Kwun Tong Kowloon, Hong Kong

Social Worker-led Mindfulness-based Intervention for Older People

Mindfulness-based cognitive therapy (MBCT) is a promising approach to managing a series of health and psychological conditions among older adults. To increase its acceptability, feasibility, and scalability, MBCT has been adapted and delivered in a variety of formats. Apart from delivering the intervention in person by a certified mindfulness teacher, MBCT has been adapted to be self-taught, delivered online, or partially led by social workers. In a previous study conducted by the investigators, it was found that a task-shared approach with modified MBCT supported by social workers is effective in producing change in older adults' mental health and mindfulness. However, whether social workers are competent to lead a mindfulness-based intervention (MBI) informed by MBCT on their own and produce effective changes in outcome measures pertaining to mental health remains unclear. Furthermore, the effects of incorporating peer supporters into mental health interventions are unclear. The uses and implementation of peer support across mental health contexts vary greatly and the effects are mixed. In a pilot study on men with advanced prostate cancer, it has been suggested that the presence of peer support in modified mindfulness-based cognitive therapy group intervention may reinforce intervention effects. Furthermore, in an online intervention for older adults with elevated depressive symptoms, peer support has been found to improve engagement and adherence to the intervention. However, in a systematic review and meta-analysis, it has been found that while incorporating one-to-one peer support in mental health services has a modest positive impact on self-reported psychosocial outcomes such as self-rated recovery and empowerment, there is no evidence for improvement in clinical outcomes. With the growing older people population and a need for greater social welfare capacity to promote older adults' well-being, the current study aims to examine the effectiveness of social worker-led MBI informed by MBCT in improving depression in older adults with mild to moderate depressive symptoms. In addition, the effectiveness of incorporating peer supporters into the intervention will be examined.

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases

This research study is to find out if study treatment DFV890 is safe and tolerable, and can help patients who were diagnosed with a myeloid disease such as: very low, low or intermediate risk myelodysplastic syndromes (MDS) and very low, low or intermediate risk chronic myelomonocytic leukemia (CMML). The study seeks to determine the optimal dose of DFV890 that is safe and efficacious in patients with myeloid disease. The effectiveness and safety/tolerability of the study treatment is not yet confirmed in this disease setting. Eligible patients meeting all study entry requirements will be required to provide a sample from their bone marrow at screening and at select study timepoints. All enrolled patients will be dosed for a minimum of twenty-four weeks (6 cycles of treatment) unless they experience side effects related to the study treatment requiring dose interruption/discontinuation, worsening of the disease, and/or if treatment is discontinued at the discretion of the investigator or the patient.

A Study to Evaluate Mezigdomide in Combination With Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma (SUCCESSOR-2)

Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07)

The primary objectives of the study are Progression Free Survival (PFS) and Overall Survival (OS) as first line therapy in participants with programmed death-ligand 1 (PD-L1) TPS <50% and advanced or metastatic NSCLC without actionable genomic alternations. Eligible participants will be randomized in a 1:1:1 ratio to a) Dato-DXd plus pembrolizumab plus platinum; b) Dato-DXd plus pembrolizumab; or c) pembrolizumab plus pemetrexed plus platinum. Platinum therapy will be either carboplatin or cisplatin at investigator discretion. The study will be divided into three periods: Screening Period (including tissue screening), Treatment Period, and Follow-up Period.

