araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias

Summary: Human induced pluripotent stem cells (hiPSCs) have driven a paradigm shift in the modeling of human disease; the ability to reprogram patient-specific cells holds the promise of an enhanced understanding of disease mechanisms and phenotypic variability, with applications in personalized predictive pharmacology/toxicology, cell therapy and regenerative medicine. This research will collect blood or skin biopsies from patients and healthy controls for the purpose of generating cell and tissue models of Mendelian heritable forms of heart disease focusing on cardiomyopathies, channelopathies and neuromuscular diseases. Cardiomyocytes derived from hiPSCs will provide a ready source of disease specific cells to study pathogenesis and therapeutics.

Detailed description: Further study details as provided by Gordon F. Tomaselli, Johns Hopkins University:
  Biospecimen Retention: Blood or tissue samples, hiPSCs and cardiomyocytes reprogrammed from hiPSCs Eligible patients will be approached and the study will be explained in full as a part of obtaining informed consent for the study. The subjects will have an opportunity to ask questions about the study. Control subjects, often but not exclusively family member that meet the eligibility criteria will undergo a similar procedure for informed consent. Subjects will be evaluated in clinic and will have a 1-3 mm skin biopsy or blood draw (30 cc). The subjects will be asked about their medical history during the clinic visit but this information will not be transmitted to the research laboratories where the iPSCs are generated and re-programmed, only the disease genotype will be associated with the samples. The samples that will be frozen and stored are whole blood, white blood cells, skin biopsies, hiPSCs and reprogrammed cardiomyocytes.

Eligibility: Inclusion Criteria:
  -  All patients and family members 18 years of age or older with inherited cardiac arrhythmias including LQTS, Brugada Syndrome (BrS), cathecholaminergic polymorphic ventricular tachycardia (CPVT) or early repolarization syndrome (ERS) are eligible for enrollment.
  -  All enrolled patients will have undergone clinically indicated genetic testing.
  Exclusion Criteria:
  -  Age <18 years
  -  >85 years
  -  pregnant women
  -  life-limiting co-morbidities
  -  immunocompromise

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: 5-HT3 Antagonists (Antiemetics) and Cardiac Safety

Summary: 5-HT3 antagonists (ondansetron) are highly effective medications for the treatment of nausea and vomiting. However, these medications also associated with potentially severe and life-threatening cardiac adverse drug reactions (ADRs), particularly QT prolongation. Data regarding the cardiac safety and inter-individual variability in cardiac effects of ondansetron when used in vulnerable populations such as children and pregnant women are very limited. The results of this study will enable better-informed therapeutic decision-making regarding the use of ondansetron in children and pregnant women, with the overall goal to improve the safety of these commonly used antiemetic medications. Furthermore, predictive pharmacogenetic markers of severe 5-HT3 antagonist toxicity could be used to identify patients at risk of cardiac toxicity before the drug is administered.

Detailed description: The specific objectives are to:
  1. Determine and compare the cardiac safety profile of ondansetron in children, when used for prevention and management of post-operative nausea and vomiting and chemotherapy induced nausea and vomiting. Identify clinical factors including pre-existing cardiac conditions or physiological conditions that predispose to ventricular arrhythmias, concomitant cardiotoxic chemotherapy or concomitant volatile anaesthetic agents and investigate their impact on cardiac adverse effects of ondansetron.
  2. Determine and compare the cardiac safety profile of ondansetron when used in pregnant women or women of a reproductive age for the treatment of hyperemesis gravidarum or post-operative nausea and vomiting. Identify clinical factors including pre-existing cardiac conditions or physiological conditions, which predispose to ventricular arrhythmias that may support implementation of risk mitigation actions.
  3. Identify genetic variants associated with 5-HT3 antagonist-induced prolongation of QT interval.

