndrome, inflammatory arthritis, and inflammatory bowel disease) frequently accompany skin alterations, because of systemic inflammation. Pathogenesis of hidradenitis suppurativa is complex and includes innate immune mechanisms (eg, macrophages, neutrophils, IL-1β, tumour necrosis factor [TNF], and granulocyte colony-stimulating factor), T-cell mechanisms (eg, IL-17 and IFN-γ), and B-cell mechanisms (eg, associated with dermal tertiary lymphatic structures and autoantibodies). Chronic inflammation leads to irreversible skin damage with tunnel formation and morbid scarring. Current treatment includes drug therapy (for the initial, purely inflammatory phase), combined drug and surgical therapy (for the destructive phase), or surgery alone (for the burnout phase). The first systemic therapies approved for hidradenitis suppurativa targeting TNF (adalimumab) and IL-17 (secukinumab and bimekizumab) have expanded drug therapy options for moderate-to-severe disease, which were previously mainly restricted to oral antibiotics. Moreover, there is a robust pipeline of immunomodulatory drugs in various stages of development for hidradenitis suppurativa. Aims of management should include early intervention to prevent irreversible skin damage, adequate control of symptoms including pain, and mitigation of extra-cutaneous comorbidities, all requiring early diagnosis and an interdisciplinary, holistic and personalised approach.

Keywords 
hidradenitis suppurativa

What Is Hospice?

Author/s: 
Vanessa Wagner, Adam Marks

Hospice is a specialized model of medical care for people with terminal illness.

The goal of hospice is to provide compassionate care to maximize a person’s comfort and quality of life during the natural dying process. Hospice care teams are composed of doctors, nurses, social workers, chaplains, and other individuals who work together to address the physical, emotional, social, and spiritual needs of people with a terminal illness and to support their families. This generally includes alleviating symptoms (such as pain, shortness of breath, or anxiety), establishing a comfortable and peaceful environment, and facilitating meaningful time with loved ones.

Keywords 
end of life care palliative care hospice

Sexual Dysfunction in Women

Author/s: 
Susan R Davis

The Clinical Problem
Because there is no universal definition of normal sexual function, what constitutes sexual difficulty is determined by a person’s subjective definition of unsatisfactory sexual well-being. The condition is usually described as unsatisfactory interest, arousal, orgasm, or other aspects of sexuality (e.g., sexual self-image), and the symptoms often coexist. The term “sexual dysfunction” is used when at least one of the symptoms is of substantial concern to the affected person. Sexual dysfunction negatively affects mental health, vitality, and social functioning and has an overall effect on quality of life that is of similar magnitude to that associated with chronic back pain or diabetes.

Keywords 
Sexual Dysfunction Estrogen Replacement Therapy Hysterectomy Libido menopause Women's Health

How useful are direct-to-consumer hearing aids?

Author/s: 
Émélie Braschi, Samantha S Moe

Clinical question
Do self-fitted hearing aids improve hearing for adults with mild to moderately severe hearing loss?

Bottom line
Some, not all, direct-to-consumer (DTC) self-fitted hearing aids are likely comparable to audiogram-fitted conventional hearing aids and tend to cost less.

Keywords 
hearing hearing aids hearing loss Deafness
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