Lviv - Vinnyky, Ukraine

Anal High-risk HPV, HSIL, and Microbiome Among Hispanic Peoples Living With HIV (PLWH)

PRIMARY OBJECTIVE: I. Study the relationship between anal high-risk HPV (hr-HPV) infection and the anal microbiome among three distinct populations of Hispanic people living with HIV (PLWH) in Mexico, Puerto Rico, and California. OUTLINE: This is an observational study. Participants undergo collection of 3 anal swab samples, complete questionnaires, and have their medical records reviewed on study. Participants with visible lesions undergo high resolution anoscope with anal biopsy per usual care on study.

Optimization of Cervical Cancer Screening Among Women Living With HIV in Latin American Countries

The overall goal of this research is to develop a point of care high-risk HPV (hrHPV) test and molecular testing that optimizes specificity to detect high-grade squamous intraepithelial lesions (HSIL), specifically cervical intraepithelial neoplasia of grade 2 or more (CIN 2+), in women living with HIV (WHIV) in Latin America while maintaining high test sensitivity. To accomplish this goal, the protocol will optimize cervical screening by modifying the cycle threshold/genotype interpretation of Xpert HPV assay output. In a secondary manner, the protocol will also evaluate whether triage with HPV/host DNA methylation improves the specificity of Xpert alone. The hypotheses for this protocol includes: • The Xpert HPV test can be optimized for HSIL detection (CIN2+) in WHIV to significantly improve test specificity, when compared to unmodified test output using manufacturer guidelines. To evaluate this hypothesis, the protocol will enroll 1000 cisgender women or transgender men age 25-65 years living with HIV who are undergoing routine cervical cancer screening. These individuals will be recruited from affiliated clinical sites of the National Institute of Public Health in Cuernavaca, Mexico and University of São Paulo, Brazil. Participants will provide a first void urine sample and will be instructed how to self-collect a vaginal swab. An oral gargle specimen will be collected for HPV testing, HPV methylation, and Epstein-Bar Virus (EBV) co-infection. They will receive a baseline questionnaire about risk factors for HPV and cervical cancer, and provide a blood specimen for CD4 count, plasma viral load, DNA methylation of biological aging, circulating tumor HPV DNA (ctHPVDNA) analysis, and stored sera. Next, a provider will collect an anal swab. Then the participant will undergo a speculum exam and a provider will collect a cervical cytobroom sample for cytology and HPV testing followed by a swab for stored specimens. Finally, acetic acid will be applied followed by a digital image of the cervix. Then at least two cervical biopsies will be obtained. Material from one provider-collected cervical swab will undergo cervical cytology assessment using Bethesda Criteria. Cervical histology results from the collected biopsies will be interpreted according to the Lower Anogenital Squamous Terminology (LAST). HSIL will be defined as CIN 2 with diffuse p16 staining, CIN 2-3, or CIN 3. Women diagnosed with HSIL will be treated according to local standards. The local histology result will be used for the management of participants. Any lesions suspicious for invasive cancer will be referred to the appropriate specialist. Women with HSIL on cytology, but no HSIL on histology will be treated according to the local standard. The management options include repeat colposcopy, endocervical curettage, or a diagnostic loop electro-excision procedure. Similarly, women with a Type 3 transformation zone should have endocervical curettage and be managed according to local standards. After local pathology review, all histology specimens will be shipped centrally for Histology Endpoint Adjudication; these adjudicated histology results will be used for reporting research findings. The details of this process will be in the Manual of Procedures. Discordance between the local and central pathology review will be adjudicated with a second central pathologist. The final histology result will be sent back to the local site and provided to the participant and their providers. Women found to have vulvar, vaginal or perianal lesions suspicious for HSIL will be referred for appropriate evaluation. The self-collected vaginal swab and material from the provider-collected cytobroom sample will be tested for HPV using Xpert HPV. Xpert testing of self- and provider-collected samples will be conducted locally (at the point of care) in Brazil and Mexico. Remaining material from the vaginal and cervical samples will be shipped to Dr. Villa's lab in Brazil to allow for S5 methylation testing of any WHIV with hrHPV detected. Residual samples, as well as the collected urine, will be stored in Dr. Villa's lab for future studies. Women with hrHPV detected on a provider-collected cervical sample using a locally available and approved test, but who were negative for HSIL as determined by cervical biopsy, will be asked to return for a follow-up study visit at 6-month to receive the same procedures described above (with the exception of blood draws). If at the 6-month follow-up visit WHIV continue to have detection of hrHPV, but are HSIL negative by biopsy, they will be asked to return for an additional follow-up study visit 6 months later (12-months post-baseline) to receive the same procedures. We estimate that approximately 40% of the population will have hrHPV detected and may need to return for a follow-up visit; and 7% will be HSIL+ and referred for treatment.

