Patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

alkiviadis.1961 shared this article with you from Inoreader [Articles] Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study Via The Lancet Neurology In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Nothing to be ashamed of: sex robots for older adults with disabilities

alkiviadis.1961 shared this article with you from Inoreader Nothing to be ashamed of: sex robots for older adults with disabilities Via Journal of Medical Ethics Online First This paper spotlights ways in which sexual capacities relate to central human capabilities, such as the ability to generate a personally meaningful story of one's life; be physically, mentally and emotionally healthy; experience bodily integrity; affiliate and bond with others; feel and express a range of human emotions; and choose a plan of life. It sets forth a dignity-based argument for affording older people access to sex robots as part of reasonable efforts to support their central human capabilities at a flo or level. The argument develops stepwise: (1) first, I dispel ageism and negative stereotypes about later-life sexuality, showing their deep historical roots in medicine and science; (2) second, I set forth a positive argument, grounded in capability accounts of justice, for deploying sex robots for older people with disabilities; (3) finally, after responding to objections, I conclude that sex robots are a reasonable way to support later-life sexuality for persons with disabilities. While often depicted as a product for younger, able-bodied people, this paper is a bid for reimagining sex robots as a product for older, disabled people. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers

alkiviadis.1961 shared this article with you from Inoreader EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers Via Gut Online First Objective Epidermal growth factor receptor (EGFR) inhibition may be effective in biomarker-selected populations of advanced gastro-oesophageal adenocarcinoma (aGEA) patients. Here, we tested the association between outcome and EGFR copy number (CN) in pretreatment tissue and plasma cell-free DNA (cfDNA) of patients enrolled in a randomised first-line phase III clinical trial of chemotherapy or chemotherapy plus the anti-EGFR monoclonal antibody panitumumab in aGEA (NCT00824785). Design EGFR CN by eith er fluorescence in situ hybridisation (n=114) or digital-droplet PCR in tissues (n=250) and plasma cfDNAs (n=354) was available for 474 (86%) patients in the intention-to-treat (ITT) population. Tissue and plasma low-pass whole-genome sequencing was used to screen for coamplifications in receptor tyrosine kinases. Interaction between chemotherapy and EGFR inhibitors was modelled in patient-derived organoids (PDOs) from aGEA patients. Results EGFR amplification in cfDNA correlated with poor survival in the ITT population and similar trends were observed when the analysis was conducted in tissue and plasma by treatment arm. EGFR inhibition in combination with chemotherapy did not correlate with improved survival, even in patients with significant EGFR CN gains. Addition of anti-EGFR inhibitors to the chemotherapy agent epirubicin in PDOs, resulted in a paradoxical increase in viability and accelerated progression through the cell cycle, associated with p21 and cycli n B1 downregulation and cyclin E1 upregulation, selectively in organoids from EGFR-amplified aGEA. Conclusion EGFR CN can be accurately measured in tissue and liquid biopsies and may be used for the selection of aGEA patients. EGFR inhibitors may antagonise the antitumour effect of anthracyclines with important implications for the design of future combinatorial trials. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

LSG vs MGB-OAGB: 5-Year Follow-up Data and Comparative Outcome of the Two Procedures over Long Term—Results of a Randomised Control Trial

alkiviadis.1961 shared this article with you from Inoreader LSG vs MGB-OAGB: 5-Year Follow-up Data and Comparative Outcome of the Two Procedures over Long Term—Results of a Randomised Control Trial Via Latest Results for Obesity Surgery Abstract Background Bariatric surgery is a durable and effective way for the management of obesity and resolution of related comorbidities. The aim of this study is to evaluate the outcome of laparoscopic sleeve gastrectomy (LSG) and one-anastomosis gastric bypass (OAGB) over long term in a South Asian population. Materials and Methods This is a prospective randomised trial comparing the outcome of 100 and 101 LSG and OAGB patients respectively after 5-year follow-up. This study is in continuity with previous published papers with 1- and 3-year follow-up. 71 LSG and 73 OAGB patients followed at 5 years. The results of these patients were analysed and compared in terms of %EWL, comorbidity resolution and quality of life (QoL) at 5 years. Bariatric analysis reporting and outcome system (BAROS) was used to assess the outcome of patients. Results At 5-year follow-up, both LSG and OAGB patients performed well and patients had significant improvement in BMI (kg/m2). The mean preoperative BMI of LSG and OAGB patients was 44.89 ± 7.94 and 45.32 ± 8.24, and their mean BMI at 5 years was 33.41 ± 6.02, 30.80 ± 3.40 respectively. At 5 years, %EWL was 55.95 ± 27.01 and 65.28 ± 13.98 for LSG and OAGB patients respectively. The QoL score of LSG and OAGB patients was 1.86 ± 0.56 and 2.35 ± 0.41 while comorbidity score was 1.84 ± 0.68 and 2.24 ± 0.62 respectively at 5 years. Conclusions Both LSG and OAGB are effective bariatric procedures over long term with respect to weight loss, comorbidity resolution and improvement in QoL. OAGB is significantly better than LSG in all the three parameters at 5 years. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

