quality of life

Importance Restless legs syndrome (RLS) is a sleep-related movement disorder that affects approximately 3% of US adults to a clinically significant extent and can cause substantial sleep disturbance.

Observations Restless legs syndrome is characterized by an overwhelming urge to move the limbs, typically the legs, often accompanied by unpleasant limb sensations (eg, achiness, tingling). Symptoms, provoked by immobility, are relieved while moving and are typically present or most severe in the evening or at night. Restless legs syndrome symptoms may lead to difficulty falling asleep, staying asleep, or returning to sleep. According to population-based studies, approximately 8% of US adults experience RLS symptoms of any frequency annually and 3% experience moderately or severely distressing symptoms at least twice weekly. Patients with RLS have impaired quality of life and elevated rates of cardiovascular disease (29.6% with coronary artery disease, stroke, or heart failure), depression (30.4%), and suicidal ideation or self-harm (0.35 cases/1000 person-years). Restless legs syndrome is common among patients with multiple sclerosis (27.5%), end-stage kidney disease (24%), and iron deficiency anemia (23.9%); during pregnancy and especially in the third trimester (22%); with peripheral neuropathy (eg, diabetic, idiopathic; 21.5%); and with Parkinson disease (20%). Other risk factors include family history of RLS, northern European descent, female sex (2:1 vs male sex), and older age (RLS prevalence of 10% in adults ≥65 years). Restless legs syndrome is diagnosed based on clinical history; polysomnography is not recommended for diagnosis. Iron supplementation with ferrous sulfate (325-650 mg daily or every other day) or intravenous iron (1000 mg) should be initiated for serum ferritin level less than or equal to 100 ng/mL or transferrin saturation less than 20%. If possible, medications associated with RLS, including serotonergic antidepressants, dopamine antagonists, and centrally acting H1 antihistamines (eg, diphenhydramine), should be discontinued. Gabapentinoids (eg, gabapentin, gabapentin enacarbil, pregabalin) are first-line pharmacologic therapy. In randomized clinical trials, approximately 70% of patients treated with gabapentinoids had much or very much improved RLS symptoms vs approximately 40% with placebo (P < .001). Dopamine agonists (eg, ropinirole, pramipexole, rotigotine) are no longer recommended as first-line medications due to the risk of augmentation, an iatrogenic worsening of RLS symptoms, which has an annual incidence of 7% to 10% with these medications. Patients who do not improve with first-line treatment or have augmented RLS often benefit from low-dose opioids (eg, methadone 5-10 mg daily).

Conclusions and Relevance Restless legs syndrome affects approximately 3% of adults and can have negative effects on sleep and quality of life. Initial management includes cessation of exacerbating medications, as well as iron supplementation for patients with low-normal iron indices. If medication therapy is indicated, gabapentinoids are first-line treatment.

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.

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.

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.)