Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone

Management of latent Mycobacterium tuberculosis infection:WHO guidelines for low tuberculosis burden countries

ABSTRACT Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of &lt;100 per 100000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing an

Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy, December 2021 to January 2022

Background: The SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021. Aim: To comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level. Methods: We analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility. Results: Omicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9-80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7-3.3 days. As of 17 January 2022, Delta variant represented &lt; 6% of cases. During the Omicron expansion in December 2021, the esti-mated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduc-tion in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant repro-duction numbers' decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022. Conclusion: Estimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at popula-tion level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection

Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer

Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institution study was a pooled analysis of AR status, determined by droplet digital PCR, on pre-treatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in AR-gain [hazard ratio (HR)=1.61, 95% confidence interval (CI)=1.08-2.39, p=0.018), but not PFS (HR=1.04, 95%CI 0.74-1.46, p=0.8), nor PSA response [odds ratio (OR)=1.14, 95%CI=0.65-1.99, p=0.7)]. We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 7 chemotherapy-naïve, abiraterone/enzalutamide-treated patients with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR=0.27,95%CI=0.11-0.68, p=0.005) and PFS (HR=0.28, 95%CI=0.12-0.64, p=0.002). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR-normal (HR=1.93, 95%CI=1.19-3.12, p=0.008) and a suggestion favoring docetaxel for AR-gained patients (HR=0.53, 95%CI=0.24-1.16, p=0.11). These data suggest that AR-normal patients should receive abiraterone/enzalutamide and AR-gained docetaxel. This treatment selection merits prospective evaluation in a randomized trial. // Patient summary: We investigated whether plasma androgen receptor (AR) predicted outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel, and we performed an exploratory analysis in patients treated with docetaxel or AR-directed drugs as first-line mCRPC therapy. We showed that plasma AR normal favored hormonal treatment, whilst plasma AR-gained patients may have had a longer response to docetaxel, suggesting that plasma AR status could be a useful treatment selection biomarker

Enhancing the quality and reproducibility of research: Preferred Evaluation of Cognitive and Neuropsychological Studies - The PECANS statement for human studies

Are scientific papers providing all essential details necessary to ensure the replicability of study protocols? Are authors effectively conveying study design, data analysis, and the process of drawing inferences from their results? These represent only a fraction of the pressing questions that cognitive psychology and neuropsychology face in addressing the “crisis of confidence.” This crisis has highlighted numerous shortcomings in the journey from research to publication. To address these shortcomings, we introduce PECANS (Preferred Evaluation of Cognitive And Neuropsychological Studies), a comprehensive checklist tool designed to guide the planning, execution, evaluation, and reporting of experimental research. PECANS emerged from a rigorous consensus-building process through the Delphi method. We convened a panel of international experts specialized in cognitive psychology and neuropsychology research practices. Through two rounds of iterative voting and a proof-of-concept phase, PECANS evolved into its final form. The PECANS checklist is intended to serve various stakeholders in the fields of cognitive sciences and neuropsychology, including: (i) researchers seeking to ensure and enhance reproducibility and rigor in their research; (ii) journal editors and reviewers assessing the quality of reports; (iii) ethics committees and funding agencies; (iv) students approaching methodology and scientific writing. PECANS is a versatile tool intended not only to improve the quality and transparency of individual research projects but also to foster a broader culture of rigorous scientific inquiry across the academic and research community

Urothelial Cancer: Inflammatory Mediators and Implications for Immunotherapy

Urothelial cancer (UC) represents one of the most frequent malignancies, which causes about 150,000 deaths per year worldwide. To date, only a few chemotherapeutic drugs have been approved against UC, showing poor results, and limited effective molecular markers. In the last years, several studies have evaluated the correlation between bladder cancer and phlogosis, showing that some cytokines produced by different stimuli can enhance invasion and migration of tumor cells. In more recent years, antibodies blocking immune checkpoints have exhibited oncologic efficacy, including increased overall survival, in various tumor types. To date, several studies evaluated the role of immune-checkpoint inhibitors in metastatic UC showing exiting results, compared to those of classic chemotherapeutic regimens. In this review, we summarized data on inflammatory mediators and discussed implications for treatment with new immune-related drugs in UC patients

Profile of gantenerumab and its potential in the treatment of Alzheimer's disease

Alzheimer's disease, which is characterized by gradual cognitive decline associated with deterioration of daily living activities and behavioral disturbances throughout the course of the disease, is estimated to affect 27 million people around the world. It is expected that the illness will affect about 63 million people by 2030, and 114 million by 2050, worldwide. Current Alzheimer's disease medications may ease symptoms for a time but are not capable of slowing down disease progression. Indeed, all currently available therapies, such as cholinesterase inhibitors (donepezil, galantamine, rivastigmine), are primarily considered symptomatic therapies, although recent data also suggest possible disease-modifying effects. Gantenerumab is an investigational fully human anti-amyloid beta monoclonal antibody with a high capacity to bind and remove beta-amyloid plaques in the brain. This compound, currently undergoing Phase II and III clinical trials represents a promising agent with a disease-modifying potential in Alzheimer's disease. Here, we present an overview of gantenerumab ranging from preclinical studies to human clinical trials

Tuberculosis contact investigations in congregate settings in Rome, Italy: contribution of migration

Abstract Background In middle to low incidence countries tuberculosis (TB) is known to concentrate in big cities as national incidence falls: in the last decade TB incidence in Rome metropolitan area and in Lazio region has been higher than the national estimates; TB incidence among foreign born fell by more than half despite remaining higher than among Italian born. We aimed to describe the current dynamics of TB transmission among residents of our local health unit in Rome metropolitan area in order to drive specific TB control interventions at local level. Methods We retrospectively evaluated characteristics of TB cases and results of contact investigations among the residents of ASL Roma 2 in congregate settings over year 2018. Results Overall 217 TB cases were notified, of which 70.5% with pulmonary involvement. Male/female ratio was 2.4/1 and age group most affected was 25-44 among foreign born and &amp;gt;65 among natives. During the study period foreign born cases accounted for 65% of the total number of TB cases. 19/141 (13.5%) foreign born patients were hosted in a reception center. 479 exposed close contacts were screened, with no evidence of secondary TB disease transmission. No identifiable links were found among cases occurred in the same immigrant reception center. Conclusions Italian guidelines recommend symptom screening for TB and LTBI testing both of new entrants and of long term residents -including second–generation migrants- from high TB burden countries. These findings suggest that local public health efforts should prioritize the identification of reactivations of remotely acquired latent TB rather than of new postarrival infections acquired in the host county through local transmission. Key messages City-specific data on TB incidence trends among native and foreign-born residents help understanding the wider interaction between migration and TB. To prevent TB incidents in congregate settings remotely acquired latent TB should be targeted. </jats:sec