Amagasak, Japan

Clinical Study Evaluating Pharmacogenomics-informed Pharmacotherapy Versus Dosing As Usual in Psychiatric Disorders

Effective pharmacotherapeutic treatments for mental disorders are available, but their effectiveness is limited by low compliance due to frequent side effects. This is partly due to patient heterogeneity in the genes encoding for drug-metabolising enzymes. Pharmacogenetic testing allows the assessment of person-specific genetic factors that are thought to predict clinical response and side effects. Recent studies have suggested that genotyping genes encoding drug-metabolizing enzymes may improve treatment efficacy and tolerability, potentially benefitting millions of patients. PSY-PGx is the first initiative to propose a large-scale non-industry sponsored clinical study that aims to demonstrate the clinical benefits and potential of the implementation of pharmacogenetics for psychiatric patients in existing medical settings. This is an international 24-week, patient- and rater-blinded, two-arm, parallel-group controlled, and multi-centre randomized clinical trial (RCT) to establish the benefits of pharmacogenetics-informed pharmacotherapy versus dosing as usual (DAU) in psychiatric patients suffering from mood, anxiety, or psychotic disorders.

Evaluation and Further Development of an Artificial Intelligence-based Algorithm for Clinical Decision Support

The Use of Coronary Displaced Flap and Deepithelialized Free Graft in the Treatment of Multiple Gingival Recessions