18F-Fluorocholine PET/CT is a highly sensitive but poorly specific tool for identifying malignancy in thyroid nodules with indeterminate cytology: The Chocolate study.

alkiviadis.1961 shared this article with you from Inoreader 18F-Fluorocholine PET/CT is a highly sensitive but poorly specific tool for identifying malignancy in thyroid nodules with indeterminate cytology: The Chocolate study. Via thyroid Related Articles 18F-Fluorocholine PET/CT is a highly sensitive but poorly specific tool for identifying malignancy in thyroid nodules with indeterminate cytology: The Chocolate study. Thyroid. 2020 Nov 12;: Authors: Ciappuccini R, Licaj I, Lasne-Cardon A, Babin E, de Raucourt D, Blanchard D, Bastit V, Saguet-Rysanek V, Lequesne J, Peyronnet D, Grellard JM, Clarisse B, Bardet S Abstract Background Refining the risk of malignancy in patients presenting thyroid nodules with indeterminate cytology (IC) is a critical challenge. We investigated the performances of 18F-Fluorocholine (FCH) PET/CT to predict malignancy. Methods Between May 2016 and March 2019, 107 patients presenting a thyroid nodule ≥15 mm with IC and eligible for surgery were prospectively included (ClinicalTrials.gov identifier: NCT02784223). Head-and-neck PET/CT acquisitions were performed 20 min and 60 min after injection of 1.5 MBq/kg of FCH. PET/CT acquisition was scored positive when maximal standardized uptake value in the IC nodule was higher than in the thyroid background. Pathology was the gold standard. Results At pathology, 19 (18%) nodules were malignant, 87 were benign and one was a non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) of FCH PET/ CT in detecting cancer or NIFTP were respectively 90%, 50%, 55%, 29% and 96% at 20 min and 85%, 49%, 67%, 28%, and 94% at 60 min. Higher specificity (58% vs 33%, p=0.01) was observed in non-oncocytic (n=72) than in oncocytic IC nodules (n=35). The pre-PET/CT probability of cancer or NIFTP in Bethesda III-IV nodules was 11% and the post-PET/CT probability was 19% in PET-positives and 0% in PET-negatives. A posteriori, 42% of surgeries were unnecessary after PET/CT and 81% before (p<0.001), resulting in a hypothetical 48% reduction (95% CI, 32-64). Conclusions FCH PET/CT offers high NPV to reliably exclude cancer in PET-negative IC nodules but suffers from low PPV, particularly in those with oncocytic cytology. PMID: 33183159 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Congenital hypothyroidism: Space-time clustering of thyroid dysgenesis indicates a role for environmental factors in disease etiology.

alkiviadis.1961 shared this article with you from Inoreader Congenital hypothyroidism: Space-time clustering of thyroid dysgenesis indicates a role for environmental factors in disease etiology. Via thyroid Related Articles Congenital hypothyroidism: Space-time clustering of thyroid dysgenesis indicates a role for environmental factors in disease etiology. Thyroid. 2020 Nov 12;: Authors: McNally R, Jones JH, Shaikh MG, Donaldson M, Blakey K, Cheetham T Abstract BACKGROUND: The etiology of most cases of congenital hypothyroidism (CHT) due to thyroid dysgenesis is unknown. If transient environmental factors can impact on thyroid gland development then clustering of cases in time and / or space may occur and this would be more likely in thyroid dysgenesis than dyshormonogenesis. METHODS: The newborn screening programme for CHT in Scotland is linked to a central database that includes case details such as post-code. The etiology of CHT is investigated in many cases of CHT using scintigraphy and/or ultrasonography. We looked for evidence of a change in CHT incidence with year of birth and according to season of the year. We then undertook space-time clustering analysis (using a method based on K-functions, with nearest neighbor thresholds) of CHT in Scotland 1979-2015. We also looked for evidence of overall changes associated with sex and area-based birth density. RESULTS: Of 531 cases with CHT during the study period, 290 had been categorized as dysgenesis (229) or dyshormonogenesis (61) following more detailed investigation. The incidence of CHT increased with year of birth and was in part linked to changing methodology but there was no seasonality. There was no evidence of overall space-time clustering (p = 0.06), but there was evidence of clustering in babies with dysgenesis (p = 0.007). This picture appeared to be most closely linked to underlying thyroid gland hypoplasia rather than thyroid gland agenesis or ectopia. There was significant space-time clustering for both males and females, but clustering was restricted to lesser birth density areas. There was also evidence of clustering for unknown cases (p < 0.001). Clustering of these cases was restricted to females, but was present for cases from both greater and lesser birth density areas. There was no evidence of clustering in cases of dyshormonogenesis. CONCLUSIONS: These data suggest that an unidentified environmental factor or factors may be involved in the etiology of thyroid dysgenesis in Scotland. The variation in CHT incidence observed internationally may reflect environmental as well as genetic factors. PMID: 33183175 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

