cyrilzakka/clinical-trials huggingface dataset:
A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study were to be guided by a Bayesian Logistic Regression Model (BLRM).

Once MTD/RP2D had been determined, patients were to be enrolled in two Phase II arms. Patients with PIK3CA mutated or amplified hormone receptor positive breast carcinoma were to be enrolled in Arm 1; patients with PIK3CA mutated or amplified ovarian carcinoma were to be enrolled in Arm 2. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.

Eligibility Criteria:
Key inclusion criteria:

* Written informed consent.
* Patients aged ≥ 18 years (male or female).
* Patients with the following histologically/cytologically-confirmed advanced solid tumors with documented somatic PIK3CA mutations or amplifications in tumor tissue:
* Hormone receptor positive breast carcinoma
* Ovarian carcinoma
* Other tumors upon agreement with sponsor
* Adequate organ function
* Negative serum pregnancy test

Key exclusion criteria:

* Patients with known history of severe infusion reactions to monoclonal antibodies.
* Patients with primary CNS tumor or CNS tumor involvement.
* History of thromboembolic event requiring full-dose anti-coagulation therapy any time prior to enrollment.
* Clinically significant cardiac disease.
* History of another malignancy within last 2 years.
* Pregnant or nursing (lactating) women.
The Effect of Weight on Vitamin D Dose Response

Vitamin D3 is a vitamin that is an essential component of biological regulating systems in humans. Sun exposure is the predominant source of vitamin D3. Previous research has shown that vitamin D3 deficiency is common worldwide. It is especially common in northern countries with long winters due to inadequate sun exposure during winter. In the US, an estimated 36% to 57% of healthy middle-aged to elderly adults have vitamin D3 deficiency. Current research indicates that obesity is associated with a low vitamin D3 level.

Obesity is a known risk factor for vitamin D deficiency. Adequate levels of vitamin D are important, not only for bone health, but appear to be important for prevention of certain autoimmune diseases, infections and cancers. Current FDA recommendations for vitamin D intake do not differentiate between lean and obese people. There are no published studies indicating if the 25(OH)D response to a given daily dose of vitamin D is any less in an obese person than a normal weight person. The purpose of this study is to characterize the quantitative relationship between steady state cholecalciferol input and the resulting serum 25 (OH)D concentration in obese subjects. Data obtained in this study will be compared to published normative data for non-obese subjects. Recommendations will be provided for optimal treatment of vitamin D deficiency in obese men and women.

Eligibility Criteria:
Inclusion Criteria:

* men aged 19 to 60 with BMI \> 30.0.
* They will have low (\<1,000 IU) usual intake of vitamin D (from milk, multivitamins, supplements, and fortified foods)

Exclusion Criteria:

* Subjects will not have history of hepatic or renal disease.
* Subjects will not be taking medications known to affect vitamin D metabolism such as anti-seizure medications and/or corticosteroids.
* They will not be on hydrochlorothiazide medications which could cause hypercalcemia.
* They will not have diseases causing malabsorption of vitamin D, such as celiac sprue or small bowel surgeries.
* Pregnancy is also an exclusion criterion.
Use of Sorafenib and/or Regorafenib in Liver Cancer (Hepatocellular Carcinoma) Subsequent to Another Systemic First-line Treatment

Researchers already did trials that showed Sorafenib and Regorafenib worked for patients with hepatocellular carcinoma (most common liver tumor type).

In this trial, they want to learn more about the same patient group in which Sorafenib or Regorafenib is given after other drugs. Patients participating in this study will be observed until 12 months after the last patient has been enrolled to collect data on how safe the drugs are and how well they are working when used as second line or beyond treatment.


Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of hepatocellular cancer in stage BCLC-B or BCLC-C
* Decision to initiate treatment with Nexavar (sorafenib) and/or Stivarga (regorafenib) as 2nd-line or beyond treatment was made as per investigator's routine treatment practice. Stivarga (regorafenib) must be used according to its indication, i.e. after prior progression under Nexavar (sorafenib) treatment.

