Search

Serological assays are being used to monitor antibody responses in individuals who had SARS-CoV-2 infection and those who received a COVID-19 vaccine. We aimed to determine whether such assays can predict neutralising antibody titres as antibody levels wane and viral variants emerge.We measured antibody levels in serum samples from a cohort of 112 participants with SARS-CoV-2 infection using ten high-throughput serological tests and functional neutralisation assays. Serum samples were taken at baseline and at up to four subsequent visits. We assessed the effects of time and spike protein sequence variation on the performance and predictive value of the various assays. We did correlation analyses for individual timepoints using non-parametric Spearman correlation, and differences between timepoints were determined by use of a two-tailed Wilcoxon matched-pairs signed rank test.Neutralising antibody titres decreased over the first few months post-infection but stabilised thereafter, at about 30% of the level observed shortly after infection. Serological assays commonly used to measure antibodies against SARS-CoV-2 displayed a range of sensitivities that declined to varying extents over time. Quantitative measurements generated by serological assays based on the spike protein were better at predicting neutralising antibody titres than those based on nucleocapsid, but performance was variable, and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralising activity. Although we observed some deterioration in correlation between serological measurements and functional neutralisation activity, some assays maintained an ability to predict neutralising titres, even against variants of concern.The ability of high-throughput serological assays to predict neutralising antibody titres is likely to be crucial for evaluation of immunity at the population scale. These data can facilitate the selection of the most suitable assays as surrogates of functional neutralising activity and suggest that such measurements might be useful in clinical practice.US National Institutes of Health and National Health Service Research Scotland BioResource.

BackgroundSerological assays are being deployed to monitor antibody responses in SARS-CoV-2 convalescents and vaccine recipients. There is a need to determine whether such assays can predict immunity, as antibody levels wane and viral variants emerge.MethodsWe measured antibodies in a cohort of SARS-CoV-2 infected patients using several high-throughput serological tests and functional neutralization assays. The effects of time and spike protein sequence variation on the performance and predictive value of the various assays was assessed.FindingsNeutralizing antibody titers decreased over the first few months post-infection but stabilized thereafter, at about 30% of the level observed shortly after infection. Serological assays commonly used to measure antibodies against SARS-CoV-2 displayed a range of sensitivities that declined to varying extents over time. Quantitative measurements generated by serological assays based on the spike protein were better at predicting neutralizing antibody titers than assays based on nucleocapsid, but performance was variable and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralizing activity. Even though there was some deterioration in correlation between serological measurements and functional neutralization activity, some assays maintained an ability to predict neutralizing titers, even against variants of concern.InterpretationThe ability of high throughput serological assays to predict neutralizing antibody titers is likely crucial for evaluation of immunity at the population scale. These data will facilitate the selection of the most suitable assays as surrogates of functional neutralizing activity and suggest that such measurements may have utility in clinical practice.

Background Patients with end-stage kidney disease require complex and expensive medical management. Kidney transplantation remains the treatment of choice for end-stage kidney disease and is considered superior to all other modalities of renal replacement therapy or dialysis. However, access to kidney transplant is limited by critical supply and demand, making it extremely important to ensure longevity of transplanted kidneys. This is prevented through lifelong immunosuppression, with caution not to overly suppress the immune system, resulting in toxicity and harm. Transition of care to community nephrologists after initial kidney transplantation and monitoring at a transplant center is an important process to ensure delivery of effective and patient-centric care closer to home. Once transplanted, laborious surveillance of the immune system and monitoring for potential rejection and injury are undertaken through an armamentarium of screening modalities. Posttransplant surveillance for kidney function and injury remains key to follow-up care. While kidney function, quantified by estimated glomerular filtration rate and serum creatinine, and kidney injury, measured by proteinuria and hematuria, are standard biomarkers used to monitor injury and rejection posttransplant, they have recently been demonstrated to be inferior in performance to that of AlloSure (CareDx Inc, Brisbane, CA) circulating donor-derived, cell-free DNA (dd-cfDNA). Objective The outcomes and methods of monitoring renal transplant recipients posttransplant have remained stagnant over the past 15 years. The aim of this study is to consider intensive surveillance using AlloSure dd-cfDNA in an actively managed protocol, assessing whether it increases long-term allograft survival in kidney transplant recipients compared with current standard clinical care in community nephrology. Methods The study protocol will acquire data from a phase IV observational trial to assess a cohort of renal transplant patients managed using AlloSure dd-cfDNA and patient care managers versus 1000 propensity-matched historic controls using United Network for Organ Sharing U.S. Scientific Registry of Transplant Recipients data. Data will be managed in a centralized electronic data server. The primary outcome will be superior allograft survival, as a composite of return to dialysis, retransplant, death due to allograft failure, and death with a functional graft (infection, malignancy, and cardiovascular death). The secondary endpoints will assess improved kidney function through decline in estimated glomerular filtration rate and immune activity through development of donor-specific antibodies. Results The total sample is anticipated to be 3500 (2500 patients managed with AlloSure dd-cfDNA and 1000 propensity-matched controls). Active enrollment began in November 2020. Conclusions Based on a significant literature base, we believe implementing the surveillance of dd-cfDNA in the kidney transplant population will have a positive impact on graft survival. Through early identification of rejection and facilitating timely intervention, prolongation of allograft survival versus those not managed by dd-cfDNA surveillance protocol should be superior. International Registered Report Identifier (IRRID) PRR1-10.2196/25941

