araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Atherosclerosis in Familial Hypercholesterolemia

Summary: Familial hypercholesterolemia (FH) is a common inherited disorder with a frequency of 1 in 500 in the UK. Our aim is compare the carotid and coronary artery atherosclerosis in monogenic FH and polygenic hypercholesterolemia with means of a carotid ultrasound, a coronary CT angiogram and biochemical biomarkers.

Detailed description: Familial hypercholesterolemia (FH) is a common inherited disorder with a frequency of 1 in 500 in the UK. Previous Studies showed that risk of heart attack in these patients is at least 50% higher in men and 30% higher in women compared to the general population as they have high blood cholesterol since birth. We propose to develop a screening model based on non-invasive visualisation of the heart blood vessels (coronary arteries) by CT scan, ultrasound of the neck vessels (carotid arteries) and blood tests to access the extend of cholesterol deposit in the blood vessels in these patients. Participants with confirmed diagnosis of FH would be recruited from FH database registry at Royal Free Hospital. They would have a CT coronary angiogram, an ultrasound of carotid arteries and a blood test. The study is divided into overlapping stages of recruitment and data collection and data analysis. If CT scan shows more than 70% obstruction in their coronary arteries, they would be offered a coronary angiogram and an intracoronary Optical Coherence Tomography for assessment of their blood vessel blockage.

Eligibility: Inclusion Criteria:
  -  The subjects must give written informed consent to participate in the study, Male and female subjects ≥ 18 years old, documentation of clinical diagnosis of familial Hypercholesterolemia
  Exclusion Criteria:
  -  Estimated GFR <45, pregnant women, Atrial fibrillation or unstable heart rate, Established ischemic heart disease, previous Percutaneous Coronary Investigations (PCI) or Coronary Artery Bypass Surgery (CABG), Known allergy to iodine contrast

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: The Effect of a Plant Sterols-Enriched Low-Fat Milk on Lipid Profile in Healthy Southern Chinese (COME-PASS)

Summary: This is a randomized, double-blind, single-center, two-arm, placebo-controlled clinical trial that examine the effect of the consumption of a plant sterols-enriched low-fat milk. Half of the participants will consume of 1.5g of plant sterols daily as provided by two servings of the plant sterols-enriched low-fat milk product for 3 consecutive weeks, while the other half will consume placebo low-fat milk.

Detailed description: Plant sterols are the naturally occurring functional equivalent of mammalian cholesterol. Plant sterols differ structurally from cholesterol by a methyl or ethyl group in their side chains and are not synthesized by the human body. These structural differences render them minimally absorbable in the intestine. It has been consistently reported that dietary incorporation of plant sterols(1.5-2 g/day) reduces serum low-density lipoprotein cholesterol (LDL-C) levels with minimal adverse events. The hypochoelsterolemic effects of plant sterols is explained by an inhibition of cholesterol absorption, which is ascribed to a competition with intestinal cholesterol for incorporation into mixed micelles, although other possible mechanistic explanation have been proposed.

Eligibility: Inclusion Criteria:
  -  Southern Chinese male or female ≥ 18years.
  -  In good general health as evidenced by medical history
  -  Have the ability to understand the requirements of the study, provide written informed consent, including consent for the use and discloser of research-related health information, and comply with the study data collection procedures. Provide signed and dated informed consent form
  Exclusion Criteria:
  -  Subject with familial hypercholesterolemia
  -  Ingestion of drugs known to interfere with lipid profiles, such as hormone replacement treatment, diuretics, beta-blockers, statin or other hypochoelsterolemic drug treatment
  -  Smoking > 10 cigarettes/day
  -  Subject with heavy alcohol intake (Alcohol > 3 glasses wine, or 2 beers, or 1 shot hard alcohol/day)
  -  Having milk intolerance or dislike
  -  Having major diseases such as diabetes (type I and type II), renal or liver diseases
  -  Subject presenting known allergy or hypersensitivity to milk proteins, soy and peanut
  -  Subject refusing to stop the consumption of plant sterols-enriched products if any during the study (other than the studied product)
  -  Subject receiving systemic treatment or topical treatment likely to interfere with evaluation of the study parameters
  -  Subject currently involved in a clinical trial or in an exclusion period following participation in another clinical trial
  -  Pregnancy or lactation
  -  Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin

