Nyt fra tidsskrifterne

Introduction…

Background…

Antimicrobial stewardship (AMS) programmes include actions to improve antibiotic use.

Through oxidative phosphorylation, mitochondria play a central role in energy production and are an important production source of reactive oxygen species (ROS). Not surprisingly, viruses have evolved to exploit this organelle in order to support their infection cycle. Beyond its role in the cellular antiviral response, induction of oxidative stress has emerged as a common strategy employed by many viruses to promote their replication. Here, we review the key molecular mechanisms employed by viruses to interact with mitochondria and induce oxidative stress.

Almost two years into the COVID-19 pandemic it remains to be determined how helminths interact with SARS-CoV-2. We discuss how helminths may alter susceptibility to infection, COVID-19 pathology and efficiency of vaccines by combined analysis of available COVID-19 data and previous investigations of the effect of helminths in viral infections.

Trypanosoma evansi, the causative agent of 'surra', is a flagellated hemoprotozoan parasite. It kills thousands of animals every year and causes significant animal morbidity and loss of productivity. T. evansi originated from Trypanosoma brucei through deletion of the maxicircle kinetoplast DNA which conferred the capacity for mechanical transmission by flies and allowed T. evansi to expand beyond the tsetse belt. Presently, it is the most widely distributed pathogenic trypanosome in Africa, Asia, and Latin America, but its potential for geographical extension is not limited, as shown by recent sporadic cases in Spain and France.

Abstract

Background

Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD).

Methods

This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed.

Results

Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate.

Conclusions

Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

…

Abstract

Background

Fever of unknown origin (FUO) is a challenge for clinicians treating patients with HIV/AIDS. CD4 counts can be helpful in the diagnosis and treatment. This study aimed to determine several common etiologies of FUO stratified by CD4 count levels in HIV/AIDS patients.

Methods

A cross-sectional retrospective and prospective study was conducted in 195 HIV/AIDS patients with FUO admitted to the National Hospital for Tropical Diseases from January 2016 to June 2019. Clinical parameters, immune status, and etiologies for each patient were recorded. Odds ratios were calculated to compare the distributions of common etiologies in groups with two different CD4 count levels: < 50 cells/mm3 and ≥ 50 cells/mm3.

Results

The proportions of opportunistic infections and noninfectious etiologies were 93.3% and 3.6%, respectively. Tuberculosis was the most common opportunistic infection (46.7%), followed by talaromycosis (29.2%) and Pneumocystis jiroveci (PCP) infection (20.5%). Tuberculosis was predominant in all CD4 level groups. Most patients with talaromycosis had CD4 counts below 50 cells/mm3. In total, 53.8% of the patients were infected by one pathogen. The risks of tuberculosis and talaromycosis in FUO-HIV patients were high when their CD4 counts were below 50 cells/mm3.

Conclusions

Opportunistic infections, especially tuberculosis, are still the leading cause of FUO in HIV/AIDS patients. Tuberculosis and Talaromyces marneffei (TM) infection should be considered in patients with CD4 cell counts < 50 cells/mm3. This study implies that guidelines for appropriate testing to identify the etiology of FUO in HIV/AIDS patient based on the CD4 cell count should be developed, thereby reducing resource waste.

…

Science, Ahead of Print. …

Science Translational Medicine, Ahead of Print. …

Infection and Immunity, <a href='https://journals.asm.org/toc/iai/0/ja'>Volume 0, Issue ja</a>, -Not available-. …

Infection and Immunity, <a href='https://journals.asm.org/toc/iai/0/ja'>Volume 0, Issue ja</a>, -Not available-. …

A 57-year-old man with HIV (CD4 cell count, 16/mm3; HIV viral load >10 million copies/mL) had blurred vision, weight loss, and gastrointestinal bleeding. A sample of small bowel showed inflammation of the lamina propria, with numerous cytoplasmic and nuclear inclusions with an “owl eye” appearance; dilated retinal examination revealed extensive macular hemorrhage with peripapillary whitening. What is the diagnosis and what would you do next?…

In the Original Investigation titled “Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial,” published in the November 9, 2021, issue of JAMA, there was an incorrect equivalent dose listed and incorrect P values in Figure 3. In the second paragraph of the article, the last sentence should have been “Pharmacodynamic studies suggest dose-dependent activation of the corticosteroid receptor with increasing doses up to 60 mg of prednisone (equivalent to 9 mg of dexamethasone).10” In Figure 3, a coding error was recently detected revealing that the majority of P values were incorrect. In the last column of Figure 3, the P values should have been .32 instead of .57; .76 instead of .83; .31 instead of .53; .36 instead of .44; .13 instead of .59; and .25 instead of .64. This article was corrected online.