Exclusion Criteria:

* Patients concurrently participating in an investigational program for the treatment of HCC with interventions outside of routine clinical practice.
* Stivarga (regorafenib) treatment without prior therapy with Nexavar (sorafenib). NOTE: Nexavar (sorafenib) treatment could have been given as treatment for HCC outside of this non-interventional study. In this case Stivarga (regorafenib) would NOT constitute the second-line therapy after direct pretreatment with Nexavar (sorafenib) but e.g. 3rd-line treatment directly after a different drug.
* Contra-indications according to the local marketing authorization.
Creatine Monohydrate Use for Preventing Altitude Induced Depression

This study involves the use of an investigational drug called Creatine Monohydrate. This means that the drug has not yet been approved by the Food \& Drug Administration (FDA) for treatment of altitude-induced depression. However, the FDA has not objected to its use to study its safety and effectiveness for preventing altitude-induced depression. This study will help find out what effects, good and/or bad, Creatine Monohydrate has on treating symptoms for altitude-induced depression. Creatine Monohydrate is believed to have an effect on improving symptoms of depression. The safety of Creatine Monohydrate in humans has been tested in prior research studies; however, some side effects may not yet be known.

Subjects will be in this research study if they moved to Creech AFB from an elevation of less than 2.000 feet within the last month. The purpose of this study is to see if creatine monohydrate is effective in preventing altitude-induced depression. This study will enroll approximately 75 subjects.

This study involves the use of an investigational drug called Creatine Monohydrate. This means that the drug has not yet been approved by the Food \& Drug Administration (FDA) for treatment of altitude-induced depression. However, the FDA has not objected to its use to study its safety and effectiveness for preventing altitude-induced depression. This study will help find out what effects, good and/or bad, Creatine Monohydrate has on treating symptoms for altitude-induced depression. Creatine Monohydrate is believed to have an effect on improving symptoms of depression. The safety of Creatine Monohydrate in humans has been tested in prior research studies; however, some side effects may not yet be known.

Creatine Monohydrate is a dietary supplement that is believed to aid in the building of muscle mass.

The placebo being used in this study is Maltodextrin (a sugar). Maltodextrin is an FDA approved food additive made from a highly processed starch product typically made from corn.

Eligibility Criteria:
PATIENTS MUST BE ABLE TO GET CARE AT NELLIS AIR FORCE BASE (A MILITARY INSTALLATION) IN ORDER TO PARTICIPATE IN THIS STUDY

Inclusion Criteria:

* Male and Female Active Duty members and DoD beneficiaries ages 18-65
* Moved to CREECH AFB from an altitude of less than 2,000 feet within the last month

Exclusion Criteria:

* Preexisting depression as noted in a review of their medical record or on their PHQ9 (score of 10 or greater)
* Preexisting anxiety as noted in a review of their medical record or on their GAD 7 (score of 10 or greater)
* Clinical or laboratory evidence of liver disease.
* Serum creatinine \>1.5
* Existing kidney disease
* Existing Type I or Type II Diabetes Mellitus
* Taking creatine as a dietary supplement
* Moved to CREECH AFB from an altitude of greater than 2000 feet
* Pregnant, breast feeding, or trying to become pregnant
Feasibility of Sending a Direct Send HPV Self-sampling Kit to Long-term Screening Non-attenders

All women in one Swedish county who had not participated in the organized screening program for at least 10 years were sent an HPV self-sampling kit. Women who were positive for HPV were referred to a gynecological examination including colposcopy and further testing according to national guidelines.

In this cohort study nested in the organized cervical screening program, all women who had not participated in the organized screening program for at least 10 years in one Swedish county were eligible. Women were identified through the screening hub register that administrates for all invitations, referrals, and monitoring of the cervical screening program. The county screening hub invites approximately 30 000 women yearly to routine screening. Those who had opted out of the screening program, undergone hysterectomy, or changed their personal identification number (PNR) were excluded. HPV self-sampling kits with instructions and invitation letters were sent from the Department of Laboratory Medicine, Falun Hospital, in batches over 4 weeks. Lists of invitees were checked against changes in the screening hub register for individuals who moved, emigrated, died, or had taken a routine screening sample before sending a kit. Samples were received and HPV-analysis was performed.