A Study to Understand How the Study Medicine (PF-06823859) Works in People With Active Idiopathic Inflammatory Myopathies [Dermatomyositis (DM) and Polymyositis (PM)]

The Willow LTE Study With M5049 in Participants With SCLE, DLE and/or SLE (WILLOW LTE)

A Study to Learn About the Safety of Litifilimab (BIIB059) Injections and Whether They Can Improve Symptoms of Adult Participants Who Have Systemic Lupus Erythematosus

EPIC-Peds: A Study to Learn About the Study Medicine Called PF-07321332 (Nirmatrelvir)/Ritonavir in Patients Under 18 Years of Age With COVID-19 That Are Not Hospitalized But Are at Risk for Severe Disease

A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )

Primary objectives This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage F2 or F3 and consists of 2 sequential parts - an initial double-blind placebo-controlled (DBPC) period (Part A) followed by a double-blind active treatment extension (ATE) period (Part B), with the following primary objectives: Part A To assess the safety and efficacy of lanifibranor compared to placebo on 'NASH resolution and improvement of fibrosis' assessed by liver histology. Part B To assess the safety of lanifibranor beyond the DBPC period. Secondary objectives Key secondary objectives of Part 1: - To assess the effect of lanifibranor compared to placebo on NASH resolution and no worsening of fibrosis - To assess the effect of lanifibranor compared to placebo on improvement of fibrosis with no worsening of NASH Other secondary objectives of both Part 1 and Part 2: - To assess the effect of lanifibranor on other key histological features of NASH (only for DBPC period) - To assess the effect of lanifibranor on NASH resolution and improvement of fibrosis in diabetic patients (only for DBPC period) - To assess the effect of lanifibranor on liver tests - To assess the effect of lanifibranor on glycaemic parameters - To assess the effect of lanifibranor on lipid parameters - To assess the effect of lanifibranor on liver stiffness and steatosis assessed by elastography. - To assess the effect of lanifibranor on health-related quality of life - To assess the safety of lanifibranor - To assess population PK modeling through plasma levels of lanifibranor using sparse sampling scheme (only for DBPC period)

Effectiveness and Safety of Sphaeralcea Angustifolia Standardized Extract as a Topical Treatment of Knee Osteoarthritis

In order to identify possible participants, the project will be promoted in the outpatient waiting rooms for family medicine and specialties of the General Hospital of Zone # 1 of the Mexican Institute of Social Security (IMSS) in Cuernavaca, Morelos. People interested in participating will be asked to go to the clinical research office so that the supporting physician will perform a medical history in addition to a physical examination, in this way the clinical diagnosis of knee osteoarthritis will be made and it will be defined if the patient meets the clinical criteria necessary to be included in the study. Once it is determined that the patient is a possible candidate and the diagnostic, treatment and follow-up procedures can be continued, the patient will need to sign an informed consent letter, duly completed and authorized by the Ethics Committee. Otherwise, if patient decide not to participate, an interconsultation with the corresponding family doctor will be given. To make the radiological diagnosis, the patient will be submitted to X-ray office, in order to take a front to back and lateral knee (s) radiograph. Once the diagnosis is corroborated, the participants will prepare a file that will contain a questionnaire with questions related to sociodemographic, personal, family and condition history, in addition, treatment will be assigned with the corresponding folio number upon admission. Each of the patients will be given oral and written instructions on how the treatment should be administered and the hygienic measures that must be followed during their participation in the study. The first administration of the treatment will be in the research office, in order to teach the participant how to do it; later, instructions about how the medication should be administered three times a day in the affected knee (s), for four weeks will be given. Patients will be cited every week for four weeks where their evolution will be assessed; in each of the appointments. Patients will undergo a complete evaluation of their condition, there will be a format in which each of the data that is collected will be recorded, either at the interrogation or on the physical examination. The patients will be summoned every week in order to evaluate the evolution of the disease, and consequently the therapeutic efficacy by means of the Visual Analogue Scale of pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of function, a scale used to evaluate function of the knee. The presence of adverse effects (Therapeutic tolerability) and the adherence to the treatment (based on the days of administration) will be evaluated. A concentrate related to tolerability and adherence to treatment will be filled in each of the patients.

