Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to ...treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 10
cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.
Medication nonadherence is a significant public health problem as it contributes to poor clinical outcomes and increased healthcare costs. Older patients with multimorbidity and polypharmacy often ...have low medication adherence. These patients also have a high prevalence of potentially inappropriate medication (PIM) use.
To explore risk factors related to medication nonadherence in older patients with multimorbidity and polypharmacy and examine the association between medication nonadherence and PIM use.
A multicenter cross-sectional study was conducted from May to December 2019 in 16 tertiary hospitals from 12 provinces and cities in China. Data were collected from outpatients 65 years or older with multimorbidity and polypharmacy. The PIMs were evaluated using the 2019 Beers Criteria. Self-reported medication adherence was assessed using the Visual Analog Scale (VAS).
A total of 773 outpatients were recruited. The prevalence of medication nonadherence was 31.8%. In the univariate analysis, nonadherence was significantly associated with sex, cognitive impairment, stroke, visiting the same physicians, self-administration of medication, the percentage of drug costs ≥ 10% of the medical expenses, and PIMs for the alimentary tract and metabolism. In the multivariate analysis, the results almost paralleled those of the univariate associations. Notably, the use of PIM was significantly associated with medication adherence.
Several factors that influence medication adherence were identified. Targeted interventions can be implemented to improve medication adherence, such as encouraging self-administering medications and reducing medication expenses.
Background: Hepatitis A vaccine has been used in mass and routine public vaccination programs in China. Long-term follow-up studies are required to determine the duration of protection and the need ...for booster vaccinations.
Methods: A prospective, randomized, open-label clinical trial was performed to compare the geometric mean concentration (GMC) and seroprotection rates of anti-Hepatitis A virus (HAV) antibodies elicited by the inactivated vaccines Healive and Havrix. 400 healthy children were randomly assigned 3:1 ratio to receive two doses of Healive or Havrix at 0 and 6 months. Persistence of anti-HAV antibodies for 5 years post immunization has been reported The current study reports new data at 11 years post immunization for the purpose of showing antibody persistence. Sensitivity analyzes were performed to assess the results. In addition, predictions for long-term antibody persistence were performed using a statistical model. Two different serological assays were used that were shown to be 98.3% concordant for detecting anit-HAV antibody.
Results: GMCs were significantly higher following Healive compared to Havrix at 1, 6, 7, 66, 112 and 138 months post-vaccination. In addition, the GMCs obtained using sensitivity analysis were very similar to those obtained using the original models. Prediction analysis indicated that the duration of protection for both vaccines was at least 30 years after immunization, with a lower limit of the 95% confidence interval for GMC of greater than 20mIU/mL.
Conclusions: Healive is more immunogenic than Havrix in children at 11 years post full immunization. Prediction analysis indicated at least 30 years of antibody persistence for both vaccines.
Hot flashes are the common and debilitating symptom among prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Strong evidence from multiple rigorously designed studies ...indicated that pharmacological option such as venlafaxine provides partial relief, but the tolerability is poor when dose is not tapered. Hence, alternative therapy is needed. Previous studies reported that acupuncture may be helpful in the management of hot flashes. However, the insufficient randomized controlled trial limited the quality of evidence.
Five hospitals will recruit 120 acupuncture naïve patients with moderate-to-severe hot flashes after prostate cancer received ADT in China from February 2023 to December 2024. Participants will be randomly 2:1:1 allocated to the 18 sessions of verum acupuncture at true acupuncture points plus usual care, 18 sessions of non-penetrating sham acupuncture at non-acupuncture points plus usual care, or usual care alone over 6 weeks. The primary outcome measure is the change of mean weekly hot flashes symptom severity score (HFSSS) at the end of treatment compared with baseline.
We will be able to measure the effectiveness of acupuncture for patients with PCa suffering from ADT-induced hot flashes and whether acupuncture is superior to sham acupuncture and usual care. The proposed acupuncture treatment might provide an alternative option for those patients.
Clinicaltrials.gov (NCT05069467).
Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed.
To evaluate the efficacy and ...adverse effects of convalescent plasma therapy for patients with COVID-19.
Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled.
Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity.
Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 discharge to 6 death). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours.
Of 103 patients who were randomized (median age, 70 years; 60 58.3% male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% 95% CI, -10.4% to 28.0%; hazard ratio HR, 1.40 95% CI, 0.79-2.49; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 95% CI, 1.07-4.32; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 95% CI, 0.30-2.63; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 95% CI, 0.22-1.59; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 95% CI, 0.88-2.95; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 95% CI, 3.91-33.18; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care.
Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.
Chinese Clinical Trial Registry: ChiCTR2000029757.
To evaluate the safety and efficacy of a next-generation, all-suture anchor in patients undergoing arthroscopic repair of rotator cuff tears, compared with that of an established solid suture anchor.
