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

Clinical trial: Long QT and Hearing Loss Registry

Summary: The purpose of this study is to determine the true incidence of long QT (LQT) amongst a large cohort of subjects diagnosed with unilateral (right/left) or bilateral sensorineural hearing loss.

Detailed description: The purpose of this study is to determine the true incidence of long QT (LQT) amongst a large cohort of subjects diagnosed with unilateral (right/left) or bilateral sensorineural hearing loss.
  The goal of this study is to answer the following questions:
  1. What is the incidence of an abnormal ECG (QTc > 450 msec) in neonates greater than a week of age with either unilateral or bilateral Sensorineural hearing loss?
  2. What percentage of neonates greater than one week of age with either bilateral or unilateral sensorineural hearing loss and an abnormal ECG have an identifiable genetic mutation?
  3. What is the incidence of an abnormal genetic mutation consistent with long QT regardless of the ECG in neonates with bilateral sensorineural hearing loss?

Eligibility: Inclusion Criteria:
  -  All newborns who demonstrate a refer in one or both ears on a routine newborn hearing screen
  -  Documentation of informed consent
  -  Inborn
  -  Ability to perform an ABR (auditory brainstem response screen technology) screening test
  -  No major anomalies
  -  Subjects' parents willing to provide follow-up data on their child
  Exclusion Criteria:
  -  Newborns with a syndromic cause of hearing loss
  -  Parents unwilling to provide follow-up data
  -  Major congenital anomalies
  -  Major medical problem or conditions. (i.e., hypoxic ischemic encephalopathy (HIE), persistent pulmonary hypertension neonate (PPHN), meconium aspiration, etc.)
  -  Congenital cytomegalovirus (CMV)

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

Clinical trial: The Mechanism of TCF7L2 and SLC30A8 on Antipsychotic-induced Metabolic Syndrome

Summary: Almost all of antipsychotics can induce metabolic syndrome,Genetic factors play a key role in the development of metabolic syndrome,TCF7L2 and SLC30A8 are strongestly correlated with metabolic syndrome.Moreover,Antipsychotics have an effect on the expression of TCF7L2 and SLC30A8 genes.It indicates the variations of TCF7L2 and SLC30A8 play an important part in the development of antipsychotics-induced metabolic syndrome.

Detailed description: -  In this study, we will determine the effect of olanzapine on the expression of TCF7L2 and SLC30A8.
  -  The relationship of the polymorphism of TCF7L2 and SLC30A8 with antipsychotic-induced metabolic syndrome in schizophrenia patients.

Eligibility: Inclusion Criteria:
  -  Clinical diagnosis of first episode schizophrenia
  -  Must be able to swallow tablets
  -  Take only one antipsychotics
  Exclusion Criteria:
  -  liver or renal or cardiovascular diseases
  -  pregnant or lactating women
  -  drug and alcohol dependence

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

Clinical trial: Evaluating Ventricular Arrhythmia in Subjects With Implantable Cardioverter Defibrillator or Cardiac Resynchronization Therapy-Defibrillator

Summary: The primary objective of this study is to evaluate the effect of eleclazine (GS-6615) compared to placebo on the overall occurrence of appropriate implantable cardioverter-defibrillator (ICD) interventions (antitachycardia pacing [ATP] or shock) in adults with ICD or cardiac resynchronization therapy-defibrillator (CRT-D).


