Kornimate/medical-research-clean huggingface dataset:
study of a tankyrase inhibitor rk-582 for patients with unresectable metastatic colorectal cancer

Conditions: Unresectable Colorectal Neoplasm Metastasis

Summary: tankyrase, the fifth and sixth members of the poly(adp-ribose) polymerase (parp) family (parp-5a/b), is responsible for poly(adp-ribosyl)ation (parylation), and was originally identified as a factor that promotes the function of telomerase, an enzyme that elongates telomeres. subsequently, it was reported that tankyrase enhances wnt/beta-catenin signaling by parylation and subsequent degradation of axin, a negative regulator of wnt/beta-catenin signaling, suggesting that tankyrase inhibitors may be a new treatment for colorectal cancer. rk-582 was discovered through lead optimization from a tankyrase inhibitor that suppresses the growth of human colorectal cancer cells. it was confirmed that rk-582 selectively inhibited tankyrase among the parp family enzymes, suppressed the growth of wnt/beta-catenin signal-dependent human colorectal cancer cells at both the levels of cultured cells and xenograft tumors in immunodeficient mice, and accumulated axin to decrease beta-catenin and downregulate the target gene expression as pharmacodynamic biomarkers. based on these findings, rk-582 is thought to have potential as a new treatment for colorectal cancer patients. at present, however, the efficacy and safety of rk-582 in humans have not been confirmed. thus, this clinical trial is conducted with the aim of investigating the tolerability and safety of rk-582 for patients with unresectable advanced or recurrent colorectal cancer as a first-in-human trial, in which rk-582 is administered to humans for the first time.


Eligibility criteria:
inclusion criteria: * patients with histologically or cytologically diagnosed colorectal cancer * patients who are refractory or intolerant to standard treatment for unresectable advanced or recurrent colorectal cancer * patients with measurable disease according to recist guideline ver 1.1 * patients who are able to take capsules orally exclusion criteria: * patients with clinically relevant gastrointestinal, hepatic, musculoskeletal, respiratory, cerebral/cardiovascular, hematologic, oncologic, endocrine, immunologic, psychiatric, neurologic, or genitourinary diseases, or patients with conditions that are judged to threaten the safety of the participant or to affect the outcome of this clinical trial by the investigators * patients with medical history of interstitial lung disease * patients with chronic nausea, vomiting or diarrhea that may interfere with oral administration of the investigational drug * patients with pulmonary embolism or central deep vein thrombosis. * patients receiving treatment with strong cyp3a4 inhibitors or inducers. * patients diagnosed and treated for osteoporosis or patients with a bone mineral density of less than t-score -2.5 at the time of screening * patients with obvious bone metastases in the long bones, vertebrae, or other parts of the leg where gravity is applied

Keywords: colorectal neoplasm colorectal cancer tankyrase inhibitor
physiology as guidance to evaluate the direct impact of coronary lesion treatment: the predict study

Conditions: Coronary Artery Disease; Stable Angina; Unstable Angina; Ischemic Heart Disease; Chest Pain

Summary: the purpose of this study is to assess whether the use of physiology parameters as guidance post-percutaneous coronary interventions (pci) is associated with less risks of target vessel failure (tvf) and angina-related events than standard angiographic guidance.

fractional flow reserve (ffr) measurement involves determining the ratio between the maximum achievable blood flow in a diseased coronary artery and the theoretical maximal flow in a normal coronary artery. an ffr of 1.0 is widely accepted as normal. an ffr value less than or equal to 0.80 is generally considered to be associated with myocardial ischemia. ffr is easily measured during routine coronary angiography by using a pressure wire to calculate the ratio between coronary pressure distal to a coronary artery stenosis and aortic pressure under conditions of maximum myocardial hyperemia. this ratio represents the potential decrease in coronary flow distal o the coronary stenosis. recently, other physiology ratios called non-hyperemic ratios (nhpr) have been developed. both types of physiology measures (ffr and nhpr) have been increasingly used in cardiac catheterization laboratories as a diagnostic tool. they provide a quantitative assessment of the functional severity of a coronary artery stenosis identified during coronary angiography and cardiac catheterization. however, they are underutilized as tools for the assessment of success of coronary interventions. the predict study is a pilot study which aims to prospectively determine whether post-pci physiology guidance is associated with better clinical outcomes than standard angiographic guidance.

