Riviste scientifiche

[Correspondence] p16 status and choice of chemotherapy in the KEYNOTE-040 study

The Lancet - Sa, 12/10/2019 - 00:00
In the KEYNOTE-040 study,1 published in The Lancet, Ezra Cohen and colleagues reported that pembrolizumab provides a survival benefit compared with standard-of-care treatment (methotrexate, docetaxel, or cetuximab) in patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Patients with p16-negative disease who were treated with pembrolizumab had longer overall survival than did those treated with standard-of-care chemotherapy (hazard ratio [HR] 0·77 [95% CI 0·61–0·97]), whereas no overall survival differences were observed among patients with p16-positive disease (0·97 [0·63–1·49]).

[Correspondence] p16 status and choice of chemotherapy in the KEYNOTE-040 study

The Lancet - Sa, 12/10/2019 - 00:00
As shown for several other tumour types, the results of the KEYNOTE-040 study,1 showed that the immune checkpoint inhibitor pembrolizumab increased overall survival compared with standard of care in patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Although findings for nivolumab in the CheckMate 141 trial2 were similar, the absolute difference in median overall survival compared with standard of care was smaller for pembrolizumab (1·5 months)1 than for nivolumab (2·4 months).

[Correspondence] p16 status and choice of chemotherapy in the KEYNOTE-040 study – Authors' reply

The Lancet - Sa, 12/10/2019 - 00:00
We thank Xin Yang and colleagues and Sander Bins and Ron Mathijssen for their comments regarding the KEYNOTE-040 study.1 This phase 3 trial showed a clinically meaningful improvement in overall survival1 and stable health-related quality of life2 in patients who received pembrolizumab compared with those who received the standard-of-care treatment. Both author groups discuss specific patient subsets that were notable for differences in survival: Yang and colleagues highlight p16 status and Bins and Mathijssen discuss the choice of chemotherapy.

[Correspondence] Abortion as a moral good?

The Lancet - Sa, 12/10/2019 - 00:00
While clearly aiming to provoke discussion by positioning abortion as a moral good, it is a pity that Katie Watson's Perspective1 tries to overly smooth out the moral discomfort about abortion experienced by clinicians who do not wish to be labelled—and potentially dismissed in arguments—as either pro-life or pro-choice.

[Correspondence] A role for palliative care in advancing health in conflict settings

The Lancet - Sa, 12/10/2019 - 00:00
In March, 2019, we were privileged to attend the Lancet Palestinian Health Alliance conference in Amman, Jordan. This network of global researchers aims to advance the health of Palestinians through “a common commitment to human health to build trust and confidence between communities”.1 The conference concluded as the citizens of the Gaza Strip were marking the first anniversary of the Great March of Return demonstrations for Palestinians' rights. The past year has seen staggering numbers of deaths and injuries in Gaza.

[Department of Error] Department of Error

The Lancet - Sa, 12/10/2019 - 00:00
Nicholas S Hopkinson, Deborah Arnott, Nick Voulvoulis. Environmental consequences of tobacco production and consumption. Lancet 2019; 394: 1007–08—In this Correspondence, Nick Voulvoulis's affiliation was incorrect and has been changed to Centre for Environmental Policy, Imperial College London, London, UK; and Deborah Arnotts' affiliation was incorrect and has been changed to Action on Smoking and Health, London, UK. These corrections have been made to the online version as of Oct 10, 2019.

[Clinical Picture] Hypothyroidism to Graves' disease and late appearance of pretibial myxoedema

The Lancet - Sa, 12/10/2019 - 00:00
A 57-year-old man attended our clinic complaining of orbital pain, anxiety, and a tremor. On examination, he had oedema and retraction of his eyelids and an obvious tremor. 6 months earlier, he had been diagnosed with autoimmune hypothyroidism after he began to gain weight and complained of feeling tired: his thyroid-stimulating hormone (TSH) concentration was raised at 83 mIU/L (normal range 0·3–4·6), free thyroxine (T4) concentration was 5·9 pmol/L (normal range 10–23), and the antithyroid peroxidase antibody concentration was markedly elevated at 1488 IU/mL (normal level <101).

[Series] Frailty: implications for clinical practice and public health

The Lancet - Sa, 12/10/2019 - 00:00
Frailty is an emerging global health burden, with major implications for clinical practice and public health. The prevalence of frailty is expected to rise alongside rapid growth in the ageing population. The course of frailty is characterised by a decline in functioning across multiple physiological systems, accompanied by an increased vulnerability to stressors. Having frailty places a person at increased risk of adverse outcomes, including falls, hospitalisation, and mortality. Studies have shown a clear pattern of increased health-care costs and use associated with frailty.

