Efficacy of Electroacupuncture Combined with Chinese Herbal Medicine on Pain Intensity for Chronic Sciatica Secondary to Lumbar Disc Herniation: Study Protocol for a Randomised Controlled Trial.

Purpose: Chinese herbal medicine and electroacupuncture (EA) have been used to control pain for many decades in China. We aim to explore the efficacy of intervening patients whose discogenic sciatica symptoms lasting longer than 3 months with these conservative treatments. Patients and Methods: This is a single-center, parallel-group, patient-unblinded Randomized Controlled Trial (RCT) with blinded outcome assessment and statistician. One hundred and twenty-four patients will be assigned randomly into 2 groups including conservative treatment group (Shenxie Zhitong capsule combined with EA treatment) and Nonsteroidal Anti-inflammatory Drugs (Nonsteroidal Anti-inflammatory Drugs, NSAIDs) control group (Celecoxib) in a 1:1 ratio. The trial involves a 4-week treatment along with follow-up for 6 months. The primary outcome is the leg pain intensity measured by the visual analogue scale (VAS) at 6 months after randomization. Secondary outcomes include leg pain intensity at other time points, back pain intensity, leg pain and back pain frequency, functional status, quality of life, return to work status and satisfaction of patients. Adverse events will also be recorded. Strengths and Limitations of This Study: Through this study, we want to observe the efficacy of electroacupuncture combined with Chinese herbal medicine on pain intensity for chronic sciatica secondary to Lumbar Disc Herniation. If the final results are favorable, it is expected to be a safe, economical, and effective treatment for patients. The study design has the following limitations: the setup of control group was less than perfect; patients and doctors could not be blinded in this trial; we skipped the feasibility study. We have tried our best to minimize adverse impacts. Trial Registration: ChiCTR2300070884 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 25th April 2023).

5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Efficacy of whole system ayurveda management protocol in major depressive disorder- A randomized controlled clinical trial.

BACKGROUND: Major Depressive Disorder (MDD) is one of the common depressive disorder. MDD has high comorbidity and has greater implications on quality of life. Whole system Ayurveda management protocol (WSAP) is explored for it's possible role in management of MDD. OBJECTIVE: To evaluate the efficacy of Whole system Ayurveda management protocol on Major Depressive Disorder. MATERIAL AND METHODS: Study was a randomized controlled trial. Total 50 patients of MDD meeting the DSM V criteria, age group 20-70 years of either sex participated in the study. They were randomly divided into two groups, control group received Escitalopram 10 mg twice a day and Ayurveda group was on WSAP. Interventions were for 60 days. Assessments were done through various clinical parameters like Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Brief psychiatric rating scale (BPRS), Pittsburgh Sleep Quality Index (PSQI), WHO Quality of Life- BREF (WHOQOL-BREF), Clinical Global Improvement scale (CGI), UKU Side effect scale. Assessments during intervention was on every 15th day. RESULTS: Study showed that Ayurveda group produced significant outcome improvement compared to control group in HDRS (p = 0.01), HARS (p = 0.03), PSQI (p = 0.03), WHOQOL-Bref (p < 0.001) and UKU side effect scale (p = 0.02). Both the group showed improvements in all the parameters except in WHOQOL-Bref where Ayurveda group only showed improvements (p < 0.001). Effect size showed large effect in WHOQOL-Bref. Mild side effects were reported in control group and none in Ayurveda group. CONCLUSION: WSAP was effective in management of MDD and had better side effect profile. Further studies needed.

Effects of transcutaneous electrical nerve stimulation on pain, function, and descending inhibition in people with non-specific chronic low-back pain: a study protocol for a randomized crossover trial.

BACKGROUND: Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP. METHODS/DESIGN: This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2-125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05. DISCUSSION: This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT05812885. Registered on 24th May 2023.

Carotenoid Extraction from Plant Tissues.

Carotenoids are the natural pigments available in nature and exhibit different colors such as yellow, red, and orange. These are a class of phytonutrients that have anti-cancer, anti-inflammatory, anti-oxidant, immune-modulatory, and anti-aging properties. These were used in food, pharmaceutical, nutraceutical, and cosmetic industries. They are divided into two classes: carotenes and xanthophylls. The carotenes are non-oxygenated derivatives and xanthophylls are oxygenated derivatives. The major source of carotenoids are vegetables, fruits, and tissues. Carotenoids also perform the roles of photoprotection and photosynthesis. In addition to the roles mentioned above, they are also involved and act as precursor molecules for the biosynthesis of phytohormones such as strigolactone and abscisic acid. This chapter briefly introduces carotenoids and their extraction method from plant tissue. Proposed protocol describes the extraction of carotenoid using solvents chloroform and dichloromethane. Reverse-phase HPLC can be performed with C30 columns using gradient elution. The column C30 is preferred to the C18 column because the C30 column has salient features, which include selective nature in the separation of structural isomers and hydrophobic, long-chain compounds, and shows the best compatibility with highly aqueous mobile phases. A complete pipeline for the extraction of carotenoids from plant tissue is given in the present protocol.