This study would be a single-centre, randomized clinical trial (RCT) and would be structured according to the CONSORT statement (http://vvv.consort-statement.org/). The study would include 50 systemically healthy patients who came to the Clinic for Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade for the treatment of multiple gingival recessions, and who meet the inclusion criteria. STUDY DESIGN The study will include patients who voluntarily gave and signed their consent to participate in the research based on written and oral information about the type, duration and expected outcome of the research (document attached). Split mouth design will be applied in the study. Both sides of the same jaw will be treated using CAF and D-FGG. Immediately before the surgery, using computerized randomization tables,the method of de-epithelialization of the graft will be determined. The contralateral side will be treated no earlier than two months after the first surgical procedure, and FGG will be de-epithelialized using a technique that was not used in the previous intervention. Clinical examination and initial therapy After filling out the anamnestic sheet and signing the consent to participate in the study, the patient will undergo a periodontal examination. In order to verify the periodontal status and the level of oral hygiene, the following clinical parameters will be recorded: - Periodontal probing depth (PPD) - Clinical attachment level (CAL) - Bleeding on probing (BOP) - Plaque Index (PI) Clinical parameters will be recorded in six reference points (vestibulomesial, vestibulomedial, vestibulodistal, oromesial, oromedial, orodistal) on all present teeth (except third molars) using a periodontal probe (PCPUNC-15; HU-Friedy , Chicago, IL, USA). All measurements will be rounded to the nearest 0.5 mm and will be performed by a pre-calibrated dentist. The following parameters will be measured on teeth with gingival recessions, at the mid-buccal point of the treated tooth: - Recession depth (RD) - measured distance from the gingival margin to the CEJ. - Recession width (RW) - horizontal dimension of gingival recession at the level of CEJ. - Keratinized tissue width (KTW) - measured distance from the gingival margin to the mucogingival line (MGL), where the location of the MGL will be determined by the functional method - Gingival thickness (GT) - will be measured in the middle of the buccal surface of the tooth, 1 mm apical from the bottom of the gingival sulcus, using an endodontic needle (K files, 10, FKG, Swiss Endo) Clinical measurements will be recorded at the beginning of the study and 3, 6 and 12 months, 5 and 10 years after surgical therapy. In the first visit, after anamnesis and clinical examination, patients will rinse their mouths with 15 ml of 0.12% chlorhexidine solution for 1 min (Curasept ADS 212, Curasept S.p.A. Saronno (VA), Italy), and then supra- and subgingival plaque and calculus will be removed using mechanical instruments (MiniPiezon, EMS Electro Medical Systems, Switzerland). After that, patients will be trained on proper maintenance of oral hygiene. Surgical therapy of gingival recession will be scheduled in case PI and BOP are <15%. Surgical procedure All surgical procedures will be performed by the same surgeon (NNJ). After administration of local anesthesia, exposed root surfaces will be treated with Gracie's curettes (Hu-Friedy). The modified CAF will be formed in the region of the teeth behind the recessions and will include at least one more tooth mesial and distal to the tooth with gingival recession. Oblique incisions in the area of the interdental papillae will prepare a half-thickness flap in order to form the so-called surgical papillae. These incisions will be joined by intrasulcular incisions, and then a full-thickness flap will be elevated in the area of the exposed roots by blunt dissection. Apicallly from the mucogingival line, in order to enable flap mobilization in the coronary direction, two incisions will be made: one to cut the periosteum, and the other to cut the muscles underneath mucosa. After that, the anatomical papillae will be deepithelialized. The D-FGG will be fixed at the recipient site with single sutures (5.0, Surgicryl Monofilament Polydioxanone, SMI AG, St. Vith Belgium), and then the flap will be sutured 1-2 mm more coronal than the CEJ with sling sutures (6.0, Polypropylene Blue, SMI AG). In both groups, D-FGG will be taken in the region from the distal surface of the maxillary canine to the distal surface of the maxillary first/second molar. Intraoral deepithelialization of FGG will be performed using a 2.3 mm diameter diamond bur (801G/023, EMS, Aldrich Co.) with continuous application of saline (ID group), while the second group of grafts will be deepithelialized extraorally using a scalpel N°15C (Swann-Morton). to achieve an optimal thickness of 1-1.5 mm (ED group). In both groups, for the purpose of better hemostasis and protection of the donor site from external influences, a gelatin sponge (Cutanplast©) will be placed on the hard palate in the wound area and fixed with crossed mattress sutures (5-0 silk sutures, Dogsan sutures, Trabzon, Turkey). Immediately after separating the graft from the donor site, the thickness, length (mesial-distal dimension) and width (apical-coronal dimension) of the graft will be measured with a digital caliper (Alpha Tools Digital Caliper) with a resolution of 0.05. In the ED group, the thickness of the graft will be measured before and after deepithelialization. For histological analysis in both groups of grafts, they will take the most distal part of the graft, 2 mm wide, which will include the coronary and apical part of the graft. The duration of graft deepithelialization in each group, as well as the total duration of surgical intervention will be recorded. Post-surgical protocol All patients will be advised to avoid mechanical trauma, tooth brushing and flossing in the surgical regions during the postoperative two weeks until the sutures are removed. In order to achieve biofilm control, a 0.12% chlorhexidine-gluconate mouthwash solution will be prescribed 2 times a day for 1 min for 2 weeks. Patients will be prescribed 600 mg of ibuprofen (Ibuprofen 600 mg, FAMARA S.A., Athens, Greece) immediately after surgery and one tablet 6 h after surgery. Also, they will be asked to record the additional intake of analgesics (number and dose) on a daily basis during the second week after surgery. After suture removal, 2 weeks after surgery, biofilm removal will begin with a soft toothbrush and rotary brushing technique. Two months after surgery, patients will be instructed to return to regular oral hygiene habits. Pain intensity after the intervention will be evaluated with the help of the Visual Analogue Scale (VAS). By drawing a vertical line, on a scale whose value describes the degree of pain (0- complete absence of pain, and 10- the strongest possible pain), the patient will rate the pain he feels after the operation. The presence and intensity of pain will be recorded in the first 7 days, as well as 1, 3 and 6 months after surgery. On the first day, patients will assess discomfort 5 hours after surgery, as well as every morning between 8 a.m. and 10 a.m. for the next 7 days. Also, an independent researcher will evaluate the aesthetic parameters of the surgically treated region 3, 6 and 12 months. 5 and 10 years after the intervention using the IRoot esthetic score. HISTOLOGICAL ANALYSIS Histological analyzes will be performed by a senior oral pathologist (XX) who will not know by which procedure D-FGG was deepithelialized, in serial sections (5 sections for each sample). For the histological analysis of D-FGG samples, 2 mm long graft will be taken from the distal end of the graft and fixed in 10% neutral buffered formalin solution for 24 hours. After that, it will be rinsed with running water for 1 hour, then immersed in a 50% alcohol solution for 24 hours, after which it will be placed in a 70% alcohol solution and kept until further processing for histological analysis. Samples were prepared on 5 mm thick histological sections and stained with hematoxylin-eosin (H&E) and Masson's trichrome stain. Assessment of the presence and abundance of epithelial remnants, inflammatory infiltrate and connective tissue cellularity will be performed on H&E sections.

