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BACKGROUND: The American Joint Committee on Cancer (AJCC) method of staging melanoma is dated and inaccurate. It ignores important prognostic melanoma features, especially the patient's age. BAUSSS is more accurate in determining survival risk for primary cutaneous melanoma patients who have no clinical or imaging evidence of nodal or distant metastases. BAUSSS is an algorithm incorporating analysis of Breslow thickness, Age, Ulceration, Subtype of melanoma, Sex and Site. These are the six features from the patient history along with the details from the melanoma pathology report that are most predictive of mortality outcome. OBJECTIVE: To develop a single-page document that allows the clinician to determine BAUSSS biomarker-predicted prognosis in consultation with the patient. METHOD: From various data sources, we developed an algorithm to predict melanoma mortality using the BAUSSS biomarker system. The single-page algorithm was made available to download at https://globalmelanoma.net/bausss-survival-chart, thus being readily available without charge to all clinicians and their patients. RESULTS: BAUSSS method of determining melanoma prognosis is more accurate and less costly than the AJCC staging system. The only surgery the patient requires is wide local excision of the primary tumour. This method of ascertaining melanoma risk does not require added surgery, costs, hospitalization, tests and anaesthesia, such as would be required if sentinel lymph node biopsy was undertaken. BAUSSS can be a useful tool in determining which primary melanoma patients are at sufficiently high risk to be considered for adjuvant drug therapy. CONCLUSION: We encourage clinicians to download and print in colour this single-page BAUSSS mortality prediction tool, laminate it, and use it face to face with the patient in consultations. Not only will the patient be able to recognize his/her long-term prognosis but will also be able to see how their tumour severity compares with others.
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BACKGROUND: Melanoma disease patterns vary with patient age. AIM: To evaluate sentinel lymph node biopsy (SLNB) in managing melanoma at differing patient ages. METHODS: Online prediction tools were applied to compare SLNB positivity (SLNB+) and survival risk at patient ages 20-80. Tübingen melanoma data were used to determine variations in the hazard ratio of SLNB+ for mortality at different patient ages. RESULTS: Regardless of tumour thickness, predicted SLNB+ rates were markedly higher than mortality rates for 20-year-old patients. For 80-year-old patients, it is the opposite. DISCUSSION: If 1000 20-year-olds with a 0.4 mm thickness non-ulcerated melanoma underwent SLNB, 100 would likely be positive. If all 100 were to be offered adjuvant drug therapy (ADT), fewer than three more melanoma deaths in those 1000 patients would be avoided. In total, 97 patients would have received medication they may never have needed. If 1000 80-year-olds with a 3 mm thickness non-ulcerated melanoma underwent SLNB, only 40 would likely be positive. In total, 274 patients would be predicted to die of melanoma, 245 being SLNB negative and 29 SLNB+. ADT linked to SLNB+ could deny treatment to 89% of these high-risk patients. LIMITATIONS: The authors relied on published risk data. CONCLUSION: SLNB has poor specificity at predicting mortality in young melanoma patients and poor sensitivity in older patients. SLNB is not indicated in managing cutaneous melanoma for patients under 40 or over 60 years of age. Many such patients could be managed with wide local excision alone in their clinician's office-based practice. For all cutaneous melanoma patients at all ages, linking ADT to BAUSSS biomarker, (an algorithm of Breslow thickness, age, ulceration, subtype, sex and Site) rather than SLNB+ is likely more appropriate. BAUSSS provides a more accurate melanoma-specific mortality risk assessment for patients without burdening them with added surgery, hospitalization, costs or morbidity risk.
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Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Persona de Mediana Edad , Anciano , Adulto Joven , Adulto , Anciano de 80 o más Años , Melanoma/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Estadificación de Neoplasias , Ganglio Linfático Centinela/patología , Pronóstico , Estudios RetrospectivosRESUMEN
Evaluating healthcare digitalisation, where technology implementation and adoption transforms existing socio-organisational processes, presents various challenges for outcome assessments. Populations are diverse, interventions are complex and evolving over time, meaningful comparisons are difficult as outcomes vary between settings, and outcomes take a long time to materialise and stabilise. Digitalisation may also have unanticipated impacts. We here discuss the limitations of evaluating the digitalisation of healthcare, and describe how qualitative and quantitative approaches can complement each other to facilitate investment and implementation decisions. In doing so, we argue how existing approaches have focused on measuring what is easily measurable and elevating poorly chosen values to inform investment decisions. Limited attention has been paid to understanding processes that are not easily measured even though these can have significant implications for contextual transferability, sustainability and scale-up of interventions. We use what is commonly known as the McNamara Fallacy to structure our discussions. We conclude with recommendations on how we envisage the development of mixed methods approaches going forward in order to address shortcomings.
