A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy.

Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials. Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

Renal effects and safety between Asian and non-Asian chronic kidney disease and type 2 diabetes treated with nonsteroidal mineralocorticoid antagonists.

BACKGROUND: Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non-Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP-5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes. RESULTS: Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non-Asians: (weighted mean difference [WMD], -0.59, 95% CI, -0.73 to -0.45, p < .01) vs (WMD, -0.29, 95% CI, -0.32 to -0.27, p < .01), respectively. The average decline of estimated glomerular filtration rate (eGFR) was similar in Asians and non-Asians (p > .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, -5.12, 95% CI, -5.84 to -4.41, p < .01) compared to non-Asians (WMD, -3.64, 95% CI, -4.38 to -2.89, p < .01). A higher incidence of hyperkalemia and eGFR decrease ≥30% was found in Asians than non-Asians (p < .01). CONCLUSIONS: Nonsteroidal MRAs exhibited significant renal benefits by decreasing UACR and lowering SBP in Asian than that of non-Asian patients with CKD and T2DM, without increase of adverse events except hyperkalemia and eGFR decrease ≥30%.

PRESOLRE: study protocol for a primary school-based, cluster randomised controlled trial of three sun exposure risk prevention strategies on Reunion Island.

INTRODUCTION: Reunion Island, a French overseas department, is located in the southern hemisphere, close to the Capricorn tropic. This island has a multicultural and multiethnic population of 860 000 inhabitants, a quarter of whom are at high risk of developing skin cancer due to intense ultraviolet radiation. Melanoma is responsible for the majority of skin cancer deaths. The early prevention of melanoma is based on sun protection in childhood, but French regulations are not adapted to the environmental conditions of this tropical region.The main objective of our study is to evaluate the effectiveness of three sun protection programs conducted in Reunionese primary schools through a pupil knowledge questionnaire. METHODS AND ANALYSIS: PRESOLRE is an interventional, open-label, cluster-randomised controlled trial, in four parallel arms, that is being conducted throughout 2022-2023 on Reunion Island. The trial design assumes an escalation interventional effect using: first, a control arm without proposed intervention (arm 1); second, an arm whose classes are encouraged to use the validated educational programme 'Living With the Sun' (LWS) (arm 2); third, an arm whose classes are encouraged to use both 'LWS' combined with 'Mission Soleil Réunion's sun protection awareness programme (arm 3); fourth, an arm benefiting from an intervention similar to arm 3, combined with the distribution of hats, sunglasses and sun creams (arm 4). In all, 1780 pupils from 18 classes of 20 pupils, on average, will be included. Randomisation applies to the classes of pupils (so defined as clusters). The primary outcome is based on the proportion of correct answers to the knowledge questions after the awareness programme, compared between the four arms using a linear mixed model with random intercept. ETHICS AND DISSEMINATION: The study obtained ethics approval in 2022 (ID: 2022-A00350-43). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05367180.

Effect of a 3D-printed reconstruction automated matching system for selecting the size of a left double-lumen tube: a study protocol for a prospective randomised controlled trial.

INTRODUCTION: Lung isolation is primarily accomplished using a double-lumen tube (DLT) or bronchial blocker. A precise and accurate size of the DLT is a prerequisite for ensuring its accurate placement. Three-dimensional (3D) reconstruction technology can be used to accurately reproduce tracheobronchial structures to improve the accuracy of DLT size selection. Therefore, we have developed automatic comparison software for 3D reconstruction based on CT data (3DRACS). In this study, we aimed to evaluate the efficiency of using 3DRACS to select the DLT size for endobronchial intubation in comparison with using the 'blind' DLT intubation method to determine the DLT size, which is based on height and sex. METHODS AND ANALYSIS: This is a prospective, single-centre, double-blind randomised controlled trial. In total, 200 patients scheduled for lung resection using a left DLT will be randomly allocated to the 3D group or the control group at a 1:1 ratio. A 3DRACS will be used for the 3D group to determine the size of the DLT, while in the case of the control group, the size of the DLT will be determined according to patient height and sex. The primary outcome is the success rate of placement of the left DLT without fibreoptic bronchoscopy (FOB). The secondary outcomes include the following: successful intubation time, degree of pulmonary atrophy, grade of airway injury, oxygenation during one-lung ventilation, postoperative sore throat and hoarseness, and number of times FOB is used. ETHICS AND DISSEMINATION: Ethical approval has been obtained from our local ethics committee (approval number: SCCHEC-02-2022-155). Written informed consent will be obtained from all participants before randomisation, providing them with clear instructions about the purpose of the study. The results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT06258954.