BACKGROUND Patients with end-stage kidney disease require complex and expensive medical management. Kidney transplantation remains the treatment of choice for end-stage kidney disease and is considered superior to all other modalities of renal replacement therapy or dialysis. However, access to kidney transplant is limited by critical supply and demand, making it extremely important to ensure longevity of transplanted kidneys. This is prevented through lifelong immunosuppression, with caution not to overly suppress the immune system, resulting in toxicity and harm. Transition of care to community nephrologists after initial kidney transplantation and monitoring at a transplant center is an important process to ensure delivery of effective and patient-centric care closer to home. Once transplanted, laborious surveillance of the immune system and monitoring for potential rejection and injury are undertaken through an armamentarium of screening modalities. Posttransplant surveillance for kidney function and injury remains key to follow-up care. While kidney function, quantified by estimated glomerular filtration rate and serum creatinine, and kidney injury, measured by proteinuria and hematuria, are standard biomarkers used to monitor injury and rejection posttransplant, they have recently been demonstrated to be inferior in performance to that of AlloSure (CareDx Inc, Brisbane, CA) circulating donor-derived, cell-free DNA (dd-cfDNA). OBJECTIVE The outcomes and methods of monitoring renal transplant recipients posttransplant have remained stagnant over the past 15 years. The aim of this study is to consider intensive surveillance using AlloSure dd-cfDNA in an actively managed protocol, assessing whether it increases long-term allograft survival in kidney transplant recipients compared with current standard clinical care in community nephrology. METHODS The study protocol will acquire data from a phase IV observational trial to assess a cohort of renal transplant patients managed using AlloSure dd-cfDNA and patient care managers versus 1000 propensity-matched historic controls using United Network for Organ Sharing U.S. Scientific Registry of Transplant Recipients data. Data will be managed in a centralized electronic data server. The primary outcome will be superior allograft survival, as a composite of return to dialysis, retransplant, death due to allograft failure, and death with a functional graft (infection, malignancy, and cardiovascular death). The secondary endpoints will assess improved kidney function through decline in estimated glomerular filtration rate and immune activity through development of donor-specific antibodies. RESULTS The total sample is anticipated to be 3500 (2500 patients managed with AlloSure dd-cfDNA and 1000 propensity-matched controls). Active enrollment began in November 2020. CONCLUSIONS Based on a significant literature base, we believe implementing the surveillance of dd-cfDNA in the kidney transplant population will have a positive impact on graft survival. Through early identification of rejection and facilitating timely intervention, prolongation of allograft survival versus those not managed by dd-cfDNA surveillance protocol should be superior. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/25941

Background Alcohol withdrawal syndrome (AWS) is routinely treated with B-vitamins. However, the relationship between thiamine status and outcome is rarely examined. The aim of the present study was to examine the relationship between thiamine and magnesium status in patients with AWS. Methods Patients (n = 127) presenting to the Emergency Department with AWS were recruited to a prospective observational study. Blood samples were drawn to measure whole blood thiamine diphosphate (TDP) and serum magnesium concentrations. Routine biochemistry and haematology assays were also conducted. The Glasgow Modified Alcohol Withdrawal Score (GMAWS) measured severity of AWS. Seizure history and current medications were also recorded. Results The majority of patients (99%) had whole blood TDP concentration within/above the reference interval (275–675 ng/gHb) and had been prescribed thiamine (70%). In contrast, the majority of patients (60%) had low serum magnesium concentrations (2 (p Conclusion The prevalence of low circulating thiamine concentrations were rare and it was regularly prescribed in patients with AWS. In contrast, low serum magnesium concentrations were common and not prescribed. Low serum magnesium was associated more severe AWS and increased 1-year mortality.

