cyrilzakka/clinical-trials huggingface dataset:
Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet

Epclusa® is a pan-genotypic, once-daily tablet for the treatment of chronic hepatitis C virus (HCV) infection containing the NS5B- polymerase inhibitor sofosbuvir (SOF, nucleotide analogue) 400 mg and the NS5A inhibitor velpatasvir (VEL) 100 mg.

For patients with swallowing difficulties, administration of whole tablets can be problematic. In addition, HCV patients that are hospitalized (at intensive care units) due to severe illness (co-infections/ liver failure) might not be able to swallow medication. Therefore it is useful to know whether it is possible to administer SOF/VEL through a different route, like a feeding tube.

In daily practice, information about the safety and efficacy of crushed tablets is lacking which might result in interruption or discontinuation of expensive HCV therapy. However, it is not recommended to interrupt treatment because there is no evidence about the efficacy of the therapy after discontinuation (and restart).

Currently, patients and healthcare professionals are crushing SOF/VEL tablets without information about efficacy and safety. Depending on the biopharmaceutical characteristics of a drug formulation, crushing tablets can lead to altered pharmacokinetics of drugs.

It is important to know whether pharmacokinetic parameters are influenced by crushing of tablets; both a decrease and an increase in exposure may occur. A decrease of the plasma concentrations of SOF and/or VEL potentially reduces the therapeutic effect of the drugs. Higher doses or switching to other HCV-drugs might be needed. In contrast, in case a higher Cmax,ss and/or exposure occurs there might be an increased risk of toxicity.

As a result, crushing the drug is a contra-indication based on the available data.

Therefore this study will be conducted to investigate whether a crushed SOF/VEL tablet is bioequivalent to SOF/VEL as a whole tablet.


Eligibility Criteria:
Inclusion Criteria:

1. Patients with SOF/VEL treatment for the treatment of chronic HCV genotype 1 through 6.
2. Patient is at least 18 at the day of screening.
3. Patient is able and willing to sign the Informed Consent Form.
4. Patient is able and willing to follow protocol requirements.

Exclusion Criteria:

1. Pregnant female (as confirmed by an hCG urine test performed at screening) or breast-feeding female.
2. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
3. Inability to understand the nature and extent of the study and the procedures required.
4. Clinically relevant low hemoglobin concentration at screening judged by the patient's own hepatologist.
Predictive Factors for Medullary Thyroid Cancer Aggressiveness

This study is a retrospective study trying to find the predictive factors for medullary thyroid aggressiveness in terms of tumor metastasis and patients' survival.

This study is a retrospective study trying to find the predictive factors for medullary thyroid aggressiveness in terms of tumor metastasis and patients' survival. The predictive factors included in this study are central and lateral compartment lymph node metastases as well as distant metastasis up to 1 year postoperatively, while biochemical predictors (meaning ratios such as lymphocyte to monocyte ratio etc and CEA and calcitonin drop levels) and histological predictors (such as nuclear atypia, amyloid, immunohistochemistry, desmoplasia) are included as secondary outcomes. In this study , patients \>18 years old that underwent surgery for medullary thyroid cancer (total thyroidectomy, completion thyroidectomy) +/- central/lateral neck dissection) will be enrolled.

Eligibility Criteria:
Inclusion Criteria:

* Patients who underwent thyroidectomy for medullary thyroid cancer (total thyroidectomy, completion thyroidectomy) +/- central/lateral neck dissection

Exclusion Criteria:

* Age \< 18 years
Silver Nanoparticle Investigation for Treating Chronic Sinusitis

Chronic rhinosinusitis is a highly prevalent disease resulting in high economic burden. Effective therapeutic options are needed. Rhinosinusitis-related biofilms are a likely contributor to recalcitrant disease. Emerging evidence shows that colloidal silver nanoparticles may be effective for reducing biofilms. The investigators intend to perform a randomized, double-blinded, placebo-controlled clinical trial to evaluate the effectiveness and safety of intranasal colloidal silver nanoparticles in adult patients with chronic rhinosinusitis. The investigators hypothesize that compared to placebo, treatment with intranasal colloidal silver for chronic rhinosinusitis will lead to a significant improvement in symptom scores and will not be associated with increased rate of adverse effects.


