Project description:ImportanceUse of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care.ObjectiveTo develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies.Evidence reviewThe MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed.FindingsThe MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility.Conclusions and relevanceMore evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.
Project description:After reaching a nadir at the turn of the century, syphilis rates in the United States have increased since 2000. Treponema pallidum may disseminate to the central nervous system within hours to days after inoculation. In this review, we focus on knowledge gaps and areas of controversy in neurosyphilis epidemiology, diagnosis, and management. Modern estimates of the prevalence of neurosyphilis are hindered by the lack of consistent reporting data and are based on relatively small retrospective cohort studies. The various diagnostic modalities for neurosyphilis have significant limitations. Although several novel biomarkers for neurosyphilis have been evaluated, none to date have found a place in clinical practice. The role of a cerebrospinal fluid examination in patients without neurological symptoms continues to be an area of controversy, whereas the data for the use of antibiotic regimens other than intravenous aqueous or intramuscular procaine penicillin for the treatment of neurosyphilis are limited. As syphilis incidence continues to increase unabated in many countries around the world, it is critical to address these gaps of knowledge.
Project description:Although first described more than 120 years ago, much remains unknown about coccidioidomycosis. In this review, new information that has led to changing concepts will be reviewed and remaining gaps in our knowledge will be discussed. In particular, new ideas regarding ecology and epidemiology, problems and promises of diagnosis, controversies over management, and the possibility of a vaccine will be covered.
Project description:A valuable strategy to support conservation planning is to assess knowledge gaps regarding primary species occurrence data to identify and select areas for future biodiversity surveys. Currently, increasing accessibility to these data allows a cost-effective method for boosting knowledge about a country's biodiversity. For understudied countries where the lack of resources for conservation is more pronounced to resort to primary biodiversity data can be especially beneficial. Here, using a primary species occurrence dataset, we assessed and mapped Mozambique's knowledge gaps regarding terrestrial mammal species by identifying areas that are geographically distant and environmentally different from well-known sites. By comparing gaps from old and recent primary species occurrence data, we identified: (i) gaps of knowledge over time, (ii) the lesser-known taxa, and (iii) areas with potential for spatiotemporal studies. Our results show that the inventory of Mozambique's mammal fauna is near-complete in less than 5% of the territory, with broad areas of the country poorly sampled or not sampled at all. The knowledge gap areas are mostly associated with two ecoregions. The provinces lacking documentation coincide with areas over-explored for natural resources, and many such sites may never be documented. It is our understanding that by prioritising the survey of the knowledge-gap areas will likely produce new records for the country and, continuing the study of the well-known regions will guarantee their potential use for spatiotemporal studies. The implemented approach to assess the knowledge gaps from primary species occurrence data proved to be a powerful strategy to generate information that is essential to species conservation and management plan. However, we are aware that the impact of digital and openly available data depends mostly on its completeness and accuracy, and thus we encourage action from the scientific community and government authorities to support and promote data mobilisation.
Project description:Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), accounting for around 1-5% of the global TB caseload, with mortality of approximately 20% in children and up to 60% in persons co-infected with human immunodeficiency virus even in those treated. Relatively few centres of excellence in TBM research exist and the field would therefore benefit from greater co-ordination, advocacy, collaboration and early data sharing. To this end, in 2009, 2015 and 2019 we convened the TBM International Research Consortium, bringing together approximately 50 researchers from five continents. The most recent meeting took place on 1 st and 2 nd March 2019 in Lucknow, India. During the meeting, researchers and clinicians presented updates in their areas of expertise, and additionally presented on the knowledge gaps and research priorities in that field. Discussion during the meeting was followed by the development, by a core writing group, of a synthesis of knowledge gaps and research priorities within seven domains, namely epidemiology, pathogenesis, diagnosis, antimicrobial therapy, host-directed therapy, critical care and implementation science. These were circulated to the whole consortium for written input and feedback. Further cycles of discussion between the writing group took place to arrive at a consensus series of priorities. This article summarises the consensus reached by the consortium concerning the unmet needs and priorities for future research for this neglected and often fatal disease.