Because venous and arterial thromboembolism are common among patients hospitalized with COVID-19, anticoagulant therapies were among the first to be evaluated in clinical trials to improve outcomes in moderately ill patients hospitalized with COVID-19. These studies have yielded thus far somewhat mixed results, varying from beneficial effects of therapeutic doses of low-molecular-weight heparin in the ATTACC, ACTIV-4a, and REMAP-CAP trials to no difference between therapeutic and prophylactic doses of low-molecular-weight heparin in the INSPIRATION, ACTION, and RAPID trials. Therefore, it remains to be determined whether the addition of antiplatelet therapy will yield different results.

To the Editor I have several questions about the study investigating the effect of fractional carbon dioxide laser vs sham treatment on symptom severity in women with postmenopausal vaginal symptoms. First, I would like to know whether this study’s treatment protocol included a 90° probe introital treatment in addition to the straight probe vaginal treatment. In clinical practice, this additional introital therapy substantially enhances the treatment effect of the carbon dioxide laser therapy. Second, in relation to the histological evaluation of the vaginal tissue before and after treatment, do the authors have an explanation for the change in vaginal histology in the sham group to premenopausal status in 3 of the 24 patients? Third, did patients with recurrent vulvovaginal candidiasis receive antifungal medication prior to treatment with the fractional carbon dioxide laser? Fourth, were women with vulvodynia excluded from this trial? In clinical practice, patients with untreated vulvovaginal candidiasis and/or vulvodynia typically do not have improvement in their vaginal symptoms with laser therapy unless these underlying conditions are addressed and managed.

This randomized clinical trial evaluates the benefits and risks of the addition of a P2Y12 inhibitor to anticoagulant therapy compared with anticoagulant therapy only among non–critically ill patients hospitalized for COVID-19.

This retrospective study compares ambulatory care patterns before and in the first year of the COVID-19 pandemic among patients insured by public and private insurance programs.

Policies requiring people to show proof that they’ve been vaccinated against COVID-19, recovered from the illness, or recently tested negative for SARS-CoV-2 before they can travel internationally or go to nightclubs, gyms, or other public places could increase vaccinations in countries with low uptake, according to a study of these policies in 6 European countries.

The COVID-19 pandemic appears to have halted a more than decade-long increase in life expectancy, according to global mortality data that showed decreases in 2020 in 31 out of 37 high-income countries.

Fewer children and adolescents with HIV infection are close to meeting global viral suppression goals compared with adults, an international research consortium’s study suggested.

This Viewpoint proposes a multistep plan that US can implement to achieve a “new normal” of living, in which the combined risk of all viral respiratory illnesses, including COVID-19, does not exceed the risk during prepandemic years.

This Viewpoint discusses the areas on which the US needs to improve its public health infrastructure in order to reduce COVID-19 transmission and achieve a “new normal”: testing, surveillance, masking, and ventilation.

This Viewpoint examines the lessons that the COVID-19 pandemic can provide public health institutions and health care personnel to advance preparedness, detection, and response regarding future pandemics.

This Medical News Quick Uptake looks at how recently authorized monoclonal antibodies for COVID-19 preexposure prophylaxis will be allocated.

This Medical News article discusses how structure-based vaccinology has advanced long-awaited progress on RSV vaccines.

This study examines the risk of multisystem inflammatory syndrome in children among those aged 12 years or older by COVID-19 vaccination status during September 2021 and October 2021 in France.

This study investigates the immunogenicity of extended mRNA vaccine dosing intervals.

