Kornimate/medical-research-clean huggingface dataset:
cyp2d6 screening for adverse drug reactions to codeine in breast milk

Conditions: Cytochrome P450 2D6 Ultra-rapid Metabolism

Summary: the purpose of this study is to determine if non-invasive salivary genetic screening of breastfeeding mothers taking codeine will allow for the successful identification of mother-infant pairs susceptible to adverse events and to prevent these adverse events by personalizing their medication to their genetics.

currently, the opioid analgesic codeine is commonly administered to breastfeeding mothers after caesarean section for pain relief. codeine was originally considered safe to use while breastfeeding however, increased risk of adverse drug reactions has been demonstrated in mothers taking codeine, as well as their breastfed infants, when the mother possesses a genetic variation resulting in cytochrome p450 2d6 (cyp2d6) ultra-rapid metabolizer (um) phenotype. on average, most people convert about 10-15% of their codeine dose to morphine resulting in pain relief however, um individuals can convert up to 50% of their codeine doses into active morphine. as many as 4% of north americans may be ums and these mothers and their breastfed infants are at high risk of serious adverse events despite "safe" codeine dosing due to morphine overproduction and accumulation in the mother and her breast milk. observed side effects include severe sedation, decreased rate and depth of breathing and even infant death. in response to this problem, our hospital-based clinical trial strives to identify at-risk um mother-infant pairs by performing a genetic test on non-invasive, voluntary saliva samples from mothers giving birth by caesarean section and who will need codeine for pain relief while breastfeeding. we believe that this test will allow us to reliably identify at-risk um mother-infant pairs and prevent adverse drug reactions in both by tailoring analgesic therapy to their genetic results: mothers identified as being ums will be given other suitable analgesics, such as ibuprofen, in place of codeine-containing preparations. we propose that this prospective study will generate high-level data supporting the cost-effective genetic screening of mothers who will be taking codeine while breastfeeding before they begin taking their medications. such testing is currently possible on a nation-wide scale through collaboration with the canadian pharmacogenomics network for drug safety (cpnds).

Eligibility criteria:
inclusion criteria: women who: * have a pre-scheduled caesarean section * provide dna for cyp2d6 genetic analysis * breastfeed their infants * take codeine-containing medication during breastfeeding (retrospective screening group and non-cyp2d6 ultrarapid metabolizers in prospective screening group) exclusion criteria: * mothers who do not provide consent prior to caesarian section surgery * mothers who take other sedative medications besides codeine during breastfeeding (these include benzodiazepines, skeletal muscle relaxants, psychotropic agents).

Keywords: cyp2d6 genetic polymorphism codeine breastfeeding
prostate reirradiation toxicity outcomes feasibility study

Conditions: Prostate Cancer; Radiotherapy Side Effect

Summary: the ro-pip trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage ultra-hypofractionated external beam radiotherapy or high dose rate brachytherapy and provide prospective data on patient recorded toxicity outcomes that will inform a future phase iii trial.

radiotherapy is the most common curative treatment for non-metastatic prostate cancer, however up to 13% of patients will develop local recurrence within 10 years. patients can undergo further and potentially curative treatment including salvage surgery, brachytherapy (bt), external beam radiotherapy (ebrt), high intensity focused ultrasound and cryotherapy. systematic review shows that high dose rate (hdr) bt and stereotactic body radiotherapy (sbrt) have the best outcomes in terms of biochemical control and lowest side effects. the ro-pip trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage hdr-bt or sbrt and provide prospective data on patient recorded toxicity outcomes that will inform a future phase iii trial. the primary endpoint of the ro-pip feasibility study is to evaluate the patient recruitment potential over 2 years to a trial randomising to either sbrt or hdr-bt for patients who develop local recurrence of prostate cancer following previous radiation therapy. the aim is to recruit 60 patients across 3 sites over 2 years and randomise 1:1 to sbrt or hdr-bt. secondary objectives include recording clinician and patient reported outcome measures (proms) to evaluate treatment-related toxicity. in addition, the study aims to identify potential imaging, genomic and proteomic biomarkers that are predictive of toxicity and outcome based on hypoxia status, a prognostic marker of prostate cancer.

