Kornimate/medical-research-clean huggingface dataset:
adjusting antiretroviral therapy dosage using therapeutic drug monitoring

Conditions: Human Immunodeficiency Virus; HIV Infections

Summary: background low concentrations of protease inhibitors (pis) or nonnucleoside reverse transcriptase inhibitors (nnrtis) are associated with an increased risk of virological failure. likewise, excessive antiretroviral drug concentrations increase the risk of toxicity. therapeutic drug monitoring (tdm) may identify and correct excessively high or low pi and/or nnrti concentrations, and thus minimize toxicity and risk of treatment failure. treatment guidelines only recommend using tdm to help optimize arv therapy in selected patients, and there are no clear recommendations to guide the clinician who decides to adjust drug doses. prospective studies have demonstrated the relationship between efv plasma concentration and neuropsychiatric symptoms. moreover, efv is metabolized mainly by cytochrome p450 2b6 and its concentration was reported to be associated with the cyp2b6 516grt genetic polymorphism. for drugs such as efv or lpv/r, lower doses than the ones validated for standard clinical use have demonstrated efficacy in dose-ranging studies. the investigators will use a standardised algorithm to reduce doses in patients with plasma efv or lpv/r concentration above percentile 75. this algorithm is based on a bayesian approach from the pharmacology unit in lausanne. the investigators hypothesize that a dosage individualisation is feasible and safe. 2.2 study aims the investigators aim at testing a simplified algorithm for dose reduction in patients with documented virological efficacy, treated by a stable lpv/r or efv based regimen with elevated plasma concentration of these drugs. study design prospective open label study in which all eligible patients screened with a plasma drug concentration of either efv or lpv/r above percentile 75 will be included. after confirmation of the results at baseline, patients will be offered to decrease drug dosage by a third or a half according to a standardised algorithm. all patients will undergo hivrna, biochemistry and validated questionnaires after 3 and 6 months to assess the safety and the benefit of this strategy.


Eligibility criteria:
inclusion criteria: * stable regimen including either efv or lpv/r * hivrna below 40 copies since at least 3 months * antiretroviral drug concentration (efv, lpv/r) plasma concentration at screening above p75 * signed consent for the shcs genetics core project exclusion criteria: * concomitant medication:amiodarone, bepidril, flecainide, propafenone, quinidine,astemizole, terfenadine,dihydroergotamine, ergotamine,midazolam, triazolam,cisapride,pimozide,rifabutin * renal or hepatic impairment * pregnancy or wish to become pregnant within the next 6 months * both efv and lpv/r as part of the antiretroviral drug regimen

Keywords: hiv adjusting antiretroviral therapy dosage using therapeutic drug monitoring swiss hiv cohort study hiv geneva lopinavir efavirenz treatment experienced
a study to evaluate the pharmacokinetics and the safety after administration of br1018 and coadministration of br1018a and br1018b in healthy adult volunteers

Conditions: Essential Hypertension; Primary Hypercholesterolemia

Summary: the purpose of this clinical study is to evaluate the pharmacokinetics and the safety after administration of br1018 and coadministration of br1018a and br1018b in healthy volunteers