Eligibility: Key Inclusion Criteria:
  -  Have an ICD or CRT-D implanted for primary or secondary prevention and at least one ICD intervention for ventricular tachycardia/ventricular fibrillation (VT/VF) [shock or ATP] within 60 days prior to screening or a documented VT/VF episode (prior to implantation) within 60 days prior to screening
  -  Use of highly effective contraception methods if female of childbearing potential or sexually active male
  -  Must be hemodynamically stable
  Key Exclusion Criteria:
  -  New York Heart Association (NYHA) Class IV heart failure
  -  Myocardial infarction, unstable angina, coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) within 4 weeks prior to screening or during the screening period before randomization
  -  Hemodynamically significant primary obstructive valvular disease
  -  History of congenital heart disease
  -  Inherited arrhythmia such as Brugada syndrome. Individuals with long QT syndrome Type 3 (LQT-3) or hypertrophic cardiomyopathy (HCM) may be considered.
  -  Individuals who are being considered for cardiac transplantation and are on a cardiac transplant list
  -  History of seizures or epilepsy
  -  Cardiac ablation within 3 months prior to screening or planned cardiac ablation during the study
  -  Severe renal impairment
  -  Abnormal liver function tests
  -  Currently taking Class I and Class III antiarrhythmic drugs; such medications should be discontinued 5 half-lives (or 28 days for chronic use of amiodarone) prior to randomization
  -  Currently taking drugs or products that are strong inhibitors or inducers of CYP3A; such medications should be discontinued 5 half-lives prior to randomization
  -  Currently taking ranolazine; ranolazine should be discontinued at least 7 days prior to randomization
  -  Females who are pregnant or are breastfeeding
  -  Individuals with a subcutaneous ICD
  -  Body mass index (BMI) ≥ 36 kg/m^2
  Note: Other protocol defined Inclusion/Exclusion criteria may apply

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

Clinical trial: A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy

Summary: Recent data suggest that areas of fibrosis and hibernating myocardium develop in patients with non ischemic dilated cardiomyopathy. Ranolazine is a new drug, developed to releave symptoms of angina in patients with stable coronary disease that is not suitable for surgical or percutaneous revascularization. It has been shown that in patients with stable coronary disease Ranolazine improves myocardial perfusion as shown with myocardial nuclear imaging. The aim of this trial is to evaluate effects of ranolazine on myocardial perfusion in patients with dilated cardiomyopathy.

Detailed description: Recent data suggest that areas of fibrosis and hibernating myocardium develop in patients with non ischemic dilated cardiomyopathy. Ranolazine is a new drug, developed to releave symptoms of angina in patients with stable coronary disease that is not suitable for surgical or percutaneous revascularization. The main mechanism of action of Ranolazine is the inhibition of late I(Na) thus decreasing the Ca++ load in the cardiomyocites. Consequently oxygen consumption also decreases. It has also been shown that in patients with stable coronary disease Ranolazine improves myocardial perfusion as shown with myocardial nuclear imaging. The aim of this trial is to evaluate effects of ranolazine on myocardial perfusion in patients with dilated cardiomyopathy.
  Primary end-point: To determine wheather Ranolazine improves perfusion of the myocardium in patients with non-ischemic dilated cardiomyopathy.
  Secondary end-points: To determine wheather Ranolazine improves patients' NYHA functional class, excercise capacity, LV systolic and diastolic function and weather ranolazine affects supraventricular and ventricular arrhythmia occurance/frequency.

Eligibility: Inclusion Criteria:
  -  established diagnosis of non-ischemic dilated cardiomyopathy
  -  EF < 35%
  -  NYHA f.c. II - IV
  -  Optimal medical management > 6 months
  -  Age < 75 years and > 18 years
  Exclusion Criteria:
  -  known hypersensitivity to the medication
  -  age > 75 years or < 18 years
  -  EF > 35%
  -  renal insufficiency (GF < 30)
  -  liver dysfunction (liver tests > 3x the upper normal limit))
  -  LQT syndrome
  -  drugs that affect CYP3A4 metabolism (azoles, macrolides, calcineurin inhibitors etc.)
  -  dementia
  -  active hemathological or malignant disease

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

Clinical trial: A Thorough QT Study of Telotristat Etiprate

Summary: The purpose of this study is to demonstrate that telotristat etiprate does not differ from placebo in the mean change from Baseline QT interval corrected for heart rate.