Eligibility: Inclusion Criteria:
  1. Children 6 months - 18 years of age who are being treated with ondansetron for prevention and management of post-operative nausea and vomiting and chemotherapy-induced nausea and vomiting.
  2. Pregnant women and women of a reproductive age (18-45 years of age) who are being treated with ondansetron for hyperemesis gravidarum or postoperative nausea and vomiting.
  Exclusion Criteria:
  1. Patients with congenital long QT syndrome.
  2. Subjects who do not speak and understand English.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Study Assessing Deep Molecular Response in Adult Patients With CML in Chronic Phase Treated With Nilotinib Firstline.

Summary: The main purpose of this study is evaluation of deep molecular response (MR4.5; BCR-ABL IS < 0.0032%) after 24 months of therapy with nilotinib in newly diagnosed patients with chronic phase CML. Via the use of MR4.5 EUTOS ('European Treatment and Outcome Study for CML') laboratories adequate and reliable molecular monitoring as a key parameter for assessing molecular milestones is fostered. Furthermore this trial aims to investigate early prediction of outcome in newly diagnosed patients with nilotinib by assessing the individual decline of BCR-ABL transcripts. Quality of life will bemeasured via use of the EORTC CML-24 questionnaire.


Eligibility: Inclusion Criteria:
  -  Patients with newly diagnosed (within 6 months) Philadelphia chromosome positive CML in chronic phase; Patients must be previously untreated for CML with the exception of 6 months treatment with hydroxyurea and a maximum of 6 weeks treatment with imatinib
  Exclusion Criteria:
  -Known impaired cardiac function like long QT syndrome, history of myocardial infarction or unstable angina in the past 12 months. Patients who are pregnant or breast feeding.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Exercise in Genetic Cardiovascular Conditions

Summary: The goal is to determine how lifestyle and exercise impact the well-being of individuals with hypertrophic cardiomyopathy (HCM) and long QT syndrome (LQTS).

Detailed description: Yale is the central site for this multicenter study. Patients with HCM and LQTS will be recruited via high-volume HCM and LQTS sites, patient-groups, and websites. Information about exercise participation will be acquired via interview and online instruments at enrollment and every six months for three years. Quality of Life questionnaires will be filled out at enrollment and at the end of the study. Participants will receive a Fitbit (pedometer) and will wear it initially for two weeks and then one week every three months. The Fitbit is used for assessment of exercise level only. Clinical records will be obtained from treating physicians. Participants will also be asked to call the central site if they experience syncope, appropriate ICD (implantable cardioverter defibrillator) shock, or resuscitated arrest. Information regarding the patient's activity at the time of event will then be obtained by phone interview. Follow-up clinical records will be obtained as indicated to corroborate endpoints.

Eligibility: Inclusion Criteria:
  -  Individuals with Hypertrophic Cardiomyopathy or Long QT Syndrome
  Exclusion Criteria:
  -  Individuals with Hypertrophic Cardiomyopathy with systolic or diastolic heart failure which precludes vigorous exercise will not be enrolled (NYHA III/IV)

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: PPI And Food Effect Study For PF-06463922 In Healthy Volunteers

Summary: The current study will be conducted in healthy adult subjects to evaluate the effect of proton pump inhibitor and food on pharmacokinetics of PF-06463922, to evaluate the bioavailability of the oral solution relative to the tablet formulation of PF-06463922.

Detailed description: PF-06463922 is a selective, ATP competitive small molecule tyrosine kinase inhibitor (TKI) of the Anaplastic Lymphoma Kinase (ALK) positive (ALK+) or ROS oncogene 1 (ROS1) positive (ROS1+) receptor tyrosine kinases (RTK) that also potently inhibits ALK kinase domain mutations responsible for resistance to crizotinib. PF-06463922 is being developed as a novel anticancer agent for the treatment of patients with advanced ALK+ NSCLC or ROS1+ NSCLC.
  The current study is a Phase 1, randomized, open label, 4 period, 4 treatment, 4 sequence, crossover study conducted in healthy adult subjects. Each subject will receive four single oral doses of 100 mg PF-06463922 as tablets alone, tablets with food, tablets with rabeprazole, and oral solution after overnight fasting with at least a 10 day washout period between each PF-06463922 dose.
  Twenty four (24) subjects will be enrolled to obtain at least 20 evaluable subjects who complete all treatments. Subjects who withdraw will not be replaced unless the total number of completed subjects falls below 20.