Transcranial Pulse Stimulation for Depression

RCT on Robotic vs. Endo-laparoscopic Approach for Difficult Choledocholithiasis

Background (i) Background information Gallstone disease is a very common disease identity in developed countries, causing a major health burden. There is an estimate of 20 - 25 million adults diagnosed to have gallstone disease annually, resulting in more than 260,000 hospitalization for cholecystitis in the year 2000 in US. In Asia, the prevalence rate ranges from 5% to 20% of population. Common bile duct (CBD) stone (choledocholithiasis) occurs when there is migration of stone from gallbladder to CBD in up to 22% of cases. The resulting acute cholangitis and acute biliary pancreatitis leads to substantial morbidity and mortality to patients. Traditionally, choledocholithiasis can be managed successfully by therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with interval cholecystectomy in 85% of patients. However, standard ERCP fails to clear choledocholithiasis in around 15% of the patients, and these cases are referred as "difficult choledocholithiasis". According to European Society of Gastrointestinal Endoscopy guideline, difficult choledocholithiasis can be managed by either two-stage endo-laparoscopic approach or one-stage surgical approaches. The two-stage endo-laparoscopic approach involves ERCP using advanced endoscopic stone-clearing techniques with interval laparoscopic cholecystectomy (LC) in two weeks' time. On the other hand, the one-stage surgical approach is carried out by performing CBD exploration with simultaneous cholecystectomy using minimally invasive or open method. Potentially, the latter holds the advantage of treating two disease identities (choledocholithiasis and gallstone) by single operation under general anaesthesia. From the guideline, whether to proceed to two-stage endo-laparoscopic or one-stage surgical approach still requires high-level evidence. (ii) Research gap By far, most centers adapt sequential two-stage endo-laparoscopic approach for difficult choledocholithiasis, and reserving one-stage LCBDE plus LC for selected patient. A Cochrane review on 16 randomized clinical trials comparing endoscopic and surgical approaches for treatment of choledochothiliasis in 1758 patients was published in 2016.5 There was no difference in mortality, morbidity and stone clearance rate between one-stage laparoscopic approach and two-stage endo-laparoscopic approach. More recently, another meta-analysis on studies comparing these two approaches has shown different findings. The two-stage endo-laparoscopic approach had higher CBD stone clearance rate, lower postoperative bile leakage rate and higher rate of pancreatitis than one-stage laparoscopic approach, which might help to shorten the hospital stay. One major critic is that the nature of choledocholithiasis, whether it was difficult choledocholithiasis or not, was poorly defined in all of those randomized studies. The resulting heterogeneity in patient selection makes the results from these studies difficult to compare and convincing conclusion is hard to generate. Thus, a well-designed randomized clinical trial comparing the two-stage endo-laparoscopic with one-stage minimally invasive approach for difficult choledocholithiasis with clear-cut stone clearance rate as primary outcome measure is needed. With advancement of da Vinci robotic system, there are 3-dimensional dual cameras providing high-quality intraoperative view and 7-degree of freedom of robotic instruments. The system is able to cope with complex hepatobiliary surgical procedure, especially those procedure involving intra-corporeal suturing techniques. To tackle difficult choledocholithiasis, one-stage robotic common bile duct exploration (RCBDE) and robotic cholecystectomy (RC) could be an effective method with high successful rate and low complication. Ji et al. published the first series of one-stage RCBDE plus RC in 5 patients. There was no conversion to laparoscopic or open surgery. One patient developed chest complication. The average hospital stay was 5.8 days and the stone clearance rate was 100%. Alkhamesi et al. compared RCBDE with open surgery in a retrospective study. The robotic approach posed an advantage of shorter hospital stay when compared with open approach. From European Association of Endoscopic Surgeons consensus statement, robotic assistance may facilitate complex biliary surgery, including RCBDE. Theoretically, one-stage RCBDE plus RC is superior than traditional two-stage endo-laparoscopic approach for difficult choledocholithiasis because of the following two reasons. 