A protocol for stakeholder engagement in deliver-EE: A pragmatic randomized comparative effectiveness trial evaluating effects of meal delivery on the ability of homebound older adults to remain in the community.

BACKGROUND: Few clinical trials include a detailed protocol for stakeholder engagement in the design and execution of the clinical trial. Deliver-EE is a pragmatic clinical trial to assess how different types of home-delivered meals can affect older adults' health and well-being. We present the protocol for stakeholder engagement in this national, multi-site trial and initial findings from our efforts. METHODS: Twenty-nine participants were recruited to two stakeholder advisory panels. The "Lived Experience Perspectives" panel is defined as the clients, caregivers, and meal delivery drivers with first-hand knowledge and lived experiences with meal delivery. The "System Perspectives" panel is defined as representatives from the larger financial, clinical, regulatory, and operational environments in which meal delivery to homebound older adults operate. Together, these two groups holistically represent interested parties that coordinate the interdependent elements of meal delivery to homebound older adults in order to: 1) inform our understanding of what matters most to older adults, their families, and the larger health and social care systems; 2) provide strategies to overcome challenges conducting the study; 3) enhance dissemination and uptake of study findings; and 4) identify opportunities for future research. RESULTS: Although stakeholder partners share a common goal of using home-delivered meals as a method to improve outcomes for homebound older adults, individuals have different goals for participating as advisors in this research. CONCLUSIONS: Understanding what individual stakeholders hope to gain from their participation is critical in designing an effective engagement protocol and critical for meaningful and rigorous stakeholder engagement in clinical trials.

Effect of oral vitamin C administration along with iron supplementation for treating anaemia among adolescent girls - Protocol for systematic review and meta-analysis.

Background: Anemia among adolescent girls is a worldwide public health problem. Although anemia has several causes, the most common and significant is iron deficiency. Treatment of anemia with iron alone may result in reduced compliance on account of adverse effects. Various studies have revealed that use of vitamin C in addition to iron improves its absorption and reduces the ill effects of the therapy. However, a concrete evidence of adding vitamin C to iron for treating iron deficiency anemia is lacking. Aims: Protocol for current systematic review was prepared and registered with the aim to generate evidence on role of vitamin C in addition to iron for treatment of anemia. Materials and Methods: Present protocol has been prepared based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with International Prospective Register of Systematic Reviews. Data extraction will be done by the reviewers independently. Cochrane risk of bias assessment tool will be used for risk of bias assessment. Results: For primary outcome and each of the other outcomes pairwise random effects meta-analysis and network meta-analysis will be performed. Sensitivity analysis will be performed in case of any heterogeneity is detected to find out the difference of the effect estimation between subsets. Conclusions: The evidence for role of vitamin C as an adjunct in iron and folic acid for treatment of anemia in adolescent girls will be generated once the systematic review and meta-analysis is completed.

An Acupuncture Protocol for the Treatment of Erectile Dysfunction: A Delphi Process.