Personalised functional imaging-guided multitarget continuous theta burst stimulation for post-stroke aphasia: study protocol for a randomised controlled trial.

INTRODUCTION: Continuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of post-stroke aphasia (PSA) patients shows promising results in clinical trials. However, existing PSA studies have focused on single-target rTMS, leaving unexplored the potential benefits of multitarget brain stimulation. Consequently, there is a need for a randomised clinical trial aimed to evaluate the efficacy and safety of cTBS targeting on multiple critical nodes in the language network for PSA. METHODS AND ANALYSIS: This is a prospective, multicentre, double-blind, two-arm parallel-group, sham-controlled randomised trial. The study will include a total of 60 participants who will be randomly assigned in a 1:1 ratio to either the active cTBS group or the sham cTBS group. Using precision resting-state functional MRI for each participant, we will map personalised language networks and design personalised targets in the inferior frontal gyrus, superior temporal gyrus and superior frontal gyrus. Participants will undergo a 3-week cTBS intervention targeting the three personalised targets, coupled with speech and language therapy. The primary outcome is the change in the Western Aphasia Battery-Revised aphasia quotient score among participants after a 3-week treatment. Secondary outcomes include Boston Diagnostic Aphasia Examination severity ratings, Token Test and the Chinese-version of the Stroke and Aphasia Quality of Life Scale 39-generic version. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of Affiliated Hospital of Hebei University, Hebei General Hospital and Affiliated Hospital of Chengde Medical University. The findings of this study will be reported in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: The study has been registered on ClinicalTrials.gov (NCT05957445).

Comparison of three diagnostic strategies for suspicion of pulmonary embolism: planar ventilation-perfusion scan (V/Q), CT pulmonary angiography (CTPA) and single photon emission CT ventilation-perfusion scan (SPECT V/Q): a protocol of a randomised controlled trial.

INTRODUCTION: Pulmonary embolism (PE) is a challenge to diagnose and when missed, exposes patients to potentially fatal recurrent events. Beyond CT pulmonary angiography (CTPA) and planar ventilation/perfusion (V/Q) scan, single photon emission CT (SPECT) V/Q emerged a new diagnostic modality of scintigraphic acquisition that has been reported to improve diagnostic performances. To date, no management outcome study or randomised trial evaluated an algorithm based on SPECT V/Q for PE diagnosis. We present the design of a randomised multicentre, international management study comparing SPECT V/Q with validated strategies. MATERIAL AND METHODS: We will include a total of 3672 patients with suspected PE requiring chest imaging, randomised into three different groups, each using a different diagnostic strategy based on SPECT V/Q, CTPA and planar V/Q scan. Randomisation will be unbalanced (2:1:1), with twice as many patients in SPECT V/Q arm (n=1836) as in CTPA and planar V/Q arms (n=918 in each). Our primary objective will be to determine whether a diagnostic strategy based on SPECT V/Q is non-inferior to previously validated strategies in terms of diagnostic exclusion safety as assessed by the 3-month risk of thromboembolism in patients with a negative diagnostic workup. Secondary outcomes will be the proportion of patients diagnosed with PE in each arm, patients requiring additional tests, the incidence of major and clinically relevant non-major bleeding and the incidence and cause of death in each arm. ETHICS AND DISSEMINATION: This trial is funded by a grant from Brest University Hospital and by INVENT. The study protocol was approved by Biomedical Research Ethics Committee. The investigator or delegate will obtain signed informed consent from all patients prior to inclusion in the trial. Our results will inform future clinical practice guidelines and solve the current discrepancy between nuclear medicine guidelines and clinical scientific society guidelines. TRIAL REGISTRATION NUMBER: NCT02983760.

Preoperative walking exercise to improve prognosis in patients with supratentorial brain tumours after craniotomy: protocol for a randomised controlled trial.