Summary: Primary Objective:
  To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab administration as add-on therapy to non-statin lipid modifying therapy (LMT) including diet therapy alone or the lowest strength of statin in comparison with placebo after 12 weeks of treatment in participants with hypercholesterolemia.
  Secondary Objective:
  -  To evaluate the effect of two treatment regimens of alirocumab on other lipid parameters: apolipoprotein B (Apo-B), non-high-density lipoprotein cholesterol (non HDL-C), total cholesterol (TC), lipoprotein (a) (Lp[a]), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and apolipoprotein A-1 (Apo A-1).
  -  To evaluate the safety and tolerability of alirocumab administration.
  -  To evaluate the development of anti-alirocumab antibodies.
  -  To evaluate the pharmacokinetic and pharmacodynamic profiles of alirocumab administration.
  -  To evaluate the long-term safety in participants receiving open-label alirocumab administration.

Detailed description: The duration of study per participant was approximately 71 weeks consisting of a run-in period (4 weeks), a screening period (3 weeks), a double-blind treatment period (12 weeks), and an open-label treatment period (52 weeks).

Eligibility: Inclusion criteria :
  Participants with hypercholesterolemia (heFH or non-FH) receiving non statin LMTs or the lowest strength of statin.
  Exclusion criteria:
  -  LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (Week -3) in participants with heFH or in participants with non-FH who have a history of documented coronary heart disease.
  -  LDL-C <120 mg/dL (<3.10 mmol/L) at the screening visit (Week -3) in participants with non-FH participants who had a history of documented diseases or other risk factors classified as primary prevention category III as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
  -  Not on a stable dose of LMT (including diet therapy alone) in the run-in period or the screening period.
  -  Fasting serum TGs >400 mg/dL (>4.52 mmol/L) at the screening period.
  -  Systolic blood pressure (BP) >160 mmHg or diastolic BP >100 mmHg at the run-in visit (Week -7) or the screening visit (Week -3) or the randomization visit (Week 0).
  The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Evolocumab Compared to LDL-C Apheresis in Patients Receiving LDL-C Apheresis Prior to Study Enrollment

Summary: To evaluate the efficacy of subcutaneous (SC) evolocumab, compared to regularly scheduled low-density lipoprotein cholesterol (LDL-C) apheresis, on reducing the need for future apheresis.


Eligibility: Inclusion Criteria:
  -  Male or female, ≥ 18 years of age
  -  Subject has been receiving regular apheresis for LDL-C lowering for at least 3 months immediately prior to lipid screening and has a treatment goal of LDL-C < 100 mg/dL (2.6 mmol/L), and has been receiving LDL-C apheresis during the last ≥ 4 weeks prior to lipid screening at regular QW or Q2W schedule and with no changes in apheresis type
  -  Subject is receiving lipid-lowering pharmacological background therapy which includes a high-intensity statin dose (moderate-intensity statin dose with attestation that a higher dose is not appropriate for the subject) unless the subject has a history of statin intolerance
  -  Lipid-lowering therapy status (ie, any therapy for lowering lipids, including apheresis type and frequency) must be unchanged for ≥ 4 weeks prior to LDL-C screening
  -  Pre-apheresis LDL-C is ≥ 100 mg/dL (≥ 2.6 mmol/L) and ≤ 190 mg/dL (≤ 4.9 mmol/L) at screening
  -  Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L) at screening.
  Exclusion criteria:
  -  Known homozygous familial hypercholesterolemia
  -  Missing any apheresis session is medically contraindicated or inappropriate
  -  Stopping apheresis would be inappropriate in the opinion of the investigator even if LDL-C is controlled to < 100 mg/dL with other therapies
  -  Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization.
  -  Uncontrolled hypertension

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Open Label Study to Evaluate Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Pediatric Subjects (10 to 17 Years of Age) With Heterozygous Familial Hypercholesterolemia (HeFH) or Homozygous Familial Hypercholesterolemia (HoFH).

Summary: To describe the safety and tolerability of 80 weeks of subcutaneous (SC) evolocumab (AMG 145) when added to standard of care in pediatric subjects 10 to 17 years of age with HeFH or HoFH.

Detailed description: An open label, single arm study to evaluate the safety and tolerability of 80 weeks of SC evolocumab when added to standard of care in pediatric subjects 10 to 17 years of age with HeFH or HoFH.