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Atención a la Salud , Proyectos de Investigación , HumanosRESUMEN
Artificial intelligence (AI) and machine learning medical tools have the potential to be transformative in care delivery; however, this change will only be realized if accompanied by effective governance that ensures patient safety and public trust. Recent digital health initiatives have called for tighter governance of digital health. A correct balance must be found between ensuring product safety and performance while also enabling the innovation needed to deliver better approaches for patients and affordable efficient health care for society. This requires innovative, fit-for-purpose approaches to regulation. Digital health technologies, particularly AI-based tools, pose specific challenges to the development and implementation of functional regulation. The approaches of regulatory science and "better regulation" have a critical role in developing and evaluating solutions to these problems and ensuring effective implementation. We describe the divergent approaches of the European Union and the United States in the implementation of new regulatory approaches in digital health, and we consider the United Kingdom as a third example, which is in a unique position of developing a new post-Brexit regulatory framework.
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Inteligencia Artificial , Atención a la Salud , Humanos , Unión Europea , Reino Unido , Aprendizaje AutomáticoRESUMEN
Integrating health and social care delivery with the help of digital technologies is a grand challenge. We argue that previous attempts have largely failed to achieve their objectives because implementers and decision makers disregard the complex socio-organizational dimensions of change associated with initiatives. These include structural and organizational complexity inhibiting the development of shared care pathways; professional jurisdictions, interests, and expertise; and existing data and governance structures. We provide an overview of those dimensions that can inform strategic decisions going forward, thereby contributing to the chances of success of shared care initiatives.
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Atención a la Salud , Apoyo Social , Humanos , Probabilidad , Prestación Integrada de Atención de SaludAsunto(s)
Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Trombosis , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Puente Cardiopulmonar/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/cirugíaRESUMEN
We modeled 3D structures of all SARS-CoV-2 proteins, generating 2,060 models that span 69% of the viral proteome and provide details not available elsewhere. We found that Ë6% of the proteome mimicked human proteins, while Ë7% was implicated in hijacking mechanisms that reverse post-translational modifications, block host translation, and disable host defenses; a further Ë29% self-assembled into heteromeric states that provided insight into how the viral replication and translation complex forms. To make these 3D models more accessible, we devised a structural coverage map, a novel visualization method to show what is-and is not-known about the 3D structure of the viral proteome. We integrated the coverage map into an accompanying online resource (https://aquaria.ws/covid) that can be used to find and explore models corresponding to the 79 structural states identified in this work. The resulting Aquaria-COVID resource helps scientists use emerging structural data to understand the mechanisms underlying coronavirus infection and draws attention to the 31% of the viral proteome that remains structurally unknown or dark.
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Enzima Convertidora de Angiotensina 2/metabolismo , Interacciones Huésped-Patógeno/genética , Procesamiento Proteico-Postraduccional , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/química , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/genética , Sitios de Unión , COVID-19/genética , COVID-19/metabolismo , COVID-19/virología , Biología Computacional/métodos , Proteínas de la Envoltura de Coronavirus/química , Proteínas de la Envoltura de Coronavirus/genética , Proteínas de la Envoltura de Coronavirus/metabolismo , Proteínas de la Nucleocápside de Coronavirus/química , Proteínas de la Nucleocápside de Coronavirus/genética , Proteínas de la Nucleocápside de Coronavirus/metabolismo , Humanos , Proteínas de Transporte de Membrana Mitocondrial/química , Proteínas de Transporte de Membrana Mitocondrial/genética , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Modelos Moleculares , Imitación Molecular , Neuropilina-1/química , Neuropilina-1/genética , Neuropilina-1/metabolismo , Fosfoproteínas/química , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Mapeo de Interacción de Proteínas/métodos , Multimerización de Proteína , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas de la Matriz Viral/química , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/metabolismo , Proteínas Viroporinas/química , Proteínas Viroporinas/genética , Proteínas Viroporinas/metabolismo , Replicación ViralRESUMEN
PURPOSE OF REVIEW: To improve our clinical understanding of facial onset sensory and motor neuronopathy (FOSMN). RECENT FINDINGS: We identified 29 new cases and 71 literature cases, resulting in a cohort of 100 patients with FOSMN. During follow-up, cognitive and behavioral changes became apparent in 8 patients, suggesting that changes within the spectrum of frontotemporal dementia (FTD) are a part of the natural history of FOSMN. Another new finding was chorea, seen in 6 cases. Despite reports of autoantibodies, there is no consistent evidence to suggest an autoimmune pathogenesis. Four of 6 autopsies had TAR DNA-binding protein (TDP) 43 pathology. Seven cases had genetic mutations associated with neurodegenerative diseases. SUMMARY: FOSMN is a rare disease with a highly characteristic onset and pattern of disease progression involving initial sensory disturbances, followed by bulbar weakness with a cranial to caudal spread of pathology. Although not conclusive, the balance of evidence suggests that FOSMN is most likely to be a TDP-43 proteinopathy within the amyotrophic lateral sclerosis-FTD spectrum.
