Kornimate/medical-research-clean huggingface dataset:
ascorbic acid treatment in congenital glucocorticoids and mineralocorticoids deficiency due to nnt mutation

Conditions: Glucocorticoids Deficiency

Summary: nicotinamide nucleotide transhydrogenase (nnt) mutations cause glucocorticoid and mineralocorticoid deficiencies through decreased detoxification of reactive oxygen species (ros) in adrenocortical cells. ascorbic acid is well known by its high antioxidant activity due to the neutralization of free radicals and other reactive oxygen species. preliminary results of nnt_p.g200s homozygous fibroblasts' treatment with 10 micro molar l-ascorbic acid shows significant improvement in mitochondrial morphology and in ros content. the aim of this study is to figure out if ascorbic acid treatment improves the phenotype of nnt patients by reducing ros in their adrenocortical cells and preventing their apoptosis.

most cases of familial glucocorticoid and mineralocorticoid deficiency are caused by mutations interrupting steroidogenesis such as 21- hydroxylase deficiency. recently, nicotinamide nucleotide transhydrogenase (nnt) mutations were found to cause isolated glucocorticoid deficiency or combined mineralocorticoid and glucocorticoid deficiency through decreased detoxification of reactive oxygen species (ros) in adrenocortical cells. nnt mutation in mice causes also glucose intolerance. ascorbic acid is an essential water-soluble vitamin with excellent reducing properties, well known by its high antioxidant activity due to the neutralization of free radicals and other reactive oxygen species. this vitamin acts as the first line of defense during oxidative stress in the human body. ascorbic acid treatment for variant disease (e.g. - cancer, type 2 diabetes, anxiety, depression, asthma and cardiovascular diseases) have been meticulously studies with no major adverse effects. in a previous study, the investigators demonstrated a higher ros levels, a lower atp content and a change in mitochondrial morphology in nnt_p.g200s homozygous fibroblasts compared with control fibroblasts. preliminary results of nnt_p.g200s homozygous fibroblasts' treatment with 10 micro molar l-ascorbic acid shows significant improvement in mitochondrial morphology and in ros content. the aim of this study is to figure out if ascorbic acid treatment improves the phenotype of nnt patients by reducing ros in their adrenocortical cells and preventing their apoptosis. during the study nnt_p.g200s homozygous patients (no.-3) will be hospitalised for acth and ogtt tests and start ascorbic acid treatment at a doses of 75-80% of the upper limit of allowance according to iom. acth and ogtt will be repeated 6 months later to assess improvement in glucocorticoids production and insulin resistance.

Eligibility criteria:
inclusion criteria: * nnt mutation homozygous patients with glucocorticoids deficiency
cognitive-behavioral treatment for mild alzheimer's patients and their caregivers

Conditions: Alzheimer Disease

Summary: the purpose of this study is to determine whether a comprehensive cognitive-behavioral therapy-based, multi-component treatment programme is effective in the treatment of neuropsychiatric symptoms of patients with mild alzheimer's dementia.

mild alzheimer's dementia (ad) cases are with 15 millions worldwide the largest fraction of all ad cases. most patients are cared for by their family at home. neuropsychiatric symptoms are very common in ad, even as early as in mild ad: about 90% of all mild ad cases experience neuropsychiatric symptoms, most frequently depression, anxiety, and irritability. these symptoms are associated with greater morbidity, reduced quality of life for the patient, increased burden and depression for the caregiver, higher costs of care, and nursing home placement. thus, interventions aimed at treating these symptoms could have a tremendous effect on pa-tients, caregivers, and society. this study is a randomized, controlled trial (rct) evaluating a comprehensive cbt-based, multi-component treatment programme consisting of eight modules (diagnosis and goal-setting; psycho-education; engagement in pleasant activities; cognitive restructuring; life review; training caregiver in behavior management techniques; interventions for the caregiver; couples counseling) and 20 sessions. this trial aims at significantly reducing depressive and other neuropsychiatric symptoms in the ad patients, and secondary in reducing burden and depressive symptoms of the caregivers. patients with ad alone or mixed ad and vascular dementia that are in the mild stage and suffer under any neuropsychiatric symptom will be included. the patients and their caregiver will be randomized to either the cbt-based intervention or to the control condition that receives treatment as usual (tau).