Eligibility: Inclusion Criteria:
  -  Healthy adult males or females ≥18 to ≤55 years of age (inclusive) at the time of Screening
  -  Body mass index ≥18 to ≤32 kg/m2 at Screening
  -  Vital signs (after at least 5 minutes resting in a supine position) at Screening which are within the following ranges: Systolic blood pressure 90 to 140 mm Hg, Diastolic blood pressure 50 to 90 mm Hg, heart rate 45 to 100 beats per minute (bpm)
  -  Clinical laboratory evaluations (including clinical chemistry panel [fasted at least 10 hours], complete blood count, and urinalysis [UA]) within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator
  -  Able to tolerate prolonged periods of quiet, motionless, supervised rest
  -  Willing to adhere to the prohibitions and restrictions specified in this protocol
  -  Able to comprehend and willing to sign an Informed Consent Form
  Exclusion Criteria:
  -  Presence of clinically significant physical, laboratory, or ECG findings at Screening that, in the opinion of the Investigator or Sponsor, may interfere with any aspect of study conduct or interpretation of results
  -  >30 premature ventricular beats per hour on the Holter ECG monitoring at Day -1 of Period 1 (monitored at the clinic via telemetry)
  -  History of additional risk factors for torsade de pointes or the diagnosis or suggestion of a family history of short QT syndrome or long QT syndrome
  -  History of renal disease or significantly abnormal kidney function tests
  -  History of hepatic disease or significantly abnormal liver function tests
  -  History of any clinically significant psychiatric, renal, hepatic, pancreatic, cardiovascular, neurological, or gastrointestinal abnormality
  -  Concurrent conditions that could interfere with safety and tolerability measurements
  -  Positive hepatitis panel (including hepatitis B surface antigen and hepatitis C virus antibody) or positive human immunodeficiency virus antibody screens
  -  Use of tobacco, use of medications, or history of any disease or condition that might interfere with the conduct of the study in the opinion of the investigator

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

Clinical trial: Darbepoetin Alfa MDS Companion Protocol

Summary: The primary objective of the study was to provide required access of investigational product (darbepoetin alfa) beyond the end of the active treatment period (EOATP) of the darbepoetin alfa MDS 20090160 (NCT01362140) study for patients who had continued demonstration of benefit from darbepoetin alfa treatment and to describe the safety of longer-term use in this patient population.

Detailed description: This is a phase 3b, multi-centre, open-label, single-arm companion study to the MDS 20090160 study (NCT01362140) for the treatment of anaemic patients with MDS. Participants who completed the active-treatment period of the darbepoetin alfa MDS 20090160 study and met the eligibility criteria could be enrolled into this study to continue treatment of darbepoetin alfa for up to 73 weeks or until progression to acute myelogenous leukemia (AML), whichever occurs first.

Eligibility: Inclusion Criteria:
  -  Subject or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/ procedures being initiated;
  -  Subject must continue long term follow up within parent study (20090160);
  -  Subject must have an ongoing clinically relevant erythroid response as assessed by the Investigator using current response criteria (ie, International Working Group (IWG) response criteria);
  Exclusion Criteria:
  -  Transfusion dependence defined as receiving a total of ≥ 4 units of red blood cell (RBC) transfusion in the previous 8-week period prior to enrolment;
  -  Known diagnosis of acute myelogenous leukemia (AML) or marrow collagen fibrosis;
  -  Known refractory anaemia with excess blast-2 (RAEB-2);
  -  Known diagnosis of intermediate-2 or high risk MDS per International Prognostic Scoring System (IPSS);
  -  Subjects received thrombopoiesis-stimulating factors (eg, eltrombopag, romiplostim) in the MDS 20090160 study or planning to receive such agents during the study;
  -  Other protocol defined inclusion and exclusion criteria may apply.

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

Clinical trial: Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3

Summary: The primary objective of this study is to evaluate the effect of oral eleclazine on mean daytime QTcF interval after 24 weeks of treatment with elecalzine in participants with long QT syndrome Type 3. During the single-blind treatment period (24 weeks), participants will receive eleclazine and/or eleclazine placebo. Following the single-blind treatment period, participants who have not permanently discontinued study drug will be eligible, at the discretion of the investigator, to continue receiving eleclazine during an open-label extension (OLE) phase.