Eligibility criteria:
inclusion criteria: * those who have body mass index (bmi) of more than 18.0kg/m2 and less than 30.0kg/m2 at screening visit. * for men, those who weigh 50 kg or more * for women, those who weigh 45 kg or more * those who sign written consent spontaneously after listening to and understanding sufficient explanation of the purpose and contents of this clinical trial, characteristics of the investigational products, expected adverse events, etc. * those who agree to rule out the possibility of their and their spouses' or sexual partners' pregnancy by using methods of contraception accepted in clinical trial\*(except for hormone drugs) from the date of consent to 14 days after the last administration and disagree to provide their sperm or ovum. * methods of contraception accepted in clinical trial: combined use of intrauterine device, vasectomy, tubal ligation, and barrier methods (male condom, female condom, cervical cap, contraceptive diaphragm, sponge, etc.) or combined use of two or more barrier methods if spermicide is used. exclusion criteria: * those who have taken drugs that induce and inhibit metabolizing enzymes such as barbiturate within 30 days before the first administration date or have taken drugs concerned about affecting this clinical trial within 10 days before the first administration date. (however, participation is possible considering pharmacokinetics and pharmacodynamics such as interaction of investigational products, half-life of concomitant drugs, etc.) * those who have a medical history of gastrointestinal resection or gastrointestinal diseases that may affect the absorption of drugs. (except for simple appendectomy, hernia surgery) * those who have participated in other clinical trials(including bioequivalence tests) and administered their investigational products within 6 months before the first administration date. (however, the termination for participation in other clinical trials are based on the last administration date of their investigational products) * those who can't discontinue a diet (ex. raw grapefruit, grapefruit juice or food containing grapefruit, etc.) that may affect the absorption, distribution, metabolism, and excretion of the drug within 48 hours before the first administration date * in the case of a female subject, those suspected pregnancy or pregnant woman or lactating woman.
drug interactions with risk of qt-prolongation in a general hospital

Conditions: QT-prolongation

Summary: in this epidemiological point prevalence study, medication profiles of patients with haloperidol treatment will be checked for drug interactions with risk of qt-prolongation. additional clinical risk factors for developing qt-prolongation and safety measurements will be documented.

study design: epidemiological point prevalence study target population: patients with haloperidol treatment the following aspects will be investigated: * the medication profiles will be checked for drug interactions with risk of qt-prolongation. * clinical risk factors for developing qt-prolongation (gender, age, (history of) cardiovascular disease, comorbidity,...) and lab results will be collected. * safety measurements (e.g. ecg) will be documented.

Eligibility criteria:
inclusion criteria: * treatment with haloperidol (started in the hospital) exclusion criteria: * age \< 18 years

Keywords: qt-prolongation torsade de pointes haloperidol drug interactions
brass mesh bolus in rotational post-mastectomy radiation therapy

Conditions: Breast Cancer

Summary: the hypothesis is that the daily use of brass mesh bolus achieves a comparable dose to every-other-day use of superflab bolus (current standard of care) in chest wall post-mastectomy patients treated with rotational 6 mv photon delivery.

intervention: during a standard-of-care 15 fraction radiotherapy treatment, a brass mesh bolus will be used for a single fraction. small in-vivo dosimeters will be used for three treatment fractions to measure and compare skin doses for quantification purposes. comparator: superflab and no bolus applied as per the treating physician's practice, typically on alternate days. the intervention and comparator tools are to be utilized on each participant. primary outcome 1. to determine the skin dose under brass mesh bolus and compare it with the skin dose under superflab bolus (current standard of care). 2. to determine the number of fractions for which brass mesh bolus should be used to achieve an acceptable skin dose.

Eligibility criteria:
inclusion criteria: women undergoing rotational chest wall radiotherapy following mastectomy for breast cancer treatment who would utilize superflab bolus on some, but not all, days of radiotherapy treatment. exclusion criteria: patients who require daily bolus due to skin involvement or other high-risk features requiring a high skin dose will not be included.

Keywords: breast cancer radiation therapy brass mesh bolus skin dose
evaluate the effects of formoterol and beclomethasone dipropionate combination therapy on small airways function

Conditions: COPD; Emphysema; Small Airway Disease

Summary: inuvair® is a novel fixed combination product used in the treatment of asthma and under clinical development for the treatment of copd. thanks to the extrafine particle size, it is able to target the whole bronchial tree, including the small airways and hence, is expected to act in these airways and it may thus be beneficial in copd in that sense. in copd, its action on the small airways is not directly demonstrated thus far. by way of contrast, dear evidence is present that treatment with bronchodilators alone does not beneficially alter small airway function. the study hypothesis states that the effects of inhaled corticosteroids or ics/laba combinations on small airway is present and can be objectivated.


