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Various clinical studies have been conducted worldwide to evaluate the effectiveness of acupuncture; however, designing an adequate control group is challenging. Sham acupuncture tools, designed to mimic real acupuncture without skin penetration, aim to address this challenge, but their efficacy and blinding success are debated. In this study, we conducted a randomized, double-blind, parallel-group clinical trial to validate a newly developed sham acupuncture method for future double-blind trials. Sixty-six healthy participants were randomly assigned to verum or sham acupuncture groups. Verum acupuncture targeted LI4 and ST36, common acupuncture points, while sham acupuncture aimed to mimic verum without skin penetration to ensure participant blinding. Blinding (Bang’s Blinding Index), penetration, pain, and deqi sensations were evaluated using a standardized questionnaire and an 11-point Numeric Rating Scale. Participant blinding was successfully maintained at ST36, whereas “more correct guesses” were observed for verum acupuncture than expected by chance for sham acupuncture at LI4. Furthermore, the practitioners randomly guessed the verum and sham acupuncture that they had administered to both points. Penetration and pain were higher in the verum group for both points, while deqi sensations had mixed responses. There were no adverse events in the verum acupuncture and sham acupuncture groups. The newly developed sham acupuncture demonstrated potential in blinding participants and practitioners, particularly at ST36. However, challenges were observed, especially at LI4, indicating limitations in blinding efficacy. This study underscores the importance of additional validation studies with larger sample sizes, diverse acupuncture points, and specific patient populations. Clinical Research Information Service of the Republic of Korea (registration number: KCT0008335, https://cris.nih.go.kr). •Participant blinding was successfully maintained at ST36.•Blinding efficacy was low at L14.•Sham acupuncture method may be used as a control group in double-blind trials.•Further validation in many patients and various acupuncture points is needed.

In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b) extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics. This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88) or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93) orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone). The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS) score from baseline to completion of treatment. The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was -0.4 mm (95% CI -5.9 to 5 mm) by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets relative to oxycodone tablets. The incidence of adverse events was 80.7% (71 of 88) in the hydromorphone group and 83.7% (77 of 93) in the oxycodone group. The most common adverse events were nausea, vomiting, somnolence, diarrhea, and constipation, most of which are commonly observed with opioid analgesics. The efficacy and safety of hydromorphone extended-release tablets were equivalent to those of the oxycodone extended-release formulation.

Although some probiotic bacteria have been reported to prevent infections in children, there are few well-designed double-blind studies. Here we evaluated the effects of a probiotic strain of lactic acid bacteria (LAB), Pediococcus acidilactici K15, on viral respiratory tract infections in preschool children. A four-month, randomized, double-blind, placebo-controlled study was performed in 172 healthy children aged 3 to 6 years. Subjects were administered dextrin alone or dextrin including heat-killed K15 (5 × 1010 bacteria). The number of febrile days was the primary outcome. The number of absent days from preschools and the influenza incidence were secondary outcomes. Secretory IgA (sIgA) concentrations in saliva were measured as an exploratory outcome. The primary and secondary outcomes were not significantly different between both groups. Analyses in children with little intake of fermented foods including LAB showed that the duration of a fever significantly decreased by K15 intake. The salivary sIgA level in the K15 group was maintained significantly higher than it was in the placebo group. The effects of K15 on preventing viral respiratory tract infections were not observed without the restriction of fermented foods intake. However, K15 supported anti-infectious immune systems in children who took less fermented foods and the maintenance of salivary sIgA levels in all subjects.

In a randomized trial involving more than 900 patients undergoing resection of advanced melanoma, adjuvant nivolumab was associated with a higher rate of 12-month recurrence-free survival than ipilimumab (70.5% vs. 60.8%) and with fewer adverse events.