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer

Investigators hypothesize that malnutrition has an adverse impact on the clinical course of patients with advanced PDAC treated with chemotherapy. Aims: To investigate the association between the nutritional status and pancreatic exocrine function and the clinical outcomes of patients with advanced PDAC. Study design: The PAncreatic Cancer MAlnutrition and exocrine pancreatic INsufficiency in the course of chemotherapy in unresectable pancreatic cancer (PAC-MAIN) study is a non-profit, international, multicentre, prospective, observational, cohort study evaluating the effect of the nutritional status and pancreatic exocrine function on the main outcomes of patients with advanced PDAC. The study will be carried out in Russia, Turkey, Serbia, Romania, Italy, and Spain as a part of the Pancreas 2000 Educational Program. Pancreas 2000 is a post-graduate educational program that prepares young gastroenterologists, surgeons, radiologists, and other physicians for specialization in Pancreatology. Patient-related: - sex, race, age at diagnosis - Mini-Nutritional Assessment (MNA) score - sarcopenia (measured with computed tomography (CT) fat free mass is reduced; i.e. appendicular\L2 skeletal muscle mass index <7.2 kg/m2 (men) or <5.5 kg/m2 (women)); - cachexia (weight loss (WL)>5% in last 6 months, or WL>2% if body mass index (BMI) <20 kg/m² or sarcopenia); - 12-item functional assessment of anorexia/cachexia therapy anorexia/cachexia subscale (FAACT-A/CS-12) - a biliary stent - a duodenal stent - total and direct bilirubin - ECOG status - European Organization for Research and Treatment of Cancer (EORTC) QLQ-PAN26 scale - Date of diagnosis, visit 1, visit 2 (3 months), and death/loss from follow up - Check up on survival at 6m Tumor-related: - Tumor site documented by endoscopic ultrasound, CT, or magnetic resonance imaging (head, body, or tail) - Stage according to the TNM classification - Vessels involved - Presence and site of metastatic disease - Ascites - CA-19-9 - Response evaluation criteria in solid tumors (RECIST) (for visit 2) Nutritional parameters: - Leucocytes (lymphocytes, neutrophils), neutrophil to lymphocytes ratio, erythrocytes, hemoglobin, hematocrit, platelets - C-reactive protein, total protein, albumin, cholesterol, iron, transferrin, ferritin, magnesium, zinc - International normalized ratio, activated partial thromboplastin time - Blood fasting glucose, glycated hemoglobin Pancreatic function and treatment: - PEI, fecal elastase-1, pancreatic enzyme replacement therapy (PERT), date of starting PERT, the dosage of daily taken PERT - Diabetes mellitus (DM), date of DM diagnosis, DM type, DM treatment Treatment-related: - Planned chemotherapy protocol Dosages of chemotherapy planned (mg/m2) - Percent of standard chemotherapy dose delivered - Percent of planned chemotherapy delivered - Changes to the predefined schedule (dose reduction, schedule modifications, stop before planned) - Date of treatment start and end - Adverse events (National Cancer Institute toxicity scale for visit 2) Description of the intervention (schedule of visits): Visit 1 (screening, within 1 month from initial diagnosis). Patients will be informed about the study. Once patients agree with the inclusion in the study the investigators will evaluate the inclusion and exclusion criteria. Those patients who meet all the inclusion criteria and none of the exclusion criteria will be finally included in the study. In this visit, patients, tumor-related variables, and general patients' features will be recorded, and quality of life questionnaire will be administered. The researcher will record weight, height, body mass index (BMI), unplanned WL % for the last 6 months. Each patient's baseline nutrition status will be evaluated using the MNA scores prior to starting chemotherapy. Patients will be classified as in the group with no nutritional risk, at risk of malnutrition, or malnourished. Nutritional parameters and pancreatic function will be evaluated through blood tests and a fecal test. Visit 2 (3 months after the first dose of planned chemotherapy). The researcher will record in the case report form (CRF) the planned chemotherapy, schedule, doses, dose reduction, and any adverse event. The same variables recorded at Visit 1 will be checked again. Check up 3 (end of the study, 6 months). The researcher will record in the CRF the overall survival and time until progression. Medication of the study: The study is of observational nature, so a pre-planned treatment is not considered. However, the use of pancreatic enzyme replacement treatment will be recorded as well as data regarding the employed chemotherapy regimen. Power size calculation: The expected percent of chemotherapy delivered in well-nourished patients was based on a study that assessed the chemotherapy dose intensity in gastrointestinal malignancies included pancreaticobiliary disease during the firsts 8 weeks after the start of the chemotherapy23. Based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished, 163 patients per group in case of a difference of 15% between both groups and 356 patients per group in case of 10% of difference. Discussion: Given the sparse overall scientific data on the subject, the investigators have designed a study that addresses the impact of patient's nutritional status and dietary intervention on the clinical course of patients with advanced PDAC treated with chemotherapy and is aimed at establishing whether it affects both tolerance and tumor response to medical therapy. PAC-MAIN will be the first study specifically investigating whether the nutritional status influences the possibility to complete planned chemotherapy in patients with advanced PDAC.