INTRODUCTION: Cardiopulmonary complications and cognitive impairment following craniotomy have a significantly impact on the general health of individuals with brain tumours. Observational research indicates that engaging in walking is linked to better prognosis in patient after surgery. This trial aims to explore whether walking exercise prior to craniotomy in brain tumour patients can reduce the incidence of cardiopulmonary complications and preserve patients' cognitive function. METHODS AND ANALYSIS: In this randomised controlled trial, 160 participants with supratentorial brain tumours aged 18-65 years, with a preoperative waiting time of more than 3-4 weeks and without conditions that would interfere with the trial such as cognitive impairment, will be randomly assigned in a ratio of 1:1 to either receive traditional treatment or additional combined with a period of 3-4 weeks of walking exercise of 10 000-15 000 steps per day. Wearable pedometer devices will be used to record step counts. The researchers will evaluate participants at enrolment, baseline, 14 days preoperatively, 3 days prior to surgery and 1 week after surgery or discharge (select which occurs first). The primary outcomes include the incidence of postoperative cardiopulmonary complications and changes in cognitive function (gauged by the Montreal Cognitive Assessment test). Secondary outcomes include the average length of hospital stay, postoperative pain, participant contentment, healthcare-associated costs and incidence of other postoperative surgery-related complications. We anticipate that short-term preoperative walking exercises will reduce the incidence of surgery-related complications in the short term after craniotomy, protect patients' cognitive function, aid patients' postoperative recovery and reduce the financial cost of treatment. ETHICS AND DISSEMINATION: The study protocol has been approved by Ethics Committee of Xiangya Hospital of Central South University (approval number: 202305117). The findings of the research will be shared via publications that have been reviewed by experts in the field and through presentations at conferences. TRIAL REGISTRATION NUMBER: NCT05930288.

Restore and Rebuild (R&R): a protocol for a phase 2, randomised control trial to compare R&R as a treatment for moral injury-related mental health difficulties in UK military veterans to treatment as usual.

BACKGROUND: Exposure to potentially morally injurious events is increasingly recognised as a concern across a range of occupational groups, including UK military veterans. Moral injury-related mental health difficulties can be challenging for clinicians to treat and there is currently no validated treatment available for UK veterans. We developed Restore and Rebuild (R&R) as a treatment for UK veterans struggling with moral injury-related mental health difficulties. This trial aims to examine whether it is feasible to conduct a pilot randomised controlled trial (RCT) of R&R treatment compared with a treatment-as-usual (TAU) control group. METHODS: We will use a feasibility single-blind, single-site RCT design. The target population will be UK military veterans with moral injury-related mental health difficulties. We will recruit N=46 veteran patients who will be randomly allocated to R&R (n=23) or TAU (n=23). Patients randomised to R&R will receive the 20-session one-to-one treatment, delivered online. Veterans allocated to TAU, as there are currently no manualised treatments for moral injury-related mental health problems available, will receive the one-to-one treatment (online) typically provided to veterans who enter the mental health service for moral injury-related mental health difficulties. We will collect outcome measures of moral injury, post-traumatic stress disorder (PTSD), alcohol misuse, common mental disorders and trauma memory at pretreatment baseline (before randomisation), end of treatment, 12 weeks and 24 weeks post-treatment. The primary outcome will be the proportion of patients who screen positive for PTSD and moral injury-related distress post-treatment. ETHICS AND DISSEMINATION: This trial will establish whether R&R is feasible, well-tolerated and beneficial treatment for veterans with moral injury-related mental health difficulties. If so, the results of the trial will be widely disseminated and R&R may improve access to effective care for those who struggle following moral injury and reduce the associated negative consequences for veterans, their families and wider society. TRIAL REGISTRATION NUMBER: ISRCTN99573523.

Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

BACKGROUND: Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. METHODS: Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. DISCUSSION: This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. TRIAL REGISTRATION: Trial registered on Australian New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.

Effectiveness of a school-based Life Gatekeeper Training Program on suicide prevention in China: protocol for a randomized controlled trial.

BACKGROUND: With suicide as a leading cause of death, the issue of children and adolescent suicide risks is in the spotlight today. To empower teachers in primary and secondary schools to serve as gatekeepers and to ensure the safety of children and adolescents, the systematically tailored and localized Life Gatekeeper suicide prevention program was designed for Chinese schools. OBJECTIVE: With the ultimate goal of preventing child and adolescent suicide, we aim to outline a research protocol for examining outcomes of the recently created standardized school-based Life Gatekeeper program in reducing teachers' stigma, increasing their knowledge, willingness to intervene, and perceived competence. METHODS: Participants will be recruited from eligible primary and secondary schools. Cluster sampling will be used to randomly assign each school to either the intervention group or the control group. The primary outcomes are stigma against suicide, suicide literacy, perceived competence, and willingness to intervene with suicidal individuals, which will be measured using the Stigma of Suicide Scale, the Literacy of Suicide Scale, and the Willingness to Intervene Against Suicide Questionnaire, respectively. Measurements will be taken at four time points, including pre-intervention, immediately after the intervention, 6-month follow-up, and 1-year follow-up. CONCLUSIONS: The current study features innovative implementation in the real world, by using a randomized controlled trial design to examine the effectiveness of a school-based gatekeeper program among primary and secondary school teachers, following a sequence of defined and refined steps. The research will also investigate the viability of a school-based gatekeeper program for primary and secondary school teachers that could be quickly and inexpensively implemented in a large number of schools.