Eligibility criteria:
inclusion criteria: * male individuals aged over 18 years * histologically confirmed locally recurrent prostate cancer (following previous radiotherapy no less than 2 years ago) * no metastatic disease * able and willing to provide an informed consent to participate * world health organisation (who) performance status 0-2 * reasonable urinary function (ipss \ 10 ml/second on flow tests) * greater than 10 year life expectancy exclusion criteria: * patients who are unfit for a general anaesthetic due to other comorbidities * clinical or radiological evidence of metastatic prostate disease * any patient with a medical or psychiatric condition that impairs their ability to give informed consent * contraindication or intolerance of magnetic resonance scanning * prior prostatectomy * history of inflammatory bowel disease.
the mechanism of dexmedetomidine in improving delirium after cardiac surgery

Conditions: Dexmedetomidine; Delirium; Cardiac Surgery

Summary: the investigators aim to evaluate the roles of α7nachr in the mechanisms of dexmedetomidine in improving delirium after cardiac surgery. the results of this study would lay the foundation for revealing the mechanisms of dexmedetomidine improving delirium after cardiac surgery and provide a new idea to the early treatment of delirium.


Eligibility criteria:
inclusion criteria: * icu patients underwent cardiac surgery * age ≥ 60 years exclusion criteria: * preoperative cognitive decline, mental illness, * preoperative long-term use of hormone patients, * preoperative alcohol dependence, * patients with alcohol withdrawal symptoms
a trial comparing the safety and efficacy of insulin degludec and insulin glargine, with or without oads in subjects with type 2 diabetes

Conditions: Diabetes; Diabetes Mellitus, Type 2

Summary: this trial is conducted in the united states of america (usa). the aim of the trial is to compare the safety and efficacy of insulin degludec (ideg) and insulin glargine (iglar) with or without oads (oral anti-diabetic drugs) excluding sus (sulfonylureas)/glinides in subjects with type 2 diabetes.


Eligibility criteria:
inclusion criteria: - male or female, age at least 18 years at the time of signing informed consent - subjects fulfilling at least one of the below criteria: a) experienced at least one severe hypoglycaemic episode within last year (according to the ada (american diabetes association) definition, april 2013), b) moderate chronic renal failure, defined as glomerular filtration rate 30 - 59 ml/min/1.73 m\^2 per ckd-epi (chronic kidney disease epidemiology collaboration) by central laboratory analysis, c) hypoglycaemic symptom unawareness, d) exposed to insulin for more than 5 years, e) recent episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (below or equal to 70 mg/dl \[below or equal to 3.9 mmol/l\])) within the last 12 weeks prior to visit 1 (screening) - type 2 diabetes mellitus (diagnosed clinically) for at least 26 weeks prior to visit 1 - current treatment with any basal insulin (od or bid) ± any combination of oads (metformin, dpp-4 inhibitor, alpha-glucosidase inhibitor, thiazolidinediones, and sglt2-inhibitor) for 26 weeks or longer prior to visit 1 for subjects on bid the total daily dose should be below 75 units - hba1c (glycosylated haemoglobin) below or equal to 9.5 % by central laboratory analysis - bmi (body mass index) below or equal to 45 kg/m\^2 exclusion criteria: - treatment with a bolus insulin separately or contained in an insulin mix product within the last 26 weeks prior to visit 1 - use of any other anti-diabetic agent(s) than those stated in the inclusion criteria within the last 26 weeks prior to visit 1
the comfort and adherence of rivelin® plain patches in vulva lichen sclerosus patients

Conditions: Vulvar Lichen Sclerosus

Summary: this explorative investigation will assess the adhesion and tolerability of the rivelin® plain patch when applied directly on lesions in subjects with vulvar lichen sclerosus (vls).

the rivelin® plain patch works by forming a protective barrier over a lesion, protecting it from further irritation and thus providing pain relief in much the same way as the adhesive pastes and films that are available to treat vls. however, the adhesion/protection time of the rivelin® plain patch is expected to be longer compared to current treatment with bioadhesive agents, thereby potentially increasing the pain free period for the subject. this study is undertaken to gather information covering adhesion time and tolerability of the rivelin® plain patch on areas affected by vls. since protecting a lesion with a physical barrier could reduce the sensation of pain caused by normal function, this investigation will also explore subject experienced pain and/or symptom relief during use of the patch for further development.