Eligibility: Inclusion Criteria:
  -  Healthy female subjects of non-childbearing potential and/or male subjects
  -  Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
  -  Evidence of a personally signed and dated informed consent document.
  -  Subject must be willing to avoid direct sunlight exposure or any high intensity ultraviolet light exposure
  Exclusion Criteria:
  -  Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular
  -  Any condition possibly affecting drug absorption
  -  A positive urine drug screen.
  -  Use of tobacco- or nicotine containing products within 90 days of screening or a positive urine cotinine test and history of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males within 6 months of Screening.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome

Summary: Phase 2, double-blind, placebo-controlled study to assess the safety and efficacy of NBI-98854 administered once daily (qd) for a total of 8 weeks of treatment. This study will enroll approximately 90 male and female subjects clinically diagnosed with Tourette Syndrome.


Eligibility: Inclusion Criteria:
  1. Have a clinical diagnosis of Tourette Syndrome (TS)
  2. Have at least moderate tic severity
  3. Have TS symptoms that impair school, occupational, and/or social function
  4. If using maintenance medication(s) for TS or TS spectrum diagnoses (e.g. obsessive-compulsive disorder [OCD], Attention-Deficit Hyperactivity Disorder [ADHD]), be on stable doses
  5. Be in good general health
  6. Have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, or opiates, and a negative alcohol screen
  7. Subjects of childbearing potential who do not practice total abstinence must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study
  Exclusion Criteria:
  1. Have an active, clinically significant unstable medical condition within 1 month prior to screening
  2. Have a known history of long QT syndrome or cardiac tachy-arrhythmia
  3. Have a known history of neuroleptic malignant syndrome
  4. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed)
  5. Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors
  6. Have a known history of substance dependence, substance (drug) or alcohol abuse
  7. Have a significant risk of suicidal or violent behavior
  8. Are currently pregnant or breastfeeding
  9. Have initiated Comprehensive Behavioral Intervention for Tics (CBIT) during the screening period or at baseline or plan to initiate CBIT during the study
  10. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study
  11. Have a blood loss ≥550 mL or donated blood within 30 days prior to screening

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: A Study of Enfuvirtide (Fuzeon) in Participants With Advanced Human Immunodeficiency Virus (HIV) Infection

Summary: This study assessed the safety and tolerability of enfuvirtide in participants with advanced HIV genotype 1 (HIV-1) disease. Eligible participants who failed treatment with regimens containing at least one product from each anti-retroviral class, or had experienced intolerance to previous anti-retroviral regimens received enfuvirtide, 90 milligrams (mg) subcutaneously (SC) twice daily (BID) as long as there were no enfuvirtide related treatment limiting toxicities and participants benefited from study treatment as per investigator's discretion. The anticipated time on study treatment was based on the commercial availability of enfuvirtide in Thailand, and the target sample size was 30 individuals.


Eligibility: Inclusion Criteria:
  -  Individuals at least 16 years of age infected with HIV-1
  -  CD4 lymphocyte count less than equal to (<=) 100 cells per cubic millimeter (cells/mm^3) and HIV-1 ribonucleic acid (RNA) viral load greater than equal to (>=) 10,000 copies/mL while on highly active antiretroviral therapy (HAART)
  -  Genotypic or phenotypic resistance and/or treatment-limiting toxicity on previous antiretroviral regimens
  Exclusion Criteria:
  -  Evidence of ongoing alcohol and/or drug or substance abuse
  -  Prior non-adherence to antiretroviral treatment regimens
  -  Evidence of active, untreated opportunistic infection, intercurrent illness, drug toxicity or any other condition.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Study to Evaluate the Effect of XmAb®5871 on Disease Activity in Patients With IgG4-Related Disease (RD)