Eligibility Criteria:
Inclusion Criteria:

Twelve (12) weeks or longer of two or more of the following signs and symptom consistent with chronic rhinosinusitis (CRS):

* mucopurulent drainage (anterior, posterior, or both), nasal obstruction (congestion), facial pain-pressure-fullness, or decreased sense of smell

AND inflammation is documented by one or more of the following findings:

* purulent (not clear) mucus or edema in the middle meatus or ethmoid region
* polyps in nasal cavity or the middle meatus
* and/or radiographic imaging showing inflammation of the paranasal sinuses

Exclusion Criteria:

* Unable to speak English
* History of nasal or sinus surgery within past 6 weeks
* History of comorbid ciliary dyskinesia, cystic fibrosis or any other mucociliary condition
* Dependence on prolonged corticosteroid therapy for comorbid condition
* History of renal impairment
* History of cerebrospinal fluid leak
Trans-cranial Direct Current Stimulation on Alcohol Craving

The goal of thisclinical trial is to investigate the efficacy of trans cranial direct current stimulation (tDCS) for alcohol craving in individuals with alcohol dependence. The main question it aims to answer is whether 10 sessions of tDCS can reduce craving for alcohol.

Participants will be randomized into active group and sham group. Researchers will compare the severity of craving in these groups.

Craving is defined as strong desire for substance use, and is one of the core symptoms of alcohol dependence which is highly correlated with relapse. Transcranial direct current stimulation (tDCS) involves applying a small direct current (1-2mA) to the prefrontal cortex; its therapeutic effect for depression and cognition has been demonstrated by several randomized studies. Our preliminary study has shown that tDCS has the potential to reduce craving in alcohol-dependent patients without adverse events. Furthermore, our previous studies have shown that serum brain-derived neurotrophic factor (BDNF) level is elevated after alcohol withdrawal. The current study aims at examining the association between craving and serum BDNF level in alcohol-dependent patients receiving tDCS. The study recruits 40 patients with alcohol dependence. Patients will receive tDCS for 2 weeks during admission, and followed for 2 weeks after tDCS. We'll compare their improvements in craving scores every week, and investigate the correlation between craving and serum BDNF level. This study will bring innovations to the treatment of alcohol dependence based on our previous studies.

Eligibility Criteria:
Inclusion Criteria:

1. Be between 20-65 years of age
2. have sufficient cognitive function to understand the study and complete the informed consent process
3. Be diagnosed with alcohol dependence as defined by DSM-IV through a structured interview (Mini-International Neuropsychiatric Interview, M.I.N.I.)

Exclusion Criteria:

1. Intellectual disabilities
2. bipolar disorder
3. Psychosis (schizophrenia)
4. Major physical illness (brain hemorrhage, brain tumor, myocardial infarction, epilepsy or history of seizures)
5. intracorporeal electronic or metal implants (e.g., cardiac pacemaker)
6. Pregnant or breastfeeding women
7. Allergy to headgear and electrode materials
8. Trauma or infection to the head
9. Intracranial space occupied lesion (such as brain tumor, AVM, etc.) or patients who have undergone brain surgery, meningitis and encephalitis
10. Patients who are expected to undergo brain and major surgery during the trial period
Validation of a Wearable Sensor for Stress Response in a Virtual Reality Environment

Monitor stress response in a virtual reality environment using a wearable sensor to analyze and track heart rate variability (HRV).

Wearable sensor technology is being developed that may allow, for the first time, the ability for individuals to better recognized their level of stress in any given situation on a continuous basis. A major focus of many of these wearable sensors is being able to accurately analyze and track heart rate variability (HRV), which is indicative of primarily parasympathetic/vagal tone and emotional state.3 However there is a need to validate the reliability of this measured response and understand any inter-individual variability.

The present study will take advantage of virtual reality scenarios to expose healthy volunteers to controlled stressful situations during monitoring with several standardized lab-based non-invasive physiological sensors as well as a novel wrist band sensor device to track individual response to stress.