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Despite their severely impaired episodic memory, individuals with amnesia are able to comprehend ongoing events. Online representations of a current event are thought to be supported by a network of regions centred on the posterior midline cortex (PMC). By contrast, episodic memory is widely believed to be supported by interactions between the hippocampus and these cortical regions. In this MRI study, we investigated the encoding and retrieval of real life-like events (video clips) in a patient with severe amnesia likely resulting from a stroke to the right (and possibly the left) thalamus, and a group of 20 age-matched controls. Structural MRI revealed grey matter reductions in left hippocampus and left thalamus in comparison to controls. We first characterised the regions activated in the controls while they watched and retrieved the videos. There were no differences in activation between the patient and controls in any of the regions. We then identified a widespread network of brain regions, including the hippocampus, that were functionally connected with the PMC in controls. However, in the patient there was a specific reduction in functional connectivity between the PMC and a region of left hippocampus when both watching and attempting to retrieve the videos. A follow up analysis of the control group revealed that, when watching the videos, the functional connectivity between these two regions was correlated with memory performance. Taken together, these findings support the view that the interactions between the PMC and the hippocampus enable the encoding and retrieval of naturalistic events.
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Amnesia/fisiopatología , Conectoma , Hipocampo/fisiopatología , Red Nerviosa/fisiopatología , Anciano , Amnesia/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Tálamo/patologíaRESUMEN
BACKGROUND: Maximising survival for patients with invasive melanoma hinges on early diagnosis of primary melanoma and appropriate management. Despite well-documented guidelines, many patients with melanoma have not been managed ideally. OBJECTIVE: The aim of this paper is to identify suboptimal aspects of melanoma management. DISCUSSION: Delayed or erroneous diagnosis is more likely to occur when a shave or punch biopsy is used to obtain histopathology. Wherever feasible, local excision with a narrow margin is the preferred biopsy choice for a suspected melanoma. The Breslow thickness of the primary melanoma remains the greatest predictor of outcome. Ulceration is associated with a poorer prognosis. Most invasive melanomas are managed with a margin of ≥10 mm of normal tissue. Patients who have developed one primary melanoma are at high risk of a second tumour. Ongoing management includes regular lifelong skin checks. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet radiation are useful. Imaging is largely used when metastases are suspected on the basis of clinical symptoms or signs.
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BACKGROUND: Several new medications have shown improved survival rates in high-risk patients with melanoma. OBJECTIVE: The aim of this article is to discuss the new medications and outline their roles, the expected benefit from each and the risk of adverse events. We explain the place of sentinel lymph node biopsy (SLNB) and ultrasonography with fine needle aspiration (US-FNA) in assessing and treating patients with melanoma. DISCUSSION: Ipilimumab has limited efficacy and a very concerning complication profile. More than 50% of patients taking ipilimumab have severe or life-threatening adverse events. BRAF inhibitors have greater efficacy and fewer adverse events than ipilimumab. Combining BRAF inhibitors with mitogen-activated protein kinase inhibitors enhances their effect and improves the overall adverse event profile. BRAF inhibitors are only effective when the melanoma has a BRAF gene mutation, something that occurs in only 50% of cases. Programmed cell death protein 1 medications are also more effective and have a much more acceptable adverse event profile than ipilimumab. Both SLNB and US-FNA can detect early node involvement in patients with melanoma, although US-FNA is a safer procedure.
