Systematic review of patients’ and healthcare professionals’ views on patient‐initiated follow‐up in treated cancer patients

Background: Current follow‐up models in cancer are seen to be unsustainable and inflexible, and there is growing interest in alternative models, such as patient‐initiated follow‐up (PIFU). It is therefore important to understand whether PIFU is acceptable to patients and healthcare professionals (HCPs). Methods: Standard systematic review methodology aimed at limiting bias was used for study identification (to January 2022), selection and data extraction. Thematic synthesis was undertaken for qualitative data, and survey findings were tabulated and described. Results: Nine qualitative studies and 22 surveys were included, mainly in breast and endometrial cancer. Women treated for breast or endometrial cancer and HCPs were mostly supportive of PIFU. Facilitators for PIFU included convenience, control over own health and avoidance of anxiety‐inducing clinic appointments. Barriers included loss of reassurance from scheduled visits and lack of confidence in self‐management. HCPs were supportive of PIFU but concerned about resistance to change, unsuitability of PIFU for some patients and costs. Conclusion: PIFU is viewed mostly positively by women treated for breast or endometrial cancer, and by HCPs, but further evidence is needed from a wider range of cancers, men, and more representative samples. A protocol was registered with PROSPERO (CRD42020181412)

Contractile efficiency of dystrophic mdx mouse muscle: In vivo and ex vivo assessment of adaptation to exercise of functional end points

Progressive weakness is a typical feature of Duchenne muscular dystrophy (DMD) patients and is exacerbated in the benign mdx mouse model by in vivo treadmill exercise. We hypothesized a different threshold for functional adaptation of mdx muscles in response to the duration of the exercise protocol. In vivo weakness was confirmed by grip strength after 4, 8 and 12 weeks of exercise in mdx mice. Torque measurements revealed that exercise-related weakness in mdx mice correlated with the duration of the protocol, while wild-type (wt) mice were stronger. Twitch and tetanic forces of isolated diaphragm and extensor digitorum longus (EDL) muscles, were lower in mdx compared to wt mice. In mdx, both muscle types exhibited greater weakness after a single exercise bout, but only in EDL after a long exercise protocol. As opposite to wt muscles, mdx EDL ones did not show any exercise-induced adaptations against eccentric contraction force drop. qRT-PCR analysis confirmed the maladaptation of genes involved in metabolic and structural remodeling, while damage-related genes remained significantly upregulated and angiogenesis impaired. Phosphorylated AMP kinase level increased only in exercised wt muscle. The severe histopathology and the high levels of muscular TGF-β1 and of plasma matrix metalloproteinase-9 confirmed the persistence of muscle damage in mdx mice. Then, dystrophic muscles showed a partial degree of functional adaptation to chronic exercise, although not sufficient to overcome weakness nor signs of damage. The improved understanding of the complex mechanisms underlying maladaptation of dystrophic muscle paves the way to a better managment of DMD patients

LESÃO NA REGIÃO METACARPIANA DO MEMBRO TORÁCICO ESQUERDO DE BEZERRA GIR DECORRENTE DE CONTENÇÃO PARA PESAGEM

Bone fractures and dislocations are more common in young animals and mostly occur due to incorrect handling of these animals, which can lead to a short or long-term drop in production, generating economic and productive losses of animals of high genetic standard. This study aimed to report the occurrence of a fracture in the metacarpal region of the left thoracic limb of a 12-day-old Gir heifer, caused by an ineffective restraint during weighing. The animal from a farm in Umirim/CE was sent to the Veterinary Hospital of Large Animals of the University Center INTA in Sobral/CE. The radiographic examination found a fracture in the metacarpal region of the left thoracic limb. The animal was manually immobilized following semiological methods to minimize stress. For the limb immobilization, a modified Thomas crutch and bandages associated with pain control with the drugs Flunixin meglumine (1.1mg/kg) and Phenylbutazone (4.4mg/kg) were used. After immobilization, the animal remained hospitalized at HOVET-GA and after 18 days a new radiograph was performed to evaluate the progress achieved with the treatment adopted. It was found the formation of a bone callus with the ossification of the fracture, not requiring the surgical referral of the animal. Thus, the treatment with the modified Thomas crutch was effective for the recovery of the fractured limb, in addition to being a low-cost and easy-to-apply treatment. The animal showed a good response to the therapeutic treatment for pain control.Fraturas ósseas e luxações são mais comuns em animais jovens e, na maioria das vezes, essas fraturas ocorrem devido ao manejo incorreto desses animais, podendo levar a uma queda de produção a curto ou longo prazo, gerando perdas econômicas e produtivas de animais de alto padrão genético. Nesse contexto, o objetivo deste trabalho foi relatar a ocorrência de uma fratura na região metacarpiana do membro torácico esquerdo de uma bezerra Gir de 12 dias de idade, causada por uma contenção ineficaz durante a pesagem. O animal proveniente de uma fazenda em Umirim/CE foi encaminhado ao Hospital Veterinário de Grandes Animais do Centro Universitário INTA em Sobral/CE. Ao passar pelo exame radiográfico, foi constatada a fratura na região metacarpiana do membro torácico esquerdo. O animal foi imobilizado de forma manual, seguindo-se métodos semiológicos para minimizar o estresse. Para a imobilização do membro, foi utilizada a muleta de Thomas modificada e bandagens, associadas ao controle da dor com as drogas Flunixin meglumine (1,1mg/kg) e Fenilbutazona (4,4mg/kg). Depois da imobilização, o animal seguiu internado no HOVET-GA e, após 18 dias, foi realizada uma nova radiografia para ver o progresso a partir do tratamento adotado. Constatou-se a formação de um calo ósseo, com a ossificação da fratura, não sendo necessário o encaminhamento cirúrgico do animal. Assim, o tratamento com muleta de Thomas modificada foi efetivo para a recuperação do membro fraturado, além de ser um tratamento de baixo custo e fácil aplicação, tendo o animal apresentado uma boa resposta ao tratamento terapêutico para controle da dor