...Between April 2019 and January 2021, a prospective, comparative, randomized controlled noninferiority study conducted on people with Chinese ethnicity at 3 tertiary hospitals enrolled patients (18-75 years) requiring arthroscopic treatment for rotator cuff tears. Patients were randomized into 2 cohorts receiving either all-suture anchor or solid suture anchor and followed for 12 months. The primary outcome was the Constant-Murley score at the 12-month follow-up. Magnetic resonance imaging assessments determined the rate of retear of rotator cuff repair (defined as Sugaya classification 4 and 5). Safety evaluation was performed at all follow-up points to determine the adverse events (AEs).
In total, 120 patients with rotator cuff tears (mean age, 58.3 years; 62.5% female; 60 receiving all-suture anchor) underwent treatment. Five patients were lost to follow-up. Both cohorts showed significant improvement in Constant-Murley scores between baseline and 6 months (P < .001) and between 6 and 12 months (P < .001). There were no significant differences in Constant-Murley scores between the 2 cohorts at 12 months (P = .122) after operation. The retear rate at 12 months was 5.7% and 1.9% in the all-suture and solid suture anchor cohorts, respectively (P = .618). There were 2 cases of intraoperative anchor pullout, both of which were successfully resolved. No cases of postoperative reoperation or other anchor-related AEs were reported.
The all-suture anchor offered equivalent clinical performance to an established solid suture anchor at the 12-month follow-up in patients undergoing arthroscopic repair of rotator cuff tears. The retear rate was not statistically significantly different between the 2 cohorts.
Level I, randomized controlled trial.
The effect of reference treatment over placebo, known as M1, is essential in the development of non-inferiority margin. We proposed a M1 adjustment approach to reduce the selection bias for collected ...data of historical trials. A quantitative illustration of selection bias of historical data is also defined. Simulation study shows that the proposed approaches would significantly reduce the bias when the proportion of positive studies in historical data is noticeably larger than the power of studies include in historical data. When historical data are constituted by only positive studies, the performance of the proposed method is also appreciable. However, when the proportion of positive studies is close to the power of studies included or the number of studies included is too small, the performance of the proposed approach may not be reliable. A real-data application is also presented. The proposed bias-adjustment approach is a reasonable method to reduce the over-estimate of effect size in the specification of non-inferiority margin. It could also be applied in most non-inferiority margin specification methods or be cooperate used with other bias-adjustment approaches.
Background
Geriatric outpatients with polypharmacy have a high risk of potentially inappropriate medication (PIM) use.
Aim
To identify differences in both prevalence and patterns of PIMs and ...drug-related problems (DRPs) in older outpatients who visited the tertiary hospitals (THs) and community health centers (CHCs) and analyze associated factors.
Method
A prospective cross-sectional study was conducted in five THs and five CHCs from September 2018 to November 2019 in Beijing, China. Data were collected from outpatients aged ≥ 65 years with chronic diseases and polypharmacy. PIMs were evaluated using the 2015 and 2019 Beers Criteria and the Screening Tool of Older Persons' Prescriptions (STOPP) criteria. DRPs were classified using the Helper-Strand DRP Classification. The prevalence and types of PIMs and DRPs were compared, and relevant factors were analyzed.
Results
The prevalence of PIMs based on the 2015 Beers Criteria was higher in patients from the THs, while PIMs based on the 2019 Beers Criteria did not show a significant difference. PIM prevalence based on STOPP Criteria and DRPs was higher in patients from CHCs. Visiting CHCs was an independent factor of PIMs based on the 2015 Beers Criteria (OR 0.774, 95% CI 0.604–0.992) and the STOPP Criteria (OR 2.427, 95% CI 1.883–3.128), and DRPs (OR 3.612, 95% CI 2.682–4.865).
Conclusion
Differences in PIM and DRP might be due to the patients and settings. Specific measures to improve the appropriateness of medications in both settings should be used.
To increase market transparency, independent system operators (ISOs) have been working on minimizing uplift payments based on convex hull pricing theorems. Along this direction, in this paper, based ...on the analysis of specific generator features in the Midcontinent ISO (MISO) system, besides reviewing integral formulations for several special cases, we develop two integral formulations of a single generator that can capture these features. We then build a compact convex hull pricing formulation based on these integral formulations, which guarantees to obtain an exact convex hull price by solving a large-scale linear program. Meanwhile, to address the computational challenges caused by the large-scale MISO system, we propose innovative iterative algorithms with convergence properties, plus a complementary algorithm, to obtain an approximated convex hull price. The case studies on MISO instances with and without transmission constraints indicate that our algorithms lead to an exact convex hull price for all numerical studies and, the solutions can be obtained within 20 minutes.
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