Summary: The purpose of this Phase 2 study is to investigate the effect of XmAb5871 on IgG4-Related Disease (RD) activity


Eligibility: Inclusion Criteria:
  -  Active IgG4-RD
  -  Compatible pattern of organ involvement consistent with IgG4-RD that cannot be attributed to other causes
  -  Histopathologically-proven diagnosis of IgG4-RD
  -  Peripheral blood plasmablast count >900 cells/mL and/or elevated IgG4-RD levels during screening
  -  Able and willing to complete the entire study according to the study schedule
  -  Able and willing to provide written informed consent
  Exclusion Criteria:
  -  History or evidence of a clinically unstable/uncontrolled disorder, condition or disease other than IgG4-RD that, in the opinion of the Investigator would pose a risk to the patient safety or interfere with the study evaluation, procedures or completion
  -  Malignancy within 5 years (except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin, or prostate cancer with no recurrence ≥3 years following prostatectomy)
  -  Presence of recurrent or chronic infections, defined as ≥3 infections requiring antimicrobials over the past 6 months prior to screening
  -  Active infection requiring hospitalization or treatment with parenteral antimicrobials within the 60 days prior to randomization or oral antimicrobials within the 21 days prior to enrollment
  -  Patient is taking >40 mg of prednisone QD
  -  Prior use of rituximab (or other B cell depleting agents) within 6 months of enrollment. Prior use of any B cell depleting agent greater than 6 months from enrollment is allowed if the CD19+ B cell count is within the normal reference range during screening
  -  Use of any investigational agent within 5 half-lives of the agent (or 6 months if the half-life is unknown) prior to enrollment
  -  Immunosuppressive agent use within the three months prior to enrollment
  -  Has received live vaccines within 2 months of enrollment
  -  Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to end-of-study visit
  -  Unable or unwilling to partake in the follow-up assessments or required protocol procedures

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Metabolism of Patients With Genetically Caused Cardiac Arrhythmia

Summary: Loss-of-function mutations in voltage-gated potassium channels cause long QT syndrome (LQTS) due to a prolonged cardiac repolarisation phase. Hypoteses: patients with loss-of-function mutations also exhibit altered hormone release upon glucose ingestion.

Detailed description: Loss-of-function mutations in voltage-gated potassium channels cause long QT syndrome (LQTS) due to a prolonged cardiac repolarisation phase.
  Voltage-gated potassium (Kv-) channels are known for their relation to malignant cardiac arrhythmias, but also play a role in pancreatic alpha- and beta cell hormone secretion, and possibly in incretin hormone secretion. We hypothesised that patients with loss-of-function mutations also exhibit altered hormone release upon glucose ingestion.

Eligibility: Inclusion Criteria:
  LQTS Gain of function Matched healthy controls
  Exclusion criteria:
  none

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: A Study To Evaluate The Effect Of PF-04447943 On Qtc Interval In Healthy Adult Subjects

Summary: This is a study designed to ascertain the effect of PF-04447943 on QT interval in healthy adult subjects. This is conducted as part of standard drug development.


Eligibility: Inclusion Criteria:
  -  Healthy female subjects of non childbearing potential and/or healthy male subjects, between the ages of 18 and 55 years.
  -  Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg.
  Exclusion Criteria:
  -  Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
  -  History of cerebrovascular accident, transient ischemic attack (TIA), or traumatic brain injury.
  -  History of seizures or history or physical examination findings (eg localizing signs on neurologic examination) suggestive of structural central nervous system (CNS) abnormalities which may place patient at increased risk of seizures.
  -  History of orthostatic blood pressure changes or clinically significant orthostatic symptoms.
  -  Self reported history or risk factors for QT prolongation or torsades de pointes (eg, organic heart disease, congestive heart failure, hypokalemia, hypomagnesaemia, congenital long QT syndrome, myocardial ischemia or infarction), congenital deafness, family history of sudden death, and family history of long QT syndrome.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Hydroxyzine and Risk of Prolongation of QT Interval

