The COVID-19 pandemic is an unprecedented global crisis. Many countries have implemented restrictions on population movement to slow the spread of severe acute respiratory syndrome coronavirus 2 and ...prevent health systems from becoming overwhelmed; some have instituted full or partial lockdowns. However, lockdowns and other extreme restrictions cannot be sustained for the long term in the hope that there will be an effective vaccine or treatment for COVID-19. Governments worldwide now face the common challenge of easing lockdowns and restrictions while balancing various health, social, and economic concerns. To facilitate cross-country learning, this Health Policy paper uses an adapted framework to examine the approaches taken by nine high-income countries and regions that have started to ease COVID-19 restrictions: five in the Asia Pacific region (ie, Hong Kong Special Administrative Region, Japan, New Zealand, Singapore, and South Korea) and four in Europe (ie, Germany, Norway, Spain, and the UK). This comparative analysis presents important lessons to be learnt from the experiences of these countries and regions. Although the future of the virus is unknown at present, countries should continue to share their experiences, shield populations who are at risk, and suppress transmission to save lives.
Health care workers (HCW) are a high-risk population to acquire SARS-CoV-2 infection from patients or other fellow HCW. This study aims at estimating the seroprevalence against SARS-CoV-2 in a random ...sample of HCW from a large hospital in Spain. Of the 578 participants recruited from 28 March to 9 April 2020, 54 (9.3%, 95% CI: 7.1-12.0) were seropositive for IgM and/or IgG and/or IgA against SARS-CoV-2. The cumulative prevalence of SARS-CoV-2 infection (presence of antibodies or past or current positive rRT-PCR) was 11.2% (65/578, 95% CI: 8.8-14.1). Among those with evidence of past or current infection, 40.0% (26/65) had not been previously diagnosed with COVID-19. Here we report a relatively low seroprevalence of antibodies among HCW at the peak of the COVID-19 epidemic in Spain. A large proportion of HCW with past or present infection had not been previously diagnosed with COVID-19, which calls for active periodic rRT-PCR testing in hospital settings.
...it is difficult to define vulnerable populations; what is considered vulnerable might change depending on the setting and over time. ...the condition of vulnerability might also be present ...intermittently (eg, immunosuppression in people living with HIV), or a higher tuberculosis risk might still remain after the condition that is perceived as making an individual vulnerable has been removed (eg, people formerly deprived of liberty or ex-miners).5 Fourth, the effect of some vulnerabilities might be distinct depending on the stage of the cascade of tuberculosis care; these effects might differently increase the risk of Mycobacterium tuberculosis infection, the risk of tuberculosis disease, or the risk of tuberculosis mortality. ...an increased risk of M tuberculosis infection might not be associated with HIV infection but might be correlated with living in slum settings. ...it is crucial to understand how these differences might affect the generalisability of pooled burden of disease estimates for particular population groups to provide more meaningful and tailored policy.
Low- and middle-income countries (LMICs) are facing a combined affliction from both tuberculosis (TB) and noncommunicable diseases (NCDs), which threatens population health and further strains the ...already stressed health systems. Integrating services for TB and NCDs is advantageous in tackling this joint burden of diseases effectively. Therefore, this systematic review explores the mechanisms for service integration for TB and NCDs and elucidates the facilitators and barriers for implementing integrated service models in LMIC settings.