Massage for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to evaluate the effectiveness of massage for postoperative rehabilitation after total knee arthroplasty (TKA). DATA SOURCES: The PubMed, Web of Science, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were systematically searched from inception to May 2024. STUDY SELECTION: Any randomized controlled trials on the use of massage for postoperative TKA rehabilitation were included. DATA EXTRACTION: A meta-analysis of outcomes, including postoperative pain, knee range of motion (ROM), postoperative D-dimer levels, and length of hospital stay, was performed. The Cochrane Risk of Bias Assessment Tool was used to assess the risk of bias, and the data for each included study were extracted independently by two researchers. DATA SYNTHESIS: Eleven randomized controlled clinical trials with 940 subjects were included. The results showed that compared with the control group, the massage group experienced more significant pain relief on the 7th, 14th and 21st days after the operation. Moreover, the improvement in knee ROM was more pronounced on postoperative days 7 and 14. In addition, the massage group reported fewer adverse events. However, there was no statistically significant difference in the reduction in postoperative D-dimer levels between the patients and controls. Subgroup analysis revealed that massage shortened the length of hospital stay for postoperative patients in China but not significantly for patients in other regions. Nevertheless, the heterogeneity of the studies was large. CONCLUSIONS: Increased massage treatment was more effective at alleviating pain and improving knee ROM in early post-TKA patients. However, massage did not perform better in reducing D-dimer levels in patients after TKA. Based on the current evidence, massage can be used as an adjunctive treatment for rehabilitation after TKA.

4-Aminopyridine treatment for nerve injury resulting from radical retro-pubic prostatectomy: a single-center double-blind, randomized, placebo-controlled study.

BACKGROUND: Prostate cancer (PCa) is the most common non-cutaneous malignancy in men and leads to the second most common cause of cancer related mortality in men. Early detection of PCa allows for a potentially curative intervention. Most men will live over a decade from the time of their PCa diagnosis. Thus, treatments must balance curative interventions with their impact on quality of life. Radical prostatectomy (RP) is one such potentially curative intervention but often leads to erectile dysfunction (ED) and urinary incontinence (UI). Approximately 90,000 RPs are performed each year in the USA. Post-operative ED and UI is thought to occur in part from traumatic peripheral nerve injury (TPNI) to the neurovascular bundles that surround the prostate. Thus, patients undergoing RP may be a population that would benefit from clinical studies that look at TPNI. METHODS: The study is a single-institution, double-blinded placebo-controlled, randomized clinical trial in which patients immediately post-RP receive either 4-aminopyrdine (4AP) or placebo in a 1:1 fashion. The primary outcome is evaluation of the efficacy of 4AP in accelerating the early return of baseline erectile and urinary function post-radical prostatectomy. DISCUSSION: This study is critical as it could reduce the morbidity associated with RP, a commonly performed operation, and identify a patient population that may greatly benefit into further TPNI research. TRIAL REGISTRATION: ClinicalTrials.gov NCT03701581. Prospectively registered on October 10, 2018.

High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial).

INTRODUCTION: The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). METHODS: In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. DISCUSSION: This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Telemedicine home-based management in patients with chronic heart failure and diabetes type II: study protocol for a randomized controlled trial.

BACKGROUND: Heart failure and type 2 diabetes are prevalent public health issues in Europe. These complex chronic conditions require extensive pharmacological management, ongoing self-care, and behavioral changes. Despite the known benefits of lifestyle changes, such as regular exercise and better control of blood sugar levels, patients may need help implementing the recommended changes. This study aims to assess the effectiveness of a telemedicine program for managing heart failure and type 2 diabetes at home. The program focuses on promoting lifestyle changes. METHODS AND ANALYSIS: During scheduled outpatient cardiology evaluations, eligible patients are recruited and randomly assigned to either an intervention or control group in a 1:1 ratio. The intervention group receives support from a nursing case manager through a structured home-based teleassistance program and a trainer for daily physical activity stimulation. They also have access to teleconsultations with cardiologists and diabetes specialists as needed, telemonitoring of vital signs, and daily step tracking. An app records and monitors daily drug treatment, glycemia, blood pressure, heart rate, and other clinical parameters. Patients can also self-report symptoms and communicate via a chat and videoconference system with a Nurse Case Manager. The control group receives routine care. Data collection occurs before intervention and 6 months after baseline during a new outpatient cardiology evaluation. The primary outcome is to measure the difference in the distance walked during a 6-min walk test between baseline and after 6 months. The key secondary outcomes include improving the disease status and physical activity profile. Data will be analyzed according to the intention-to-treat principles. DISCUSSION: This study will provide evidence on the efficacy of a telemedicine home-based management model to maintain correct lifestyles in patients with both heart failure and type 2 diabetes, improving self-management, their empowerment on the diseases, and increasing their knowledge and ability to recognize symptoms early. TRIAL REGISTRATION: ClinicalTrials.gov NCT05633784. Registered on November 30, 2022.