[Series] Management of frailty: opportunities, challenges, and future directions

The Lancet - Sa, 12/10/2019 - 00:00
Frailty is a complex age-related clinical condition characterised by a decline in physiological capacity across several organ systems, with a resultant increased susceptibility to stressors. Because of the heterogeneity of frailty in clinical presentation, it is important to have effective strategies for the delivery of care that range across the continuum of frailty severity. In clinical practice, we should do what works, starting with frailty screening, case identification, and management of frailty.

Characterization of Parkinson’s disease using blood-based biomarkers: A multicohort proteomic analysis

PLoS Medicine - Ve, 11/10/2019 - 23:00

by Marijan Posavi, Maria Diaz-Ortiz, Benjamine Liu, Christine R. Swanson, R. Tyler Skrinak, Pilar Hernandez-Con, Defne A. Amado, Michelle Fullard, Jacqueline Rick, Andrew Siderowf, Daniel Weintraub, Leo McCluskey, John Q. Trojanowski, Richard B. Dewey Jr, Xuemei Huang, Alice S. Chen-Plotkin

Background

Parkinson’s disease (PD) is a progressive neurodegenerative disease affecting about 5 million people worldwide with no disease-modifying therapies. We sought blood-based biomarkers in order to provide molecular characterization of individuals with PD for diagnostic confirmation and prediction of progression.

Methods and findings

In 141 plasma samples (96 PD, 45 neurologically normal control [NC] individuals; 45.4% female, mean age 70.0 years) from a longitudinally followed Discovery Cohort based at the University of Pennsylvania (UPenn), we measured levels of 1,129 proteins using an aptamer-based platform. We modeled protein plasma concentration (log10 of relative fluorescence units [RFUs]) as the effect of treatment group (PD versus NC), age at plasma collection, sex, and the levodopa equivalent daily dose (LEDD), deriving first-pass candidate protein biomarkers based on p-value for PD versus NC. These candidate proteins were then ranked by Stability Selection. We confirmed findings from our Discovery Cohort in a Replication Cohort of 317 individuals (215 PD, 102 NC; 47.9% female, mean age 66.7 years) from the multisite, longitudinally followed National Institute of Neurological Disorders and Stroke Parkinson’s Disease Biomarker Program (PDBP) Cohort. Analytical approach in the Replication Cohort mirrored the approach in the Discovery Cohort: each protein plasma concentration (log10 of RFU) was modeled as the effect of group (PD versus NC), age at plasma collection, sex, clinical site, and batch. Of the top 10 proteins from the Discovery Cohort ranked by Stability Selection, four associations were replicated in the Replication Cohort. These blood-based biomarkers were bone sialoprotein (BSP, Discovery false discovery rate [FDR]-corrected p = 2.82 × 10−2, Replication FDR-corrected p = 1.03 × 10−4), osteomodulin (OMD, Discovery FDR-corrected p = 2.14 × 10−2, Replication FDR-corrected p = 9.14 × 10−5), aminoacylase-1 (ACY1, Discovery FDR-corrected p = 1.86 × 10−3, Replication FDR-corrected p = 2.18 × 10−2), and growth hormone receptor (GHR, Discovery FDR-corrected p = 3.49 × 10−4, Replication FDR-corrected p = 2.97 × 10−3). Measures of these proteins were not significantly affected by differences in sample handling, and they did not change comparing plasma samples from 10 PD participants sampled both on versus off dopaminergic medication. Plasma measures of OMD, ACY1, and GHR differed in PD versus NC but did not differ between individuals with amyotrophic lateral sclerosis (ALS, n = 59) versus NC. In the Discovery Cohort, individuals with baseline levels of GHR and ACY1 in the lowest tertile were more likely to progress to mild cognitive impairment (MCI) or dementia in Cox proportional hazards analyses adjusting for age, sex, and disease duration (hazard ratio [HR] 2.27 [95% CI 1.04–5.0, p = 0.04] for GHR, and HR 3.0 [95% CI 1.24–7.0, p = 0.014] for ACY1). GHR’s association with cognitive decline was confirmed in the Replication Cohort (HR 3.6 [95% CI 1.20–11.1, p = 0.02]). The main limitations of this study were its reliance on the aptamer-based platform for protein measurement and limited follow-up time available for some cohorts.

Conclusions

In this study, we found that the blood-based biomarkers BSP, OMD, ACY1, and GHR robustly associated with PD across multiple clinical sites. Our findings suggest that biomarkers based on a peripheral blood sample may be developed for both disease characterization and prediction of future disease progression in PD.

Prediction of recurrent venous thrombosis in all patients with a first venous thrombotic event: The Leiden Thrombosis Recurrence Risk Prediction model (L-TRRiP)

PLoS Medicine - Ve, 11/10/2019 - 23:00

by Jasmijn F. Timp, Sigrid K. Braekkan, Willem M. Lijfering, Astrid van Hylckama Vlieg, John-Bjarne Hansen, Frits R. Rosendaal, Saskia le Cessie, Suzanne C. Cannegieter

Background

Recurrent venous thromboembolism (VTE) is common. Current guidelines suggest that patients with unprovoked VTE should continue anticoagulants unless they have a high bleeding risk, whereas all others can stop. Prediction models may refine this dichotomous distinction, but existing models apply only to patients with unprovoked first thrombosis. We aimed to develop a prediction model for all patients with first VTE, either provoked or unprovoked.