Eligibility criteria:
inclusion criteria: * patients have to meet nincds-adrda criteria for probable or possible ad (mckhann et al., 1984). mixed alzheimer and vascular dementia cases will also be included. * only ad cases with a mild dementia severity will be included, determined by the clinical dementia rating (cdr) scale (i.e. scores of 0.5 or 1, morris, 1993) and by the mini mental state examination (mmse) (i.e. scores of 20 or more, folstein, folstein, \& mchugh, 1975). * the patient must suffer under any non-cognitive symptom that motivates him to accept psy-chotherapeutic help. * a caregiver must be available to take part in most of the therapy sessions. exclusion criteria: * concomitant alcohol or drug addiction and a history of a malignant disease, severe organ failure, metabolic or hematologic disorders, neurosurgery or neurological condition such as parkinson's disease, epilepsy, postencephalitic and postconcussional syndrome

Keywords: cognitive behavior therapy early dementia, alzheimer type
correction of nonsense mutations in cystic fibrosis

Conditions: Cystic Fibrosis

Summary: the presence of a nonsense mutation leads to the rapid degradation of the carrier mrna mutation by a mechanism called nmd (nonsense-mediated mrna decay) \[6, 13\]. there are currently 3 main strategies at least for correcting nonsense mutations: exon skipping, inhibition of nmd and nonsense mutation readthrough. in the laboratory, we developed a strategy for correcting nonsense mutations combining inhibition of nmd and activation of translecture. for this purpose, we have constructed screening systems to identify nmd-inhibiting and/or readthrough enhancers. the molecules thus identified are then tested on cell lines and in murine models carrying a nonsense mutation. one of our goals is to select a set of molecules that can correct effectively nonsense mutations. for this we have to test these molecules on a great diversity of nonsense mutations. this work will: * determine if we can correct all the nonsense mutations tested with at least one of our molecules * determine what is common within a group of mutations corrected by a given molecule * be able to assign the parameters that make one mutation is corrected by one molecule and not or little by another. this study will therefore improve our theoretical knowledge on the recognition of premature stop codons but also to propose therapeutic approaches for the correction of nonsense mutations of the cftr gene in cystic fibrosis in a targeted way for a patient.


Eligibility criteria:
inclusion criteria: * male / female adults and minors aged 8 years and over * patients with cystic fibrosis and carry a nonsense mutation on the 2 alleles of the gene coding for the cftr channel. * patients whose genotype of patients concerning the cftr gene is known. * patients with social security * major patients who have given their consent * minor patients with parental authorization exclusion criteria: * patients who have a mutation other than nonsense in the cftr gene * patients whose cftr gene was not sequenced on the 2 alleles * patients not wishing to participate in this study or persons not giving or not able to give consent. * pregnant or lactating women * patients under curatorship or guardianship

Keywords: cystic fibrosis nonsense mutations cftr gene nasal epithelial cells nonsense mutation readthrough
novottf-100a therapy for refractory cns involved small cell lung cancer

Conditions: Small Cell Lung Cancer; Brain Metastasis

Summary: the hypothesis of this study is that the addition of novottf-100a system treatment to salvage chemotherapy will significantly increase time to treatment failure in the brain of small cell lung cancer patients.