Nature Medicine, Published online: 14 January 2022; doi:10.1038/s41591-022-01700-xPeripheral ancestral SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by BNT162b2 vaccination cross-react to the Omicron variant at higher levels than those induced by prior SARS-CoV-2 infection…

by Felipe de Andrade Vieira Alves, Lucca de Lima S. Oliveira, Natália Gedeão Salomão, David William Provance Jr, Carlos Alberto Basilio-de-Oliveira, Rodrigo Basílio-de-Oliveira, Leandro Junqueira Moragas, Jorge José de Carvalho, Ronaldo Mohana-Borges, Kíssila Rabelo, Marciano Viana Paes

Dengue viral (DENV) infections can lead to acute pancreatitis and associated tissue damage. This study examined the pancreas from two fatal cases of DENV for histopathological changes as well as for the detection of cytokines, and other inflammatory mediators. Tissue sections were prepared for examination by ultrastructural and histopathological techniques. Sections from the pancreas of non-infected individuals were prepared in parallel as a control. The presence of viral replication in macrophages was detected by co-staining for the proteins NS3 and CD68 by immunofluorescence. Immunohistochemistry was used to detect cells that expressed cytokines and inflammatory mediators to characterize the inflammatory response. Edema, acinar necrosis and fibrosis areas associated with a mononuclear infiltrate were found in infected tissues. The major site of virus replication appeared to be macrophages based on their exclusive presentation of the viral protein NS3. Pancreatic tissues from the infected individuals also displayed increased levels of high mobility group box-1, caspase-3, gelatinase B and tumor necrosis factor alpha compared to controls. The presence of virus replicating macrophages in the pancreas was associated with multiple changes in tissue structure that included elevated levels of cytokines and inflammatory markers that may differentiate acute pancreatitis due to DENV infections from other causes.

by Guillermo A. Guaracha-Basáñez, Irazú Contreras-Yáñez, Gabriela Hernández-Molina, Viviana A. Estrada-González, Lexli D. Pacheco-Santiago, Salvador S. Valverde-Hernández, José Roberto Galindo-Donaire, Ingris Peláez-Ballestas, Virginia Pascual-Ramos

Background Previous models that assess quality-of-Life (QoL) in patients with rheumatic diseases have a strong biomedical focus. We evaluated the impact of COVID-19 related-health care interruption (HCI) on the physical, psychological, social relationships and environment QoL-dimensions, and explored factors associated with QoL when patients were reincorporated to the outpatient clinic, and after six-month follow-up. Patients and methods Study phase-1 consisted of a COVID-19 survey administered from June 24th-October 31st 2020, to outpatients with rheumatic diseases who had face-to-face consultation at outpatient clinic reopening. Study phase-2 consisted of 3 consecutive assessments of patient´s QoL (WHOQOL-BREF), disease activity/severity (RAPID-3), and psychological comorbidity/trauma (DASS-21 and IES-R) to patients from phase-1 randomly selected. Sociodemographic, disease and treatment-related information, and comorbidities were obtained. Multiple linear regression analysis identified factors associated with the score assigned to each WHOQOL-BREF dimension. Results Patients included (670 for phase-1 and 276 for phase-2), had primarily SLE and RA (44.2% and 34.1%, respectively), and all the dimensions of their WHOQOL-BREF were affected. There were 145 patients (52.5%) who referred HCI, and they had significantly lower dimensions scores (but the environment dimension score). Psycho-emotional factors (primarily feeling confused, depression and anxiety), sociodemographic factors (age, COVID-19 negative economic impact, years of scholarship, HCI and having a job), and biomedical factors (RAPID-3 score and corticosteroid use) were associated with baseline QoL dimensions scores. Psycho-emotional factors showed the strongest magnitude on dimensions scores. Most consistent predictor of six-month follow-up QoL dimensions scores was each corresponding baseline dimension score, while social determinants (years of scholarship and having a job), emotional factors (feeling bored), and biomedical aspects (RAPID 3) had an additional impact. Conclusions HCI impacted the majority of patient´s QoL dimensions. Psycho-emotional, sociodemographic and biomedical factors were consistently associated with QoL dimensions scores, and these consistently predicted the QoL trajectory.…

