Are Published Cancer Care Trial Protocols With Traditional Chinese Medicine Interventions Concordant With SPIRIT-TCM Extension 2018? A Scoping Review on Published Trial Protocols Between 2019 and 2022.

BACKGROUND: The SPIRIT-TCM Extension 2018 was created to guide the design and reporting of Traditional Chinese Medicine (TCM) clinical trial protocols. This study aims to investigate the extent of concordance with this guideline in the relevant field of cancer care research. METHODS: A scoping review of TCM cancer trial protocols published in English and Chinese since January 2019 was conducted. Five major academic databases (MEDLINE, EMBASE, CINAHL, CENTRAL, and China National Knowledge Infrastructure) were searched. Concordance with the SPIRIT-TCM Extension 2018 was assessed by descriptive analysis. RESULTS: Fifty-three TCM cancer care trial protocols were identified, comprising 23 acupuncture, 26 Chinese herbal medicine (CHM), and 4 Tai Chi/Qigong (TCQ) interventions. The majority of the checklist items had a low rate of concordance, especially in the reporting of quality control and safety, dosage, TCM diagnostic patterns, possible interactions between Western Medicine and TCM interventions, and TCM-related outcome assessments. CONCLUSIONS: Although the SPIRIT-TCM Extension 2018 guideline was established through extensive Delphi consultation, there are low rates of concordance between published TCM cancer care clinical trial protocols with the guideline. Further research is necessary to understand the low rate of concordance and how scientific rigors of reporting can be improved in TCM cancer care research.

History of Changes in the Protocol of Clinical Trial of Zinc Supplementation in Treatment of COVID-19 by Hydroxychloroquine.

An article published in this journal used a randomized controlled trial to evaluate the efficacy of combining chloroquine/hydroxychloroquine (CQ/HCQ) and zinc in the treatment of COVID-19 patients. Findings from this study indicate that zinc supplements did not enhance the clinical efficacy of hydroxychloroquine in improving COVID-19 treatment. Although this finding is consistent with many previous studies, several concerns regarding study protocol and trial registration, including interventions and primary outcomes, have been raised in which the protocol has been changed after the completion of the recruitment.

Effectiveness of nonpharmacological interventions for reducing postpartum fatigue: a meta-analysis.

BACKGROUND: Postpartum fatigue is the most common issue among postnatal women and it could not only seriously affect the health of mothers but also bring about adverse impacts on their offspring. This meta-analysis aims to synthesize nonpharmacological evidence and evaluate the effectiveness of interventions for reducing postpartum fatigue among puerperae. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, PsycINFO, CINAHL and ProQuest databases were searched for papers published from inception until June 2021. Grey literature was searched using OpenGrey. Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) evaluating nonpharmacological interventions conducted during 0 ~ 78 weeks postpartum for fatigue reduction were eligible for inclusion. The methodological quality of the included studies was independently assessed by two reviewers using the Cochrane risk-of-bias tool and the risk of bias in nonrandomized studies of interventions. Cohen's kappa coefficient was used to measure inter-rater agreement. The meta-analysis was conducted using Review Manager 5.3. RESULTS: Seventeen published clinical trials matched the eligibility criteria and ten studies involving 1194 participants were included in this meta-analysis. The intervention start time varied from immediately postpartum care to 1 year after delivery, and duration ranged from 1 day to 3 months. The results revealed that exercise (SMD = - 1.74, 95% CI = -2.61 to - 0.88) and drinking tea (MD = - 3.12, 95% CI = -5.44 to - 0.80) resulted in significant improvements in women's postpartum fatigue at postintervention. Drinking tea may have beneficial effects on depression (MD = - 2.89, 95% CI = -4.30 to - 1.49). Positive effects of psychoeducational interventions on postpartum fatigue or depression were not observed. Physical therapies including mother-infant skin-to-skin contact, taking warm showers and breathing lavender oil aroma were used for reducing postpartum fatigue. No significant risk of publication bias was found. Small number of included studies and sample sizes, not time-matched conditions of control groups, high heterogeneity and the risk of bias within the included studies were the main limitations of our review. CONCLUSIONS: This review provides evidence that exercise and drinking tea may be effective nonpharmacological interventions for relieving postpartum fatigue. More effective and targeted exercise programs need to be further studied. Rigorous RCTs of drinking tea are needed. Caution is required when interpreting the findings due to the limitations of our study. Further studies are still needed to validate our findings and increase confidence in the results.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced 'PANIC' attack.

