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by Patience A. Afulani, Akua O. Gyamerah, Jerry J. Nutor, Amos Laar, Raymond A. Aborigo, Hawa Malechi, Mona Sterling, John K. Awoonor-Williams Introduction The COVID-19 pandemic has compounded the global crisis of stress and burnout among healthcare workers. But few studies have empirically examined the factors driving these outcomes in Africa. Our study examined associations between perceived preparedness to respond to the COVID-19 pandemic and healthcare worker stress and burnout and identified potential mediating factors among healthcare workers in Ghana. Methods Healthcare workers in Ghana completed a cross-sectional self-administered online survey from April to May 2020; 414 and 409 completed stress and burnout questions, respectively. Perceived preparedness, stress, and burnout were measured using validated psychosocial scales. We assessed associations using linear regressions with robust standard errors. Results The average score for preparedness was 24 (SD = 8.8), 16.3 (SD = 5.9) for stress, and 37.4 (SD = 15.5) for burnout. In multivariate analysis, healthcare workers who felt somewhat prepared and prepared had lower stress (β = -1.89, 95% CI: -3.49 to -0.30 and β = -2.66, 95% CI: -4.48 to -0.84) and burnout (β = -7.74, 95% CI: -11.8 to -3.64 and β = -9.25, 95% CI: -14.1 to –4.41) scores than those who did not feel prepared. Appreciation from management and family support were associated with lower stress and burnout, while fear of infection was associated with higher stress and burnout. Fear of infection partially mediated the relationship between perceived preparedness and stress/burnout, accounting for about 16 to 17% of the effect. Conclusions Low perceived preparedness to respond to COVID-19 increases stress and burnout, and this is partly through fear of infection. Interventions, incentives, and health systemic changes to increase healthcare workers’ morale and capacity to respond to the pandemic are needed.

Abstract Background In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma. Methods The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 μM. The “BX-1 AIDS treatment instrument” was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR. Results BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL. Conclusion BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.

by Lauren E. Parmley, Kieran Hartsough, Oliver Eleeza, Akopon Bertin, Bockarie Sesay, Amon Njenga, Mame Toure, Ginika Egesimba, Haja Bah, Alex Bayoh, Abdulraheem Yakubu, Ellen A. B. Morrison, Susan Michaels-Strasser After a decade of civil war and the 2014–2016 West African Ebola outbreak, Sierra Leone now faces the COVID-19 pandemic with a fragile health system. As was demonstrated during Ebola, preparedness is key to limiting a health crisis’ spread and impact on health systems and ensuring continued care for vulnerable populations including people living with HIV (PLHIV). To assess COVID-19 preparedness and inform interventions to ensure continuity of HIV services at health facilities (HFs) and community service points (CSPs), we conducted site readiness assessments in Freetown, the epicenter of COVID-19 in Sierra Leone. Data were collected at nine high-volume HIV HFs and seven CSPs in April 2020, a month after COVID-19 was declared a pandemic. CSPs comprised three community drop-in centers providing HIV counseling and testing services as well as HIV prevention services (e.g., condoms and lubricants) for key and priority populations and four community-based support groups serving PLHIV. At the time of assessment, CSPs did not provide antiretroviral therapy (ART) but were considered potential sites for expansion of differentiated service delivery (DSD)—a client-centered approach to HIV care—in the context of COVID-19. Overall, 5/9 HFs had trained staff on use of personal protective equipment (PPE) and prevention of COVID-19 transmission. Most had access to masks (5/9) and gloves (7/9) for management of suspected/confirmed COVID-19 cases, and 4/9 HFs had triage procedures for isolation of suspected cases. Conversely, few CSPs had access to masks (2/7) or gloves (2/7) and no staff were trained on PPE use or COVID-19 transmission. 7/9 HFs had adequate ART stock for multi-month dispensing though few had procedures for (3/9) or had trained staff in providing DSD (2/9). Among CSPs where measures were applicable, 2/4 had procedures for DSD, 1/3 had staff trained on DSD and none had adequate ART stock. Identification of gaps in COVID-19 preparedness is a critical step in providing support for infection control and modified service delivery. Findings from this assessment highlight gaps in COVID-19 preparedness measures at sites supporting PLHIV in Sierra Leone and indicate CSPs may require intensive supervision and training to ensure HIV services are uninterrupted while minimizing COVID-19 risk, especially if used as sites to scale up DSD.