by Mohadeseh Zarei Ghobadi, Rahman Emamzadeh

Human T-cell Leukemia Virus type-1 (HTLV-1) is an oncovirus that may cause two main life-threatening diseases including a cancer type named Adult T-cell Leukemia/Lymphoma (ATLL) and a neurological and immune disturbance known as HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). However, a large number of the infected subjects remain as asymptomatic carriers (ACs). There is no comprehensive study that determines which dysregulated genes differentiate the pathogenesis routes toward ATLL or HAM/TSP. Therefore, two main algorithms including weighted gene co-expression analysis (WGCNA) and multi-class support vector machines (SVM) were utilized to find major gene players in each condition. WGCNA was used to find the highly co-regulated genes and multi-class SVM was employed to identify the most important classifier genes. The identified modules from WGCNA were validated in the external datasets. Furthermore, to find specific modules for ATLL and HAM/TSP, the non-preserved modules in another condition were found. In the next step, a model was constructed by multi-class SVM. The results revealed 467, 3249, and 716 classifiers for ACs, ATLL, and HAM/TSP, respectively. Eventually, the common genes between the WGCNA results and classifier genes resulted from multi-class SVM that also determined as differentially expressed genes, were identified. Through these step-wise analyses, PAIP1, BCAS2, COPS2, CTNNB1, FASLG, GTPBP1, HNRNPA1, RBBP6, TOP1, SLC9A1, JMY, PABPC3, and PBX1 were found as the possible critical genes involved in the progression of ATLL. Moreover, FBXO9, ZNF526, ERCC8, WDR5, and XRCC3 were identified as the conceivable major involved genes in the development of HAM/TSP. These genes can be proposed as specific biomarker candidates and therapeutic targets for each disease.

by Fartima Yeemard, Peeradone Srichan, Tawatchai Apidechkul, Naphat Luerueang, Ratipark Tamornpark, Suphaphorn Utsaha

Background Suboptimal glycemic control among patients with type 2 diabetes mellitus (DM) is a significant public health problem, particularly among people living with poor education and economic statuses, including those with a unique dietary culture. This study aimed to estimate the prevalence and identify the factors associated with suboptimal glycemic control among patients with type 2 DM during the coronavirus disease-2019 (COVID-19) pandemic. Methods A hospital-based cross-sectional study was used to elicit information from DM patients attending six hospitals located in Chiang Rai Province, northern Thailand, between February and May 2021. A validated questionnaire and 5 mL blood specimens were used as the research tools. Glycated hemoglobin (HbA1c) greater than 7.0% among DM patients at least two years after diagnosis was defined as suboptimal glycemic control. Chi-square tests and logistic regression were used to identify the associations between variables at the significance level α = 0.05. Results A total of 967 patients were recruited for this study; 54.8% 530 had suboptimal glycemic control, 58.8% were female, 66.5% were aged 50-69 years, and 78.5% were married (78.5%). Six variables were found to be associated with suboptimal glycemic control in multivariable logistic regression. Participants aged…

by Adam V. Wisnewski, Jian Liu, Carolina Lucas, Jon Klein, Akiko Iwasaki, Linda Cantley, Louis Fazen, Julian Campillo Luna, Martin Slade, Carrie A. Redlich

Background Tests for SARS-CoV-2 immunity are needed to help assess responses to vaccination, which can be heterogeneous and may wane over time. The plaque reduction neutralization test (PRNT) is considered the gold standard for measuring serum neutralizing antibodies but requires high level biosafety, live viral cultures and days to complete. We hypothesized that competitive enzyme linked immunoassays (ELISAs) based on SARS-CoV-2 spike protein’s receptor binding domain (RBD) attachment to its host receptor, the angiotensin converting enzyme 2 receptor (ACE2r), would correlate with PRNT, given the central role of RBD-ACE2r interactions in infection and published studies to date, and enable evaluation of vaccine responses. Methods and results Configuration and development of a competitive ELISA with plate-bound RBD and soluble biotinylated ACE2r was accomplished using pairs of pre/post vaccine serum. When the competitive ELISA was used to evaluate N = 32 samples from COVID-19 patients previously tested by PRNT, excellent correlation in IC50 results were observed (rs = .83, p < 0.0001). When the competitive ELISA was used to evaluate N = 42 vaccinated individuals and an additional N = 13 unvaccinated recovered COVID-19 patients, significant differences in RBD-ACE2r inhibitory activity were associated with prior history of COVID-19 and type of vaccine received. In longitudinal analyses pre and up to 200 days post vaccine, surrogate neutralizing activity increased markedly after primary and booster vaccine doses, but fell substantially, up to…