A systematic search was conducted in the Cochrane Library, MEDLINE, Embase, PubMed, Bibliography of Asian Studies, and the Global Index Medicus from database inception to November 4, 2021. For our search strategy, the terms "tuberculosis" AND "NCDs" (and their synonyms) AND ("delivery of healthcare, integrated" OR a range of other terms representing integration) were used. Articles were included if they were descriptions or evaluations of a management or organisational change strategy made within LMICs, which aim to increase integration between TB and NCD management at the service delivery level. We performed a comparative analysis of key themes from these studies and organised the themes based on integration of service delivery options for TB and NCD services. Subsequently, these themes were used to reconfigure and update an existing framework for integration of TB and HIV services by Legido-Quigley and colleagues, which categorises the levels of integration according to types of services and location where services were offered. Additionally, we developed themes on the facilitators and barriers facing integrated service delivery models and mapped them to the World Health Organization's (WHO) health systems framework, which comprises the building blocks of service delivery, human resources, medical products, sustainable financing and social protection, information, and leadership and governance. A total of 22 articles published between 2011 and 2021 were used, out of which 13 were cross-sectional studies, 3 cohort studies, 1 case-control study, 1 prospective interventional study, and 4 were mixed methods studies. The studies were conducted in 15 LMICs in Asia, Africa, and the Americas. Our synthesised framework explicates the different levels of service integration of TB and NCD services. We categorised them into 3 levels with entry into the health system based on either TB or NCDs, with level 1 integration offering only testing services for either TB or NCDs, level 2 integration offering testing and referral services to linked care, and level 3 integration providing testing and treatment services at one location. Some facilitators of integrated service include improved accessibility to integrated services, motivated and engaged providers, and low to no cost for additional services for patients. A few barriers identified were poor public awareness of the diseases leading to poor uptake of services, lack of programmatic budget and resources, and additional stress on providers due to increased workload. The limitations include the dearth of data that explores the experiences of patients and providers and evaluates programme effectiveness.
Integration of TB and NCD services encourages the improvement of health service delivery across disease conditions and levels of care to address the combined burden of diseases in LMICs. This review not only offers recommendations for policy implementation and improvements for similar integrated programmes but also highlights the need for more high-quality TB-NCD research.
Abstract Background This study retrospectively evaluated the capability of computed-tomography (CT) based radiomic features to predict EGFR mutation status in surgically-resected peripheral lung ...adenocarcinomas in an Asian cohort of patients. Materials and Methods 298 patients with surgically resected peripheral lung adenocarcinomas were investigated in this institutional review board-approved retrospective study with waived consent. 219 quantitative 3D features were extracted from segmented volumes of each tumor, and 59 of these which were considered as independent features were included in the analysis. Clinical and pathological information were obtained from the institutional database. Results Mutant EGFR was significantly associated with female gender ( p =0.0005); never smoker status ( p <0.0001), lepidic predominant adenocarcinomas ( p =0.017), and low or intermediate pathologic grade ( p =0.0002). Statistically significant differences were found in 11 radiomic features between EGFR mutant and wild type groups on univariate analysis. Mutant EGFR status could be predicted by a set of five radiomic features that fall in three broad groups: CT attenuation energy, tumor main direction and texture defined by wavelets and Laws (AUC 0.647). Multiple logistic regression model showed that adding radiomic features to a clinical model resulted in a significant improvement of predicting power, as the AUC increased from 0.667 to 0.709 ( p <0.0001). Conclusions CT based radiomic features of peripheral lung adenocarcinomas can capture useful information regarding tumor phenotype, and the model we built can be useful to predict the presence of EGFR mutations in peripheral lung adenocarcinoma in Asian patients when mutational profiling is not available or possible.
In the past decade, tuberculosis incidence has declined in much of the world, but has risen in central and South America. It is not yet clear what is driving this reversal of progress in tuberculosis ...control. Since 2000, the incarcerated population in central and South America has grown by 206%, the greatest increase in the world. Over the same period, notified tuberculosis cases among the incarcerated population (hereinafter termed persons deprived of their liberty PDL, following the Inter-American Commission on Human Rights) have risen by 269%. In both central and South America, the rise of disease among PDL more than offsets tuberculosis control gains in the general population. Tuberculosis is increasingly concentrated among PDL; currently, 11% of all notified tuberculosis cases in central and South America occur among PDL who comprise less than 1% of the population. The extraordinarily high risk of acquiring tuberculosis within prisons creates a health and human rights crisis for PDL that also undermines wider tuberculosis control efforts. Controlling tuberculosis in this region will require countries to take urgent measures to prioritise the health of PDL.