INTRODUCTION: Erectile dysfunction (ED) is a widespread disorder, and the worldwide incidence is rapidly increasing. Acupuncture, an intervention out of the spectrum of traditional Chinese medicine (TCM), has a long tradition as treatment for ED. Nonetheless, a best-practice treatment protocol is currently missing. A recent systematic review and meta-analysis confirmed a huge diversity of acupuncture treatments for ED and concluded that there is an urgent need to standardise acupuncture treatment for ED. Consequently, the authors conducted a Delphi process with the aim to achieve an expert consensus as a basis for the development of a best-practice protocol. METHODS: The Delphi process consisted of four rounds of questionnaires with closed and open-ended questions. Eleven acupuncture experts participated. The therapeutic aim was defined as "to achieve an erection sufficient for sexual satisfaction." RESULTS: Consensus was achieved on 24 acupoints corresponding to 12 TCM syndromes. The syndromes were KI Yang xu, KI Yin xu, KI Qi xu, Ki and HT not harmonised, LR Qi Stagnation, LR Qi stagnation and Heat, Liver Blood xu, Liver Blood xu and Liver Qi stagnation, Damp-heat sinking to the lower Jiao5, HT and GB Qi xu, SP xu and HT Blood xu, Yin xu. The suggested optimal dose was between 11 and 15 treatments given once or twice a week. CONCLUSION: An expert consensus-based, semi-standardised best-practice treatment protocol for the treatment of ED was developed. Moreover, the Delphi process also revealed inconsistencies as to which signs and symptoms constitute a TCM syndrome. Further Delphi studies including a broader range of experts from various acupuncture traditions are needed to establish further agreement. Nonetheless, the best-practice protocol introduced in this study provides a first point of departure for the implementation of a more standardised treatment approach. Moreover, since a recent meta-analysis concluded that more high-quality clinical studies on the topic are needed, this study provides a first standardised acupuncture treatment protocol for ED.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose-effect relationship of acupuncture. METHODS/DESIGN: This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. DISCUSSION: This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Understanding the mechanism of acupuncture in acute cerebral infraction through a proteomic analysis: protocol for a prospective randomized controlled trial.

Background: Acute cerebral infarction (ACI), being the predominant form of stroke, presents challenges in terms of the limited effectiveness of various treatments in improving the neurological function. Although acupuncture shows promise in addressing ACI, the availability of high-quality evidence regarding its efficacy, safety, and underlying mechanism remains insufficient. In this study, we design a multicenter, prospective, single-blind, randomized controlled trial with the aim of evaluating the efficacy and safety of acupuncture for ACI, making an attempt to unveil the molecular mechanisms by proteomic. Methods: A total of 132 patients involving four hospitals will be randomized at a 1:1:1 ratio in the acupuncture group, control group, and sham acupuncture group. All the patients will receive basic treatment, and the patients in the acupuncture and sham acupuncture groups will also receive either acupuncture or sham acupuncture treatment, respectively, at six sessions each week for a 2 weeks period, followed by 3 months of follow-up. The primary outcome will be the change in the National Institute of Health Stroke Scale (NIHSS) scores after treatment. The secondary outcomes will include the Fugl-Meyer Assessment (FMA) scale scores and the Barthel Index (BI). Adverse events that occur during the trial will be documented. To discover differentially expressed proteins (DEPs) and their roles between the ACI subjects and healthy controls, we will also perform 4D-DIA quantitative proteomics analysis, and the DEPs will be confirmed by enzyme-linked immunosorbent assay (ELISA). This study was approved by the institutional review board of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (TYLL2023043). Written informed consent from patients is required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2300079204). Trial results will be published in a peer-reviewed academic journal. Discussion: The results of this study will determine the preliminary efficacy and safety of acupuncture in ACI patients and whether the mechanism of this form of non-pharmacologic stimulation is mediated by a novel therapeutic target for neurorehabilitation through our proteomic analysis. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2300079204.

Study protocol for a zinc intervention in the elderly for prevention of pneumonia, a randomized, placebo-controlled, double-blind clinical pilot trial.

Pneumonia is a major public health problem for older adults, being one of the leading causes of hospitalization and death, particularly for elderly nursing home residents. We previously conducted a clinical trial in which we demonstrated that 29% of nursing home residents had low serum zinc levels coinciding with a two-fold increase in pneumonia incidence and duration in comparison to individuals with adequate serum zinc levels. However, causality could not be inferred and necessitates a double-blind clinical trial. To determine the appropriate supplementation dose for such a trial we are conducting a randomized, placebo-controlled, double-blind clinical pilot trial aimed at delineating the optimal dosage (30 and 60 mg/day elemental Zn) and establishing safety. The results from the pilot study will be leveraged to inform our larger randomized clinical trial designed to study the effect of zinc supplementation in nursing home elderly with low serum zinc levels on respiratory infections, antibiotic use, and duration of sick days with pneumonia. In tandem with dose optimization, we will evaluate the correlation between serum zinc and pan-T cell zinc levels, given that T cells and their zinc levels are important in the response and resolution of respiratory infections but whose correlation has only been extrapolated and not demonstrated. Herein we present the study rationale and protocol, as well as discuss specific challenges we encountered in securing a manufacturer for the study agents and when recruiting from nursing home populations during the COVID-19 pandemic. In light of these experiences, we provide recommendations for future clinical trials under circumstances where supply chains are disrupted, and recruitment pools are constrained or unavailable. Clinical trial registration: https://clinicaltrials.gov/, NCT05527899.