by Zorimar Rivera-Núñez, Manuel E. Jimenez, Benjamin F. Crabtree, Diane Hill, Maria B. Pellerano, Donita Devance, Myneka Macenat, Daniel Lima, Marsha Gordon, Brittany Sullivan, Robert J. Rosati, Jeanne M. Ferrante, Emily S. Barrett, Martin J. Blaser, Reynold A. Panettieri Jr., Shawna V. Hudson

Black and Latinx individuals, and in particular women, comprise an essential health care workforce often serving in support roles such as nursing assistants and dietary service staff. Compared to physicians and nurses, they are underpaid and potentially undervalued, yet play a critical role in health systems. This study examined the impact of the coronavirus disease 2019 (COVID-19) pandemic from the perspective of Black and Latinx health care workers in support roles (referred to here as HCWs). From December 2020 to February 2021, we conducted 2 group interviews (n = 9, 1 group in English and 1 group in Spanish language) and 8 individual interviews (1 in Spanish and 7 in English) with HCWs. Participants were members of a high-risk workforce as well as of communities that suffered disproportionately during the pandemic. Overall, they described disruptive changes in responsibilities and roles at work. These disruptions were intensified by the constant fear of contracting COVID-19 themselves and infecting their family members. HCWs with direct patient care responsibilities reported reduced opportunities for personal connection with patients. Perspectives on vaccines reportedly changed over time, and were influenced by peers’ vaccination and information from trusted sources. The pandemic has exposed the stress endured by an essential workforce that plays a critical role in healthcare. As such, healthcare systems need to dedicate resources to improve the work conditions for this marginalized workforce including offering resources that support resilience. Overall working conditions and, wages must be largely improved to ensure their wellbeing and retain them in their roles to manage the next public health emergency. The role of HCWs serving as ambassadors to provide accurate information on COVID-19 and vaccination among their coworkers and communities also warrants further study.

by Harumasa Yokota, Hiroki Hayashi, Junya Hanaguri, Satoru Yamagami, Akifumi Kushiyama, Hironori Nakagami, Taiji Nagaoka

Prorenin is viewed as an ideal target molecule in the prevention of diabetic retinopathy. However, no drugs are available for inhibiting activation of prorenin. Here, we tested the effect of a prorenin peptide vaccine (VP) in the retina of a murine model of type 2 diabetes (T2D). To choose the optimal vaccine, we selected three different epitopes of the prorenin prosegment (E1, E2, and E3) and conjugated them to keyhole limpet hemocyanin (KLH). We injected C57BL/6J mice twice with KLH only (as a control vaccine), E1 conjugated with KLH (E1-KLH), E2-KLH, or E3-KLH and compared antibody titers. E2-KLH showed the highest antibody titer and specific immunoreactivity of anti-sera against prorenin, so we used E2-KLH as VP. Then, we administered injections to the non-diabetic db/m and diabetic db/db mice, as follows: db/m + KLH, db/db + KLH, and db/db + VP. Retinal blood flow measurement with laser speckle flowgraphy showed that the impaired retinal circulation response to both flicker light and systemic hyperoxia in db/db mice improved with VP. Furthermore, the prolonged implicit time of b-wave and oscillatory potentials in electroretinography was prevented, and immunohistochemical analysis showed reduced microglial activation, gliosis, and vascular leakage. The enzyme-linked immunosorbent spot assay confirmed vaccinated mice had no auto-immune response against prorenin itself. The present data suggest that vaccination against prorenin is an effective and safe measure against the early pathological changes of diabetic retinopathy in T2D.