1. One-stage robotic approach can achieve much higher stone clearance rate than two-stage endo-laparoscopic approach. Potentially, one-stage procedure can have nearly 100% stone clearance rate since it eliminates both gallstone and choledocholithiasis in one surgery. In contrast, two-stage approach may have time lag between initial therapeutic ERCP and interval LC. There is always a chance of stone migration into CBD during waiting period for LC. 2. With an aid of robotic instruments, closure of CBD opening can be safely performed without the risk of postoperative bile leak, which happens in around 5% of LCBDE. (iii) Novelty of proposed study So far, there is no prospective clinical trial from the registry of clinical trials provided by the US National Library of Medicine to test the hypothesis that one-stage robotic approach is superior than two-stage endo-laparoscopic approach for difficult choledocholithiasis. The principle investigator thus propose a single-center randomized trial (REAL trial) with the primary objective of testing the superiority of one-stage robotic approach over two-stage endo-laparoscopic approach for difficult choledocholithiasis, with primary outcome measure of stone clearance rate. (iv) Preliminary data The average number of ERCP performed in the principle investigator's center is over 700 per year in recent 3 years. From the prospectively collected database on management of difficult choledocholithiasis in the principle investigator's center from 2018 - 2020, there were 362 patients with difficult choledocholithiasis treated by therapeutic ERCP (endoscopic papillary large balloon dilatation, and / or mechanical lithotripsy, and / or cholangioscopy-assisted lithotripsy). The median number of sessions was 3 (ranged 2 - 8). Post-ERCP complication rate was 26.7%, including acute pancreatitis (14%), papillotomy bleeding (9.1%) and bowel perforation (3.5%). There was no hospital mortality. Interval cholecystectomy can be completed in 223 patients (61.6%). Among these patients undergone ERCP plus interval cholecystectomy, the stone clearance rate was 78.4%. During the same study period, there were 20 patients receiving one-stage RCBDE plus RC. There was no hospital mortality. The postoperative complication rate was much lower than that of two-stage endo-laparoscopic approach (5% vs. 26.7%). The stone clearance rate was 100%, which was much higher than two-stage approach. The median hospital stay was 4 days (ranged 3 - 7 days). (Unpublished data) From these preliminary results, it is obvious that one-stage robotic approach is superior to two-stage endo-laparoscopic approach, in terms of higher stone clearance and lower procedure-related complications. Research Plan and Methodology Study design: Single-center randomized trial Center involved: Department of Surgery, The Chinese University of Hong Kong Inclusion and Exclusion Criteria: Consecutive patients with newly diagnosed difficult choledocholithiasis by diagnostic radiological studies (ultrasonography or CT scan or MRI cholangiography) will be recruited into the trial. Initial endoscopic retrograde cholangiopancreatography (ERCP) will be performed to confirm the diagnosis of difficult choledocholithiasis and temporarily plastic biliary stent will be inserted to bypass biliary obstruction. The followings are inclusion criteria: 1. Definition of difficult choledocholithiasis: stone size > 1.5cm, and/or multiple stones > 3, and/or narrow and angled distal common bile duct (CBD) (< 135o) 2. Diagnostic ERCP with successful CBD deep cannulation and temporarily CBD stenting 3. No history of cholecystectomy with provisional diagnosis of choledocholithiasis originating from gallstone disease 4. General condition fit for anaesthesia for both advanced therapeutic ERCP or robotic surgery The following patients will be excluded: 1. History of recurrent pyogenic cholangitis 2. Failed endoscopic biliary stenting by initial ERCP 3. Complications (acute pancreatitis, papillotomy bleeding or bowel perforation) from initial ERCP 4. Previous upper abdominal surgery, including gastrectomy 5. General condition unfit for anesthesia Randomization: Patients, with their consent, will be recruited to participate by investigators after considering the inclusion and exclusion criteria. Treatment allocation to the eligible patients will follow a randomization schedule. A total of 90 patients will be randomized 1:1 to one of the two treatment arms: 1. Robotic group: Patients receive one-stage robotic common bile duct exploration and simultaneous robotic cholecystectomy 2. Endo-laparoscopic group: Patients receive two-stage therapeutic ERCP and interval laparoscopic cholecystectomy The randomization schedule will be generated by the Clinical Trials Centre (CTC) of principle investigator's center, prior to the start of the study. Block randomization is used to maintain good balance to each treatment group. The randomization list will be kept in a set of tamper-evident envelopes. The envelopes will be identical and sealed. The trial identifier with a sequential number will be printed on each envelope and the inside will contain the treatment allocation. Envelopes will be unsealed to reveal the allocation treatment one day prior to the surgery. Pre-treatment Investigations and Assessments: All patients undergo the following pre-treatment