Eligibility criteria:
inclusion criteria: * histologically confirmed small cell lung cancer histology with cns metastases * parenchymal disease, ten or less lesions, and supratentorial * ps 70% or greater * prior cns radiotherapy. * no previous or currently active second malignancy * age \> 22 years. * life expectancy of ≥ 3 months. exclusion criteria: * significant liver function impairment - ast or alt \> 3 times the upper limit of normal; total bilirubin \> upper limit of normal. * significant renal impairment (serum creatinine \> 1.7 mg/dl). * coagulopathy (as evidenced by pt or aptt \>1.5 times in control patients not undergoing anticoagulation).thrombocytopenia (platelet count \< 100 x 103/μl). * neutropenia (absolute neutrophil count \< 1 x 103/μl). * anemia (hb \< 10 g/l). * severe acute infection. serious non-healing wound or ulcer on scalp * significant co-morbidities within 4 weeks prior to enrollment. * implanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmias. * active implanted medical device (e.g. deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmable shunts). * skull defect (e.g. missing bone with no replacement). * shunt * bullet fragments * evidence of increased intracranial pressure (midline shift \> 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness). * sensitivity to conductive hydrogels. * pregnant or lactating women

Keywords: cancer brain lung small-cell
determine af burden with ppg trial - detection and quantification of episodes of atrial fibrillation

Conditions: Paroxysmal Atrial Fibrillation

Summary: in this prospective single-center trial, a wearable photoplethysmographic (ppg) sensor coupled with a cloud analytics service will be used to detect and quantify atrial fibrillation (af) episodes in patients with known paroxysmal af. patients will simultaneously receive the ppg sensor in form of a smartwatch or bracelet and a holter ecg for 48 hours. correctly identified af episodes and af burden determined by both methods will be compared.

atrial fibrillation (af) is the most common cardiac arrhythmia and a major risk factor for cerebrovascular insults. paroxysmal af is defined as an episode of af that terminates spontaneously or with intervention within 7 days. patients with af may present with palpitations, shortness of breath or sensation of light-headedness but asymptomatic episodes are also possible, especially in paroxysmal af. the lack of continuous heart rate monitoring options makes early diagnosis of paroxysmal af challenging. in this prospective single-center trial, the ppg wearable corsano cardiowatch 287 sensor will be used to conduct continuous heart rate and -rhythm monitoring in patients with known paroxysmal af. collected data will then be analysed using a cloud analytics service (preventicus heartbeats algorithm) and compared with data from simultaneously obtained 48-hour holter ecg. correctly identified af episodes, their cumulative duration per 48 hours (af burden) and the number of asymptomatic episodes will be assessed. in the primary analyses, the sensitivity of the ppg analysing algorithm to detect af episodes is estimated by performing a logistic regression on detection (yes/no) with only an intercept as predictor, which is then translated to a proportion (the sensitivity). in the secondary analyses we are comparing the cumulative duration of af episodes over 48 hours (af burden) obtained with the ppg-sensor and holter-ecg. in summary, the purpose of the study is to evaluate the performance and efficacy of the wearable ppg sensor and the cloud analytics service in detecting and quantifying af episodes in patients with known history of paroxysmal af.

Eligibility criteria:
inclusion criteria: * known paroxysmal atrial fibrillation * patient ≥ 18 years old * written informed consent as documented by signature from the patient exclusion criteria: * cardiac implanted electronic device (pacemaker, icd) * smartwatch/bracelet and/or ecg device cannot be worn due to comprehensible reasons (allergic reactions, wounds, amputations, other) * patients unable or not willing to sign informed consent significant mental or cognitive impairment

Keywords: wearables af burden photoplethysmography (ppg) atrial fibrillation
combining brain stimulation and physiotherapy for the management of chronic low back pain

Conditions: Chronic Low-back Pain (cLBP)

Summary: chronic low back pain (clbp) is a major health challenge in canada, leading to substantial disability and socioeconomic burden, particularly among veterans. in military veterans, lbp is the most common chronic pain condition. conventional interventions have limited effectiveness. the refractoriness to interventions suggests that specific clbp mechanisms may be missed by current treatments, prompting a shift towards psychologically informed approaches which aim to address emotional and cognitive factors alongside biomedical aspects. the integration of these concepts into physiotherapy is called psychologically informed physiotherapy (pip). despite promising results of pip from randomized controlled trials, residual pain and disability often persist in veterans. non-invasive brain stimulation, such as repetitive transcranial magnetic stimulation (rtms), may enhance the effectiveness of pip by modulating cognition, emotion, and pain. this proposal seeks to determine whether non-invasive brain stimulation can enhance the effects of pip.