A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Daoyin therapy in chronic neck pain: study protocol for a randomized controlled trial.

BACKGROUND: Daoyin therapy (DT), an ancient therapeutic approach with a history spanning thousands of years, has traditionally been employed to address musculoskeletal pain and psychosomatic disorders. However, the application of DT for chronic neck pain (CNP) has received limited attention in the existing literature, and systematic randomized clinical trials (RCTs) in this context remain scarce. This manuscript outlines an RCT protocol designed to investigate whether DT is more effective at alleviating CNP in adult individuals compared to other interventions. METHODS: A 12-week RCT was conducted, with participants undergoing randomization into one of three groups: DT, Meditation + Fitness Exercise (M+FE), or a control group. Participants in the DT and M + FE groups attended their respective training classes three times per week for 12 weeks. Participants in the control group were required to attend health education workshops every 2 weeks. Following the 12-week intervention period, all participants underwent follow-up assessments at the 16th week. Outcome measures encompassed the Simplified Chinese Neck Pain and Disability Scale (SC-NPAD) and Visual Analog Scale (VAS) for pain assessment, Static Neck Posture Assessment (SNPA) to evaluate neck and shoulder posture and function, Short Form-36 (SF-36) to assess quality of life, and blood tests measuring 5-Hydroxytryptamine (5-HT), Norepinephrine/Noradrenaline (NE/NA), γ-aminobutyric acid (GABA), Adreno-Cortico-Tropic-Hormone (ACTH), ß-Endorphin (ß-EP), and Calcitonin-Gene-Related Peptide (CGRP) levels via high-performance liquid chromatography (HPLC), chemiluminescence immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). Brain activity changes were monitored through MRI scans. Repeated measures analyses of variance (ANOVAs) will be used to evaluate the outcomes at baseline, at the 12th week, and at the 16th week. Generalized Estimating Equation (GEE) models will be applied to analyze changes in outcomes over time and differences between groups. DISCUSSION: This trial aims to evaluate the efficacy of DT in comparison to other interventions and explore the neuroendocrine mechanisms underlying its effects in adults with CNP. If the intervention and procedures demonstrate feasibility and acceptability, there are plans to conduct a more extensive controlled trial. This could potentially pave the way for the broader application of DT, not only in the context of CNP but also for other chronic diseases. TRIAL REGISTRATION: This trial has been registered with the Chinese Clinical Trial Registry (Registration ID: [ChiCTR2400079571]).

Real-time evaluation and adaptation to facilitate rapid recruitment in a large, prospective cohort study.

BACKGROUND: Recruiting large cohorts efficiently can speed the translation of findings into care across a range of scientific disciplines and medical specialties. Recruitment can be hampered by factors such as financial barriers, logistical concerns, and lack of resources for patients and clinicians. These and other challenges can lead to underrepresentation in groups such as rural residents and racial and ethnic minorities. Here we discuss the implementation of various recruitment strategies for enrolling participants into a large, prospective cohort study, assessing the need for adaptations and making them in real-time, while maintaining high adherence to the protocol and high participant satisfaction. METHODS: While conducting a large, prospective trial of a multi-cancer early detection blood test at Geisinger, an integrated health system in central Pennsylvania, we monitored recruitment progress, adherence to the protocol, and participants' satisfaction. Tracking mechanisms such as paper records, electronic health records, research databases, dashboards, and electronic files were utilized to measure each outcome. We then reviewed study procedures and timelines to list the implementation strategies that were used to address barriers to recruitment, protocol adherence and participant satisfaction. RESULTS: Adaptations to methods that contributed to achieving the enrollment goal included offering multiple recruitment options, adopting group consenting, improving visit convenience, increasing the use of electronic capture and the tracking of data and source documents, staffing optimization via leveraging resources external to the study team when appropriate, and integrating the disclosure of study results into routine clinical care without adding unfunded work for clinicians. We maintained high protocol adherence and positive participant experience as exhibited by a very low rate of protocol deviations and participant complaints. CONCLUSION: Recruiting rapidly for large studies - and thereby facilitating clinical translation - requires a nimble, creative approach that marshals available resources and changes course according to data. Planning a rigorous assessment of a study's implementation outcomes prior to study recruitment can further ground study adaptations and facilitate translation into practice. This can be accomplished by proactively and continuously assessing and revising implementation strategies.

Ketamine intolerance in patients on enhanced recovery after surgery protocols undergoing colorectal operations.