PRECAMA: Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women

Breast cancer (BC) has become a major public health problem in Latin America (LA), as it is the most common form of cancer among women. In Women are more likely to develop BC at younger age, and to be diagnosed at an advanced stage compared to western women. Over the past twenty years, the mortality from BC in LA has also been increasing very rapidly, and is currently the leading cause of cancer mortality among LA women. The large number of incident BC cases among premenopausal women, which is only partly explained by the population age-structure, is therefore of major concern. Little is known on specific risk factors for premenopausal BC in general, and in LA in particular, and risk factors related to diet, obesity and low physical activity play a role on incidence and mortality. Estrogen receptor (ER) and/or Progesterone receptor (PR) expression in breast tumors may differ according to risk factors and to molecular pathological characteristics. There is a lack of specific knowledge on tumor molecular and pathological characteristics of BC in premenopausal women, particularly in lower resource countries where the hormone-dependence status is poorly documented. This has major consequences on cancer treatment and survival. To improve our understanding of determinants of BC incidence and mortality in young Latin America women and support preventive actions, we implemented an international, population-based multi-center case-control study in LA: the PRECAMA study (Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women (PRECAMA): a multicenter population-based case-control study). PRECAMA is coordinated by the International Agency for Research on Cancer (IARC), and is conducted within 4 Latin American countries: Mexico, Costa Rica, Colombia and Chile. Major aims of the project are the following: 1. To develop a multi-centric population-based case-control study on BC in premenopausal women in several countries in LA with structured collection of individual, clinical, pathological information and biological specimens, according to strictly controlled protocols 2. To characterize, in these populations, the subtypes of premenopausal BC on the basis of their molecular and pathological phenotypes 3. To improve the identification of specific endogenous/exogenous factors, and disentangle the interplay of these different factors with regard to breast tumor subtypes. 4. Provide advanced training, induce a structuring effect on the BC research community in LA and influence the public health agenda regarding the management of BC. Standardized methods and questionnaires have been developed and implemented as well as standard operating procedures for laboratory activities. Incident primary invasive cases aged 20-45 years are recruited from major cancer hospitals in four large Latin American cities (Mexico City, San Jose, Medellin, and Santiago) prior to any treatments. Controls for the study are selected from the population residing in the same cities for at least 3 years and matched to cases on age (+/- 5 years) and health care institution. For each subject, complete questionnaire data on socio-demographic factors, health history, reproductive history, use of hormones, early risk factors, body silhouette at different ages, physical activity, diet, occupation, environmental risk factors, ethnicity, and family history of cancer are collected. Validated and standardized food frequency questionnaires are administered to gather information on diet. Anthropometry (body weight, standing and sitting height, waist and hip circumferences) are measured according to standardized protocols. Blood and urine samples are also collected for biomarker analyses. For all cases, highly standardized immunohistochemical and molecular analyses are performed to identify BC subtypes. The results of our study will be of utmost importance to understand the etiology of breast cancer in Latin America countries in epidemiological transition, and would provide important information on the role of modifiable exposures on the disease which may provide important support for breast cancer prevention.