investigations and assessments: 1. Blood tests: complete blood count, liver and renal function tests, coagulation profile, serum carcinoembryonic antigen 2. Radiological imaging: CT scan or MRI of abdomen to exclude the possibility of recurrent pyogenic cholangitis and malignant cause of biliary obstruction 3. ECG and / or other cardiac assessment as requested by anesthetist for general anesthesia assessment Treatment Procedures Robotic group: Under general anesthesia, four robotic 8-mm trocars and one 5-mm laparoscopic assistant trocar will be inserted and pneumoperitoneum is created. A conventional approach of robotic cholecystectomy is first performed with dissection of Calot's triangle and the removal of gallbladder from liver bed. The cystic duct is then retracted laterally to facilitate the exposure of anterior wall of common bile duct (CBD). CBD is subsequently opened longitudinally for about 1.5cm using robotic scissors. If choledocholithiasis (CBD stone) is encountered over the choledochotomy site, it will be removed directly by robotic forceps. If not, a 5-mm flexible choledochoscope will be inserted into CBD through choledochotomy site to identify the stone, which will be removed by sterile saline flushing, stone basket, or electrohydraulic lithotripsy. Ductal clearance will be confirmed by choledochoscopic examination from lower CBD up to left and right intrahepatic ducts. The intraluminal plastic biliary stent, which was inserted before the procedure, will be left in-situ. The cystic duct is divided and the gallbladder is delivered. The choledochotomy site will be closed by interrupted resorbable sutures, preferably 5/0 PDS. A Fr 21 abdominal drain will be placed at right subhepatic space to observe for postoperative bile leakage. Endo-laparoscopic group: The treatment process commenced with the first stage therapeutic endoscopic retrograde cholangiopancreatography (ERCP) under general anesthesia or monitored anaesthetic control. With patient in prone position, ERCP is performed using side-view scope. Endoscopic sphincterotomy is performed via needle knife sphincterotome, which cuts papilla alongside the previous plastic biliary stent. The plastic biliary stent is then removed and the sphincterotomy side is enlarged using endoscopic papillary large balloon dilatation. The choledocholithiasis will then be removed by means of mechanical lithotripsy and / or cholangioscopy-assisted lithotripsy. If necessary, serial sessions of therapeutic ERCP will be arranged until ductal clearance of CBD is confirmed by balloon occlusion cholangiogram. Temporary plastic biliary stent will be inserted to ensure biliary drainage while waiting for cholecystectomy. Laparoscopic cholecystectomy will be arranged as second stage procedure in 2-4 weeks' interval after first stage ERCP. The procedure will be performed in a standard manner.22 Perioperative management The perioperative management of all recruited patient is standardized. All patients receive broad-spectrum antibiotics during postoperative period. For robotic group, attention is to observe for postoperative bile leakage by examining the content of abdominal drain, which will be removed if there is no evidence of bile leak in 2-3 days after surgery. Routine monitoring of liver function is carried out till patient's discharge. For endo-laparoscopic group, attention is to look for complications of therapeutic ERCP, including acute pancreatitis (elevated serum amylase), papillotomy bleeding (evidence of tarry stool or hematemesis and drop in hemoglobin level) and bowel perforation (acute peritonitis). Post-ERCP complications will be treated accordingly. Following second stage laparoscopic cholecystectomy, patients will be observed routinely. Postoperative assessments: 1. Liver function: Liver biochemistry and coagulation profile at days 1, 3 and 7 after surgery to evaluate changes in liver function 2. Postoperative morbidities according to Clavien-Dindo classification23 1. Robotic group: postoperative bile leak, pulmonary complication 2. Endo-laparoscopic group: post-ERCP complications (acute pancreatitis, post-papillotomy bleeding and bowel perforation) 3. Operative mortality (30-day mortality) and hospital mortality (any death within the same admission for surgery) 4. In both groups, post-procedure ERCP will be arranged in 4 weeks' interval to assess the possibility of residual choledocholithiasis (i.e. stone clearance rate) and to remove biliary plastic stent. 