Eligibility criteria:
inclusion criteria: 1. women (≥ 18 years) diagnosed with vls 2. has received written and oral study information 3. has given her written consent to study participation exclusion criteria: 1. pregnant 2. menstruating at the time of patch application 3. unable to communicate clearly with the examining doctors 4. under the guardianship of another person or institution

Keywords: vls
a phase iii study to evaluate the safety and efficacy of ganciclovir (dihydroxypropoxymethyl guanine [dhpg]) treatment of symptomatic central nervous system (cns) congenital cytomegalovirus (cmv) infections.

Conditions: Cytomegalovirus Infections

Summary: the purpose of this study is to evaluate the benefits and safety of the antiviral drug ganciclovir (dhpg) given intravenously to treat newborn infants who are born infected with cytomegalovirus (cmv). cmv is a herpes virus that can infect most organs of the body, resulting in death in 10-30% of babies with symptoms of cmv. it can cause severe brain damage in a large percentage of surviving babies. children in this study have a cmv infection of the central nervous system (cns).

the study will enroll 130 newborn infants 1 month of age or younger with cmv involving the cns. patients will be assigned randomly (like tossing a coin) to receive either dhpg or no study drug treatment. all babies in the study will receive standard of care treatment and clinical, diagnostic, laboratory, safety, and follow-up evaluations. follow-up evaluations, including hearing and eye exams and developmental assessments, will be done periodically until the child reaches 5 years of age. the degree of improved hearing among surviving patients will be a primary measure of drug effectiveness.

Eligibility criteria:
inclusion criteria: infants may be eligible for this study if they: * were full term infants (at least 32 weeks gestation). * are 1 month of age or younger (preferably less than 2 weeks). * weighed at least 1,200 grams (2.5 lbs) at birth. * have confirmed cytomegalovirus. * have evidence of cmv infection of the cns with or without evidence of other organ involvement. exclusion criteria: infants will not be eligible for this study if they: * have concurrent bacterial infection. * have hiv infection. * have mild symptoms or no symptoms of cmv infection at birth. * have an abnormal brain development (hydranencephaly) or any devastating brain involvement.
epidemiology and pathophysiology of parkinsonism in the caribbeans

Conditions: Atypical Parkinsonism

Summary: the primary aim of this study is to estimate the frequency and to characterize clinically atypical parkinsonism in the french west indies and guyana.

an atypical akineto-rigid parkinsonian syndrome, unresponsive to l-dopa has been evidenced in guadeloupe. abnormally frequent, this progressive supranuclear palsy (psp)-like syndrome represents a new clinical entity. unlike in classical psp 70% of patients have myoclonus, 59% hallucinations, 78% rem sleep behavior disorders. oculomotor pattern differs from classical psp suggesting that cortical dysfunction predominates over brainstem impairments. neuropathological examination in four patients has shown a widespread accumulation of the tau protein in the basal ganglia, the midbrain and cortical areas. this syndrome has been associated to the regular consumption of food products derived from plants of the annonaceae family, more specifically annona muricata (soursop), suggesting a toxic origin. we have already confirmed the neurotoxic potential of the lipophilic mitochondrial complex i inhibitor annonacin, the major acetogenin in annona muricata. this class of compounds is specific to annonaceae. nanomolar concentrations of annonacin induce the death of dopaminergic neurons in culture, by impairment of energy production. chronic systemic intoxication of rats with annonacin causes neuronal damage in the same brain regions that are damaged in patients with atypical parkinsonism. these results greatly suggest that the consumption of annonacea might contribute to the pathogenesis of the disease. the h1 subhaplotype in tau gene associated with psp in caucasians did not confer risk for psp-like atypical parkinsonism in guadeloupe.