If the self-sample HPV test was negative, the woman was returned to the screening program according to routine practice. HPV-positive women were referred without triage for further investigation to a gynecologist responsible for the clinical follow-up of high-risk women. The gynecological examination included colposcopy as well as biopsies and a liquid based cytology (LBC) sample (analyzed for cytology and HPV), which are routine examinations in clinical practice according to national and international guidelines. Colposcopies were performed within 3 months of a positive self-sample. If the colposcopic examination or the cytological/histopathological results indicated high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer, women underwent treatment by conization and/or hysterectomy according to national guidelines The Cobas® PCR Female Swab Sample Packet was used for self-sampling, as previous studies had determined that the sensitivity for HPV was high and comparable with cervical samples used in the organized screening program. The HPV analysis was performed at the Department of Laboratory Medicine, Falun Hospital using the Cobas 4800 HPV Test (Roche Molecular Systems, South Branchburg, New Jersey, USA).

Eligibility Criteria:
Inclusion Criteria:

- Women who had not participated in the organized screening program for at least 10 years

Exclusion Criteria:

- Women who were hystrectomized, moved, died
Effects of Complementary Feeding on Infant Growth and Gut Health

This study plans to learn more about how consuming different foods during the time of early complementary feeding (\~5 to 12 months) affects growth and the development of bacteria living inside your baby's gut. The results from this study will potentially help to support future recommendations and dietary guidance for infant feeding practices.

The three primary aims include:

Aim 1. Identify the impact of dietary patterns with different protein-rich foods on infant growth.

Aim 2. Identify the impact of dietary patterns with different protein-rich foods on infant gut microbiota development.

Aim 3. Identify gut microbial taxa and genes that affect infant growth.

Some details are intentionally left to out to preserve the scientific integrity of the study, and they will be included in the record after the study is completed.

Eligibility Criteria:
Inclusion Criteria:

* Full term;
* Generally healthy without conditions that would affect protein metabolism or growth
* No previous complementary food exposure
* Vaginal delivery
* No prior exposure of antibiotics during delivery or after birth
* Able to consume study foods
* Single birth.

Exclusion Criteria:

* Pre-term infants.
* Having conditions that would affect normal growth
* Had complementary foods prior to the start of the study
* Not willing to consume the complementary foods provided
* Antibiotics exposure during delivery or from birth to 5 months of life
* Multiple births
Scintigraphic Evaluation of Contractile and Coronary Reserve in Patients With Ischemic Cardiomyopathy

According to single-photon emission computed tomography, the left ventricular contractile and coronary flow reserve (CFR) will be assessed in patients with ischemic cardiomyopathy. According to these data, the criteria for predicting the effectiveness of complex surgical treatment of this pathology will be evaluated.

Before surgical intervention, all patients pass routine clinical analyzes undergo coronary angiography and 2D echocardiography. Some of patients in the ICM-1 and ICM-2 groups undergo stress echocardiography with dobutamine.

Coronary arteriography is performed using the Axiom Artis (Siemens; Erlangen, Germany) and transthoracic two-dimensional Doppler echocardiography (TTE) with the Acuson Sequoia 512 (Siemens; Erlangen, Germany)).

Besides, all of the ICM-1 and ICM-2 groups patients undergo myocardial perfusion imaging. Standard two-day stress-rest imaging protocol is used. Adenosine at a dosage of 140 mcg/kg/min (for 4 min) is used as a pharmaceutical stress agent.

ICM-1 group and Control group for GBPS undergo gated blood pool SPECT (GBPS) at rest and during increasing doses of dobutamine (5/10/15 μg/kg/min) (n = 60) ICM-2 group and Control group for CFR undergo dynamic SPECT (n = 40). This investigation is combined with routine myocardial perfusion imaging so patients are not exposed to extra stress.

