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Importance: Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.Objective: To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.Design, Setting, and Participants: This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020.Interventions: Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants).Main Outcomes and Measures: The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up.Results: Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of -2.1 vs -1.8 points, respectively (difference, -0.4 [95% CI, -0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was -1.4% vs -1.2%, respectively (difference, -0.2% [95% CI, -1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences.Conclusions and Relevance: Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA.Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347. [ABSTRACT FROM AUTHOR]

Importance: Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown.Objective: To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis.Design, Setting, and Participants: Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital.Interventions: Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs).Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay.Results: Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, -0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, -0.51 percentage points [95% CI, -0.90 to -0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group.Conclusions and Relevance: Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication.Trial Registration: anzctr.org.au Identifier: ACTRN12616000481471. [ABSTRACT FROM AUTHOR]

Importance: After severe traumatic brain injury, induction of prophylactic hypothermia has been suggested to be neuroprotective and improve long-term neurologic outcomes.Objective: To determine the effectiveness of early prophylactic hypothermia compared with normothermic management of patients after severe traumatic brain injury.Design, Setting, and Participants: The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury-Randomized Clinical Trial (POLAR-RCT) was a multicenter randomized trial in 6 countries that recruited 511 patients both out-of-hospital and in emergency departments after severe traumatic brain injury. The first patient was enrolled on December 5, 2010, and the last on November 10, 2017. The final date of follow-up was May 15, 2018.Interventions: There were 266 patients randomized to the prophylactic hypothermia group and 245 to normothermic management. Prophylactic hypothermia targeted the early induction of hypothermia (33°C-35°C) for at least 72 hours and up to 7 days if intracranial pressures were elevated, followed by gradual rewarming. Normothermia targeted 37°C, using surface-cooling wraps when required. Temperature was managed in both groups for 7 days. All other care was at the discretion of the treating physician.Main Outcomes and Measures: The primary outcome was favorable neurologic outcomes or independent living (Glasgow Outcome Scale-Extended score, 5-8 [scale range, 1-8]) obtained by blinded assessors 6 months after injury.Results: Among 511 patients who were randomized, 500 provided ongoing consent (mean age, 34.5 years [SD, 13.4]; 402 men [80.2%]) and 466 completed the primary outcome evaluation. Hypothermia was initiated rapidly after injury (median, 1.8 hours [IQR, 1.0-2.7 hours]) and rewarming occurred slowly (median, 22.5 hours [IQR, 16-27 hours]). Favorable outcomes (Glasgow Outcome Scale-Extended score, 5-8) at 6 months occurred in 117 patients (48.8%) in the hypothermia group and 111 (49.1%) in the normothermia group (risk difference, 0.4% [95% CI, -9.4% to 8.7%]; relative risk with hypothermia, 0.99 [95% CI, 0.82-1.19]; P = .94). In the hypothermia and normothermia groups, the rates of pneumonia were 55.0% vs 51.3%, respectively, and rates of increased intracranial bleeding were 18.1% vs 15.4%, respectively.Conclusions and Relevance: Among patients with severe traumatic brain injury, early prophylactic hypothermia compared with normothermia did not improve neurologic outcomes at 6 months. These findings do not support the use of early prophylactic hypothermia for patients with severe traumatic brain injury.Trial Registration: clinicaltrials.gov Identifier: NCT00987688; Anzctr.org.au Identifier: ACTRN12609000764235. [ABSTRACT FROM AUTHOR]

Importance: There is debate about benefits of acupuncture for knee pain.Objective: To determine the efficacy of laser and needle acupuncture for chronic knee pain.Design, Setting, and Participants: Zelen-design clinical trial (randomization occurred before informed consent), in Victoria, Australia (February 2010-December 2012). Community volunteers (282 patients aged ≥50 years with chronic knee pain) were treated by family physician acupuncturists.Interventions: No acupuncture (control group, n = 71) and needle (n = 70), laser (n = 71), and sham laser (n = 70) acupuncture. Treatments were delivered for 12 weeks. Participants and acupuncturists were blinded to laser and sham laser acupuncture. Control participants were unaware of the trial.Main Outcomes and Measures: Primary outcomes were average knee pain (numeric rating scale, 0 [no pain] to 10 [worst pain possible]; minimal clinically important difference [MCID], 1.8 units) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0 [no difficulty] to 68 [extreme difficulty]; MCID, 6 units) at 12 weeks. Secondary outcomes included other pain and function measures, quality of life, global change, and 1-year follow-up. Analyses were by intention-to-treat using multiple imputation for missing outcome data.Results: At 12 weeks and 1 year, 26 (9%) and 50 (18%) participants were lost to follow-up, respectively. Analyses showed neither needle nor laser acupuncture significantly improved pain (mean difference; -0.4 units; 95% CI, -1.2 to 0.4, and -0.1; 95% CI, -0.9 to 0.7, respectively) or function (-1.7; 95% CI, -6.1 to 2.6, and 0.5; 95% CI, -3.4 to 4.4, respectively) compared with sham at 12 weeks. Compared with control, needle and laser acupuncture resulted in modest improvements in pain (-1.1; 95% CI, -1.8 to -0.4, and -0.8; 95% CI, -1.5 to -0.1, respectively) at 12 weeks, but not at 1 year. Needle acupuncture resulted in modest improvement in function compared with control at 12 weeks (-3.9; 95% CI, -7.7 to -0.2) but was not significantly different from sham (-1.7; 95% CI, -6.1 to 2.6) and was not maintained at 1 year. There were no differences for most secondary outcomes and no serious adverse events.Conclusions and Relevance: In patients older than 50 years with moderate or severe chronic knee pain, neither laser nor needle acupuncture conferred benefit over sham for pain or function. Our findings do not support acupuncture for these patients.Trial Registration: anzctr.org.au Identifier: ACTRN12609001001280. [ABSTRACT FROM AUTHOR]