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered 'PANIC Attack'. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health.

[Analysis on clinical study protocols of traditional Chinese medicine for coronavirus disease 2019].

To analyze the registered clinical trial protocols of traditional Chinese medicine(TCM) for the prevention and treatment of coronavirus disease 2019(COVID-19), in order to provide information for improving the quality of research design. The website of the Chinese Clinical Trial Registry(www.chictr.org.cn) and the American Clinical Trial Registry(clinicaltrials.gov) were searched to collect protocols of TCM for COVID-19. Documents were screened following the inclusion criteria, and data were extracted in regard to registration date, study objective, type of design, sponsor, patient, sample size, intervention, and evaluation index. Descriptive analysis was conducted. A total of 49 clinical trial protocols of TCM for COVID-19 were included. Primary sponsors were mainly hospitals or universities in places like Hubei, Beijing, Zhejiang and other regions. The implementation units are mainly in Hubei, Guangdong, Zhejiang, Henan and other regional hospitals. The types of study design were mainly experimental studies(40), including 30 randomized parallel controlled trials, 7 non-randomized controlled trials, 2 single arm trials and 1 consecutively recruited trial; besides, there were also 6 observational studies, 2 health service studies and 1 preventive study. The sample size reached a total of 30 562 cases, with a maximum of 20 000 for a single study and a minimum of 30. The 49 trials subjects included healthy people(3), isolation and observation cases(1), suspected cases(10),confirmed COVID-19 patients(31) and COVID-19 recovery patients(4). Of the 31 trials planned to include confirmed COVID-19 patients, 16 protocols no definite disease classification, 3 with a clear exclusion of severe subjects, 4 with common subjects, 2 with light, common or severe subjects, 1 with light and common subjects, 1 with common or severe subjects, 3 with severe subjects, and 1 with severe or critical subjects. The experimental interventions included Chinese patent medicine(Lianhua Qingwen Capsules/Granules, Huoxiang Zhengqi Dropping Pills/Oral Liquid, Babao Dan, Gubiao Jiedu Ling, Jinhao Jiere Granules, Compound Yu-xingcao Mixture, Jinye Baidu Granules, Shufeng Jiedu Capsuless, Shuanghuanglian Oral Liquid, Tanreqing Injection, Xuebijing Injection, Reduning Injection, Xiyanping Injection), Chinese medicinal decoction and taichi. The primary evaluation outcomes mainly included antipyretic time, clinical symptom relief, novel coronavirus nucleic acid turning to negative, conversion rate of severe cases and chest CT. There was a quick response of clinical research on the prevention and treatment of COVID-19 with TCM, with the current registered protocols covers the whole process of disease prevention, treatment and rehabilitation. However, issues need to be concerned, including unclear definition of patient's condition, unclear research objectives, unclear intervention process and inappropriate outcomes, etc. In addition, researchers should consider the actual difficulties and workload of doctors in epidemic response environment, and make effort to optimize the process and improve the operability of research protocols under the principle of medical ethics.

Acupuncture for lumbar myofascial pain Protocol for a systematic review of randomized controlled trials.

BACKGROUND: Lumbar myofascial pain is a major contributor to chronic low back pain. Acupuncture has been applied as an effective treatment for chronic low back pain worldwide. However, few critical systematic reviews focus on the effect of acupuncture on chronic low back pain caused by lumbar myofascial pain have been published. The study aims to evaluate the current evidence on the efficacy of acupuncture for chronic low back pain caused by lumbar myofascial pain. METHODS: A total of 7 databases will be searched from their inception to March 2019, including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure database, the Chinese Biomedical database, and the Wanfang database. Randomized controlled trials (RCTs) that compared the effect of acupuncture for lumbar myofascial pain will be included. The primary outcomes will be reduction of lumbar myofascial pain assessed by Visual Analog Scale (VAS). Secondary outcomes are questionnaires to evaluate the effects of treatment on patients' daily life activities and psychological status; and adverse events. The primary and secondary outcomes will be assessed before (0 day) treatment and at 0, 7, 30, and 90 days after treatment. Data synthesis will be computed by RevManV.5.3.5 software when a data-analysis is allowed. Methodological quality will be evaluated with the risk of bias according to Cochrane Handbook. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: The study will provide evidence to illustrate acupuncture is an effective therapeutic intervention for chronic low back pain caused by lumbar myofascial pain. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019129735.