A Network Meta-Analysis of the Systemic Therapies in Unresectable Head and Neck Squamous Cell Carcinoma.

The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN. METHODS: We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework. RESULTS: Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy. CONCLUSION: Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.

The current standard treatment for advanced head and neck cancer involves combining radiation therapy with chemotherapy. However, there are ongoing trials exploring alternative therapies. In this study, we conducted a comprehensive analysis of existing treatments using a statistical method called network meta-analysis. Our analysis included data from randomized controlled trials published between January 2000 and July 2023. We focused on overall survival and progression-free survival as key outcome measures. The results of our analysis showed that none of the alternative treatments demonstrated significant advantages over the standard concurrent chemoradiotherapy. Nevertheless, there is potential for improved outcomes when targeted therapy or induction chemotherapy is combined with concurrent chemoradiotherapy.

A blended face-to-face and eHealth lifestyle intervention on physical activity, diet, and health outcomes in Hong Kong community-dwelling older adults: a study protocol for a randomized controlled trial.

Background: Aging individuals are vulnerable to various Noncommunicable Diseases (NCDs). Different behaviors are closely related to a decreased risk of suffering from NCDs: sufficient Physical Activity (PA) (e.g., at least 150 mins Moderate-to-vigorous Physical Activity (MVPA) per week) and a healthy daily diet (e.g., at least five portions of Fruit and Vegetable Intake (FVI), 5-6 taels (189.0-226.8 g) Meat, Fish, Egg and Alternatives (MFEA)). Traditional face-to-face interventions were effective in behavior change. However, it was revealed to be resource-intensive and limited transfer due to poor self-regulation skills outside of face-to-face sessions. Thus, eHealth could be a supplement for older adults outside traditional face-to-face settings. The blended approach combining these two interventions might optimize the intervention effects on lifestyle behavior initiation and maintenance, but little research can be found among Hong Kong older adults. Therefore, the study aims to test a blended intervention to promote PA, diet, and health outcomes among Hong Kong community-dwelling older adults. Methods: This study will adopt a 10-week three-arm randomized controlled trial. The blended group will receive weekly (1) two 60-min face-to-face sessions with one for PA and one for diet, and (2) two web-based sessions with one for PA and one for diet. The face-to-face group will receive the same intervention content as the face-to-face sessions in the blended group. The control condition will receive a biweekly telephone call. The outcomes will include MVPA (minutes/week), FVI (portions/day), MFEA consumption (taels/day), social-cognitive factors (self-efficacy, planning, social support, action control), physical health outcomes (clinical indicators, senior physical fitness), mental health outcomes (depression, loneliness) and health-related quality of life. Data collection will be implemented at the pre-test, post-test, and 3-month follow-up test. Discussion: This is the first study evaluating a blended intervention promoting multiple health behaviors among Hong Kong community-dwelling older adults. If the effect of the blended intervention is superior to the traditional face-to-face group and the control group, it will enrich lifestyle intervention approaches and can be applied to older adults, helping them obtain health benefits. Furthermore, a better understanding of mechanisms will also have implications for theory-building. Clinical trial registration: https://www.isrctn.com/ISRCTN32329348, ISRCTN32329348.

Continuous infusion versus bolus injection of loop diuretics for acute heart failure.

BACKGROUND: Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion in 5% of cases. Treatment often requires urgent escalation of diuretic therapy, mainly through hospitalisation. This Cochrane review evaluated the efficacy of intravenous loop diuretics strategies in treating AHF in individuals with New York Heart Association (NYHA) classification III or IV and fluid overload. OBJECTIVES: To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults. SEARCH METHODS: We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors. DATA COLLECTION AND ANALYSIS: Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence. MAIN RESULTS: The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics. AUTHORS' CONCLUSIONS: Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.