by Olivia L. McGovern, Mark Stenger, Sara E. Oliver, Tara C. Anderson, Cheryl Isenhour, Matthew R. Mauldin, Nia Williams, Eric Griggs, Tonny Bogere, Chris Edens, Aaron T. Curns, Joana Y. Lively, Yingtao Zhou, Songli Xu, Maureen H. Diaz, Jessica L. Waller, Kevin R. Clarke, Mary E. Evans, Elisabeth M. Hesse, Sapna Bamrah Morris, Robert P. McClung, Laura A. Cooley, Naeemah Logan, Andrew T. Boyd, Allan W. Taylor, Kristina L. Bajema, Stephen Lindstrom, Christopher A. Elkins, Christopher Jones, Aron J. Hall, Samuel Graitcer, Alexandra M. Oster, Alicia M. Fry, Marc Fischer, Laura Conklin, Runa H. Gokhale Background The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), evolved rapidly in the United States. This report describes the demographic, clinical, and epidemiologic characteristics of 544 U.S. persons under investigation (PUI) for COVID-19 with complete SARS-CoV-2 testing in the beginning stages of the pandemic from January 17 through February 29, 2020. Methods In this surveillance cohort, the U.S. Centers for Disease Control and Prevention (CDC) provided consultation to public health and healthcare professionals to identify PUI for SARS-CoV-2 testing by quantitative real-time reverse-transcription PCR. Demographic, clinical, and epidemiologic characteristics of PUI were reported by public health and healthcare professionals during consultation with on-call CDC clinicians and subsequent submission of a CDC PUI Report Form. Characteristics of laboratory-negative and laboratory-positive persons were summarized as proportions for the period of January 17−February 29, and characteristics of all PUI were compared before and after February 12 using prevalence ratios. Results A total of 36 PUI tested positive for SARS-CoV-2 and were classified as confirmed cases. Confirmed cases and PUI testing negative for SARS-CoV-2 had similar demographic, clinical, and epidemiologic characteristics. Consistent with changes in PUI evaluation criteria, 88% (13/15) of confirmed cases detected before February 12, 2020, reported travel from China. After February 12, 57% (12/21) of confirmed cases reported no known travel- or contact-related exposures. Conclusions These findings can inform preparedness for future pandemics, including capacity for rapid expansion of novel diagnostic tests to accommodate broad surveillance strategies to assess community transmission, including potential contributions from asymptomatic and presymptomatic infections.

Journal of Medical Virology, Volume 93, Issue 6, Page 3374-3382, June 2021.

by Takashi Aoyama, Tomoko Kudo The Japanese Ministry of Health requires large-scale cooking facilities to use sodium hypochlorite aqueous solution (HYP) on food preparation tools, equipment, and facilities to prevent secondary contamination. This study aimed to compare the disinfecting effect of HYP and surfactant using adenosine triphosphate (ATP) swab testing on large-scale equipment and facilities that could not be disassembled and disinfected in hospital kitchen. From May 2018 to July 2018, ATP swab tests were performed on the following six locations in the Shizuoka Cancer Centre Dietary Department Kitchen: cooking counter, mobile cooking counter, refrigerator handle, conveyor belt, tap handle, and sink. Six relative light unit (RLU) measurements were taken from each location. The log10 values of the RLU measurements were evaluated by dividing the samples into two groups: the control group (surfactant followed by HYP swabbing) and the HYP group (HYP swabbing only). The results showed that the RLUs (log10 values) in both the groups improved after disinfection (p…