Eligibility criteria:
inclusion criteria: * clinical diagnosis copd according to last updated gold guidelines (post- bronchodilator fev/fvc below 0,70, fev1 \<80% predicted) * ex-smokers (ie 1 year from the last cigarette) with at least 10 pack years. * gold stage ii and iii (fev1 \> 30% predicted) * by preference naïve to inhaled corticosteroids; in those taking inhaled corticosteroids this medication will be stopped 1 month prior to enrollment in the study * patients must have proven small airways dysfunction on routine spirometry as reflected by a drop in fef25-75 and fef75 of at least 50%. moreover, patients must have proven small airways dysfunction on mbw as reflected by sacin \>0,120 that is considered abnormal. exclusion criteria: * current smoking * active copd exacerbation * gold stage i and iv
daily activities are sufficient to induce dynamic pulmonary hyperinflation and dyspnea in chronic obstructive pulmonary disease patients

Conditions: Dynamic Lung Hyperinflation; COPD Patients; Activities of Daily Livin.

Summary: introduction: chronic obstructive pulmonary disease is a condition characterized by airflow limitation usually progressive and associated with inflammatory response of lung noxious particles. during a physical activity chronic obstructive pulmonary disease patients may develop dynamic pulmonary hyperinflation, increased dyspnea perception and decreased activity performance. the investigators hypothesize that some specific activities of daily living induce dynamic pulmonary hyperinflation in copd patients. objective: to measure dynamic lung hyperinflation and its influence in dyspnea perception in moderate and severe chronic obstructive pulmonary disease patients after activities of daily living. methods: the investigators measured inspiratory capacity, dyspnea sensation, peripheral oxygen saturation, heart rate and respiratory rate in 19 chronic obstructive pulmonary disease (copd) patients. these measurements were taken at rest and after daily living activities (such as going up and down a set of stairs, going up and down a ramp and sweeping and mopping a room).


Eligibility criteria:
inclusion criteria: * copd patients diagnosed with moderate to very severe airway obstruction according to gold classification (9) * clinical stability with no clinical exacerbation during the previous 30 days prior to the beginning of the study and to sign an informed consent form exclusion criteria: * inability to perform the slow vital capacity maneuver * excessive perceived dyspnea during the test * arterial oxyhemoglobin saturation (spo2) lower than 80% during activities and/or need of oxygen supplementation

Keywords: copd activities of daily living pulmonary hyperinflation exercise
a study to evaluate safety and exploratory efficacy of ktp-001 in subjects with lumbar disc herniation

Conditions: Lumbar Disc Herniation

Summary: the purpose of this study is to evaluate the safety and exploratory efficacy of ktp-001 in subjects with lumbar disc herniation.

this study was a first-in-human, open-label, non-controlled single ascending dose study of ktp-001 in male and female subjects between the ages of 30 and 70 years with a single herniated lumbar disc. after obtaining informed consent, subjects were evaluated during a screening period of no more than 3 weeks (21 days). this study was conducted in 10 centers in the us. subjects that met all screening requirements and inclusion criteria and none of the exclusion criteria were enrolled into the study. overall, 24 subjects were enrolled and treated: 6 subjects in each cohort. cohort 1 received a 5 μg/disc dose of ktp-001 by intradiscal injection. following administration of study drug, subjects were confined to the study center for 24 hours to collect data for safety and efficacy measures and collect blood samples for safety, pk evaluation, exploratory pd and anti-ktp-001 antibody and then returned for further assessments at various intervals from weeks 1 through to month 24. after all subjects in cohort 1 had received study drug, safety measures were evaluated by a data and safety monitoring board (dsmb) to determine whether to escalate ktp-001 administration to the next dose level. if appropriate, cohort 2 subjects received 15 μg/disc of ktp-001, cohort 3 subjects received 50 μg/disc of ktp-001, and cohort 4 subjects received 150 μg/disc of ktp-001 by intradiscal injection. all safety, pk, and exploratory efficacy assessments were performed for the subjects in the subsequent cohorts as were performed for cohort 1.