BACKGROUND: Ketamine is used in enhanced recovery after surgery (ERAS) protocols because of its beneficial antihyperalgesic and antitolerance effects. However, adverse effects such as hallucinations, sedation, and diplopia could limit ketamine's utility. The main objective of this study was to identify rates of ketamine side effects in postoperative patients after colorectal surgery and, secondarily, to compare short-term outcomes between patients receiving ketamine analgesia and controls. METHODS: This was a retrospective observational cohort study. Subjects were adults who underwent ERAS protocol-guided colorectal surgery at a large, integrated health system. Patients were grouped into ketamine-receiving and preketamine cohorts. Patients receiving ketamine were divided into tolerant and intolerant groups. Propensity score-adjusted models tested multivariate associations of ketamine tolerance/intolerance vs control group. RESULTS: A total of 732 patients underwent colorectal surgery within the ERAS program before ketamine's introduction (control). After ketamine's introduction, 467 patients received the medication. Intolerance was seen in 29% of ketamine recipients, and the most common side effect was diplopia. Demographics and surgical variables did not differ between cohorts. Multivariate models revealed no significant differences in hospital stays. Pain scores in the first 24 hours after surgery were slightly higher in patients receiving ketamine. Opiate consumption after surgery was lower for both ketamine tolerant and ketamine intolerant cohorts than for controls. CONCLUSION: Rates of ketamine intolerance are high, which can limit its use and potential effectiveness. Ketamine analgesia significantly reduced opiate consumption without increasing hospital stays after colorectal surgery, regardless of whether it was tolerated.

Cervical Manipulation and Koren Specific Technique Emotions Protocol in the Improvement of Intensive Nocturnal Dry Cough: A Case Report.

This report describes a 42-year-old female patient who presented with an intensive nocturnal dry cough persisting for over six months. Subsequent to the prolonged cough, she developed shoulder and neck discomfort, leading her to seek chiropractic care. The patient received cervical chiropractic adjustments combined with the Koren Specific Technique (KST) emotions protocol. The patient was mainly treated for her musculoskeletal complaint. However, after two treatment sessions, the patient's chronic cough showed significant improvement. Two weeks later, the cough had completely ceased, and her shoulder and neck discomfort had also improved. The cough symptoms did not reappear during the six-month follow-up. The mechanism of cough improvement remains unclear, whether it is due to spinal adjustments, the KST emotions protocol, their combined effects, or merely a placebo response. This report discusses the potential underlying mechanisms of the case improvement, suggesting a non-pharmacological adjunctive therapeutic approach that could be investigated further in future research.

LFC study: Protocol for a longitudinal follow-up cohort study on ageing and mental health in community-dwelling older adults in Singapore.

The rapid pace of population ageing worldwide has prompted the need to better understand the ageing process. The current study, titled the Longitudinal Follow-up of the CHI (LFC) study, was a 3-year follow-up study of an earlier study titled the Community Health and Intergenerational (CHI) study. The LFC study looked to examine longitudinal changes in their cognitive functioning and psychosocial outcomes across the 3-year period. Additionally, the current study built upon the earlier CHI study by collecting neuroimaging data and exploring the long-term effects of non-pharmacological interventions, which were not examined in the prior study. A total of 653 community-dwelling participants from the baseline CHI study cohort were invited to take part in the LFC study, where they underwent a battery of neuropsychological assessments, psychosocial questionnaires, a Magnetic Resonance Imaging scan and a voice recording segment. The current study would holistically track longitudinal changes in cognitive functioning and psychosocial outcomes in the ageing population in Singapore. Unique associations between linguistics and neuroimaging data alongside cognitive and psychosocial outcomes would be explored. This study also serves to guide the development of new interventions for older adults and assist in improving the well-being of the local and global ageing population.

Annual mpMRI surveillance: PI-RADS upgrading and increasing trend correlated with patients who harbor clinically significant disease.