Eligibility: Key Inclusion Criteria:
  -  Individuals with an established diagnosis of LQT3 (by genotype testing)
  -  Mean (of triplicate) QTc interval ≥ 480 msec (or ≥ 460 msec, for individuals who are currently taking ranolazine or Class I antiarrhythmic drugs such as mexiletine) at 3 or more time points, determined by standard 12-lead ECG, at screening
  Key Exclusion Criteria:
  -  Known mutations associated with type 1 long QT syndrome (LQT1) or type 2 long QT syndrome (LQT2)
  -  Known or suspected history of seizures or epilepsy
  -  History of heart failure defined as New York Heart Association (NYHA) Class IV and/or known left ventricular ejection fraction (EF) ≤ 45%
  -  Body mass index (BMI) ≥ 40 kg/m^2 at screening
  -  Severe renal impairment at screening (defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2, using the 4 Variable Modification of Diet in Renal Disease (MDRD) equation, as determined by the study center)
  -  Abnormal liver function tests at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN), or total bilirubin > 1.5 x ULN
  -  An aborted cardiac arrest (ACA), implantable cardioverter-defibrillator (ICD) implantation, syncopal episode, or appropriate ICD therapy within 3 months prior to screening
  -  Any other condition or circumstance that in the opinion of the investigator would preclude compliance with the study protocol
  Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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

Clinical trial: Intermittent ART in Primary HIV Infection

Summary: Interventions during primary HIV infection (PHI) can modify the immune control and the clinical evolution during the chronic phase. Although several studies suggest the benefit of antiretroviral treatment (ART) during PHI, indication of ART is still not universally recommended. The investigators randomized patients with PHI, with a favourable immunological profile and well controlled on ART, to undergone structured treatment interruptions alone or with low doses of IL-2, stopping ART thereafter. The endpoints were immune control of HIV replication and time to resume ART. Immunological profile, specific CD4 and CD8 responses and clinical data were analysed for both groups up to 48 weeks, and during a long follow-up, up to nine years since final ART stop.

Detailed description: The study design included two phases. The first phase consisted in four STI of 8 weeks each (off-ART), separated by 16 weeks of treatment -or the time necessary to reach again to PVL <20 copies/mL- (on-ART). At the end of the 4th off-ART cycle (week 0) an interim evaluation was performed and the second phase initiated. During the second phase, the first 6 patients received ART until they reach PVL<20 copies/mL, discontinuing thereafter (final stop). The last 6 patients received ART and low doses of IL-2. ARV therapy was stopped after reaching PVL<20 copies/mL (final stop) and IL-2 after 6 months of treatment. IL-2 was prescribed at a dose of 750.000 UI/m2 daily and was self-administrated in all patients previous trained by a specialized nurse. ART was resumed in patient dropping CD4 cell count less than 350 cell/mm3 in two consecutive determinations or in patients who developed opportunistic infections. A long term follow up analysis was performed at 3, 6 and 9 years since the final stop. It included time to resume ART, clinical events, survival rate, CD4-CD8-CD4/CD8 ratio.

Eligibility: Inclusion Criteria:
  -  PHI defined by detectable plasma viral load (PVL) or p24 antigen detection coupled with a negative or indeterminate LIA assay (according CDC criteria); negative HIV-1 EIA in the preceding 90 days or by a positive EIA and LIA assay with acute retroviral syndrome in the preceding 90 days of starting ART plus documented negative HIV-1 EIA within the previous year.
  -  ART started within 90 days from the HIV exposure and continuing in the same treatment at least 12 months before the inclusion, and they must have shown good virological and immunological responses, defined as undetectable PVL (<20 copies/mL in the last two controls) and CD4 more than 500 cells/mm3 with a CD4/CD8 ratio >1 in the last 8 months previous to enrolment
  Exclusion Criteria:
  -  Infection of more than 90 days.
  -  Age under 18 years old.
  -  AIDS defining condition

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

Clinical trial: BRCA1 and BRCA2 Mutation in Romanian Population: a Study of Genotype - Phenotype Correlation at Diagnosis With Prospective Disease Outcome and Survival

Summary: Primary objective To determine BRCA1 and BRCA2 variants in 250 Romanian women with breast/ovarian cancer selected for likeliness to harbor germline mutations in these genes by specific criteria for high-risk status including age at disease onset.
  Secondary objective Considering the fact that BRCA testing is not a routine procedure in Romania and mutation prevalence varies in different populations, we intend to look for the founder mutation in our population, running full BRCA genes sequencing to a representative population sample. This would allow a more targeted approach to real-life practice and would ensure personalized solutions for every patient in need.