Eligibility Criteria:
Inclusion Criteria:

* Adults over age 18

Exclusion Criteria:

* History of seizures
* History of vertigo or other vestibular abnormalities
* History of a chronic anxiety disorder
* History of cardiovascular disease or heart disease
Comparison of Immunization Quality Improvement Dissemination Study

Dissemination research examines the processes and factors that lead to widespread use of evidence-based interventions. There are several theories on how to best minimize the perceived and actual burdens on practitioners associated with implementing evidence-based medicine. For instance, the pay for performance model attempts to improve physician compliance with quality guidelines by providing financial incentives. Recent studies suggest pay for performance is effective in improving practitioner performance, but it is unclear whether the gains are sustainable once incentives are stopped.

Another approach to promoting best practices is the Model for Improvement whose main method is to employ Plan-Do-Study-Act (PDSA) cycles of small changes Although this approach has been successful within individual institutions, there is minimal evidence of its effect when employed simultaneously in multiple autonomous institutions. There is also little evidence of the sustainability of outcomes after intervention activities end.

The specific aims of the proposed study are to examine the effect of quality improvement dissemination models on the immunization coverage of children ages 3 to 18 months old. The investigators propose to:

1. Determine the effect on immunization compliance of two different models of dissemination which will provide physicians 12 months of quality improvement (QI) activity support for implementing CDC immunization best practices.

Hypothesis 1a: Study participants receiving the QI technical support intervention (QITS) will have more improvement in immunization rates from baseline to immediately after support ends than participants receiving the pay for performance intervention (P4P).

Hypothesis 1b: Study participants receiving QITS will increase immunization coverage for their practices over baseline.

Hypothesis 1c: Study participants receiving P4P will increase immunization coverage for their practices over baseline.


Eligibility Criteria:
Inclusion Criteria:

* regular patient of a participating practice

Exclusion Criteria:

* fewer than 2 encounters at a participating practice
* moved or gone elsewhere prior to assessment date
* medical contraindication to vaccination
Evaluation of Postural Exercises in the Treatment of Temporomandibular Disorders

Fifty-seven patients diagnosed with internal temporomandibular derangement will be included in the study and divided into three groups. All patients will be treated with a proven-effective occlusal splint. The first group will receive only occlusal splint therapy and will serve as the control group. The second group will receive occlusal splint therapy combined with Rocabado exercises, while the third group will receive occlusal splint therapy combined with postural exercises.

Before the treatment process, all patients will complete the Temporomandibular Disorders Diagnostic Criteria (TMD-DC) form. Pain intensity will be measured using the Visual Analog Scale (VAS), pain thresholds will be assessed using an algometer, and the following evaluations will be performed: Cervical Posture Assessment (Craniovertebral Angle with Goniometer)-Cervical Range of Motion Assessment (C-ROM)-Cervical Deep Flexor Muscle Endurance Test-Neck Disability Assessment (NDI - Neck Disability Index)-Psychiatric Assessment (HADS - Hospital Anxiety and Depression Scale).

After two months, patients will be recalled, and all tests will be repeated. The effectiveness of the three treatment protocols will then be evaluated.


Eligibility Criteria:
Inclusion Criteria:

* Being diagnosed with internal temporomandibular disarrangement
* aged 18 years or older
* Willingness to participate in the study
* Ability to speak and understand Turkish, with no communication difficulties severe enough to impede understanding of the exercises

Exclusion Criteria:

* History of acute trauma in the TMJ or surrounding area
* TMJ dysfunction caused by a neurological condition
* History of surgical/invasive procedures or treatments on the TMJ
* Presence of infection or tumoral structures within intraoral structures
* History of tooth loss or use of dental prostheses
* History of surgical procedures in the cervical region
Management of Warthin Tumor of Parotid Gland.

Comparison between Ultrasound-Guided Ethanol Sclerotherapy (UGES) \& surgical excision in management of warthin tumor of parotid gland.

Warthin tumor (also known as cystadenolymphoma), is a benign and frequent salivary gland neoplasm.

It represents about 2% to 15% of all primary epithelial tumors of the parotid gland.

Warthin tumor is histologically characterized by a dense lymphoid stroma and a double layer of oncocytic epithelium with a papillary and cystic architectural pattern.