Eligibility: Inclusion Criteria:
  Subjects with HeFH:
  -Completed Study 20120123 while still on assigned investigational product and did not experience a treatment‑related serious adverse event
  Subjects with HoFH:
  -  Male or female, ≥ 10 to ≤ 17 years of age at time of enrollment
  -  Diagnosis of HoFH
  -  On a low-fat diet and receiving background lipid-lowering therapy
  -  Lipid-lowering therapy unchanged for ≥ 4 weeks prior to LDL-C screening; fibrates must be stable for at least 6 weeks prior to screening.
  -  Fasting LDL-C at screening ≥ 130 mg/dL (3.4 mmol/L)
  -  Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)
  Exclusion Criteria:
  All Subjects
  -Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treament on another investigational device or drug study(s); except Study 20120123
  Subjects with HoFH:
  -  Moderate to severe renal dysfunction
  -  Active liver disease or hepatic dysfunction,
  -  CK > 3 times the ULN at screening

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4

Summary: The primary objective of the study was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin.

Detailed description: After screening participants who met all inclusion/exclusion criteria were randomized with an allocation ratio of 2:2:1:1 into 4 groups: evolocumab (AMG 145) 420 mg administered by subcutaneous injection monthly and placebo pill daily; evolocumab 140 mg administered by subcutaneous injection every two weeks and placebo pill by mouth daily; placebo 420 mg administered by subcutaneous injection monthly and ezetimibe 10 mg pill daily; placebo 140 mg administered subcutaneous injection every two weeks and ezetimibe 10 mg pill daily. Randomization was stratified by screening LDL-C level and baseline statin use. Participants on low or atypical statin dose therapy must have been on a stable dose for at least 4 weeks prior to screening and throughout the blinded portion of the study; the dose could not be adjusted during screening and for the duration of the study. After Week 12, ezetimibe was discontinued and participants moved to an open-label dose of evolocumab administered by subcutaneous injection either every two weeks or monthly and their standard of care.

Eligibility: Inclusion Criteria:
  -  Male or female ≥ 20 to ≤ 80 years of age
  -  Japanese by self-identification
  -  Not on a statin or on a low dose statin with stable dose for at least 4 weeks.
  -  Subject not at LDL-C goal
  -  History of statin intolerance to at least 2 statins
  -  Lipid lowering therapy has been stable prior to screening for at least 4 weeks
  -  Fasting triglycerides ≤ 400 mg/dL
  Exclusion Criteria:
  -  New York Heart Association (NYHA) III or IV heart failure
  -  Uncontrolled cardiac arrhythmia
  -  Uncontrolled hypertension
  -  Type 1 diabetes
  -  Poorly controlled type 2 diabetes
  -  Uncontrolled hypothyroidism or hyperthyroidism

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: The Effect of Resistance Training on Proprotein Subtilisin Convertase Kexin 9 Level After Coronary Bypass Surgery

Summary: This research will add resistance training to patients who undergo cardiac rehabilitation program after coronary bypass surgery, comparing the level of PCSK9 level on that group to another group who receives conventional rehabilitation program (only aerobic exercise)

Detailed description: The PCSK9 level will be measured before and after cardiac rehabilitation program (around 2-4 weeks), and will be compared between two groups. ELISA method will be used to measure plasma PCSK9 level.
  Resistance training will be given by professional trainer in gymnasium of National Cardiac Center Harapan Kita, following rules from American College of Sports Medicine guideline regarding to exercise after cardiac event.

Eligibility: Inclusion Criteria:
  -  post elective coronary artery bypass surgery
  -  > 18 years old
  -  sign informed consent
  Exclusion Criteria:
  -  contraindications of resistance training (unstable angina, uncontrolled blood pressure (systolic > 160 diastolic > 100), acute heart failure, pulmonary diseases, arrhythmia malignant)
  -  musculoskeletal pain, visual analog scale >3
  -  post congenital heart disease surgery
  -  post elective coronary artery bypass surgery with malfunction valves (operated or not)

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a))

Summary: A study to assess the effects of proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibition on the arterial wall inflammation in patients with elevated lipoprotein(a).