Project description:Essential tremor (ET) is a common cause of significant disability, but its etiologies and pathogenesis are poorly understood. Research has been hampered by the variable definition of ET and by non-standardized research approaches. The National Institute of Neurological Disorders and Stroke (USA) invited experts in ET and related fields to discuss current knowledge, controversies, and gaps in our understanding of ET and to develop recommendations for future research. Discussion focused on phenomenology and phenotypes, therapies and clinical trials, pathophysiology, pathology, and genetics. Across all areas, the need for collaborative and coordinated research on a multinational level was expressed. Standardized data collection using common data elements for genetic, clinical, neurophysiological, and pathological studies was recommended. Large cohorts of patients should be studied prospectively to collect bio-samples, characterize the natural history of the clinical syndrome including patient-oriented outcomes, investigate potential etiologies of various phenotypes, and identify pathophysiological mechanisms. In particular, cellular and system-level mechanisms of tremor oscillations should be elucidated because they may yield effective therapeutic targets and biomarkers. A neuropathology consortium was recommended to standardize postmortem analysis and further characterize neuropathological observations in the cerebellum and elsewhere. Furthermore, genome-wide association studies on large patient cohorts (>10,000 patients) may allow the identification of common genes contributing to risk, and whole exome or genome sequencing may enable the identification of genetic risk and causal mutations in cohorts and well-characterized families.
Project description:With an emphasis on systems analyses, the VSV-EBOVAC project harnesses state-of-the-art technologies that illuminate mechanisms behind the observed immunogenicity and reactogenicity of the rVSV-ZEBOV vaccine and ensures that such information is shared among stakeholders.
Project description:Sexually Transmitted Infections (STIs) are ambiguous burden of tremendous health, social and economic consequences. The current systematic review was conducted in order to determine awareness and knowledge of Africans toward sexually transmitted infections, not only concerning HIV/AIDS, but also other STIs such as gonorrhea, syphilis, HBV, HCV and HPV. A systematic review of literature was conducted, studies were retrieved and selected after fulfilling the inclusion criteria as well as passing the assessment procedure. Related data was extracted, quantitative analysis was conducted among participants who responded to questions related to HIV, HBV, HCV, HPV or STIs knowledge, sensitivity analysis as well as subgroup analysis were also conducted. Seventy four articles addressing knowledge among 35 African countries were included and 136 questions were analyzed and synthesized. The question "does using condom reduces HIV transmission?" was answered by 1,316,873 Africans in 35 countries, 66.8% [95% Cl; 62.6, 70.9] answered yes. While the question "is sexual contact a possible route of HBV transmission?" was answered by 7,490 participants in 5 countries; 42.5% [95% Cl; 20.4, 64.7] answered yes. The differences observed among populations are highlighting the possibility for improvement by directing light toward specific populations as well as addressing specific awareness knowledge to ensure that the general as well as the related specific preventive knowledge is improved.
Project description:Subclinical hypertrophic cardiomyopathy (HCM) is a phenotypic entity that has emerged from the increased use of cardiovascular magnetic resonance imaging in the evaluation and family screening of patients with HCM. We describe the case of a competitive athlete with a sarcomere gene mutation and family history of HCM who was found to exhibit the subclinical HCM phenotype on cardiovascular magnetic resonance imaging in the absence of left ventricular hypertrophy. We discuss the clinical uncertainties in her management. (Level of Difficulty: Advanced.).
Project description:Immunoglobulin A vasculitis (IgAV; formerly Henoch Schonlein Purpura) is the most common form of childhood vasculitis. It can occur in any age and peaks around 4-6 years old. It demonstrates seasonal variation implicating a role for environmental triggers and geographical variation. The diagnosis is made clinically and 95% of patients will present with a rash, together with any from a triad of other systems-gastrointestinal, musculoskeletal, and renal. Most cases of IgAV in children have an excellent outcome. Treatment may be required during the acute phase for gastrointestinal involvement and renal involvement, termed IgAV nephritis (previously HSP nephritis), is the most serious long-term manifestation accounting for ~1-2% of all childhood end stage kidney disease (ESKD). It therefore requires a period of renal monitoring conducted for 6-12 months. Patients presenting with nephrotic and/or nephritic syndrome or whom develop significant persistent proteinuria should undergo a renal biopsy to evaluate the extent of renal inflammation and there are now international consensus guidelines that outline the indications for when to do this. At present there is no evidence to support the use of medications at the outset in all patients to prevent subsequent renal inflammation. Consensus management guidelines suggest using oral corticosteroids for milder disease, oral, or intravenous corticosteroids plus azathioprine or mycophenolate mofetil or intravenous cyclophosphamide for moderate disease and intravenous corticosteroids with cyclophosphamide for severe disease. Angiotensin system inhibitors act as adjunctive treatment for persisting proteinuria and frequently relapsing disease may necessitate the use of immunosuppressant agents. Renal outcomes in this disease have remained static over time and progress may be hindered due to many reasons, including the lack of reliable disease biomarkers and an absence of core outcome measures allowing for accurate comparison between studies. This review article summarizes the current evidence supporting the management of this condition highlighting recent findings and areas of unmet need. In order to improve the long term outcomes in this condition international research collaboration is urgently required.