the study will compare the effects of (1) combining rtms with pip, (2) pip alone (+sham rtms), and (3) usual physiotherapy (up) on physical functioning in veterans suffering from clbp and comorbid psychological factors associated with back pain. participants will undergo an 8-week intervention program. validated questionnaires will be used to measure outcomes at baseline, 2-, 8-, and 26-week follow-ups. the main objective is to determine if the combination of pip and rtms is superior to pip and up alone to improve physical functioning in veterans suffering from clbp and comorbid psychological factors. the secondary objectives are to compare the effectiveness of these interventions on secondary outcomes, that are, pain intensity, quality of life, movement pain-related fear, pain catastrophizing, self-efficacy, depression symptoms, medication use and post-traumatic stress disorder symptoms.

Eligibility criteria:
inclusion criteria: * adults between 18 and 65 years old * military veterans with non-specific chronic low back pain (\> 3 months, \> 50% of the days in the last 6 months) * high level of psychosocial factors, scoring ≥4 on the start back screening tool psychosocial subscale * functional limitations, scoring ≥ 15% on the oswestry disability index (odi) exclusion criteria: * non-musculoskeletal conditions causing low back pain (e.g., neoplasia, fracture) * diagnosis of drug or alcohol abuse * change of drug dosage in the last month for the treatment of pain or mental health * presenting with any specific rtms-related exclusion criteria such as previous seizure/convulsion, cochlear implant, and pregnancy

Keywords: non-invasive brain stimulation comorbid psychological risk factors chronic pain repetitive transcranial magnetic stimulation physiotherapy pyschologically-informed veterans
gallant 9 tesaglitazar vs. placebo in combination with insulin

Conditions: Type 2 Diabetes Mellitus

Summary: this is a 24-week randomized, double-blind, multi-center, placebo-controlled study of tesaglitazar in patients with type 2 diabetes who are not adequately controlled on insulin (along or in combination with one or more oral antidiabetic agents in addition to diet and lifestyle advice). the study comprises a 3-week enrollment period and a 24-week randomized, double blind, multi-center, placebo-controlled treatment period and a 3-week follow-up. patients must receive at least 30 units of insulin per day and will continue their current oral antidiabetic treatment regimen throughout the study.


Eligibility criteria:
inclusion criteria: * provision of a written informed consent * men or women who are \>=18 years of age * female patients: postmenopausal, hysterectomized, or if of childbearing potential, using a reliable method of birth control * diagnosed with type 2 diabetes for less than 20 years and receiving at least 30 u insulin per day exclusion criteria: * type 1 diabetes * new york heart association heart failure class iii or iv * treatment with any thiazolidinedione class of antidiabetic agents * history of hypersensitivity or intolerance to any peroxisome proliferator-activated receptor agonist (like actos or avandia), fenofibrate, metformin or 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor (statin) * history of drug-induced myopathy or drug-induced creatine kinase elevation, liver enzyme elevations, neutropenia (low white blood cells) * creatinine levels above twice the normal range * creatine kinase above 3 times the upper limit of normal * received any investigational product in other clinical studies within 12 weeks * any clinically significant abnormality identified on physical examination, laboratory tests or electrocardiogram, which in the judgment of the investigator would compromise the patient's safety or successful participation in the clinical study

Keywords: insulin dependent type 2 diabetes
hip daa closure techniques

Conditions: Total Hip Replacement; Wound Complication

Summary: this study aims to analyze the difference in rates of wound complications using two different closure techniques in direct anterior approach for primary total hip replacement.

the use of the direct anterior approach (daa) for primary total hip arthroplasty (tha) has been increasingly popular but there has been a reported increased risk of wound complications compared with a posterior approach. wound complications can lead to increased length of stay, reoperation procedures (i.e., irrigation and debridement), patient dissatisfaction, extra visits, readmissions, increased risk of periprosthetic joint infection and overall increased costs.