Than ICM patients undergo surgical treatment of ICM in different volume. All of them receive coronary bypass grafting (CABG); some patients undergo the left ventricular reconstruction and intervention on the mitral valve.

In the early postoperative period (7-14 days), the ICM-1 group undergo rest GBPS and ICM-2 group undergo dynamic SPECT by two-day protocol. All patients undergo TTE too.

After at least 12 month, all patients undergo TTE to assess the presence of left ventricular (LV) remodeling.

Eligibility Criteria:
Inclusion Criteria:

А) For ICM group:

1. History of myocardial infarction (MI) or revascularization (CABG or PCI);
2. \> 75% stenosis of left main or proximal LAD and/ or stenosis of \> 75% of ≥2 epicardial vessels (based on coronary angiography (CA) data);
3. LV EF \<40% and increase in LV volumes according to echocardiography (ECHO)

B) For GBPS Control group

1. Absence of obstructive coronary artery lesion;
2. Absence of history of MI and revascularization.

C) For CFR Control group

1. Presence of obstructive coronary artery lesion;
2. Indications for coronary artery bypass grafting;

Exclusion Criteria (for all groups):

1. Presence of contraindications to the stress test with inotropic stimulation;
2. Inflammatory myocardial diseases;
3. The presence of severe hematological, neurological disorders, other psychosomatic conditions that impede research;
4. Life expectancy of less than 6 months (acute renal and hepatic failure, mental illness, malignant neoplasms of the final stages, unsuitable correction of brain injury).
Health Information Technology in Heart Failure Care

The objective of this proposal is to develop, implement, and test the effectiveness of a computerized clinical decision support system for hospitalized patients with heart failure.

Aim 1: Develop an electronic health record (EHR) based search method that uses both structured data and natural language processing of unstructured text to identify hospitalized patients with heart failure while they are still in the hospital.

Aim 2: Develop and test the usability of an electronic health record (EHR) based clinical decision support system (CDSS) to support delivery of evidence-based care to hospitalized heart failure patients using human computer interaction methods.

Aim 3: Assess the effect of an electronic health record (EHR) based clinical decision support system (CDSS) on processes of care for heart failure patients who are hospitalized for other causes. As part of the evaluation, we will test two implementation strategies, one of which will introduce the CDSS as an interruptive alert to providers, the second of which will introduce the CDSS as part of a provider checklist that exists on the side of the screen for each patient.


Eligibility Criteria:
Inclusion Criteria:

* Patients hospitalized 2 years prior and 18 months after the time of implementation of the Computerized clinical decision support systems (CDSS) in the (Electronic Health Record (EHR).

Exclusion Criteria:

* Patients on the obstetrical service, who died during hospitalization, or on hospice care.
Impact of Monoclonal Antibody Treatment on Post-Acute COVID-19 Syndrome

Use the Intermountain real-world MAb-treatment registry and control group to prospectively evaluate PACS symptoms at least 60 days after initial COVID-19 diagnosis.

It is now recognized that many patients who develop symptomatic COVID-19 infection continue to suffer from a variety of symptoms that persist well after the acute syndrome. This has been called post-acute COVID-19 (PACS), or "long COVID" syndrome. In a meta-analysis of studies of hospitalized patients, 70% of patients reported PACS symptoms 60 days after diagnosis. Patients with non-severe COVID-19 appear to have lower rates of PACS symptoms, although a recent study suggested that at 4 months follow-up, 28% of patients still reported at least one symptom. PACS is associated with significant morbidity, decreased quality of life, mental and behavioral health impact and healthcare cost. Neither the pathophysiology nor risk factors for PACS are well-understood and further research is needed to characterize this syndrome. Some studies have suggested that age, female gender, obesity, comorbid burden, symptoms at diagnosis and hospitalization during acute COVID-19 increase risk for PACS. Because of the significant overall impact of PACS, there is significant interest in identifying therapies to prevent this condition. Early neutralizing therapy with anti-SARS-CoV-2 monoclonal antibodies (MAbs) addresses the initial phase of disease and has now been shown to be effective at decreasing viral load and preventing progression to severe disease, hospitalization and death.