Treatment Fidelity in a Music Therapy Multi-site Cluster Randomized Controlled Trial for People Living With Dementia: The MIDDEL Project Intervention Fidelity Protocol.

High-quality clinical trials testing music therapy interventions have become more prevalent over the past decade. However, recent reviews of published music therapy trials reveal that reporting of strategies used to ensure treatment fidelity is lacking. Treatment fidelity refers to methodological strategies, put in place prior to clinical trial implementation, to strengthen the reliability and validity of intervention delivery and, therefore, safeguard research quality. This paper outlines strategies developed and implemented during the pilot phase of a randomized controlled trial involving the testing of music interventions for people living with dementia and presenting with symptoms of depression. We discuss the five recognized components of fidelity (study design, training intervention providers, treatment integrity, treatment differentiation, and treatment receipt) and describe our methods for training music intervention providers and testing interventionist competence prior to trial commencement, approaches to intervention delivery supervision, and methods for assessing intervention protocol adherence.

Nutritional Intervention for Nonsurgical Head and Neck Cancer Patients Treated with Radiation Therapy: Results from a Prospective Stepped-Wedge Clinical Protocol.

AIM: To evaluate the impact on weight loss (WL) of a standardized nutritional stepped-wedge protocol on consecutive head and neck cancer (HNC) patients treated with curative radiotherapy (RT). METHODS: We prospectively collected data of patients followed by a trained dietitian and treated according to a pre-defined stepped-wedge protocol. Patients with swallowing defect at the baseline and WL >10% 3 months prior to the beginning of RT were excluded from the analysis. Nutritional status was assessed at the baseline and weekly during the course of RT. Fluid and caloric intake were assessed through a 24-h recall. RESULTS: Between May 2010 and March 2011, 42 patients treated were evaluated. Median overall treatment time was 52.5 days. WL per CTCAE 4.03 was G0, G1 and G2 in 23 (55%), 14 (33%) and 5 (12%) patients, respectively. Thirty-five (83%) patients did not require enteral nutrition. About 90% of patients completed RT without interruption of oral feeding. CONCLUSIONS: Despite the high toxicity profile of curative RT in HN, we proposed a standardized stepped-wedge protocol allowing to prevent severe WL in most of our patients. Further larger prospective studies are warranted to validate our approach and to achieve consensus on nutritional intervention in this subset of patients.

Brief intervention on Smoking, Nutrition, Alcohol and Physical (SNAP) inactivity for smoking relapse prevention after release from smoke-free prisons: a study protocol for a multicentre, investigator-blinded, randomised controlled trial.

INTRODUCTION: Smoking remains the leading risk factor for disease burden and mortality worldwide. Heavy Smoking is often associated with poor Nutrition, Alcohol abuse and Physical inactivity (known as 'SNAP'). Australia's first prison smoking ban was introduced in the Northern Territory in July 2013. However, relapse to smoking after release from prison is normative. Holistic and cost-effective interventions are needed to maintain post-release abstinence to realise the potential public health impact of smoke-free prison policies. Rigorous, large-scale trials of innovative and scalable interventions are crucial to inform tobacco control policies in correctional settings. METHODS AND ANALYSIS: This multicentre, investigator-blinded, randomised parallel superiority trial will evaluate the effectiveness of a brief intervention on SNAP versus usual care in preventing smoking relapse among people released from smoke-free prisons in the Northern Territory, Australia. A maximum of 824 participants will be enrolled and randomly assigned to either SNAP intervention or usual care at a 1:1 ratio at baseline. The primary endpoint is self-reported continuous smoking abstinence three months after release from prison, verified by breath carbon monoxide test. Secondary endpoints include seven-day point prevalence abstinence, time to first cigarette, number of cigarettes smoked post release, Health Eating Index for Australian Adults, Alcohol Use Disorder Identification Test-Consumption and International Physical Activity Questionnaire scores. The primary endpoint will be analysed on an intention-to-treat basis using a simple log binomial regression model with multiple imputation for missing outcome data. A cost-effectiveness analysis of the brief intervention will be conducted subsequently. ETHICS AND DISSEMINATION: This study was approved by the University of New South Wales Human Research Ethics Committee (HREC), Menzies HREC and Central Australia HREC. Primary results of the trial and each of the secondary endpoints will be submitted for publication in a peer-review journal. TRIAL REGISTRATION NUMBER: ACTRN12617000217303; Pre-results.