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As the HIV population ages, the prevalence of cognitive impairment (CI) is increasing, yet few services exist for the assessment and management of these individuals. Here we provide an initial description of a memory assessment service for people living with HIV and present data from a service evaluation undertaken in the clinic. We conducted an evaluation of the first 52 patients seen by the clinic. We present patient demographic data, assessment outcomes, diagnoses given and interventions delivered to those seen in the clinic. 41 patients (79%) of those seen in the clinic had objective CI: 16 (31%) met criteria for HIV-associated Neurocognitive Disorder (HAND), 2 (4%) were diagnosed with dementia, 14 (27%) showed CI associated with mental illness and/or drugs/alcohol, 7 (13%) had CI which was attributed to factors other than HIV and in 2 (4%) patients the cause remains unclear. 32 (62%) patients showed some abnormality on Magnetic Resonance Imaging (MRI) brain scans. Patients attending the clinic performed significantly worse than normative scores on all tests of global cognition and executive function. Interventions offered to patients included combination antiretroviral therapy modification, signposting to other services, case management, further health investigations and in-clinic advice. Our experience suggests that the need exists for specialist HIV memory services and that such a model of working can be successfully implemented into HIV patient care. Further work is needed on referral criteria and pathways. Diagnostic processes and treatment offered needs to consider and address the multifactorial aetiology of CI in HIV and this is essential for effective assessment and management.
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Susac syndrome is a rare condition characterised by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. Of the few published cases, there is variability with regard to cognitive outcome. We describe the clinical course and neuropsychological performance of a 21-year-old male patient presenting with severe encephalopathy and later developing the full triad fulfilling the diagnosis of Susac syndrome.
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Trastornos del Conocimiento , Síndrome de Susac , Adulto , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Humanos , Masculino , Pruebas Neuropsicológicas , Síndrome de Susac/complicaciones , Síndrome de Susac/diagnósticoRESUMEN
BACKGROUND: The future of health care services in the European Union faces the triple challenges of aging, fiscal restriction, and inclusion. Co-production offers ways to manage informal care resources to help them cater for the growing needs of elderly people. Social media (SM) is seen as a critical enabler for co-production. OBJECTIVE: The objective of this study was to investigate how SM-private Facebook groups, forums, Twitter, and blogging-acts as an enabler of co-production in health and care by facilitating its four underlying principles: equality, diversity, accessibility, and reciprocity. METHODS: We used normalization process theory as our theoretical framework to design this study. We conducted a qualitative study and collected data through 20 semistructured interviews and observation of the activities of 10 online groups and individuals. We then used thematic analysis and drew on principles of co-production (equality, diversity, accessibility, and reciprocity) as a deductive coding framework to analyze our findings. RESULTS: Our findings point to distinct patterns of feature use by different people involved in care of elderly people. This diversity makes possible the principles of co-production by offering equality among users, enabling diversity of use, making experiences accessible, and encouraging reciprocity in the sharing of knowledge and mutual support. We also identified that explication of common resources may lead to new forms of competition and conflicts. These conflicts require better management to enhance the coordination of the common pool of resources. CONCLUSIONS: SM uses afford new forms of organizing and collective engagement between patients, carers, and professionals, which leads to change in health and care communication and coordination.
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We discuss the assessment and differential diagnoses of a young adult Hungarian man with a 1-year history of a progressive and symmetric amyotrophic lateral sclerosis-like syndrome, along with irregular action tremor and stimulus-sensitive myoclonus of the arms. MR scan of the brain showed isolated cerebellar atrophy and formal neuropsychometric testing identified significant subclinical deficits in attention, processing speed and memory. We suspected a form of GM2 gangliosidosis, and white cell enzyme analysis showed markedly reduced enzymatic activity of ß-hexosaminidase A. Genetic testing subsequently revealed two heterozygous pathogenic mutations in the HEXA gene (c.1499delT p.(Leu500fs) and c.805G>A p.(Gly269Ser)), confirming the very rare diagnosis of adult-onset Tay-Sachs disease.
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Enfermedad de Tay-Sachs/diagnóstico , Enfermedad de Tay-Sachs/fisiopatología , Adulto , Edad de Inicio , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Creatina Quinasa/sangre , Diagnóstico Diferencial , Electrocardiografía , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedad de Tay-Sachs/sangre , Tomografía Computarizada por Rayos XRESUMEN
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