Understanding how MAb therapy may impact PACS symptoms is important to determining usage and value of these products and an important contribution to our understanding of how to prevent PACS.

Study Design: Prospective electronic survey using matched case-control design

Objective: Use the Intermountain real-world MAb-treatment registry and control group to prospectively evaluate PACS symptoms at least 60 days after initial COVID-19 diagnosis. Aim 1: Determine whether ambulatory patients who received monoclonal antibody infusion for early symptomatic COVID-19 have fewer persistent symptoms of post-acute COVID-19 ("long COVID") syndrome at least 60 days after initial diagnosis.

Hypothesis: MAb therapy is associated with significantly less post-acute COVID-19 (PACS) symptoms at 120 days post diagnosis Aim 2: Explore predictors associated with PACS symptoms in high risk patients Hypothesis: Hospitalization, age, obesity, number of comorbidities and symptoms at diagnosis predict PACS

Eligibility Criteria:
Inclusion Criteria:

* Age ≥18
* Positive antigen or polymerase chain reaction test for SARS-CoV-2
* Symptomatic COVID-19
* Between day 60 and day 90 from date of positive test
* Not hospitalized or hypoxemic by day 7 of symptoms (Aim 1 only)

Exclusion Criteria:

* Unwilling to participate
* Not able to understand the English language survey questions
* Prisoners
* Inadequate cognitive capacity to provide consent and complete the survey
Antithrombin Supplementation in ECMO

Bleeding is the most feared complication during extracorporeal membrane oxygenation (ECMO) and is associated with high dosing of heparin. There is no consensus on antithrombin (AT) supplementation during ECMO. However, AT is needed by heparin to properly anticoagulate. We hypothesize that maintaining normal antithrombin levels during ECMO is associated with a less heparin dosing and more adequate level of anticoagulation.

Extracorporeal membrane oxygenation (ECMO) is a life support for patients with severe acute respiratory failure when conventional treatments failed but it is accompanied by a significant risk of bleeding. Heparin is required during ECMO to avoid circuit thrombosis and its anticoagulant effect is strictly dependent on antithrombin (AT). AT also plays a central role in mediating inflammation. Acquired AT deficiency is common in patients on ECMO, arguably due to long term anticoagulation in addition to sepsis itself. Guidelines suggest to supplement AT in ECMO only when its deficiency coexists with heparin resistance. Few studies evaluated the effect of AT supplementation during ECMO without a consensus on the appropriate level to be maintained. AT supplementation increase anti-Factor Xa (anti-Xa) levels without increasing heparin dosage. This may have a clinical impact because risk of bleeding during ECMO is associated with higher heparin dosage.

We hypothesize that maintaining normal antithrombin activity levels (80%-120%) during ECMO is associated with: I. less heparin dosage, II. a more adequate level of anticoagulation, III. less hemostasis related complications, and IV. a lower level of inflammation.

Adult patients on veno-venous ECMO for respiratory failure will be randomized to maintain AT between 80% and 100% (study group) or no supplementation unless heparin resistance occurs (control group). Sample size of at least 20 patients per group (n=40) is calculated upon the primary outcome measure of reduction of heparin use in the study group compared to the control group. AT and anti-Xa will be measured before ECMO and daily while on ECMO. Anticoagulation will be guaranteed with unfractionated heparin infusion with a target aPTT 1.5-2X normal. Study will end at ECMO removal.

Consistent literature suggests that current ECMO anticoagulation strategies are suboptimal probably due to improper antithrombin supplementation. A normal antithrombin level could guarantee an adequate anticoagulation regimen.

Eligibility Criteria:
Inclusion Criteria:

* patients requiring veno-venous ECMO for severe respiratory failure.

Exclusion Criteria:

* patients with pre-existent heparin-induced thrombocytopenia