Eligibility: Inclusion Criteria:
  Categories of patients to be recruited for complete sequencing of all BRCA1 and BRCA2 exons are subjects who have been diagnosed with breast or ovarion cancer and who are:
  1)40 years of age or younger 2)Triple negative breast cancer diagnosed before 50 years of age 3)Male with breast cancer 4)Bilateral breast cancer, first tumor diagnosed before 50 years of age 5)2) + 50 years of age or younger with at least one (first degree) relative diagnosed with breast cancer at 50 years of age or younger or a first degree relative with ovarian cancer 6)of any age with 2 or more relatives with breast cancer 7)of any age with 2 or more relatives with ovarian cancer 8)of any age with a personal history of ovarian cancer, tuba or peritoneal carcinoma 9)Two patients in same branch of the family, Prostate ca < 60 yr and 1st degree relative with BC < 50 yr 10)Two or more 1st and 2nd degree relatives of a patient with breast cancer, at least one of them <50 yr 11)of any age with a family history of male breast cancer or are at increased risk of having a BRCA mutation based on BRCAPRO or Tyrer-Cuzick models
  Exclusion Criteria:
  -

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

Clinical trial: Effect of Eleclazine on QT, Safety, and Tolerability in Adults With Long QT2 Syndrome

Summary: This study will evaluate the effect of oral eleclazine (GS-6615) on QTc interval, safety, and tolerability in adults with long QT2 syndrome.


Eligibility: Inclusion Criteria:
  -  Individuals with an established diagnosis of LQT2 (by genotype testing)
  -  Mean (of triplicate) QTc interval ≥ 480 msec for at least four out of seven time points, determined by standard 12-lead ECG, at screening
  Exclusion Criteria:
  -  Known mutations associated with LQT1 or LQT3
  -  Known or suspected history of seizures or epilepsy
  -  History of heart failure defined as New York Heart Association (NYHA) Class IV and/or known left ventricular ejection fraction (EF) ≤ 45%
  -  Body mass index (BMI) ≥ 36 kg/m^2 at screening
  -  Severe renal impairment at screening (defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2, using the 4 Variable Modification of Diet in Renal Disease (MDRD) equation), as determined by the study center
  -  Abnormal liver function tests at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN), or total bilirubin > 1.5 x ULN
  -  An aborted cardiac arrest (ACA), implantable cardioverter-defibrillator (ICD) implantation, syncopal episode, or appropriate ICD therapy within 3 months prior to screening
  -  Any other condition or circumstance that in the opinion of the investigator would preclude compliance with the study protocol

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

Clinical trial: QT-Prolongation in Lung Transplantation

Summary: Experimental intervention: electrocardiography. Control intervention: none
  Duration of intervention per patient/subject:
  5 min, observation 6 months
  Key inclusion criteria:
  -  outpatients after lung transplantation (single, double or combined)
  -  outpatients on the wait list for lung transplantation
  Key exclusion criteria:
  • no informed consent

Detailed description: Primary endpoint:
  • prevalence of significant QTc-interval prolongation (500 msec or above) after lung transplantation
  Key secondary endpoint(s):
  -  prevalence of any QTc-interval prolongation (>440 msec ) after lung transplantation
  -  prevalence of PQ prolongation (200 msec sec or above) after lung transplantation
  -  prevalence of QRS prolongation (120 msec or above) after lung transplantation
  -  prevalence of QTc-prolonging drugs in drug regimen before and after lung transplantation
  -  influence of long-term neo-macrolide (e.g. azithromycin) on QTc interval after lung transplantation
  -  intra-individual difference of QTc interval before and after lung transplantation
  -  incidence of any QTc-interval prolongation(>440 msec ) after lung transplantation
  -  incidence of any QTc-interval prolongation (>440 msec or increase by 50msec or above) after initiation of new QTc prolonging drugs (especially neo-macrolides)
  -  reversal of QTc-interval prolongation (440 msec or lower or decrease by 50msec or above) after stopping any QTc prolonging drug
  -  Assessment of safety:
  -  Incidence of new onset heart rhythm disorder during 6 months of follow-up

Eligibility: Inclusion Criteria:
  -  outpatients after lung transplantation (single, double or combined)
  -  outpatients on the wait list for lung transplantation
  Exclusion Criteria:
  -  no informed consent

Relevance to patient case: not relevant