INTRODUCTION: Prostate cancer screening has routinely identified men with very low- or low-risk disease, per the National Comprehensive Cancer Network guidelines. Current literature has demonstrated that the most appropriate management strategy for these patients is active surveillance (AS). The mainstay of AS includes periodic biopsies and biannual prostate-specific antigen tests. However, multiparametric magnetic resonance imaging (mpMRI) is uniquely posed to improve patient surveillance. This study aimed to evaluate the utility of an annual mpMRI in patients on AS, focusing on radiologic upgrading and Prostate Imaging-Reporting and Data System (PI-RADS) trends as indicators of clinically significant disease. METHODS: This prospective, single intuition, study enrolled 208 patients on AS who had at least two biopsies and 1 mpMRI with a median follow-up of 5.03 years. The main outcome variable was time to Gleason grade (GG) reclassification. RESULTS: After delineating patients on their initial PI-RADS score, men with score 3 and 5 lesions at first MRI had comparable GG reclassification-free survival to their counterparts. Conversely, men with initial PI-RADS 4 lesions showed a lower 5-year GG reclassification-free survival compared to those with PI-RADS score 1-2. The cohort was then subset to 70 patients who obtained ≥2 mpMRIs on protocol. Men experiencing uptrending mpMRI scores had an increased risk of GG reclassification, with a 35.4% difference in 5 year GG reclassification-free survival probability on the Kaplan-Meier curve analysis. CONCLUSION: In conclusion, this study demonstrates that for men on AS with stable recapitulated disease, an annual MRI may replace repeat biopsies after confirmatory sampling has been obtained. On the other hand, men who initiate AS with PI-RADS 4 and/or who display uptrending mpMRI scores require periodic biopsies along with repeat imaging. This study highlights the utility of integrating an annual MRI into AS protocols, thus promising a more effective approach to management.

Acupuncture for generalized anxiety disorder: a study protocol for a randomized controlled trial

During the COVID-19 outbreak, there was a sharp increase in generalized anxiety disorder (GAD). Acupuncture therapy has the advantages of accurate clinical efficacy, safety and reliability, few adverse reactions, and no dependence, and is gradually becoming one of the emerging therapies for treating GAD. We present a study protocol for a randomized clinical trial with the aim of exploring the mechanism of brain plasticity in patients with GAD and evaluate the effectiveness and reliability of acupuncture treatment. Transcranial magnetic stimulation (TMS) will be used to assess cortical excitability in GAD patients and healthy people. Sixty-six GAD patients meeting the inclusion criteria will be randomly divided into two groups: TA group, (treatment with acupuncture and basic western medicine treatment) and SA group (sham acupuncture and basic western medicine treatment). Twenty healthy people will be recruited as the control group (HC). The parameters that will be evaluated are amplitude of motor evoked potentials (MEPs), cortical resting period (CSP), resting motor threshold (RMT), and Hamilton Anxiety Scale (HAMA) score. Secondary results will include blood analysis of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), and brain-derived nerve growth factor (BDNF). Outcomes will be assessed at baseline and after the intervention (week 8). This study protocol is the first clinical trial designed to detect differences in cerebral cortical excitability between healthy subjects and patients with GAD, and the comparison of clinical efficacy and reliability before and after acupuncture intervention is also one of the main contents of the protocol. We hope to find a suitable non-pharmacological alternative treatment for patients with GAD.

Baduanjin Mind-Body Exercise for Cancer-Related Fatigue: Protocol for a Remotely Delivered Randomized Wait-List Controlled Feasibility Study.

BACKGROUND: People living with a cancer diagnosis often experience cancer-related fatigue (CRF). Between 9% and 45% of people report CRF as moderate to severe, negatively impacting their quality-of-life (QOL). The evidence-base for managing CRF recommends exercise-related therapies over pharmaceutical interventions. One such exercise-like therapy is Baduanjin mind-body exercise (MBE), which has additional benefits. A remotely delivered program may further benefit people with CRF. The primary objective of this pilot will test study feasibility of a remotely delivered Baduanjin MBE exercise program for people living with CRF. METHODS: This is a randomized wait-list controlled pilot study and will take place in Sydney, Australia. Subject to informed consent, 40 adults with moderate CRF levels and receiving or previously received adjuvant chemotherapy, will undertake a home-based 8-week Baduanjin MBE program supported by online resources and instructors. The primary feasibility outcomes are recruitment, enrollment, retention, and adherence rates; and safety as measured by tolerance and adverse-event frequency. Clinical outcomes (eg, changes in CRF, QOL, and participant perceptions) are assessed at pre-intervention, week 1, week 4, week 8, and post-intervention. Analyses follows the Intent-to-Treat (all participants as per randomization) and per-protocol (participants adhering to the protocol). Missing data will be imputed from previous data entries and regression models may be tested to predict missing outcomes. DISCUSSION: To our knowledge, this is the first study evaluating the feasibility and effects of Baduanjin MBE on CRF using a remote delivery method. These feasibility data will inform a fully powered future trial investigating evidence of effect on CRF and QOL.Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR 12623000177651).Ringgold ID: 651498 Chinese Medicine Centre.