COVID-SGIS: A Smart Tool for Dynamic Monitoring and Temporal Forecasting of Covid-19

alkiviadis.1961 shared this article with you from Inoreader COVID-SGIS: A Smart Tool for Dynamic Monitoring and Temporal Forecasting of Covid-19 Via Frontiers in Public Health | New and Recent Articles Background: The global burden of the new coronavirus SARS-CoV-2 is increasing at an unprecedented rate. The current spread of Covid-19 in Brazil is problematic causing a huge public health burden to its population and national health-care service. To evaluate strategies for alleviating such problems, it is necessary to forecast the number of cases and deaths in order to aid the stakeholders in the process of making decisions against the disease. We propose a novel system for real-time forecast of the cumulat ive cases of Covid-19 in Brazil. Methods: We developed the novel COVID-SGIS application for the real-time surveillance, forecast and spatial visualization of Covid-19 for Brazil. This system captures routinely reported Covid-19 information from 27 federative units from the Brazil.io database. It utilizes all Covid-19 confirmed case data that have been notified through the National Notification System, from March to May 2020. Time series ARIMA models were integrated for the forecast of cumulative number of Covid-19 cases and deaths. These include 6-days forecasts as graphical outputs for each federative unit in Brazil, separately, with its corresponding 95% CI for statistical significance. In addition, a worst and best scenarios are presented. Results: The following federative units (out of 27) were flagged by our ARIMA models showing statistically significant increasing temporal patterns of Covid-19 cases during the specified day-to-day period: Bahia, Maranhão, Piauí, Rio Grande do Norte, Amapá, Rondônia, where their day-to-day forecasts were within the 95% CI limits. Equally, the same findings were observed for Espírito Santo, Minas Gerais, Paraná, and Santa Catarina. The overall percentage error between the forecasted values and the actual values varied between 2.56 and 6.50%. For the days when the forecasts fell outside the forecast interval, the percentage errors in relation to the worst case scenario were below 5%. Conclusion: The proposed method for dynamic forecasting may be used to guide social policies and plan direct interventions in a cost-effective, concise, and robust manner. This novel tools can play an important role for guiding the course of action against the Covid-19 pandemic for Brazil and country neighbors in South America. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Learning to BREATHE “Plus”: A Multi-Modal Adaptive Supplement to an Evidence-Based Mindfulness Intervention for Adolescents

alkiviadis.1961 shared this article with you from Inoreader Learning to BREATHE "Plus": A Multi-Modal Adaptive Supplement to an Evidence-Based Mindfulness Intervention for Adolescents Via Frontiers in Public Health | New and Recent Articles Incorporating technological supplements into existing group mindfulness-based interventions (MBIs), particularly for use with adolescents, is an important next step in the implementation of MBIs. Yet there is little available content. Herein we present the development and content of a technological supplement for MBIs, which incorporates multiple technological elements to support (a) skill transfer from the group MBI to daily life, (b) the establishment of a formal mindfulness practice, and (c) the use of mi ndfulness during periods of high stress. A mixed-methods approach was used to develop this multi-method adaptive supplement. Findings about the use of this supplement will be disseminated scientifically and/or publicly as appropriate. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lockdown Exit Strategy

alkiviadis.1961 shared this article with you from Inoreader Individual Behaviors and COVID-19 Lockdown Exit Strategy: A Mid-Term Multidimensional Bio-economic Modeling Approach Via Frontiers in Public Health | New and Recent Articles As of mid-2020, eradicating COVID-19 seems not to be an option, at least in the short term. The challenge for policy makers consists of implementing a suitable approach to contain the outbreak and limit extra deaths without exhausting healthcare forces while mitigating the impact on the country's economy and on individuals' well-being. To better describe the trade-off between the economic, societal and public health dimensions, we developed an integrated bioeconomic optimization approach. We built a discrete age-structured model considering three main populations (youth, adults and seniors) and 8 socio-professional characteristics for the adults. Fifteen lockdown exit strategies were simulated for several options: abrupt or progressive (4 or 8 weeks) lockdown lift fo llowed by total definitive transitory final unlocking. Three values of transmission rate (Tr) were considered to represent individuals' barrier gesture compliance. Optimization under constraint to find the best combination of scenarios and options was performed on the minimal total cost for production losses due to contracted activities and hospitalization in the short and mid-term, with 3 criteria: mortality, person-days locked and hospital saturation. The results clearly show little difference between the scenarios based on the economic impact or the 3 criteria. This means that policy makers should focus on individuals' behaviors (represented by the Tr value) more than on trying to optimize the lockdown strategy (defining who is unlocked and who is locked). For a given Tr, the choices of scenarios permit the management of the hospital saturation level with regard to both its intensity and its duration, which remains a key point for public health. The results highlight the need for behavioral or experimental economics to address COVID-19 issues through a better understanding of individual behavior motivations and the identification of ways to improve biosecurity compliance. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Mechanisms of Type 2 Diabetes-Related White Matter Intensities: A Review