Its etiology: remains controversial. Incidence: It is the second most frequent benign neoplasm of the salivary glands after pleomorphic adenoma. Pathophysiology: Initially, Hildebrand proposed that the lesion may be remnants of the branchial pouches and a variant of the lateral cervical cyst. Later, Albrech and Artz proposed the heterotropic origin of Warthin tumor from the neoplastic proliferation of salivary gland ducts present within intra- or para-parotid nodes. Histopathology: Grossly, Warthin tumor is a well-circumscribed spherical to oval mass. On cut section, there are solid areas and multiple cysts with papillary projections.

Cytology: Smears characteristically show oncocytic epithelial cells without atypia admixed with polymorphous lymphocytes and cellular debris.

Microscopic Findings: Warthin tumors are composed of varying proportions of papillary- cystic structures lined by oncocytic epithelial cells and a lymphoid stroma with germinal centers.

Clinically, Warthin tumor presents as a rounded or an ovoid nodular painless, slow-growing, fluctuant to firm at palpation. It can be unilateral, bilateral, or multicentric and is asymptomatic in 90% of cases.

Prognosis: Warthin's tumor has a favorable prognosis and almost never recurs. Malignant degeneration of Warthin tumor is very rare.

Complications:

Local Recurrence; The local recurrence rate is low; when recurrence does occur, it is probably due to multifocal tumors or inadequate excision.

Malignant Transformation; Malignant transformation in a Warthin tumor is extremely rare. The most frequent histological types of malignant transformation in a Warthin tumor are mucoepidermoid carcinoma, squamous cell carcinoma, undifferentiated carcinoma, oncocytic adenocarcinoma, and adenocarcinoma.

Eligibility Criteria:
Inclusion Criteria:

* All new cases presented with benign parotid cyst and diagnosed as Warthin tumour in the parotid gland.

Exclusion Criteria:

* Other Parotid gland tumours e.g. solid tumours, malignant tumours and other suspicious tumours.
Study of Cavosonstat (N91115) in Patients With CF Homozygous for the F508del-CFTR Mutation

This will be a double-blind, randomized, placebo-controlled, parallel group study. The purpose of this study is to investigate the efficacy and safety of Cavosonstat (N91115) in adult patients with CF who are homozygous for the F508del-CFTR mutation and being treated with lumacaftor/ivacaftor (Orkambi™).

Primary Objective:

* Assess the efficacy of N91115 at 12 weeks when added to preexisting treatment with lumacaftor/ivacaftor in adult patients with CF who are homozygous for the F508del-CFTR mutation

Secondary Objectives:

* Assess the effect of N91115 added to lumacaftor/ivacaftor on safety
* Assess the effect of lumacaftor/ivacaftor added to N91115 on the pharmacokinetics of N91115, lumacaftor, and ivacaftor

Eligibility Criteria:
Inclusion Criteria:

* Patients must have been treated with lumacaftor/ivacaftor for at least 8 weeks prior to Day 1 (start of dosing)
* A history of Sweat Chloride (SC) ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) (either before or after starting lumacaftor/ivacaftor treatment)
* Body weight ≥ 40 kg
* ppFEV1 40 - 85 % predicted (inclusive) at screening
* Oxygen saturation ≥ 90% breathing ambient air at screening

Exclusion Criteria:

* Any acute infection that requires treatment or hospitalization within 2 weeks of Study Day 1
* Colonization with organisms associated with more rapid decline in pulmonary status, such as Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus
* Any change in the regimen for chronic therapies for CF lung disease (e.g., Pulmozyme®, hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study Day 1
* Are pregnant, planning a pregnancy, or breast-feeding at screening
* Blood hemoglobin \< 10 g/dL at screening
* Serum albumin \< 2.5 g/dL at screening
* Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN)
* History of abnormal renal function within 3 months of screening
* History of ventricular tachycardia or other clinically significant ventricular arrhythmias
* History, including the screening assessment, of prolonged QT and/or QTcF (Fridericia's correction) interval
* History of solid organ or hematological transplantation
* History of alcohol abuse or drug abuse
* Ongoing participation in another therapeutic clinical trial
* Use of continuous (24 hr/day) or nocturnal supplemental oxygen
Evaluating the Chain of Addiction Care (CAC)

The investigators want to evaluate the feasibility of a decentralised hepatitis C care pathway (the Chain of Addiction Care (CAC) pathway) in several addiction care centres in the east of the Netherlands. Secondary objective: to measure the impact of hepatitis C clearance on MET (+metabolite) and BUP (+metabolite) trough levels in patients on Opioid substitution Therapy (OST). This is an exploratory, observational study.