Our objective was to assess the effectiveness and safety of the combination of duloxetine and bupropion for treatment-resistant major depressive disorder (TRD). A retrospective chart review was conducted to identify patients with major depressive disorder (MDD) who had not experienced full remission of symptoms following an adequate trial of either duloxetine (n = 3) or bupropion (n = 7), and who then received the combination of these two antidepressants for TRD. Ten patients [37.2 +/- 11.3 years of age, five women, baseline Clinical Global Impressions (CGI) scale score 4.4 +/- 1.1], seven of whom had not remitted following treatment with bupropion (330 +/- 67 mg, 20.5 +/- 12.2 weeks), and three of whom had not remitted following treatment with duloxetine (90 +/- 30 mg, 18 +/- 2 weeks) received at least 4 weeks of combination treatment. The CGI was administered when the combination was first prescribed, and following 8.8 +/- 4.0 (range, 4-16) weeks of treatment. There was a significant decrease in CGI-S (Severity) scores (4.4 +/- 1.1 to 2.1+/-0.9, P

Se realizó un estudio transversal, descriptivo y correlacional, cuyo propósito fue analizar los niveles de violencia intrafamiliar, el consumo de alcohol y la sintomatología depresiva en un grupo de internos de un centro de readaptación social, así como determinar la relación de estas variables con el tipo de delito cometido. Se seleccionó una muestra no probabilística de 385 hombres, que se encontraban internos en un centro de readaptación social en México; el mayor porcentaje de ellos tenían entre 18 y 30 años de edad. Se utilizó un instrumento que evaluó: el consumo de alcohol, en cuanto a frecuencia y cantidad (indicadores de la Encuesta Nacional de Adicciones); la sintomatología depresiva (Cédula del Centro de Estudios Epidemiológicos, CES-D) y la violencia intrafamiliar (agresión verbal, agresión física, humillación y respeto). Los resultados mostraron que el 75,6% de los internos habían cometido robo y que más de la mitad aún se encontraban en proceso de recibir su sentencia. Respecto a los niveles de violencia intrafamiliar y el consumo de alcohol, el mayor porcentaje de los internos reportó niveles bajos (81,8 y 49,5%, respectivamente). Sin embargo, en niveles de depresión, el 50% presentó niveles altos. Se encontró un mayor número de internos que habían cometido secuestro con violencia intrafamiliar severa; se detectó un mayor porcentaje de ellos que habían cometido homicidio, con consumo severo de alcohol, y respecto a la sintomatología depresiva, se halló, en este grupo, una mayor cantidad con niveles severos, que reportaron haber cometido violaciones. A transversal, descriptive and correlational study was carried out for the purpose of analyzing domestic violence, alcohol consumption, and depressive symptomatology in a group of inmates in a social re-adaptation center, and to determine as well the relationship between these variables and the type of crimes committed. A non-probabilistic sample of 385 men confined in a social re-adaptation center in Mexico was selected, of which the highest percentage consisted of males between 18 and 30 years of age. An instrument was used to assess: alcohol consumption in terms of frequency and amount (indicators of the National Addiction Survey); depressive symptomatology (Scale of the Epidemiological Study Center CES-D), and domestic violence (verbal aggression, physical aggression, humiliation, and disrespect). The results showed that 75.6% of the inmates had committed theft, and more than half of them were still awaiting sentencing. With respect to domestic violence and alcohol consumption, the highest percentage of inmates reported low volumes (81.8 and 49.5%, respectively). Nevertheless, in depression situations, 50% exhibited high levels. It was found that a larger number of inmates with a history of intense domestic violence had committed kidnappings, and a higher percentage of those with a heavy consumption of alcohol were charged with murder or manslaughter. As per those with high depressive symptomatology rates, most of them reported having committed rapes. Um estudo transversal, descritivo e de correlação foi realizado. O objetivo foi analisar os níveis de violência doméstica, o consumo de álcool e os sintomas da depressão em um grupo de prisioneiros de um centro de reabilitação social, bem como a determinação da relação destas variáveis com o tipo de crime cometido. Uma amostra não probabilística de 385 homens foi selecionada. Os homens ficavam presos em um centro de reabilitação social no México; a maior percentagem deles tinham entre 18 e 30 anos de idade. Nós usamos um instrumento que avaliou: o consumo de álcool, em termos de frequência e quantidade (indicadores da Escola Nacional de Vícios); sintomas depressivos (Cédula do Centro de Estudos Epidemiológicos, CES-D) e violência doméstica (agressão verbal, agressão física, humilhação e respeito). Os resultados mostraram que 75,6 % dos detentos havia cometido roubo e que mais da metade estavam ainda em processo de receber sua sentença. Com relação aos níveis de violência doméstica e o consumo de álcool, a maior percentagem de detidos reportou níveis baixos (81,8 e 49,5%, respectivamente). No entanto, nos níveis de depressão, o 50% apresentou níveis elevados. Encontramos um maior número de presos que cometeram rapto com violência doméstica severa; uma percentagem mais elevada daqueles que tinham cometido assassinato foi detectada, com consumo de álcool grave e sintomas depressivos. A maioria neste grupo apresentava níveis graves, que relatou ter cometido estupro.