alkiviadis.1961 shared this article with you from Inoreader The Mechanisms of Type 2 Diabetes-Related White Matter Intensities: A Review Via Frontiers in Public Health | New and Recent Articles The continually increasing number of patients with type 2 diabetes is a worldwide health problem, and the incidence of microvascular complications is closely related to type 2 diabetes. Structural brain abnormalities are considered an important pathway through which type 2 diabetes causes brain diseases. In fact, there is considerable evidence that type 2 diabetes is associated with an increased risk of structural brain abnormalities such as lacunar infarcts (LIs), white matter hyperintensities (WMHs), and b rain atrophy. WMHs are a common cerebral small-vessel disease in elderly adults, and it is characterized histologically by demyelination, loss of oligodendrocytes, and vacuolization as a result of small-vessel ischemia in the white matter. An increasing number of studies have found that diabetes is closely related to WMHs. However, the exact mechanism by which type 2 diabetes causes WMHs is not fully understood. This article reviews the mechanisms of type 2 diabetes-related WMHs to better understand the disease and provide help for better clinical treatment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparing the LBSap, Leishmune®, and Leish-Tec® Vaccines against Canine Visceral Leishmaniasis

alkiviadis.1961 shared this article with you from Inoreader Vaccines, Vol. 8, Pages 690: Phase I and II Clinical Trial Comparing the LBSap, Leishmune®, and Leish-Tec® Vaccines against Canine Visceral Leishmaniasis Via Vaccines Vaccines, Vol. 8, Pages 690: Phase I and II Clinical Trial Comparing the LBSap, Leishmune®, and Leish-Tec® Vaccines against Canine Visceral Leishmaniasis Vaccines doi: 10.3390/vaccines8040690 Authors: Rodrigo Dian de Oliveira Aguiar-Soares Bruno Mendes Roatt Fernando Augusto Siqueira Mathias Levi Eduardo Soares Reis Jamille Mirelle de Oliveira Cardoso Rory Cristiane Fortes de Brito Henrique Gama Ker Rodrigo Corrêa-Oliveira Rodolfo Cordeiro Giunchetti Alexandre Barbosa Reis In this study, we performed a phase I and II clinical trial in dogs to evaluate the toxicity and immunogenicity of LBSap-vaccine prototype, in comparison to Leishmune® and Leish-Tec® vaccines. Twenty-eight dogs were classified in four groups: (i) control group received 1 mL of sterile 0.9% saline solution; (ii) LBSap group received 600 μg of Leishmania braziliensis promastigotes protein and 1 mg of saponin adjuvant; (iii) Leishmune®; and (iv) Leish-Tec®. The safety and toxicity of the vaccines were measured before and after three immunizations by clinical, biochemical, and hematological parameters. The clinical examinations revealed that some dogs of LBSap and Leishmune® groups presented changes at the site of vaccination inoculum, such as nodules, mild edema, and local pain, which were transient and disappeared seventy-two hours after vaccination, but these results indicate that adverse changes caused by the immunizations are tolera ble. The immunogenicity results demonstrate an increase of B lymphocytes CD21+ regarding the Leishmune® group and monocytes CD14+ concerning LBSap and Leishmune® groups. In the in vitro analyses, an increase in lymphoproliferative activity in LBSap and Leishmune® groups was observed, with an increase of antigen-specific CD4+ and CD8+ T lymphocytes in the LBSap group. A second approach of in vitro assays aimed at evaluating the percentage of antigen-specific CD4+ and CD8+ T lymphocytes producers of IFN-γ and IL-4, where an increase in both IFN-γ producing subpopulations in the LBSap group was observed, also showed an increase in IFN-γ producers in CD8+ lymphocytes in the Leish-Tec® group. Our data regarding immunogenicity indicate that the vaccination process, especially with the LBSap vaccine, generated a protective immune response compatible with L. infantum parasite control. Based on the foregoing, the LBSap vaccine wou ld be suitable for further studies of phase III clinical trial in endemic areas with high prevalence and incidence of canine visceral leishmaniasis (VL) cases. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.