Eligibility criteria:
inclusion criteria: * any patient referred for diagnostic coronary angiography and / or possible pci in native coronary vessels. * successful (\< 30% diameter stenosis and normal timi 3 flow post-stenting) and uncomplicated pci * all treated lesions stented with drug-eluting stents (except side-branches of bifurcations) exclusion criteria: * lesion in saphenous vein or arterial grafts * allergy to aspirin, thienopyridines or ticagrelor precluding treatment for 30 days * sub-optimal pci result ( \>30% residual diameter stenosis and/or \<timi3 flow) or peri-procedural complications * acute st-elevation mi (culprit lesion)

Keywords: coronary artery disease fractional flow reserve post-pci ffr angiography angioplasty
effect of rotatory upper cervical manipulation on reflex cervical vertigo

Conditions: Vertigo

Summary: cervical reflex vertigo is a non-common cause of vertigo, caused by decreased afferent input from the upper three cervical segments to vestibular nuclei.


Eligibility criteria:
inclusion criteria: * cervical pain * vertigo exclusion criteria: * severe osteoporosis * blood circulation problem
evaluation of a novel axillary lymph node ink localization technique: a feasibility study

Conditions: Breast Cancer; Axillary Lymphadenitis

Summary: patients with breast cancer and metastatic axillary lymphadenopathy routinely undergo neo-adjuvant chemotherapy. for these patients, biopsy clip markers are inserted into the biopsy proven metastatic lymph node pre-treatment, as they may reach complete clinical response post-therapy. limited axillary surgery, as opposed to a full axillary dissection, may then be indicated. it is still necessary to surgically excise the biopsy proven metastatic lymph node to accurately assess the pathologic response to therapy, and subsequently tailor post-surgical therapies appropriately. as such, these lymph nodes require pre-operative localization which, at the ottawa hospital, currently requires radioactive seed insertion under sonographic guidance, typically performed within 5 days of surgery. the procedure is often challenging, as both normal appearing lymph nodes and 3 mm biopsy clip markers are difficult and in some cases impossible, to visualize on ultrasound. at the time of surgery, the excised lymph node is radiographed, to ensure the radioactive seed and biopsy clip marker are both successfully excised. localization with ink has the potential to replace both the biopsy clip markers and radioactive seeds as the surgeons are able to directly visualize the ink intra-operatively and excise the inked lymph node. a preliminary study out of stanford on 28 patients who underwent localization of axillary lymph nodes with ink injected 1-211 days pre-operatively, in the pre neo-adjuvant and post neo-adjuvant settings, showed that lymph nodes injected with ink are visible intra-operatively months after surgery, suggesting that this is a feasible localization technique (1).


Eligibility criteria:
inclusion criteria: * english or french speaking female patients, with a personal history of current pathologically proven breast cancer, over the age of 18 years \[patients \<18 would be considered a rare occurrence\] * patients who will be undergoing neoadjuvant chemotherapy * patients who will be undergoing axillary lymph node radioactive seed localization * patients who will be undergoing axillary surgery exclusion criteria: * allergic reaction to black eye ink or any of its components * pregnancy * confirmed metastatic disease
study to assess the efficacy and safety of simtuzumab (gs-6624) in adults with idiopathic pulmonary fibrosis (ipf)

Conditions: Idiopathic Pulmonary Fibrosis

Summary: the primary objectives of this study are to determine the effect of simtuzumab (gs-6624) on progression-free survival (pfs) as determined by either a categorical decline in forced vital capacity (fvc) or all-cause mortality, in all participants enrolled or in a subset of participants who are classified as lysyl oxidase-like-2 (loxl2) high based on a prespecified level in serum at baseline.