5. MRI cholangiography (MRCP) will be arranged 3 months after index procedure for the assessment of biliary system. After completion of funding period, MRCP will be arranged in 6 months' interval up to 2 years for long-term assessment of the possibility of common bile duct stone recurrence. Outcome Measures The primary study end point (outcome measure) is stone clearance rate, as assessed by post-procedure ERCP. It is used for sample size calculation. The secondary outcome measures include bile leak rate, post-ERCP complications and othergrade IIIA or above complication according to Clavien-Dindo classification23, 30-day mortality, hospital mortality, and total hospital stay. Number of Patients to be Recruited and Expected Duration of Study Based on a previous reported stone rate of 84% after two-stage endo-laparoscopic approach for choledocholithiasis and assumed 95% after one-stage robotic approach for the same situation, an one-sided non-inferiority study is designed with a non-inferior margin of 10% allowed for robotic approach. With 80% power at the 5% Type I error (alpha), 45 patients need to be recruited to each arm (total 90 patients) in the study, allowing 15% drop-out rate. The principle investigator's unit is a major referral center for management of biliary stone disease in Hong Kong, with more than 700 cases of choledocholithiasis managed by ERCP each year. It is therefore expected that recruitment can be completed in about 33 months. The last recruited patient will be observed for at least 3 months after procedure. Hence, the total period of study including follow-up is 3 years, which is also the funding period for the grant application. After completion of funding period, the recruited patients will be followed up to 2 years with interval investigations of biliary system to look for common bile duct stone recurrence. Foreseeable risks of the study This study involves two different approaches for management of difficult choledocholithiasis, which are associated with different degree of morbidity and mortality. The one-stage robotic common bile duct exploration and cholecystectomy has potential surgical risks of 0.1% mortality and 5 - 10% complication rate (intra-abdominal sepsis, chest complications and wound complications). Meanwhile, the two-stage endo-laparoscopic approach might carry potential complications related to ERCP (~ 5%) and interval laparoscopic cholecystectomy (~ 5%). The post-ERCP complications include acute pancreatitis, post-papillotomy gastrointestinal bleeding and bowel perforation, whereas the post-cholecystectomy complications include intra-abdominal sepsis, chest complications and wound complications. The overall mortality risk following two-stage endo-laparoscopic approach would be 0.1%. Blinding of the study After randomization, the recruited patient will be allocated either robotic or endo-laparoscopic group. There will be no blinding of the randomization result to the recruited patients, the operating surgeons and clinician-in-charge. Statistical plan and data monitoring Statistical analysis will be performed using SPSS version 11.0 (SPSS Inc., Chicago, Ill) on an intention-to-treat basis. The stone clearance rate (primary outcome) will be calculated and compared between groups by Chi-squared test or Fisher's exact test. Other secondary outcome measure will be compared using Chi-squared test or Fisher's exact test for categorical variables, and Mann-Whitney U test for continuous variables. Univariate and multivariate analyses using logistic regression are performed to identify potential risk factors influencing the stone clearance rate. All tests of significance will be two-tailed, and a P value < 0.05 is considered statistically significant. All clinical data including patients' demographics, endoscopic and operative details, and clinical outcome measure will be collected in principle investigator's center. Any missing data will be documented with reasons. Continuous clinical data monitoring and interim and final analyses will be performed by principle investigator and co-investigators with the help of a research assistance. Potential problems anticipated The patient recruitment will be reviewed every 4 months. If the accrual rate is slower than expected, investigator meeting will be carried out to review the underlying reasons and the ways to improve recruitment rate. Existing Facilities This study is supported by the following existing facilities: 1. Multidisciplinary team (hepatobiliary and pancreatic surgeons, endoscopists, gastrointestinal physicians, and research assistance) of principle investigator's center is available for patients' diagnosis, recruitment, intervention and follow-up. 2. Principle investigator's center has endoscopy and operating facilities for robotic and endo-laparoscopic interventions of difficult choledocholithiasis. 3. Principle investigator's center has laboratory and radiological facilities for follow-up assessment of recruited patient. Justification of Requirements This study receives general research grant from the government of Hong Kong Special Administrative region for the following financial support: 1. Recruitment of one research assistant for assistance of patient recruitment process, coordination of randomization, clinical data collection and maintenance. 2. Conference cost: for conference registration and travel expenses for presentation in international conferences 3. Publication cost: for one to two publication in international peer-reviewed journal