Importance: There is limited evidence supporting use of physical therapy for hip osteoarthritis.Objective: To determine efficacy of physical therapy on pain and physical function in patients with hip osteoarthritis.Design, Setting, and Participants: Randomized, placebo-controlled, participant- and assessor-blinded trial involving 102 community volunteers with hip pain levels of 40 or higher on a visual analog scale of 100 mm (range, 0-100 mm; 100 indicates worst pain possible) and hip osteoarthritis confirmed by radiograph. Forty-nine patients in the active group and 53 in the sham group underwent 12 weeks of intervention and 24 weeks of follow-up (May 2010-February 2013) INTERVENTIONS: Participants attended 10 treatment sessions over 12 weeks. Active treatment included education and advice, manual therapy, home exercise, and gait aid if appropriate. Sham treatment included inactive ultrasound and inert gel. For 24 weeks after treatment, the active group continued unsupervised home exercise while the sham group self-applied gel 3 times weekly.Main Outcomes and Measures: Primary outcomes were average pain (0 mm, no pain; 100 mm, worst pain possible) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0 no difficulty to 68 extreme difficulty) at week 13. Secondary outcomes were these measures at week 36 and impairments, physical performance, global change, psychological status, and quality of life at weeks 13 and 36.Results: Ninety-six patients (94%) completed week 13 measurements and 83 (81%) completed week 36 measurements. The between-group differences for improvements in pain were not significant. For the active group, the baseline mean (SD) visual analog scale score was 58.8 mm (13.3) and the week-13 score was 40.1 mm (24.6); for the sham group, the baseline score was 58.0 mm (11.6) and the week-13 score was 35.2 mm (21.4). The mean difference was 6.9 mm favoring sham treatment (95% CI, -3.9 to 17.7). The function scores were not significantly different between groups. The baseline mean (SD) physical function score for the active group was 32.3 (9.2) and the week-13 score was 27.5 (12.9) units, whereas the baseline score for the sham treatment group was 32.4 (8.4) units and the week-13 score was 26.4 (11.3) units, for a mean difference of 1.4 units favoring sham (95% CI, -3.8 to 6.5) at week 13. There were no between-group differences in secondary outcomes (except greater week-13 improvement in the balance step test in the active group). Nineteen of 46 patients (41%) in the active group reported 26 mild adverse effects and 7 of 49 (14%) in the sham group reported 9 mild adverse events (P = .003).Conclusions and Relevance: Among adults with painful hip osteoarthritis, physical therapy did not result in greater improvement in pain or function compared with sham treatment, raising questions about its value for these patients.Trial Registration: anzctr.org.au Identifier: ACTRN12610000439044. [ABSTRACT FROM AUTHOR]

Context: Extracorporeal shock wave therapy (ESWT) is increasingly used for plantar fasciitis, but limited evidence supports its use.Objective: To determine whether ultrasound-guided ESWT reduces pain and improves function in patients with plantar fasciitis.Design: Double-blind, randomized, placebo-controlled trial conducted between April 1999 and June 2001.Setting: Participants were recruited from the community-based referring physicians (primary care physicians, rheumatologists, orthopedic surgeons, and sports physicians) of a radiology group in Melbourne, Australia.Participants: We screened 178 patients and enrolled 166; 160 completed the 15-week protocol. Entry criteria included age at least 18 years with plantar fasciitis, defined as heel pain maximal over the plantar aspect of the foot of at least 6 weeks' duration, and an ultrasound-confirmed lesion, defined as thickening of the origin of the plantar fascia of at least 4 mm, hypoechogenicity, and alterations in the normal fibrillary pattern.Interventions: Patients were randomly assigned to receive either ultrasound-guided ESWT given weekly for 3 weeks to a total dose of at least 1000 mJ/mm(2) (n = 81), or identical placebo to a total dose of 6.0 mJ/mm(2) (n = 85).Main Outcome Measures: Overall, morning, and activity pain, measured on a visual analog scale; Maryland Foot Score; walking ability; Short-Form-36 Health Survey (SF-36) score; and Problem Elicitation Technique score, measured at 6 and 12 weeks after treatment completion.Results: At 6 and 12 weeks, there were significant improvements in overall pain in both the active group and placebo group (mean [SD] improvement, 18.1 [30.6] and 19.8 [33.7] at 6 weeks [P =.74 for between-group difference], and 26.3 [34.8] and 25.7 [34.9] at 12 weeks [P =.99], respectively). Similar improvements in both groups were also observed for morning and activity pain, walking ability, Maryland Foot Score, Problem Elicitation Technique, and SF-36. There were no statistically significant differences in the degree of improvement between treatment groups for any measured outcomes.Conclusion: We found no evidence to support a beneficial effect on pain, function, and quality of life of ultrasound-guided ESWT over placebo in patients with ultrasound-proven plantar fasciitis 6 and 12 weeks following treatment. [ABSTRACT FROM AUTHOR]