Introduction Scalp psoriasis frequently goes with other disease location and may lead to a significant burden and impairment of quality of life (QoL). Adherence to local treatments is a frequent problem. A keratolytic and hydrating shampoo containing 2% salicylic acid, 5% urea, and 1% glycerin (active shampoo) has been developed for psoriasis‐prone scalp. Objective To assess the efficacy and tolerability of an active shampoo in subjects with mild to moderate scalp psoriasis. Materials and methods A single‐center, randomized, double‐blind, vehicle‐controlled study was conducted on 67 adults with mild to moderate psoriasis. The active shampoo or its vehicle were applied daily for 14 days and 3 times/week for another 14 days. Assessments included the Psoriasis Scalp Severity Index (PSSI), Investigator Global Assessment (IGA), calculated total surface affected hair, scalp greasiness, irritation, and assessed scalp dermatitis–specific quality‐of‐life issues using SCALPDEX and product acceptability. Results The active shampoo significantly (p < 0.05) reduced the PSSI by 39.0%, 37.2%, 63.0%, and 69.0% immediately after washing compared to a 22.8%, 5.5%, 19.6%, and 13.0% with the vehicle at Days 1, 8, 15, and 30, respectively. SCALPDEX items, IGA, and irritation significantly (p < 0.05) reduced with the active shampoo. Hair and scalp greasiness improved continuously with both products until Day 21. Subject‐reported symptom scores paralleled the positive evolution of clinical signs. The active shampoo was well tolerated, subjects were highly satisfied and had an improved QoL. Conclusion The active shampoo significantly improved clinical signs, symptoms, and QoL of mild‐to‐moderate scalp psoriasis compared to the vehicle. It was very well tolerated and highly appreciated by the subjects.

Peer review may be “single-blind,” in which reviewers are aware of the names and affiliations of paper authors, or “double-blind,” in which this information is hidden. Noting that computer science research often appears first or exclusively in peer-reviewed conferences rather than journals, we study these two reviewing models in the context of the 10th Association for Computing Machinery International Conference on Web Search and Data Mining, a highly selective venue (15.6% acceptance rate) in which expert committee members review full-length submissions for acceptance. We present a controlled experiment in which four committee members review each paper. Two of these four reviewers are drawn from a pool of committee members with access to author information; the other two are drawn from a disjoint pool without such access. This information asymmetry persists through the process of bidding for papers, reviewing papers, and entering scores. Reviewers in the single-blind condition typically bid for 22% fewer papers and preferentially bid for papers from top universities and companies. Once papers are allocated to reviewers, single-blind reviewers are significantly more likely than their double-blind counterparts to recommend for acceptance papers from famous authors, top universities, and top companies. The estimated odds multipliers are tangible, at 1.63, 1.58, and 2.10, respectively.

Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7–30·4). Median overall survival was 12·7 months (95% CI 11·5–13·6) in the pembrolizumab group versus 10·9 months (9·9–11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72–0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events. Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer. Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

Introduction We aimed to identify the effects of intraoperative applied leukocyte-poor platelet-rich plasma (LP-PRP) during knee arthroscopy for degenerative lesions involving pain, function and quality of life. Methods We performed a randomized controlled, double-blind trial (RCT) including 58 patients for arthroscopic knee surgery for cartilage or meniscal degeneration with allocation into the LP-PRP ( n  = 24) or control group ( n  = 34). During arthroscopy, LP-PRP was injected intra-articular in the intervention group. At baseline, 6 weeks, 6 months and 12 months pain, function, and life quality were assessed. Results 91 % of enrolled patients were available for 12 months follow-up. Pain was significantly lower in the LP-PRP group (VAS 0.9. vs. 2.3) at 6 ( p  = 0.008) but not at 12 months (VAS 1.0 vs. 1.6, p  = 0.063). LP-PRP application improved the Lysholm Score at 6 (77.5 vs. 65.6, p  = 0.033) and 12 months (83.2 vs.70.0, p  = 0.007). Assessment of life quality (SF-36) concerning the physical component summary was significantly higher at 6 weeks (33.9 vs. 25.6, p  = 0.001) and 6 months (29.9 vs. 27.1, p  = 0.027) in the LP-PRP group but equal at 1 year (31.4 vs. 30.1, p  = 0.438). Conclusions Intraoperative application of LP-PRP may enhance pain reduction and gain of knee function within 6–12 months compared to arthroscopy alone. Level of evidence II, randomized controlled clinical trial with reduced power. ClinicalTrials.gov identifier NCT02189408.