Eligibility criteria:
inclusion criteria: * subject has had a single contained or noncontained (extruded) lumbar disc herniation (l3-l4, l4-l5 or l5-s1) diagnosed by clinical symptoms and/or physical findings and confirmed by mri. * subject has leg pain with a documented positive straight leg raise (slr) test or femoral stretch test (fst). * subject has experiences herniated disc symptoms for at least 6 weeks prior to the study without relief with pain medications and other therapies. * subject has a bmi of 18 to 35 kg/m2 exclusion criteria: * subject has a sequestered lumbar disc herniation or intrathecal herniation confirmed by mri * subject has two or more symptomatic lumbar disc herniations * previous intradiscal therapeutic intervention or has had any lumbar surgery * presence of lumbar spine disease and/or deformity other than a lumbar disc herniation * active smoker or is unable to abstain from tobacco use for 2 weeks prior to study injection * subject has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
glucocorticoid therapy for acute respiratory distress syndrome

Conditions: Acute Respiratory Distress Syndrome

Summary: acute respiratory distress syndrome (ards) is a clinical syndrome of inflammatory lung injury characterized by increased pulmonary vascular permeability, loss of aerated lung tissue, severe hypoxemia and impaired compliance. despite the advance in the critical care technology, the mortality of ards remains high in the last decades. glucocorticoids have profound anti-inflammatory actions through the pleiotropic effects of the glucocorticoid receptor, which are considering a promising pharmacological therapy to mitigate the inflammatory lung injury and subsequent fibrosis in ards. previous clinical trials have repeatedly tested the efficacy of glucocorticoid therapy in ards; however, the data about hard outcomes, such as mortality, are inconsistent between these studies. investigators designed a 3x2 factorial trial of glucocorticoid therapy in ards to test the effects of glucocorticoid dosages (dose 0, dose 0.5 mg/kg, and dose 1 mg/kg of methylprednisolone equivalence) and durations (prolonged and short duration) on the treatment efficacy. in addition, investigators will measure the change of inflammatory biomarkers for post-hoc analysis to explore whether biomarkers could be used to guide patient selection and steroid tapering.


Eligibility criteria:
inclusion criteria: 1. moderate to severe ards with a p/f ratio \< 200 mmhg 2. on invasive mechanical ventilation 3. the onset of ards \< 72 hours exclusion criteria: 1. age \<20 years 2. receiving systemic glucocorticoid therapy 3. uncontrolled gastrointestinal bleeding 4. terminal cancer 5. post-operation or with large wound 6. considered by the primary care doctor to be either definitely indicated or definitely contraindicated for glucocorticoid therapy 7. anticipating to receive chemotherapy and immunotherapy in 3 months 8. uncontrolled fungal infection 9. post solid organ or bone marrow transplant 10. severe influenza without anti-viral therapy

Keywords: acute respiratory distress syndrome corticosteroid glucocorticoid
cosmic-hf - chronic oral study of myosin activation to increase contractility in heart failure

Conditions: Modified Release Oral Formulation; Left Ventricular Systolic Dysfunction; Chronic Heart Failure; History of Chronic Heart Failure; Left Ventricular Ejection Fraction; Pharmacokinetics; Echocardiogram

Summary: the primary objectives of this study are (i) to select an oral modified release (mr) formulation and dose of omecamtiv mecarbil for chronic twice daily (bid) dosing in adults with heart failure and left ventricular systolic dysfunction and (ii) to characterize its pharmacokinetics (pk) over 20 weeks of treatment.

omecamtiv mecarbil (amg 423, ck-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. this is a randomized, placebo-controlled, multicenter, phase 2 study, consisting of a dose escalation phase to select 1 of 3 omecamtiv mecarbil oral formulations in 2 dose escalation cohorts, followed by an expansion phase to evaluate 20 weeks of administration of the selected omecamtiv mecarbil formulation at 2 target dose levels, compared with placebo. this study was conducted by amgen as the ind holder, with cytokinetics as a collaborator. due to the termination of the collaboration agreement between amgen and cytokinetics in may 2021 and subsequent transfer of the omecamtiv mecarbil ind from amgen to cytokinetics, cytokinetics is now listed as the sponsor.