COVID-19 patients elicit strong responses to the nucleocapsid (N) protein of SARS-CoV-2 but binding antibodies are also detected in prepandemic individuals, indicating potential crossreactivity with ...common cold human coronaviruses (HCoV) and questioning its utility in seroprevalence studies. We investigated the immunogenicity of the full-length and shorter fragments of the SARS-CoV-2 N protein, and the crossreactivity of antibodies with HCoV. We identified a C-terminus region in SARS-CoV2 N of minimal sequence homology with HCoV that was more specific for SARS-CoV-2 and highly immunogenic. IgGs to the full-length SARS-CoV-2 N also recognized N229E N, and IgGs to HKU1 N recognized SARS-CoV-2 N. Crossreactivity with SARS-CoV-2 was stronger for alpha- rather than beta-HCoV despite having less sequence identity, revealing the importance of conformational recognition. Higher preexisting IgG to OC43 N correlated with lower IgG to SARS-CoV-2 N in rRT-PCR negative individuals, reflecting less exposure and indicating a potential protective association. Antibodies to SARS-CoV-2 N were higher in patients with more severe and longer duration of symptoms and in females. IgGs remained stable for at least 3 months, while IgAs and IgMs declined faster. In conclusion, N protein is a primary target of SARS-CoV-2-specific and HCoV crossreactive antibodies, both of which may affect the acquisition of immunity to COVID-19.
Non-tuberculous mycobacteria (NTM) can cause disease which can be clinically and radiologically undistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic challenge in high TB ...settings. We aim to describe the prevalence of NTM isolation and its clinical characteristics in children from rural Mozambique.
This study was part of a community TB incidence study in children <3 years of age. Gastric aspirate and induced sputum sampling were performed in all presumptive TB cases and processed for smear testing using fluorochrome staining and LED Microscopy, liquid and solid culture, and molecular identification by GenoType® Mycobacterium CM/AS assays.
NTM were isolated in 26.3% (204/775) of children. The most prevalent NTM species was M. intracellulare (N = 128), followed by M. scrofulaceum (N = 35) and M. fortuitum (N = 9). Children with NTM were significantly less symptomatic and less likely to present with an abnormal chest radiograph than those with M. tuberculosis. NTM were present in 21.6% of follow-up samples and 25 children had the same species isolated from ≥2 separate samples. All were considered clinically insignificant and none received specific treatment. Children with NTM isolates had equal all cause mortality and likelihood of TB treatment as those with negative culture although they were less likely to have TB ruled out.
NTM isolation is frequent in presumptive TB cases but was not clinically significant in this patient cohort. However, it can contribute to TB misdiagnosis. Further studies are needed to understand the epidemiology and the clinical significance of NTM in children.
Contaminant DNA is a well-known confounding factor in molecular biology and in genomic repositories. Strikingly, analysis workflows for whole-genome sequencing (WGS) data commonly do not account for ...errors potentially introduced by contamination, which could lead to the wrong assessment of allele frequency both in basic and clinical research.
We used a taxonomic filter to remove contaminant reads from more than 4000 bacterial samples from 20 different studies and performed a comprehensive evaluation of the extent and impact of contaminant DNA in WGS. We found that contamination is pervasive and can introduce large biases in variant analysis. We showed that these biases can result in hundreds of false positive and negative SNPs, even for samples with slight contamination. Studies investigating complex biological traits from sequencing data can be completely biased if contamination is neglected during the bioinformatic analysis, and we demonstrate that removing contaminant reads with a taxonomic classifier permits more accurate variant calling. We used both real and simulated data to evaluate and implement reliable, contamination-aware analysis pipelines.
As sequencing technologies consolidate as precision tools that are increasingly adopted in the research and clinical context, our results urge for the implementation of contamination-aware analysis pipelines. Taxonomic classifiers are a powerful tool to implement such pipelines.
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