by Nisreen N. Al Awaji, Alanoud A. AlMudaiheem, Eman M. Mortada

Purpose The study aimed to investigate changes in the role of speech-language pathologists (SLPs) during the COVID-19 pandemic in Saudi Arabia. It also assessed the SLPs’ perceptions of delivering services using telehealth as a part of their everyday clinical practice before and during the COVID-19 pandemic. Method SLPs in Saudi Arabia were invited to complete a web-based survey covering questions related to changes to the role of SLPs during the COVID-19 pandemic, changes in the ways speech services are delivered; and the benefits and barriers of using telehealth in clinical practice as identified by SLPs. Results Ninety-one SLPs completed the survey. About 94% of the respondents experienced changes in their role as a response to the COVID-19 pandemic. The nature of changes they had experienced including decreased work time, providing support and counseling to patients or caregivers using the telephone, providing assessment and therapy using telehealth, and working with a limited number of cases. Ninety-three percent of the respondents who have used telehealth started to use it only during the pandemic. Mostly seen caseloads were pediatric speech and language disorders. Further, 96% of respondents used telehealth for counseling, 69% for rehabilitation or treatment, 63% for screening, 56% for evaluation or assessment, 48% for a referral to other professional services, and 46% for differential diagnosis. About 70% of the SLPs showed interest to continue using telehealth in the future. Several benefits were identified to using telehealth, including accessibility, cost efficiency, and the ability to engage patients with their families in therapy sessions. On the other hand, barriers to using telehealth included internet and technical issues, lack of direct communication, and difficulty controlling the therapy setting. Conclusions The study has shown that SLPs in Saudi Arabia have experienced changes during the COVID-19 outbreak. The survey responses also indicate that the SLPs are adopting telehealth applications at an accelerated pace as a result of the pandemic.…

by Yit Siew Chin, Fui Chee Woon, Yoke Mun Chan

Background The COVID-19 pandemic lockdowns have affected daily lives of the communities worldwide. This study aims to determine the lifestyle behaviours and their associations with body weight changes among Malaysian adults during the Movement Control Order (MCO) due to COVID-19 pandemic. Methods A total of 1319 Malaysian adults participated in this cross-sectional online survey. Information on anthropometric data including body weight and height, and lifestyle behaviours including eating pattern, physical activity, and sleep pattern were self-reported by the respondents. A multivariable generalised linear mixed model was used to assess the associations between lifestyle behaviours and body weight changes with adjustment of confounding factors; namely, age, sex, ethnicity, and body weight status before MCO. Results During MCO, 41.2% of the respondents perceived that their eating patterns were healthier, but 36.3% reduced their physical activities, and 25.7% had a poorer sleep quality. Further, the proportion of adults who reported having lose weight (32.2%) was almost similar to those who reported having gained weight (30.7%). Lifestyle behaviours including less frequent practice of healthy cooking methods and lunch skipping were associated with weight gain, while less frequent consumption of high fat foods, more frequent physical activity, and good sleep latency were associated with lower risk of weight gain. In contrast, practicing healthy eating concept, skipped lunch, and more frequent physical activity were significantly associated with weight loss. Conclusion Lifestyle behaviours were associated with body weight changes during MCO. While the COVID-19 pandemic lockdown is necessary to prevent further spread of the disease, promoting healthy lifestyle practices during lockdown should be implemented for a healthy weight and better health.…

by Avik Biswas, Allan Haldane, Ronald M. Levy

The rapid evolution of HIV is constrained by interactions between mutations which affect viral fitness. In this work, we explore the role of epistasis in determining the mutational fitness landscape of HIV for multiple drug target proteins, including Protease, Reverse Transcriptase, and Integrase. Epistatic interactions between residues modulate the mutation patterns involved in drug resistance, with unambiguous signatures of epistasis best seen in the comparison of the Potts model predicted and experimental HIV sequence “prevalences” expressed as higher-order marginals (beyond triplets) of the sequence probability distribution. In contrast, experimental measures of fitness such as viral replicative capacities generally probe fitness effects of point mutations in a single background, providing weak evidence for epistasis in viral systems. The detectable effects of epistasis are obscured by higher evolutionary conservation at sites. While double mutant cycles in principle, provide one of the best ways to probe epistatic interactions experimentally without reference to a particular background, we show that the analysis is complicated by the small dynamic range of measurements. Overall, we show that global pairwise interaction Potts models are necessary for predicting the mutational landscape of viral proteins.

by Elaine Tomasi, Thales Moura de Assis, Paulo Guilherme Muller, Denise Silva da Silveira, Rosália Garcia Neves, Everton Fantinel, Elaine Thumé, Luiz Augusto Facchini