Eligibility criteria:
inclusion criteria: * history of chronic heart failure (hf), defined as requiring treatment for hf for a minimum of 4 weeks prior to screening * treated with stable, optimal pharmacological therapy for ≥ 4 weeks * history of left ventricular ejection fraction (lvef) ≤ 40% * elevated n-terminal prohormone b-type natriuretic peptide (nt-probnp) exclusion criteria: * severe uncorrected valvular heart disease * hospitalization within 30 days prior to enrollment * hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease * acute myocardial infarction, unstable angina or persistent angina at rest within 30 days prior to randomization * systolic blood pressure \> 160 mmhg or \ 90 mmhg * total bilirubin ≥ 2 x upper limit of normal (uln); aspartate aminotransferase (ast) or alanine aminotransferase (alt) ≥ 3 x uln * estimated glomerular filtration rate (egfr) \< 30 ml/min/1.73m\^2

Keywords: pharmacokinetics omecamtiv mecarbil amg 423 double-blind randomized placebo-controlled oral forumlation ck-1827452 cardiac myosin activator
clinical characterization of symptomatic populations

Conditions: Ametropia

Summary: this is an unmasked, non-randomized, single arm, stratified, dispensing investigation of symptomatic and asymptomatic subject populations. subjects will be assigned to a single study lens type to be worn bilaterally for approximately 4 weeks followed by no contact lens wear for 1 week.


Eligibility criteria:
inclusion criteria: * potential subjects must satisfy all of the following criteria to be enrolled in the study: 1. the subject must read, understand, and sign the statement of informed consent and receive a fully executed copy of the form. 2. appear able and willing to adhere to the instructions set forth in this clinical protocol. 3. between 18 and 55 (inclusive) years of age at the time of screening. 4. be a current soft contact lens wearer in both eyes with a minimum of 3 days/week wear time over the last 1 month by self-report. 5. have a baseline cldeq-8 score of either: 1. 7 or lower 2. 15 or greater 6. subjects must possess a functional / usable pair of spectacles and bring them to the visit (only if applicable - to the investigators discretion). 7. subjects must pass a pre-screening questionnaire. 8. subjects must be willing to discontinue all contact lens wear for approximately 1 week/ 9. subjects must present to visit 1 with their habitual lenses on eye for at least 6 hours. exclusion criteria: * potential subjects who meet any of the following criteria will be excluded from participating in the study: 1. currently pregnant or lactating, by self-report. 2. any ocular or systemic allergies, disease or use of medication which may interfere with contact lens wear (at the discretion of the investigator). 3. any active ocular abnormalities/conditions that may interfere with contact lens wear (at the discretion of the investigator). 4. any infectious diseases (e.g. hepatitis, tuberculosis) or a contagious immunosuppressive disease (e.g. hiv), by self-report. 5. any corneal distortion resulting from previous hard or rigid gas permeable contact lens wear. 6. habitual contact lens wear modality as extended wear (≥1 night per month of extended wear). 7. habitual contact lens is rigid gas permeable, toric, monovision or multi-focal 8. any previous, or planned (during the course of the study) ocular surgery (e.g., radial keratotomy, prk, lasik, etc.) 9. participation in any contact lens or lens care product clinical trial within 2 weeks prior to study enrollment. 10. employee or employee's immediate family member of clinical site (e.g., investigator, coordinator, technician). 11. current habitual use of restasis, xiidra, ocular steroids, or any medication (rx or otc) that may interfere with contact lens wear (at the discretion of the investigator).