Eligibility criteria:
key inclusion criteria: * male or female subjects from 45 to 85 years of age * definite ipf within 3 years prior to screening * be able to walk at least 50 meters key exclusion criteria: * significant diseases other than ipf * obstructive lung disease * aortic aneurysm greater than or equal to 3.5 cm in diameter * treatment with immunosuppressive, cytotoxic, or antifibrotic drugs \< 28 days prior to randomization are not permitted. * n-acetylcysteine is permitted provided the individual has been on a stable dose for \> 4 weeks prior to screening * concomitant use of pirfenidone or nintedanib must be in accordance with the approved prescribing instructions in the country where the site is located * individuals actively listed for lung transplant are excluded. however individuals at transplant centers with long waiting times (greater than 1 year) may be permitted to enter the study after discussion with medical monitor. note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: idiopathic pulmonary fibrosis ipf
quality of life of elderly patients and burnout among their care givers

Conditions: Elderly Cardiac Patients With Multimorbidity and Burnout Among Their Caregivers

Summary: older people with multimorbidity are frequent users of health care services, and there is a relationship between the number of chronic conditions and health care costs. in addition, multimorbidity increases the risk of mortality and functional decline, and this negatively impacts health-related quality of life . furthermore, research tends to focus on individual organ systems, often ignoring the complexity of care for older people with multimorbidity. moreover, patient qol is a meaningful measure in the evaluation of health care services and patient-reported outcome caregiving demands significantly reduce caregivers' opportunities to have a lifestyle in which leisure or time for themselves is available. according to different empirically supported theoretical frameworks that point to the importance for caregivers of experiencing pleasant events and receiving positive reinforcement in their daily lives in order to maintain a positive mood, not engaging in personally satisfying activities may result in more social withdrawal and depression, putting caregivers at risk of developing emotional disorders.

as the percentage of elderly cardiac population is growing and most of them have multimorbid conditions, we should find ways to improve their of life and to avoid their caregivers being burned out. asses quality of life of cardiac elderly patients with multimorbidity and to investigate the prevalence of burnout among their caregivers this study of multimorbidity among elderly cardiac patients attending sohag university cardiac outpatient clinic and burnout among their care givers aims to:- 1. study the effect of multimorbidity on health related quality of life of elderly cardiac patients. 2. study determinants of health related quality of life among elderly cardiac patients with multimorbidity. 3. study burnout prevalence among care givers

Eligibility criteria:
inclusion criteria: * elderly patients (60 years and over) \[2\] with multimorbid conditions and a cardiovascular disease is one of them . caregivers of elderly patients included in the study. exclusion criteria: * patients and caregivers who will refuse to participate in this study and patients with disturbed conscious level and mentally disabled.
trial evaluating pcsk9 antibody in subjects with ldl receptor abnormalities

Conditions: Homozygous Familial Hypercholesterolemia

Summary: a study to determine the safety, tolerability, and efficacy of evolocumab (amg 145) in patients with homozygous familial hypercholesterolemia (hofh).

study masking: part a: open label part b: double blind

Eligibility criteria:
inclusion criteria: * males and females ≥ 12 to ≤ 80 years of age * diagnosis of homozygous familial hypercholesterolemia * stable lipid-lowering therapies for at least 4 weeks * ldl cholesterol ≥ 130 mg/dl (3.4 mmol/l) * triglyceride ≤ 400 mg/dl (4.5 mmol/l) * bodyweight of ≥ 40 kg at screening. exclusion criteria: * ldl or plasma apheresis within 8 weeks prior to randomization * new york heart association (nyha) class iii or iv or last known left ventricular ejection fraction \< 30% * myocardial infarction, unstable angina, percutaneous coronary intervention (pci), coronary artery bypass graft (cabg) or stroke within 3 months of randomization * planned cardiac surgery or revascularization * uncontrolled cardiac arrhythmia * uncontrolled hypertension