Eligibility: Inclusion Criteria:
  -  Fasting lipoprotein(a) (Lp(a)) 50 mg/dL or more at screening 1
  -  Fasting Low-density lipoprotein-cholesterol (LDL-C) 100 mg/dL or more at screening 1
  -  Lipid lowering therapy including statin dose unchanged for at least 8 weeks prior to screening
  -  Target-to-background ratio (TBR) maximum higher than 1.6 (either right, left carotid or thoracic aorta) on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT).
  Exclusion Criteria:
  -  Currently receiving, or less than 4 weeks since receiving, treatment in another investigational device or drug study(ies), or participating in other investigational procedures
  -  Known diagnosis of diabetes mellitus or screening fasting serum glucose ≥ 126 mg/dL or hemoglobin A1C (HbA1C) ≥ 6.5%
  -  Subject with a history of homozygous familial hypercholesterolemia
  -  History of a Cardiovascular event
  -  Subject currently undergoing lipid apheresis
  -  Known contraindications or limitations to FDG-PET/ CT (scanner weight limit, devices that can cause image artifacts, or carotid/aortic stents/grafts
  -  Subject has had exposure to investigational drugs targeting Lp(a) within the last 12 months, prior to Screening
  -  Other Exclusion Criteria May Apply.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Chart Review of Repatha® in Subjects With Hyperlipidaemia

Summary: Review of clinical characteristics of patients who are prescribed Repatha® and how their treatment is managed.


Eligibility: Inclusion Criteria:
  Adults (>18 years) Provided informed consent Initiated on Repatha® at physician's discretion, after 1st August 2015 Received at least one dose of Repatha®
  Exclusion Criteria:
  Enrolled in an interventional study of PCSK9 inhibitor within 12 weeks prior to initiation of Repatha® Received commercially available PCSK9 inhibitor within 12 weeks prior to initiation of Repatha®

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Detection of Familial Hypercholesterolaemia in Cardiovascular Disease Registry

Summary: Familial hypercholesterolaemia (FH) is an autosomal dominant somatic mutation commonly located on the LDL-receptor, APOB, and PCKS9 gene. The estimated prevalence of homozygous FH is estimated at 1 in a million, whereas the prevalence of heterozygous FH ranges from 1/500-1/200 (0.2-0.5%) of the general population. The majority of individuals suffering from FH remain undiagnosed and without treatment. Using preexisting clinical guidelines, this study scored patients within national cardiovascular disease (CVD) registries for FH with the aim of evaluating prevalence of FH among individuals suffering from premature cardiac events within the UK.
  Following scoring of the registry, this study also examined the relationship between cholesterol and survival after a premature event in order to understand the possible ramifications of untreated FH on patient survival.

Detailed description: Familial Hypercholesterolaemia (FH) is a genetic disorder caused by a mutation in the low-density lipoprotein receptor (LDL-R) gene. Individuals suffering from FH experience elevated cholesterol levels that are outside of the accepted range of healthy cholesterol levels. When left untreated FH may cause complications in cardiovascular health and may cause premature cardiac events. Current screening methods for this disease do not successfully diagnose the majority of FH cases.
  This study applies three clinical diagnostic tools--Dutch Lipid Clinic Network Criteria (DLCN-Criteria), Make Early Diagnosis to Prevent Early Deaths (MEDPED) criteria, and the Simon Broome Register Criteria--within national registries in order to define possible, probable, and definite cases of FH. The national registries used for this study are the Myocardial Ischaemia National Audit Project (MINAP) and National Audit of Percutaneous Coronary Intervention (BCIS) audit.
  Following scoring of patients, a one-year and 30-day survival model were created in order to assess the effect of elevated cholesterol on survival, as suspected FH patients will have elevated cholesterol levels.
  Data within MINAP ranges from 2003-2013 and data from BCIS ranges from 2007-2014.
  Patient information within the audits was collected following admission to English and Welsh hospitals following a coronary event or percutaneous coronary intervention (PCI). Information related to survival and mortality was collected annually within each audit.
  Participants for this study were those experiencing a premature cardiovascular event or coronary intervention (men <55 and women<60).

Eligibility: Inclusion Criteria:
  -  Experienced a cardiac event and is therefore entered in CVD audit
  -  First registered event within audits
  Exclusion Criteria:
  -  Under age 18
  -  Previous diagnosis of FH

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: CYP4A11 and CYP4F2 Gene Variants as Makers of Cardiovascular Adverse Events of Non-steroidal Anti-inflammatory Drugs

Summary: Randomized, double-blinded, cross-over and placebo controlled clinical trial to evaluate the association between genetic polymorphism of CYP4F2 with cardiovascular adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs). Two groups were included according the CYP4F2 V433M genetic polymorphism (control - MM, N=7 vs. VV or VM variants, N=13). According the sample size planned, a mean difference of total body water delta between groups (control vs. polymorphic) of at least allow 10% could be observed.


Eligibility: Inclusion Criteria: Healthy volunteers 18-65 years-old -
  Exclusion Criteria: Use of drugs and without clinical history of adverse effects of NSAIDS
  -

Relevance to patient case: not relevant