Eligibility criteria:
inclusion criteria: * pour les patients : 1. patient ou tiers responsable ayant reçu une information sur l'étude et ayant signé le consentement éclairé 2. patient âgé de plus de 18 ans 3. patient consultant en neurologie ou en gériatrie pour symptomatologie parkinsonienne ou pour troubles cognitifs évocateurs d'une démence à corps de lewy 4. patient domicilié aux antilles-guyane pour les témoins : 5. conjoint ou accompagnant ayant reçu une information sur l'étude et ayant signé le consentement éclairé 6. personne âgée de plus de 18 ans 7. personne ne présentant pas de pathologie d'allure neurodégénérative (parkinson, démence notamment) 8. personne domiciliée aux antilles-guyane exclusion criteria: pour les patients : 1. syndrome parkinsonien secondaire (post-traumatique, vasculaire, iatrogène, post encéphalitique) 2. patient non affilié au régime de sécurité sociale 3. en cas de difficulté de suivi le patient sera exclu de l'étude longitudinale pour les témoins : 1. personnes présentant des troubles cognitifs ou un syndrome parkinsonien diagnostiqué. 2. patient non affilié au régime de sécurité sociale -

Keywords: progressive supranuclear palsy caribbean atypical parkinsonism annona muricata
(artemis-ipf) randomized, placebo-controlled study to evaluate safety and effectiveness of ambrisentan in ipf

Conditions: Idiopathic Pulmonary Fibrosis

Summary: the artemis-ipf study was conducted to determine if ambrisentan was effective in delaying disease progression and death in participants with idiopathic pulmonary fibrosis (ipf), to evaluate its safety, and to evaluate its effect on development of pulmonary hypertension, quality of life, and dyspnea (shortness of breath) symptoms in this participant population. participants were randomized in a 2:1 ratio to receive ambrisentan or placebo, respectively. participation in the study was to be up to 4 years, depending on how long it would take to enroll participants and observe study events. after randomization, visits to the clinic took place every 3 months, and laboratory procedures were performed every month.


Eligibility criteria:
inclusion criteria: * male or females from 40 to 80 years of age * diagnosis of ipf * honeycombing (fibrosis in the lung) on high-resolution computerised tomography (hrct) scan of less than or equal to 5% * willing and able to have 2 right heart catheterizations performed * willing to have monthly lab tests to monitor liver function * able to perform the 6 minute walk test (indicated adequate physical function) * must have meet lung function requirements * normal liver function tests * negative serum pregnancy test * willing to use at least 2 reliable methods of contraception * able to understand and willing to sign informed consent form exclusion criteria: * no restrictive lung disease (other than usual interstitial pneumonia or ipf) * no obstructive lung disease * no recent or active respiratory exacerbations * no recent hospitalization for an ipf exacerbation * no recent history of alcohol abuse * chronic sildenafil (or same drug class) use for pulmonary hypertension * chronic treatment with certain medications for ipf within 30 days of randomization * no other serious medical conditions

Keywords: idiopathic pulmonary fibrosis interstitial lung disease ambrisentan
biomarker study of in men with psa progression on abi for cr or cs pc (bio-stamp)

Conditions: Prostate Cancer

Summary: this is a multicenter, phase ii randomized biomarker-based therapeutic study in metastatic prostate cancer experiencing prostate specific antigen (psa) only progression (without visceral, bone or lymph node progression) while on abiraterone therapy.