Development of a core outcome set (COS) and selecting outcome measurement instruments (OMIs) for non-valvular atrial fibrillation in traditional Chinese medicine clinical trials: study protocol.

BACKGROUND: An increasing number of clinical trials of traditional Chinese medicine are being conducted in the treatment of non-valvular atrial fibrillation (NVAF) in China. However, the heterogeneity of outcomes and outcome measurement instruments has produced little evidence for traditional Chinese medicine in treating NVAF because many trials cannot be included in a meta-analysis. The majority of the trials did not report endpoint outcomes, side effects or other important outcomes for patients, which makes it difficult to evaluate the efficacy and safety of traditional Chinese medicine. Therefore, it is important to develop a core outcome set (COS). Although there are two related COSs for clinical trials of atrial fibrillation, the methodology is limited, and the perspectives of Chinese experts and patients are unclear. Therefore, we will develop a COS and recommend outcome measurement instruments after finishing the COS, which can be used for clinical trials of traditional Chinese medicine in NVAF. METHODS/DESIGN: The method of the study will include eight stages led by a national multidisciplinary Steering Committee: (1) A systematic review will be developed to identify currently reported outcomes and traditional Chinese medicine syndromes in clinical trials of NVAF, (2) Semi-structured interviews of patients will be conducted to fill gaps in potential outcomes, (3) Traditional Chinese medicine syndrome names will be identified from medical records, (4) A dataset of traditional Chinese medicine syndrome names will be developed, (5) The investigation of traditional Chinese medicine syndromes will be conducted from cross-sectional study, (6) Two rounds of Delphi surveys will be carried out, (7) A consensus meeting will be conducted to develop a COS, and (8) Recommendations of outcome measurement instruments (OMIs), which should be used in the COS, will be developed. DISCUSSION: The COS will improve the consistency of outcome reporting and reduce the reporting bias in NVAF clinical trials of traditional Chinese medicine to improve the value of traditional Chinese medicine clinical trials. TRIAL REGISTRATION: This study is not a clinical trial, so it is registered in Core Outcome Measures in Effectiveness Trials Initiative (COMET). Registration number: 941 . Registered on 22 December 2016.

Double-blind trials in hyperbaric medicine: A narrative review on past experiences and considerations in designing sham hyperbaric treatment.

Background Hyperbaric oxygen therapy, which consists of breathing 100% oxygen under a higher atmospheric pressure than normal, is utilized worldwide in the treatment of several diseases. With the growing demand for evidence-based research, hyperbaric oxygen therapy has been criticized for delivering too little high-quality research, mainly in the form of randomized controlled trials. While not always indispensable, the addition of a sham-controlled group to such a trial can contribute to the quality of the research. However, the design of a sham (hyperbaric) treatment is associated with several considerations regarding adequate blinding and the use of pressure and oxygen. This narrative review discusses information on the sham profile and the blinding and safety of double-blind trials in hyperbaric medicine, irrespective of the indication for treatment. Methods MEDLINE, Embase and CENTRAL were searched for sham-controlled trials on hyperbaric oxygen therapy. The control treatment was considered sham if patients were blinded to their allocation and treatment took place in a hyperbaric chamber, with no restrictions regarding pressurization, oxygen levels or indication. Studies involving children or only one session of hyperbaric oxygen were excluded. Information on (the choice of) treatment profile, blinding measures, patient's perception regarding allocation and safety issues was extracted from eligible studies. Results A total of 42 eligible trials were included. The main strategies for sham treatment were (1) use of a lower pressure than that of the hyperbaric oxygen group, while breathing 21% oxygen; (2) use of the same pressure as the hyperbaric oxygen group, while breathing an adjusted percentage of oxygen; and (3) use of the same pressure as the hyperbaric oxygen group, while breathing 21% oxygen. The advantages and disadvantages of each strategy are discussed using the information provided by the trials. Conclusion Based on this review, using a lower pressure than the hyperbaric oxygen group while breathing 21% oxygen best matches the inertness of the placebo. Although studies show that use of a lower pressure does allow adequate blinding, this is associated with more practical issues than with the other strategies. The choice of which sham profile to use requires careful consideration; moreover, to ensure proper performance, a clear and detailed protocol is also required.