Cost-effectiveness of Sertraline in primary care according to initial severity and duration of depressive symptoms: findings from the PANDA RCT

BACKGROUND: Antidepressants are commonly prescribed for depression, but it is unclear whether treatment efficacy depends on severity and duration of symptoms and how prescribing might be targeted cost-effectively. OBJECTIVES: We investigated the cost-effectiveness of the antidepressant sertraline compared with placebo in subgroups defined by severity and duration of depressive symptoms. METHODS: We undertook a cost-effectiveness analysis from the perspective of the NHS and Personal and Social Services (PSS) in the UK alongside the PANDA (What are the indications for Prescribing ANtiDepressants that will leAd to a clinical benefit?) randomised controlled trial (RCT), which compared sertraline with placebo over a 12-week period. Quality of life data were collected at baseline and at 2, 6, and 12 weeks post-randomisation using EQ-5D-5L, from which we calculated quality-adjusted life years (QALYs). Costs (in 2017/18£) were collected using patient records and from resource use questionnaires administered at each follow-up interval. Differences in mean costs and mean QALYs and net monetary benefits were estimated. Our primary analysis used net monetary benefit regressions to identify any interaction between the cost-effectiveness of sertraline and subgroups defined by baseline symptom severity (0-11; 12-19; 20+ on the Clinical Interview Schedule-Revised) and, separately, duration of symptoms (greater or less than 2 years duration). A secondary analysis estimated the cost-effectiveness of sertraline versus placebo, irrespective of duration or severity. RESULTS: There was no evidence of an association between the baseline severity of depressive symptoms and the cost-effectiveness of sertraline. Compared to patients with low symptom severity, the expected net benefits in patients with moderate symptoms were £24 (95% CI - £280 to £328; p value 0.876) and the expected net benefits in patients with high symptom severity were £37 (95% CI - £221 to £296; p value 0.776). Patients who had a longer history of depressive symptoms at baseline had lower expected net benefits from sertraline than those with a shorter history; however, the difference was uncertain (- £27 [95% CI - £258 to £204]; p value 0.817). In the secondary analysis, patients treated with sertraline had higher expected net benefits (£122 [95% CI £18 to £226]; p value 0.101) than those in the placebo group. Sertraline had a high probability (> 95%) of being cost-effective if the health system was willing to pay at least £20,000 per QALY gained. CONCLUSIONS: We found insufficient evidence of a prespecified threshold based on severity or symptom duration that GPs could use to target prescribing to a subgroup of patients where sertraline is most cost-effective. Sertraline is probably a cost-effective treatment for depressive symptoms in UK primary care. TRIAL REGISTRATION: Controlled Trials ISRCTN Registry, ISRCTN84544741

Changes in salivary analytes in canine parvovirus : A high-resolution quantitative proteomic study

The present study evaluated the changes in salivary proteome in parvoviral enteritis (PVE) in dogs through a high-throughput quantitative proteomic analysis. Saliva samples from healthy dogs and dogs with severe parvovirosis that survived or perished due to the disease were analysed and compared by Tandem Mass Tags (TMT) analysis. Proteomic analysis quantified 1516 peptides, and 287 (corresponding to 190 proteins) showed significantly different abundances between studied groups. Ten proteins were observed to change significantly between dogs that survived or perished due to PVE. Bioinformatics' analysis revealed that saliva reflects the involvement of different pathways in PVE such as catalytic activity and binding, and indicates antimicrobial humoral response as a pathway with a major role in the development of the disease. These results indicate that saliva proteins reflect physiopathological changes that occur in PVE and could be a potential source of biomarkers for this disease

A joint Fermi-GBM and Swift-BAT analysis of gravitational-wave candidates from the third gravitational-wave observing run

We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers

A joint Fermi-GBM and Swift-BAT analysis of Gravitational-wave candidates from the third Gravitational-wave Observing Run

We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers

SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential

The Main Sequence View of Quasars Accreting at High Rates: Influence of Star Formation*

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Highly accreting quasars show fairly distinctive properties in their optical, UV, and X spectra, and are easy to recognize because of their specific location in the quasar main sequence: they are the strongest optical FeII emitters. They show a surprisingly high rate of radio detections and, at variance with the classical radio-loud (jetted) sources, the origin of their radio emission is probably "thermal." The chemical composition of the broad line emitting gas implies high metallicity values, above 10 times solar. A fraction of highly accreting quasars at intermediate and high redshift might therefore be in a particular evolutionary stage that is unobscured albeit still involving a contribution of nuclear and circum-nuclear star formation in their multifrequency properties. © 2021. The Author(s). Published by the American Astronomical Society.A.d.O. acknowledges financial support from the Spanish MCIU grant PID2019-106027GB-C41 and from the State Agency for Research of the Spanish MCIU through the Center of Excellence Severo Ochoa award for the Instituto de Astrofsica de An- daluca (SEV-2017-0709)