The article describes the temporal evolution of prenatal quality indicators in the primary health care network in Brazil and investigates regional differences. This study used data from the external evaluation of Brazil’s National Program for Improving Primary Care Access and Quality (PMAQ) with health teams participating in Cycles I, II and III of the Program, carried out respectively in 2012, 2013/14 and 2017/18. The number of visits, physical examination procedures, guidelines and request for laboratory tests were investigated. There was a positive evolution for tests—HIV, syphilis, blood glucose and ultrasound, and for all tests, guidance on feeding and weight gain of the baby and examination of the oral cavity. The indicators that performed the worst were: performance of tetanus vaccine, six or more visits, receiving guidance on exclusive breastfeeding and care for the newborn, and the procedures—all, measurement of uterine height, gynecological exam and cervix cancer prevention. These changes had a varied behavior between the regions of the country.

Objectives

To determine the prevalence of undiagnosed hepatitis C virus (HCV) and HIV cases in a population sample tested in the emergency room (ER) and to evaluate linkage-to-care.

Setting

Canadian university hospital.

Participants

Adults born after 1945 who consulted at ER for any condition and on any shift were included. Patients unable to opt-out were excluded.

Interventions

ER nurse confirmed patients’ eligibility and provided them with the option to opt-out. A physician met patients with a new diagnosis. Linkage-to-care was assessed 3 months postdiagnosis. Patients newly diagnosed with HCV were considered linked if they had an HCV RNA test, genotype, liver fibrosis evaluation, and if indicated, treatment prescription. Patients newly diagnosed with HIV were considered linked to care if they had an HIV serology confirmation test, viral load, CD4 cell count and started antiretroviral therapy.

Primary and secondary outcome measures

Primary objective: to determine the prevalence (overall and undiagnosed cases) of HIV and HCV among the patients who consult the ER. Secondary objectives: to determine the proportion of patients who opt-out, assess the adherence of emergency staff to the offer of testing, determine the proportion of patients linked to care at 3 months.

Results

Among 6350 eligible patients informed of the screening programme, 62.1% of patients were tested for at least one virus (HIV: 3905; HCV: 3910). 25% patients opted-out, 12% were not tested for organisational reasons, 0.3% (18) patients were HCV-HIV coinfected. Overall prevalence of HCV and HIV cases were 1.9% and 1.2%, respectively. Prevalence of new cases was 0.23% (95% CI 0.12% 0.45%) for HCV and 0.05% (95% CI 0.01% to 0.20%) for HIV. Among the new cases, only two HCV-infected and one HIV-infected patients were linked-to-care 3 months postdiagnosis.

Conclusions

Identification of new cases of HCV and HIV through universal screening at the ER and linkage-to-care were both low.

Trial registration number

NCT03595527; Results.

…

Introduction

Implementation researchers could draw from participatory research to engage patients (consumers of healthcare) in implementation processes and possibly reduce healthcare disparities. There is a little consumer involvement in healthcare implementation, partially because no formal guidance exists. We will create and pilot a toolkit of methods to engage consumers from the US’ Veterans Health Administration (VHA) in selecting and tailoring implementation strategies. This toolkit, Consumer Voice, will provide guidance on what, when, where, how and why an implementer might engage consumers in implementing treatments. We will pilot the toolkit by implementing Safety Planning Intervention for suicide prevention with rural veterans, a population with suicide disparities. Safety Planning Intervention is effective for reducing suicidal behaviours.

Methods and analysis

In Aim 1, we will use participatory approaches and user-centred design to develop Consumer Voice and its methods. In Aim 2, we will pilot Consumer Voice by implementing the Safety Planning Intervention in two clinics serving rural VHA patients. One site will receive a current implementation strategy (Implementation Facilitation) only; the second will receive Implementation Facilitation plus Consumer Voice. We will use mixed methods to assess feasibility and acceptability of Consumer Voice. We will compare sites on preliminary implementation (reach, adoption, fidelity) and clinical outcomes (depression severity, suicidal ideation, suicidal behaviour). In Aim 3, we will evaluate Aim 2 outcomes at 20 months to assess sustained impact. We will gather qualitative data on sustainability of the Safety Planning Intervention.