Methods and findings

Data were used from two population-based cohorts of patients with first VTE from the Netherlands (Multiple Environment and Genetic Assessment of Risk Factors for Venous Thrombosis [MEGA] follow-up study, performed from 1994 to 2009; model derivation; n = 3,750) and from Norway (Tromsø study, performed from 1999 to 2016; model validation; n = 663). Four versions of a VTE prediction model were developed: model A (clinical, laboratory, and genetic variables), model B (clinical variables and fewer laboratory markers), model C (clinical and genetic factors), and model D (clinical variables only). The outcome measure was recurrent VTE. To determine the discriminatory power, Harrell’s C-statistic was calculated. A prognostic score was assessed for each patient. Kaplan-Meier plots for the observed recurrence risks were created in quintiles of the prognostic scores. For each patient, the 2-year predicted recurrence risk was calculated. Models C and D were validated in the Tromsø study.During 19,201 person-years of follow-up (median duration 5.7 years) in the MEGA study, 507 recurrences occurred. Model A had the highest predictive capability, with a C-statistic of 0.73 (95% CI 0.71–0.76). The discriminative performance was somewhat lower in the other models, with C-statistics of 0.72 for model B, 0.70 for model C, and 0.69 for model D. Internal validation showed a minimal degree of optimism bias. Models C and D were externally validated, with C-statistics of 0.64 (95% CI 0.62–0.66) and 0.65 (95% CI 0.63–0.66), respectively. According to model C, in 2,592 patients with provoked first events, 367 (15%) patients had a predicted 2-year risk of >10%, whereas in 1,082 patients whose first event was unprovoked, 484 (45%) had a predicted 2-year risk of <10%. A limitation of both cohorts is that laboratory measurements were missing in a substantial proportion of patients, which therefore were imputed.

Conclusions

The prediction model we propose applies to patients with provoked or unprovoked first VTE—except for patients with (a history of) cancer—allows refined risk stratification, and is easily usable. For optimal individualized treatment, a management study in which bleeding risks are also taken into account is necessary.

Crabs are being found in the Thames with stomachs full of plastic

New Scientist - Ve, 11/10/2019 - 16:13
Crabs in the Thames are ingesting “shocking” amounts of plastic and may be passing it on in high doses to other species in the river, researchers have found

Cancelled Dyson electric car project received £5m from UK government

New Scientist - Ve, 11/10/2019 - 14:32
UK taxpayers gave around £5m to the company Dyson to support the electric car project that it announced this week will be scrapped

NASA engineer's 'helical engine' may violate the laws of physics

New Scientist - Ve, 11/10/2019 - 14:10
A NASA engineer has published plans for an engine that could accelerate a rocket without using propellant. But there are questions over whether it could work

Life may have begun with simple genes made out of urine

New Scientist - Ve, 11/10/2019 - 11:00
Urea, a chemical found in urine, can be used to make simple genetic molecules similar to DNA – which could have been the basis of the first life on Earth

Quantum weirdness could allow a person-sized wormhole to last forever

New Scientist - Ve, 11/10/2019 - 07:00
We were unsure if wormholes could exist long enough to allow a person through. Now calculations indicate they are extremely rare, but could last the age of the universe

Knowledge gaps in the construction of rural healthy homes: A research agenda for improved low-cost housing in hot-humid Africa

PLoS Medicine - Gi, 10/10/2019 - 23:00

by Lorenz von Seidlein, Hannah Wood, Otis Sloan Brittain, Lucy Tusting, Alexa Bednarz, Salum Mshamu, Catherine Kahabuka, Jacqueline Deen, David Bell, Steve W. Lindsay, Jakob Knudsen

Lorenz von Seidlein and colleagues discuss improving house designs in rural Africa to benefit health.

Wealthy families in prehistoric Europe may have had live-in slaves

New Scientist - Gi, 10/10/2019 - 20:00
Ancient DNA suggests that during the Bronze Age, wealthy families once lived with poorer individuals, suggesting live-in slavery could be 1300 years older than we thought

Fridges made from twisty materials could be better for the environment

New Scientist - Gi, 10/10/2019 - 20:00
Cooling powered by twisting materials could make more efficient and sustainable fridges that don't rely on compressing greenhouse gasses

Depression may reduce the amount of white matter in the brain

New Scientist - Gi, 10/10/2019 - 18:39
Depression appears to cause changes to the structure of the brain, as well as the other way around. That may be due to behaviour changes that can shrink unused brain pathways
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