Summary: On 04/30/2015, ANSM (the National Security Agency of Medicines and Health Products) shared an information for general practicioners, pediatricians, anesthesiologists, dermatologists, geriatricians, psychiatrists, community pharmacists and hospital about using hydroxyzine and the associated risk of QT prolongation on the electrocardiogram.
  Drugs containing hydroxyzine (the best known and most used is the Atarax®) are used in France in various indications including the treatment of minor manifestations of anxiety, premedication with general anesthesia and the symptomatic treatment of urticaria.
  A prolonged QT interval is a known risk factor for occurrence of torsades de pointes which can cause sudden death. We distinguish congenital and acquired long QT interval. The main cause of acquired long QT interval is a drug inhibition of the HERG potassium channel 1. Many drugs have been reported to cause sudden death by prolongation of QT interval and occurrence of torsades de pointes (macrolides, anti -arythmics, some psychotropic ...) The molecules based on hydroxyzine are known to be at risk of prolongation of QT interval in an experimental point of view but is not clearly identified in daily clinical practice. Pharmacology unit of Caen was the first to publish a case of QT prolongation under hydroxyzine . Through this publication, associated with other clinical data, hydroxyzine has been added to the list of drugs that can induce QT prolongation .
  Despite these recent recommendations, it does not seem that hydroxyzine prescriptions were changed daily and therefore the risk of QT prolongation persists. We therefore propose the study of the impact of hydroxyzine on the QT interval measured on the electrocardiogram in patients hospitalized at the University Hospital of Caen.


Eligibility: Inclusion Criteria:
  -  Patients hospitalized at the University Hospital of Caen with a new prescription of oral hydroxyzine by their referring doctor.
  -  Patient 'stable' in hospital in a health service or surgery.
  -  Age > 18 years old.
  Exclusion Criteria:
  -  Unstable Patient hospitalized in an intensive care unit or intensive care.
  -  Patient refusing participation in the study.
  -  Age <18 years old.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: A Prospective Clinical Study for Evaluation of Safe Resection Margin in Breast Conserving Surgery in Breast Cancer

Summary: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been used for breast cancer surgery such as sentinel lymph node (SLN) mapping and breast cancer localization.
  In this study, our hypothesis are as following:
  1. As inject only indocyanine green (ICG), it provide the surgeon visual guidance to ensure better outcome.
  2. indocyanine green (ICG) permitted accurate preoperative and intraoperative detection of the SLNs as well as nonpalpable benign brest lesion in patients with breast cancer.

Detailed description: Indocyanine green, ICG (ICG-fluorescence)
  -  ICG is the most commonly used fluorophore which approve by FDA.
  -  NIR-F imaging with ICG could be used in various surgeries. For example, SLN mapping in breast cancer and localization of liver metastasis, especially superficial lesion
  -  Contains sodium iodide, patients who have history of allergy to iodides should be used as caution.
  Nonpalpable benign brest lesion localization
  -  New method for the localization and resection of non-palpable breast lesions.
  -  The breast lesion was correctly localized, and the area of ICG corresponded well to the site of the lesions.

Eligibility: Inclusion Criteria:
  -  nonpalpable breast tumor < 5cm in patients with breast cancer.
  -  consented patients with more than 18 years
  -  Eastern Cooperative Oncology Group Performance status 0 or 1
  -  patients who need breast biopsy as treatment for breast cancer.
  Exclusion Criteria:
  -  nonpalpable breast tumor ≥ 5cm in patients with breast cancer.
  -  inflammatory cancer of breast or patients who need MRM
  -  pregnancy
  -  history of severe allergy to ICG(Indocyanine Green)
  -  iode hypersensitiveness

Relevance to patient case: not relevant