The Effect of PEMF for Patients With Knee OA

A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers

This is a phase I, open-label, multi-center study of KFA115 as a single agent and in combination with pembrolizumab. The study consists of a dose escalation part, followed by dose expansion part(s) for single-agent KFA115 and KFA115 in combination with pembrolizumab. The escalation parts will characterize safety and tolerability. After the determination of the maximum tolerated dose (MTD) / recommended dose (RD), the dose expansion parts will assess the preliminary anti-tumor activity in defined patient populations and further assess the safety and tolerability at MTD/RD.

A Self-management Based Survivorship Intervention for Chinese Cancer Survivors

This study, using this SMART approach, will assess the effect of a cancer survivorship care intervention on physical symptom distress, self-efficacy in managing cancer, weight management and health-related quality of life among Chinese patients recently completing curative cancer treatment. First, the investigators will test the effect of a one-off, multidisciplinary team face-to-face assessment (namely, the cancer survivorship clinic) with personalized advice on symptom management, lifestyle modification and anxiety management in reducing the case prevalence of symptom distress, increasing the proportion meeting the weight management criteria, and improving self-efficacy and health-related quality of life among cancer survivors in post-treatment survivorship, in comparison to those receiving skills-based pamphlets for symptom management and lifestyle recommendations. Secondly, this study aims to explore if a step-up targeted personalized intervention is more effective for patients who continue to have symptom distress and/or not to meet the weight management criteria if patients have attended cancer survivorship clinic (i.e. the embedded adaptive intervention) in comparison to those receiving skills-based pamphlets.

Epidural Platelet Rich Plasma Injection for Herpes Zoster

Herpes zoster is a common disease, usually caused by the reactivation of latent varicella zoster virus in the trigeminal or dorsal root ganglion. Acute herpes zoster is characterized by severe pain and the appearance of vesicular skin rashes that usually heal in 2-3 weeks. One of the complications of acute herpes zoster is post-herpetic neuralgia (PHN), which is usually defined as persistent pain lasing 90 days or more from the onset of skin rash. The reported incidence of PHN ranges from between 5 to over 50%, and pain severity can vary from mild to severe. PHN can negatively impact one's quality of life due to serious physical, psychological, functional, and social disturbances due to consequences of chronic pain. Most strategies to prevent PHN has been shown to be limited. Epidural steroid injection is the most commonly used pain-relieving procedure in the world, and is also commonly used to treat herpes zoster pain. However, the analgesic efficacy of epidural steroid injection appears to be modest and duration limited. Repeated or continuous epidural blocks has been associated with reduced incidence of PHN. However, single epidural steroid injection did not provide benefit. This limits the use of epidural steroid injections because it is often logistically difficult to arrange multiple epidural blocks in real life clinical practice. Platelet rich plasma (PRP) is an emerging treatment option for chronic pain. It is made from centrifugation of whole blood to increase the platelet concentration to 3-5 times greater than the physiological baseline. Proposed mechanism of PRP include enhancing the body's own healing response, delivery of growth factors, activation of mesenchymal stem cells, and modulation of inflammation. While epidural steroids reduce pain by reducing inflammation, PRP also promotes the healing of nerve injury and reduces neuropathic pain. Perineural PRP has been associated with reduced diabetic neuropathic pain. There are currently no studies that has investigated the analgesic effect of epidural PRP for herpes zoster pain and prevention of PHN. We plan conduct a prospective clinical evaluation to assess the analgesic effect of epidural PRP injection in patients with acute herpes zoster. We hypothesize that the healing effect and inflammatory modulatory effect of PRP would reduce herpetic pain and possibly reduce chronic neuropathic pain. Functional capacity, psychological well-being, health related quality of life, patient satisfaction, and analgesic consumption will also be assessed.