Eligibility criteria:
inclusion criteria: * patients older than 18 years old that will undergo tha via daa exclusion criteria: * previous hip arthroplasty surgeries or scars * tha secondary to oncologic or traumatic etiologies * bmi ≥ 40 * uncontrolled diabetes (measured by a hgb a1c above 8) * reported allergy to skin adhesive
fdg pet imaging in diagnosing patients with glioblastoma

Conditions: Brain Glioblastoma

Summary: this early phase i trial studies the how well fluorodeoxyglucose f-18 (fdg) positron emission tomography (pet) imaging works in diagnosing patients with confirmed or suspected glioblastoma. diagnostic procedures, such as fdg pet, may help find and diagnose glioblastoma.

primary objectives: i. to assess the optimal fdg positron emission tomography (pet) imaging time post radiotracer administration that maximizes separation of activity between lesion and non-lesional parenchyma (measured as lesion/background \[l/b\] ratio) in patients with glioblastoma. secondary objectives: i. to identify genotypic factors in fdg tumor metabolism derived from metrics such as maximum standard uptake value (suvmax), mean standard uptake value (suvmean), total lesion glycolysis (tlg), mean tumor volume (mtv) and l/b ratio. exploratory objectives: i. to identify patterns of metabolism derived from metrics such as suvmax, suvmean, tlg, mtv, l/b ratio and magnetic resonance imaging metrics such as regional perfusion abnormalities, apparent diffusion coefficient values, fractional diffusivity measures and magnetic resonance spectroscopic finding. outline: patients receive fluorodeoxyglucose f-18 intravenously (iv) over 1 minute and then undergo pet/computed tomography (ct) scans over 30 minutes at 1 hour, 4-5 hours, and 7-8 hours after injection. patients also undergo a standard of care magnetic resonance imaging (mri) scan over 45 minutes if not already completed as part of standard of care.

Eligibility criteria:
inclusion criteria: * adult (\> 19 years of age) patients with biopsy proven (as opposed to being status post definitive surgical therapy) or highly suspected glioblastoma of the brain * cases without prior biopsy will be chosen based upon consensus of a md anderson faculty neuroradiologist and neurosurgeon for high probability of representing a glioblastoma * t1 post contrast lesion size greater than or equal to 10 mm exclusion criteria: * children * definitive/gross total lesion resection * prior brain cancer * prior whole brain radiation * known history of cerebrovascular disease, dementia or prior non-mild traumatic brain injury * known allergy to fdg or gadolinium based contrast agents * pregnant women are excluded
north american prodromal synucleinopathy consortium

Conditions: REM Sleep Behavior Disorder; Parkinson Disease; Lewy Body Disease; Dementia With Lewy Bodies; Multiple System Atrophy; REM Sleep Parasomnias

Summary: this study will enroll participants with idiopathic rapid eye movement (rem) sleep behavior disorder (rbd), for the purpose of preparing for a clinical trial of neuroprotective treatments against synucleinopathies.

rem sleep behavior disorder (rbd) is a rare disorder where people act out their dreams. people with rbd often, but not always, develop parkinson's disease, dementia with lewy bodies, multiple system atrophy, or other neurodegenerative diseases of the synucleinopathy type. the north american prodromal synucleinopathy (naps) consortium was formed with the purpose of enrolling participants with rbd, in anticipation of a future clinical trial of a neuroprotective treatment against synucleinopathies. the naps consortium will collect standardized clinical assessments, biofluids, and other data in order to develop biomarkers for synucleinopathies in the prodromal (presymptomatic) stage as well as a trial-ready registry of participants. participants procedures will include a \~2-hour clinical assessment (medical history and physical exam), questionnaires, blood draw, and (at select sites) optional lumbar puncture.

Eligibility criteria:
inclusion criteria: * idiopathic rem sleep behavior disorder exclusion criteria: * rem sleep behavior disorder secondary to another cause (ex: narcolepsy, dementia, parkinson's disease, etc) * other neurological disorder

Keywords: sleep rem rapid eye movement parkinson lewy body disease dementia with lewy bodies multiple system atrophy parasomnia synuclein synucleinopathy