Alloplastic Total Temporomandibular Joint (TMJ) Replacement Registry

More in detail this registry has the following objectives: - To describe clinical indications for TMJ replacement, and treatment patterns (including differences among regions if feasible) - To describe the clinical evolution and outcomes of patients treated with a TMJ replacement - To explore the relationship(s) between treatment, outcome(s) and quality of life (QoL). - To identify predictive factors for favorable outcomes (pain reduction, range of motion (ROM), occlusal status, QoL) in patients treated with TMJ replacement. - To describe the reasons of patients who refused TMJ replacements

Fish Oil and EPO in Breast Cancer

Breast cancer (BC) is leading cancer in women. As most of the cancers, it is characterized by inflammation and alternations in lipid and fatty acid metabolism. Patients with BC have impaired fatty acid profiles, low level of PUFAs, and high n-6/n-3 PUFAs ratio. Moreover, these changes are related to clinical outcome. Fish oil is the richest source of anti-inflammatory n-3 PUFAs. Evening primrose oil (EPO) is rich in 18:3 n-6, the only n-6 fatty acid with an anti-inflammatory effect. Dietary intake of fish oil or EPO has been shown to decrease inflammation and improve PUFAs status in patients with cancers. However, it is not known what is the effect of combined EPO and fish oil in BC patients. The study design is double-blind, controlled, randomized nutritional intervention. The participants are randomly assigned into intervention and control group before starting chemotherapy. All patients receive nutritional counseling to achieve a daily energy and protein intake according to recommended dietary allowances, with (intervention) or without (control) of milled seed mix.

Naloxone HCl PR Tablets in Patients With Opioid Induced Constipation

Combination Therapy With NC-6004 and Pembrolizumab in Head and Neck Cancer Subjects Who Have Failed Platinum Regimen