People who (have) inject(ed) drugs (PWID) are at high risk for hepatitis C infection. Establishing adequate linkage to care in this population can be a challenge. Many of these patients receive opioid substitution, hepatitis C treatment possibly influences pharmacokinetics of those substitutes. This protocol describes a study on hepatitis C in people who (have) inject(ed) drugs (PWID), consisting of two substudies. 1) An exploratory, observational study in which we evaluate the decentralised hepatitis C care pathway in addiction care centres. 2) An observational pharmacokinetic study in hepatitis C patients on opioid substitution therapy (OST) embedded within the first study.

Rationale: 1) Many PWIDs are lost during the process of testing and linkage to care and do therefore not receive adequate hepatitis C treatment. Decentralising care in addiction care centres deems hospital visits unnecessary, an approach that has become increasingly popular in this population over the last few years. This practice however has not yet been evaluated in the Netherlands. 2) In the Netherlands the PWID population is often treated for opioid addiction by opioid substitution therapy (OST) with methadone (MET) or buprenorphine (BUP). There is evidence that liver inflammation has a negative effect on pharmacokinetics of drugs. Consequently, we hypothesize that HCV treatment results in reduced liver inflammation and a decrease in MET and/or BUP levels, which is clinically relevant in the PWID/OST population.

Objective: 1) to evaluate the feasibility of a decentralised hepatitis C care pathway (the Chain of Addiction Care (CAC) pathway) in several addiction care centres in the east of the Netherlands. 2. to measure the impact of hepatitis C clearance on MET (+metabolites) and BUP (+metabolites) levels and craving in patients on OST.

Study design: This is an exploratory, observational study with a pharmacokinetic observational study embedded within the same population.

Eligibility Criteria:
Inclusion Criteria:

* Aged 18 years or older
* Able and willing to give informed consent
* Currently inject or previously injected drugs at least once, including nasal snorting of drugs using aids such as basepipes or straws.
* Visit the participating addiction care centre at least once during the study period

Exclusion Criteria:

* none
Ph II Study of Wkly Topotecan + Bevacizumab in Plat. Resistant/Recurrent Gyn Cancers

The purpose of this study is to evaluate the clinical safety and toxicity of intravenous bevacizumab (Days 1 and 15 of a 28 day cycle) in combination with weekly topotecan (Days 1, 8, 15 of a 28 day cycle) in patients with platinum resistant recurrent ovarian, fallopian tube and primary peritoneal cancer.

This study is designed as a Phase 2 study. There are no published data on the toxicity of the combination of bevacizumab and topotecan therapy. Based on data combining bevacizumab with other chemotherapy agents in non-gynecologic solid tumors, it is not likely that the toxicity of the combination of the two drugs will be greater than the individual toxicities of each drug. The toxicities of each of these agents is quite different. Specifically the toxicity of this combination will be studied using the dose of bevacizumab used in previous phase II studies of ovarian cancer, e.g. an equivalent of 5 mg/kg weekly with treatments given at least every 3 weeks. In our study, since topotecan will be given weeks 1,2 and 3 of an every 4 week cycle, it is convenient to give bevacizumab 10 mg/kg IV every other week.

Eligibility Criteria:
Inclusion Criteria:

* must have received primary taxane and platinum-based chemotherapy and no more than 1 other chemotherapy regimen
* must have platinum resistant disease(defined as recurrence within 6 months of receiving platinum based chemotherapy, first or second line)
* must have measurable disease (greater than 20mm by conventional techniques or 10mm by spiral CT) OR elevated CA-125 (\> 100 on two occasions at least one week apart
* performance status greater than or equal to 70%

Exclusion Criteria:

* prior treatment with anti-angiogenesis agent
* treatment with \> 2 cytotoxic regimens (including primary platinum and taxane chemotherapy)
* evidence of other malignancy within 3 years of study enrollment
* history of abdominal fistula, grade 4 bowel obstruction or gastrointestinal perforation
* history of intra-abdominal abscess with 6 months prior to day 0
* pregnant or lactating patients