Ethics and dissemination

These studies are overseen by the Institutional Review Board at the Central Arkansas Veterans Healthcare System. We plan to use traditional academic modalities of dissemination (eg, conferences, publications). We plan to disseminate findings through meetings with other trainers in implementation practice so they may adopt Consumer Voice. We plan to share results with local community boards.

…

Objective

This is the first British multicentre study observing the impact of the COVID-19 pandemic on orthopaedic trauma with respect to referrals, operative caseload and mortality during its peak.

Design

A longitudinal, multicentre, retrospective, observational, cohort study was conducted during the peak 6 weeks of the first wave from 17 March 2020 compared with the same period in 2019.

Setting

Hospitals from six major urban cities were recruited around the UK, including London.

Participants

A total of 4840 clinical encounters were initially recorded. 4668 clinical encounters were analysed post-exclusion.

Primary and secondary outcome measures

Primary outcomes included the number of acute trauma referrals and those undergoing operative intervention, mortality rates and the proportion of patients contracting COVID-19. Secondary outcomes consisted of the mechanism of injury, type of operative intervention and proportion of aerosolising-generating anaesthesia used.

Results

During the COVID-19 period, there was a 34% reduction in acute orthopaedic trauma referrals compared with 2019 (1792 down to 1183 referrals), and a 29.5% reduction in surgical interventions (993 down to 700 operations). The mortality rate was more than doubled for both risk and odds ratios during the COVID-19 period for all referrals (1.3% vs 3.8%, p=0.0005) and for those undergoing operative intervention (2.2% vs 4.9%, p=0.004). Moreover, mortality due to COVID-19-related complications (vs non-COVID-19 causes) had greater odds by a factor of at least 20 times. For the operative cohort during COVID-19, there was an increase in odds of aerosolising-generating anaesthesia (including those with superimposed regional blocks) by three-quarters, as well as doubled odds of a consultant acting as the primary surgeon.

Conclusion

Although there was a reduction of acute trauma referrals and those undergoing operative intervention, the mortality rate still more than doubled in odds during the peak of the pandemic compared with the same time interval 1 year ago.

…

Introduction

Voluntary medical male circumcision (VMMC) is one of the key interventions for HIV prevention. However, its uptake among men in Malawi is low. Implementation science strategies for demand creation of VMMC increase uptake. We designed an implementation science demand-creation intervention to increase the uptake of VMMC among men with sexually transmitted infections (STIs).

Methods and analysis

We designed a pragmatic pre-interventional and post-interventional quasi-experimental study combined with a prospective observational design to determine the uptake, acceptability, appropriateness and feasibility of a multifaceted intervention for scale up of uptake of VMMC among men with STIs at Bwaila STI clinic in Lilongwe, Malawi. The intervention includes transport reimbursement (R), intensified health education (I) and short messaging service (SMS)/telephonic tracing (Te) (RITe). The intervention will be implemented in phases: pre-implementation and implementation. Pre-implementation phase will be used for collecting baseline data, while the RITe intervention will be rolled-out in the implementation phase. The RITe intervention will be implemented in a sequential and incremental manner called implementation blocks: block 1: intensified health education; block 2: intensified health education and SMS/telephonic tracing; and block 3: intensified health education, SMS/telephonic tracing and transport reimbursement. The target sample size is 80 uncircumcised men for each intervention block, including the pre-implementation sample, making a total of 320 men (280 total, 70 per block will be surveyed). The primary outcome is uptake of VMMC during the implementation period. Mixed methods assessments will be conducted to evaluate the acceptability, appropriateness and feasibility of the RITe intervention.

Ethics and dissemination

The study protocol was approved by the Malawi’s National Health Sciences Research Ethics Committee (approval number: 19/10/2412), University of North Carolina at Chapel Hill’s Institutional Review Board (approval number: 19–2559) and University of the Witwatersrand’s Health Research Ethics Committee (approval number: M200328). Results will be disseminated via publication in a peer-reviewed journal and presentations at relevant scientific conferences and meetings.

Trial registration number

NCT04677374.

…

Journal of Medical Virology, Accepted Article.

Introduction…

Introduction…

Introduction…

Background…