Keywords: hypercholesterolemia familial hypercholesterolemia homozygous familial hypercholesterolemia
cochlear implant electrostimulation and the influence on the vestibular organ

Conditions: Deafness Unilateral; Deafness, Bilateral; Deafness Congenital; Deafness, Acquired

Summary: there is evidence that the sensor function of the utricle in patients with bilateral labyrinthine dysfunction (bilateral vestibulopathy) may improve balance under the influence of high frequency basal stimulation of the cochlea. the aim of the study is to measure the possible co-stimulation of the utricle (which is determined by the svv) by tonotopic (frequency-specific) cochlear stimulation and thus to objectify whether the stimulation of the auditory nerve in ci patients also leads to an unavoidable co-stimulation of the vestibular system.

the cochlea is tonotopically structured, i.e. certain frequencies are mapped on a specific part of the cochlea from basal to apical. it is not yet known whether tonotopically differentiated stimulation of the cochlea has an unavoidable side effect on other body systems, such as the vestibular organ. if the labyrinthine dysfunction occurs as a consequence of a ci implantation, this could in the future lead to the possibility of reducing vestibular complications after ci surgery by switching certain electrodes on or off. in a first investigation phase, a conventional and already implanted ce-certified cochlear implant will be used. the aim of this project is to test certain tonotopic stimulus patterns that stimulate the cochlea by varying the volume within predefined settings. thus, there is no misuse of the device and no change in performance attributes. within the framework of the clinical project planned here, the testing of vestibular co-stimulation during normal cochlear stimulation via the basal, medial and apical electrodes of the ci electrode is planned. under the influence of defined stimulation patterns, the assessment of the subjective visual vertical (svv) in project participants will be investigated. the influence of tonotopic stimulation on the svv result will have a high priority.

Eligibility criteria:
inclusion criteria: * uni- or bilaterally deafened and deaf patients with cochlear implants (one- or two- sided) from advanced bionics (ab), model hires 90k and newer * majority * given informed consent * legally competent and mentally able to follow the instructions of the personnel exclusion criteria: * unsuccessful ci implantation (device or electrode defects, incomplete electrode array insertion, missing neuronal stimulus responses) * pregnant and/or breastfeeding women * severe pre- or concomitant disease or reduced general ground condition, so that an outpatient presentation in the ent polyclinic is not possible * life expectancy of less than six months * the patient has received a study medication within the last 30 days within the framework of another study * simultaneous participation in another clinical intervention study * anticipated lack of compliance * alcohol or drug abuse * the patient is placed in an institution by order of the authorities or court * patients who are in a dependent or employed relationship with the sponsor, investigator, or their deputy

Keywords: deafness, cochlea implant
acute exposure to high altitude on heart rate and ventilation during exercise

Conditions: Pulmonary Hypertension

Summary: randomized crossover trial in patients with pulmonary hypertension (pah, cteph) to assess the acute response to high altitude (säntis; 2500m above sea level) on heart rate and ventilation changes under exercise.

low altitude baseline measurements will be performed in zurich (460m asl) including echocardiography, right heart catheterization, 6mwt, pulmonary function test, clinical assessment and blood gas analysis. randomly assigned to the order of testing, the participants will be tested in low altitude (zurich, 470m) and at high altitude (2500m). during the exposure to high altitude (2500m) and low altitude (zurich; 470m) of up to 5 hours, the participants' heart rate and ventilation will be compared under exercise.