Eligibility criteria:
inclusion criteria: * histological or cytological evidence of adenocarcinoma of the prostate * undergone orchiectomy, or have been on luteinizing hormone-releasing hormone (lhrh) agonists or antagonists for at least 3 months prior to study enrollment. patients on lhrh agonists/antagonists must remain on these agents for the duration of the study. * currently receiving abiraterone (zytiga or fda approved generic) in the castration sensitive (cspc) or castration resistant (crpc) setting with psa progression in the absence of visceral, bone or lymph node progression. psa progression is defined as an increase in the psa level of more than 50% above the nadir with two consecutive increases at least 2 weeks apart (based on prostate cancer working group criteria, version 3 (pcwg3). * minimum psa must be ≥1.0 ng/dl. * age 18 years of age or older. * ecog performance status 0 or 1. * have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to enrollment: * absolute neutrophil count (anc) ≥ 1.5 × 10\^9/l * platelets ≥ 100 × 10\^9/l * hemoglobin ≥ 10 g/dl, independent of transfusion ≤14 days of screening * aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 3 × upper limit of normal (uln); if liver metastases, then ≤ 5 × uln * total bilirubin ≤ 1.5 × uln; \< 2 × uln if hyperbilirubinemia is due to gilbert's syndrome * serum albumin ≥ 30 g/l (3.0 g/dl) * serum creatinine ≤ 1.5 x uln; or estimated glomerular filtration rate (gfr) ≥ 45 ml/min using the cockcroft gault formula * participants with partners of childbearing potential must be willing to use at least two forms of effective birth control (one form must be a barrier method) during the dutasteride treatment period and for 6 months after last dose or 3 weeks after the last dose of abiraterone whichever is longer. persons are considered to be of childbearing potential unless one or the following applies: * is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause * considered permanently sterile. permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy. * voluntary written consent prior to the performance of any research related activit exclusion criteria: * previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to 5 alpha-reductase inhibitors (i.e. finasteride). * prior use of enzalutamide, apalutamide, or darolutamide for the treatment of prostate cancer.
a study to evaluate the safety, reactogenicity, and immunogenicity of mrna-1468 in healthy adults ≥50 years of age

Conditions: Herpes Zoster

Summary: the purpose of this first-in-human study is to evaluate the safety and immunogenicity of mrna-1468.


Eligibility criteria:
inclusion criteria: * part 1: is an adult 50 years of age or older at the time of consent. part 2: is an adult 50-69 years of age at the time of consent. * has a body mass index of 18 to \<40 kilograms/meter squared at the screening visit. * females of childbearing potential: have a negative pregnancy test at the screening visit and on the day of the first vaccination (day 1); have practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to day 1; have agreed to continue adequate contraception through 3 months following vaccine administration; are not currently breastfeeding. exclusion criteria: * has a history of hz within the past 10 years. * has been previously vaccinated against varicella or hz. * is acutely ill or febrile * body temperature ≥38.0°celsius/100.4°fahrenheit 72 hours prior to or at the screening visit or on day 1. participants meeting this criterion may be rescheduled within the allowed window. * has a current or previous diagnosis of congenital or acquired immunodeficiency, immunocompromizing/immunosuppressive condition, asplenia, or recurrent severe infections. certain immune-mediated conditions that are well controlled and stable (for example, hashimoto thyroiditis) as well as those that do not require systemic immunosuppressive therapy (for example, asthma, psoriasis, or vitiligo) may be permitted at the discretion of the investigator. * has a dermatologic condition that could affect local solicited adverse reaction assessments (for example, tattoos, psoriasis patches affecting skin over the deltoid areas). * has any medical, psychiatric, or occupational condition, including reported history of substance abuse, that, in the opinion of the investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. * has a history of myocarditis, pericarditis, or myopericarditis. * has a reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mrna vaccine(s) or any components of the mrna vaccines. * has received systemic immunosuppressants for \>14 days in total within 180 days prior to screening visit (for corticosteroids ≥10 milligrams/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study. inhaled, nasal, intra-articular and topical steroids are allowed. * has received systemic immunoglobulins, long-acting biological therapies that affect immune responses (for example, infliximab) or blood products within 90 days prior to the screening visit or plans to receive them during the study. other protocol-defined inclusion/exclusion criteria apply.

Keywords: mrna-1468 herpes zoster vaccine moderna