TRAUMA DECORRENTE DE QUEDA PROVOCADA PELO CABO EXTENSOR DE UM BEZERREIRO TROPICAL

Calf rearing is one of the most important stages in dairy cattle and, prophylactic management in physical accommodation environments is crucial to avoid accidents that could compromise the productive life of these animals in the future. The tropical calf is one of the most common housings used in the Brazilian Northeast in large creations, possibly due to the low cost. This study aimed to report an accident caused by tripping over surface extender wire of the tropical calf, which caused a tibial trauma in a 2-months-old Girolando heifer. The attendance took place at the Veterinary Hospital for Large Animals of the Inta University Center (Uninta) in Sobral/Ce and the animal came from a high-production dairy farm in the city of Umirim/Ce. The clinical examination revealed that the affected region was close to the knuckle. The radiographic examination showed a fracture in the epiphyseal region of the proximal tibia. After evaluation by the clinical and surgical team, the patient was referred for corrective surgery, but before that, immobilization and bandages were established to keep the affected limb immobile until the surgical procedure was performed. The post-surgical medical treatment was conducted, in addition to the daily care of cleaning the surgical wound with local antiseptic. After the surgery, to correct the fracture with the patient stabilized, the hospital discharge occurred 17 days after hospitalization. Thus, the tropical calf, is undergoing structural and management changes to avoid further trauma caused by stumbling, tangling, and falling.A criação de bezerras é uma das fases mais importantes na bovinocultura leiteira e um manejo profilático em ambientes físicos de alojamento é crucial para evitar acidentes que possam comprometer a vida produtiva dos animais futuramente. O bezerreiro tropical é um dos alojamentos mais comuns utilizados no Nordeste brasileiro em grandes criações, possivelmente devido ao baixo custo. Diante disso, objetivou-se nesse trabalho relatar um acidente provocado por tropeço em fio extensor de superfície do bezerreiro tropical, no qual ocasionou um traumatismo tibial em uma bezerra Girolando de dois meses de idade. O atendimento ocorreu no Hospital Veterinário de Grandes Animais do Centro Universitário Inta (Uninta) em Sobral/CE e o animal foi proveniente de uma fazenda de alta produção leiteira da cidade de Umirim/CE. O exame clínico revelou que a região afetada foi próxima ao jarrete. O exame radiográfico constatou fratura na região epifisária da tíbia proximal. Após avaliação pela equipe clínica e cirúrgica, o paciente foi encaminhado para cirurgia de correção, mas antes foi estabelecida imobilização e bandagens para manter o membro afetado imóvel até a realização do procedimento cirúrgico. O tratamento clínico medicamentoso pós-cirúrgico foi conduzido, além de foram instituídos cuidados diários de limpeza do ferimento cirúrgico com antisséptico local. Após a realização da cirurgia de correção da fratura, estando o paciente estabilizado, este mesmo animal recebeu alta médica 17 dias depois da internação. Desta forma, o bezerreiro tropical está passando por mudanças estruturais e de manejo para evitar mais traumas provocados pelo tropeço, enroscamento e quedas das bezerras

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Rapid, point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection

Background Accurate rapid diagnostic tests for SARS‐CoV‐2 infection could contribute to clinical and public health strategies to manage the COVID‐19 pandemic. Point‐of‐care antigen and molecular tests to detect current infection could increase access to testing and early confirmation of cases, and expediate clinical and public health management decisions that may reduce transmission. Objectives To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Search methods Electronic searches of the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 30 Sept 2020. We checked repositories of COVID‐19 publications and included independent evaluations from national reference laboratories, the Foundation for Innovative New Diagnostics and the Diagnostics Global Health website to 16 Nov 2020. We did not apply language restrictions. Selection criteria We included studies of people with either suspected SARS‐CoV‐2 infection, known SARS‐CoV‐2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results within two hours of sample collection). We included all reference standards that define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established diagnostic criteria). Data collection and analysis Studies were screened independently in duplicate with disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability (made using the QUADAS‐2 tool) were undertaken independently in duplicate. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and pooled data using the bivariate model separately for antigen and molecular‐based tests. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status. Main results Seventy‐eight study cohorts were included (described in 64 study reports, including 20 pre‐prints), reporting results for 24,087 samples (7,415 with confirmed SARS‐CoV‐2). Studies were mainly from Europe (n = 39) or North America (n = 20), and evaluated 16 antigen and five molecular assays. We considered risk of bias to be high in 29 (37%) studies because of participant selection; in 66 (85%) because of weaknesses in the reference standard for absence of infection; and in 29 (37%) for participant flow and timing. Studies of antigen tests were of a higher methodological quality compared to studies of molecular tests, particularly regarding the risk of bias for participant selection and the index test. Characteristics of participants in 35 (45%) studies differed from those in whom the test was intended to be used and the delivery of the index test in 39 (50%) studies differed from the way in which the test was intended to be used. Nearly all studies (97%) defined the presence or absence of SARS‐CoV‐2 based on a single RT‐PCR result, and none included participants meeting case definitions for probable COVID‐19. Antigen tests Forty‐eight studies reported 58 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies. There were differences between symptomatic (72.0%, 95% CI 63.7% to 79.0%; 37 evaluations; 15530 samples, 4410 cases) and asymptomatic participants (58.1%, 95% CI 40.2% to 74.1%; 12 evaluations; 1581 samples, 295 cases). Average sensitivity was higher in the first week after symptom onset (78.3%, 95% CI 71.1% to 84.1%; 26 evaluations; 5769 samples, 2320 cases) than in the second week of symptoms (51.0%, 95% CI 40.8% to 61.0%; 22 evaluations; 935 samples, 692 cases). Sensitivity was high in those with cycle threshold (Ct) values on PCR ≤25 (94.5%, 95% CI 91.0% to 96.7%; 36 evaluations; 2613 cases) compared to those with Ct values >25 (40.7%, 95% CI 31.8% to 50.3%; 36 evaluations; 2632 cases). Sensitivity varied between brands. Using data from instructions for use (IFU) compliant evaluations in symptomatic participants, summary sensitivities ranged from 34.1% (95% CI 29.7% to 38.8%; Coris Bioconcept) to 88.1% (95% CI 84.2% to 91.1%; SD Biosensor STANDARD Q). Average specificities were high in symptomatic and asymptomatic participants, and for most brands (overall summary specificity 99.6%, 95% CI 99.0% to 99.8%). At 5% prevalence using data for the most sensitive assays in symptomatic people (SD Biosensor STANDARD Q and Abbott Panbio), positive predictive values (PPVs) of 84% to 90% mean that between 1 in 10 and 1 in 6 positive results will be a false positive, and between 1 in 4 and 1 in 8 cases will be missed. At 0.5% prevalence applying the same tests in asymptomatic people would result in PPVs of 11% to 28% meaning that between 7 in 10 and 9 in 10 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed. No studies assessed the accuracy of repeated lateral flow testing or self‐testing. Rapid molecular assays Thirty studies reported 33 evaluations of five different rapid molecular tests. Sensitivities varied according to test brand. Most of the data relate to the ID NOW and Xpert Xpress assays. Using data from evaluations following the manufacturer’s instructions for use, the average sensitivity of ID NOW was 73.0% (95% CI 66.8% to 78.4%) and average specificity 99.7% (95% CI 98.7% to 99.9%; 4 evaluations; 812 samples, 222 cases). For Xpert Xpress, the average sensitivity was 100% (95% CI 88.1% to 100%) and average specificity 97.2% (95% CI 89.4% to 99.3%; 2 evaluations; 100 samples, 29 cases). Insufficient data were available to investigate the effect of symptom status or time after symptom onset. Authors' conclusions Antigen tests vary in sensitivity. In people with signs and symptoms of COVID‐19, sensitivities are highest in the first week of illness when viral loads are higher. The assays shown to meet appropriate criteria, such as WHO's priority target product profiles for COVID‐19 diagnostics (‘acceptable’ sensitivity ≥ 80% and specificity ≥ 97%), can be considered as a replacement for laboratory‐based RT‐PCR when immediate decisions about patient care must be made, or where RT‐PCR cannot be delivered in a timely manner. Positive predictive values suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Due to the variable sensitivity of antigen tests, people who test negative may still be infected. Evidence for testing in asymptomatic cohorts was limited. Test accuracy studies cannot adequately assess the ability of antigen tests to differentiate those who are infectious and require isolation from those who pose no risk, as there is no reference standard for infectiousness. A small number of molecular tests showed high accuracy and may be suitable alternatives to RT‐PCR. However, further evaluations of the tests in settings as they are intended to be used are required to fully establish performance in practice. Several important studies in asymptomatic individuals have been reported since the close of our search and will be incorporated at the next update of this review. Comparative studies of antigen tests in their intended use settings and according to test operator (including self‐testing) are required

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.