Eligibility criteria:
inclusion criteria: * informed consent * ph diagnosed according to internation guidelines: mpap ≥ 25 mmhg along with a pawp ≤15 mmhg during right heart catheterization at the time of initial diagnosis * ph class 1 (pah) or 4 (cteph) * stable condition, on the same medication for \> 4 weeks * patient live permanently at an altitude \< 1000m asl. exclusion criteria: * resting pao2 ≤7.3 kpa corresponding to the requirement of long-term oxygen therapy \> 16hour daily (nocturnal oxygen therapy alone is allowed) * severe daytime hypercapnia (pco2 \> 6.5 kpa) * susceptibility to high altitude related diseases (ams, hape, etc.) based on previous experienced discomfort at altitudes. * exposure to an altitude \>1500m for ≥3 nights during the last 4 weeks before the study participation * residence \> 1000m above sea level * inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, neurological or orthopedic problems with walking disability * women who are pregnant or breast feeding

Keywords: high altitude exercise ventilation heart rate
a crossover study to evaluate the efficacy of simvastatin in elevating hdl-c levels in patients with type 2 diabetes (0733-216)(completed)

Conditions: HDL Cholesterol

Summary: the purpose of this study is to see how well simvastatin raises hdl levels in patients with type 2 diabetes.


Eligibility criteria:
inclusion criteria: * patient has stable type 2 diabetes mellitus at visit 1. * patient meets screening criteria based on visit 1 lab tests exclusion criteria: * patient is pregnant, breastfeeding, or at risk of becoming pregnant * patient has heart disease, uncontrolled high blood pressure, or other significant disease * patient is taking prohibited medication(s) and is unable to stop taking them for the duration of the study
pain processing in anxiety and depression

Conditions: Pain; Anxiety; Depression

Summary: the purpose of the study is to investigate pain, anxiety and depression in patients with panic anxiety disorders without pain or depression without pain compared with healthy volunteers


Eligibility criteria:
inclusion criteria: * patients with panic disorder or depression exclusion criteria: * treatment with antidepressants, anticonvulsants or any other pain medication except paracetamol, ssri and benzodiazepines * serious or unstable medical disease * prior or present diagnosis of mania, bipolar or psychotic disorder, delirium, suicidal, drug and alcohol dependence, severe agitation * patients who cannot cooperate and do not understand danish

Keywords: neuropathic pain chronic pain depression anxiety
a long-term safety and tolerability study of ezetimibe plus atorvastatin in participants with coronary heart disease, multiple risk factors, or hypercholesterolemia not controlled by atorvastatin (p01418/mk-0653-032)

Conditions: Hypercholesterolemia

Summary: the purpose of this study was to evaluate the long-term safety and tolerability of ezetimibe 10 mg once daily co-administered with atorvastatin 10 to 80 mg daily for up to 12 consecutive months in participants with heterozygous familial hypercholesterolemia (hefh) or in participants with coronary heart disease (chd) or multiple cardiovascular risk factors and primary hypercholesterolemia not controlled by a starting dose (10 mg daily) of atorvastatin.

adult participants with a diagnosis of hefh or chd or multiple risk factors (≥2) and with primary hypercholesterolemia who had successfully completed the 14-week, double-blind efficacy and safety study of ezetimibe co-administered with atorvastatin (protocol no. p00693/mk-0653-030; nct03867318) were eligible for enrollment in this long-term extension study.

Eligibility criteria:
inclusion criteria: * participants who have successfully completed the 14-week double-blind, efficacy and safety study of sch 58235 in addition to atorvastatin in participants with chd or multiple risk factors or hefh, (protocol p00693/mk-0653-030; nct03867318). entry into this protocol must occur at the time of completion of protocol p00693/mk-0653-030; nct03867318 * all women must have a negative pregnancy test prior to study entry. women of child bearing potential must agree to practice an effective barrier method of birth control for the duration of the study. in addition, participants must agree to practice an effective barrier method of birth control for 30 days following the last dose of atorvastatin administered * postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen (ert), estrogen/progestin (hrt) or raloxifene regimen during study period exclusion criteria: * participants who discontinued from the protocol p00693 due to adverse events or poor compliance * pregnant or lactating women * participants who are known to be hiv positive