Objectives: Gaps between recommended and actual levels of HIV preexposure prophylaxis (PrEP) use remain among men who have sex with men (MSM). Interventions can address these gaps, but it is unknown how public health initiatives should invest prevention funds into these interventions to maximize their population impact. Design: We used a stochastic network-based HIV transmission model for MSM in the Atlanta area paired with an economic budget optimization model. Methods: The model simulated MSM participating in up to three real-world PrEP cascade interventions designed to improve initiation, adherence, or persistence. The primary outcome was infections averted over 10 years. The budget optimization model identified the investment combination under different budgets that maximized this outcome given intervention costs from a payer perspective. Results: From the base 15% PrEP coverage level, the three interventions could increase coverage to 27%, resulting in 12.3% of infections averted over 10 years. Uptake of each intervention was interdependent: maximal use of the adherence and persistence interventions depended on new PrEP users generated by the initiation intervention. As the budget increased, optimal investment involved a mixture of the initiation and persistence interventions, but not the adherence intervention. If adherence intervention costs were halved, the optimal investment was roughly equal across interventions. Conclusions: Investments into the PrEP cascade through initiatives should account for the interactions of the interventions as they are collectively deployed. Given current intervention efficacy estimates, the total population impact of each intervention may be improved with greater total budgets or reduced intervention costs. Correspondence to Samuel M. Jenness, Emory University, 1520 Clifton Road, Atlanta, GA 30323; e-mail: samuel.m.jenness@emory.edu. Received 4 January, 2021 Revised 21 March, 2021 Accepted 31 March, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Objectives: The coronavirus disease 2019 pandemic has strained many healthcare systems. In response, U.S. hospitals altered their care delivery systems, but there are few data regarding specific structural changes. Understanding these changes is important to guide interpretation of outcomes and inform pandemic preparedness. We sought to characterize emergency responses across hospitals in the United States over time and in the context of local case rates early in the coronavirus disease 2019 pandemic. Design: We surveyed hospitals from a national acute care trials group regarding operational and structural changes made in response to the coronavirus disease 2019 pandemic from January to August 2020. We collected prepandemic characteristics and changes to hospital system, space, staffing, and equipment during the pandemic. We compared the timing of these changes with county-level coronavirus disease 2019 case rates. Setting and Participants: U.S. hospitals participating in the Prevention and Early Treatment of Acute Lung Injury Network Coronavirus Disease 2019 Observational study. Site investigators at each hospital collected local data. Interventions: None. Measurements and Main Results: Forty-five sites participated (94% response rate). System-level changes (incident command activation and elective procedure cancellation) occurred at nearly all sites, preceding rises in local case rates. The peak inpatient census during the pandemic was greater than the prior hospital bed capacity in 57% of sites with notable regional variation. Nearly half (49%) expanded ward capacity, and 63% expanded ICU capacity, with nearly all bed expansion achieved through repurposing of clinical spaces. Two-thirds of sites adapted staffing to care for patients with coronavirus disease 2019, with 48% implementing tiered staffing models, 49% adding temporary physicians, nurses, or respiratory therapists, and 30% changing the ratios of physicians or nurses to patients. Conclusions: The coronavirus disease 2019 pandemic prompted widespread system-level changes, but front-line clinical care varied widely according to specific hospital needs and infrastructure. Linking operational changes to care delivery processes is a necessary step to understand the impact of the coronavirus disease 2019 pandemic on patient outcomes. A full list of National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators is provided in the Supplemental Digital Content (http://links.lww.com/CCM/G321). The Department of Veterans Affairs did not have a role in the conduct of the study; in the collection, management, analysis, or interpretation of data; or in the preparation of the article. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the U.S. Government. Drs. Mathews and Seitz are cofirst authors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from the National Heart, Lung, and Blood Institution (3U01HL123009-06S1, U01HL123009, U01HL122998, U01HL123018, U01HL123023, U01HL123008, U01HL123031, U01HL123004, U01HL123027, U01HL123010, U01HL123033, U01HL122989, U01HL123022, and U01HL123020). The Research Electronic Data Capture data tools used for this study were supported, in part, by the National Institutes of Health/National Center for Advancing Translational Sciences UL1TR000445. Dr. Mathews reports grants from National Institutes of Health (NIH)/National Heart Lung and Blood Institute (NHBLI) (K23HL130648) and serves on a steering committee of A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE) trial, funded by Roivant/Kinevant Sciences, outside of the submitted work. Dr. Vranas reports support from the Veterans Affairs Portland Health Care System, outside the submitted work. Dr. Harhay reports editorial positions at the American Thoracic Society and receiving grants from the NIH, outside the submitted work. Dr. Chang reported receiving personal fees from PureTech and LaJolla Pharmaceuticals, outside the submitted work. Dr. Hough reports grants from the NIH during the conduct of the study. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kusum.mathews@mssm.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objectives: Haloperidol is commonly administered in the ICU to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality. Design: Post hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium prevention trial. Setting: Fourteen Dutch ICUs between July 2013 and December 2016. Patients: One-thousand four-hundred ninety-five critically ill adults free from delirium at ICU admission having an expected ICU stay greater than or equal to 2 days. Interventions: Patients received preventive haloperidol or placebo for up to 28 days until delirium occurrence, death, or ICU discharge. If delirium occurred, treatment with open-label IV haloperidol 2 mg tid (up to 5 mg tid per delirium symptoms) was administered at clinician discretion. Measurements and Main Results: Patients were evaluated tid for delirium and coma for 28 days. Time-varying Cox hazards models were constructed for 28-day and 90-day mortality, controlling for study-arm, delirium and coma days, age, Acute Physiology and Chronic Health Evaluation-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1,495 patients, 542 (36%) developed delirium within 28 days (median [interquartile range] with delirium 4 d [2–7 d]). A total of 477 of 542 (88%) received treatment haloperidol (2.1 mg [1.0–3.8 mg] daily) for 6 days (3–11 d). Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 days (hazard ratio, 0.93; 95% CI, 0.91–0.95) and 90 days (hazard ratio, 0.97; 95% CI, 0.96–0.98). Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, predelirium haloperidol exposure, and haloperidol treatment protocol adherence. Conclusions: Treatment of incident delirium and its symptoms with haloperidol may be associated with a dose-dependent improvement in survival. Future randomized trials need to confirm these results. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by ZonMw program Goed Gebruik Geneesmiddelen (dossier number 836031004). ZonMw had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Duprey’s efforts are supported by the National Institute of Aging 1F31AG066460-01. Drs. Duprey, Devlin, Briesacher, and Saczynski received support for article research from the National Institutes of Health. Dr. Duprey disclosed off-label product use of haloperidol for delirium. Dr. van den Boogaard’s institution received funding and support for research from ZonMw. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this aticle, E-mail: j.devlin@neu.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objectives: The optimal time to initiate renal replacement therapy in critically ill patients with acute kidney injury is controversial. We investigated the effect of such earlier versus later initiation of renal replacement therapy on the primary outcome of 28-day mortality and other patient-centered secondary outcomes. Design: We searched MEDLINE (via PubMed), EMBASE, and Cochrane databases to July 17, 2020, and included randomized controlled trials comparing earlier versus later renal replacement therapy. Setting: Multiple centers involved in eight trials. Patients: Total of 4,588 trial participants. Intervention: Two independents investigators screened and extracted data using a predefined form. We selected randomized controlled trials in critically ill adult patients with acute kidney injury and compared of earlier versus later initiation of renal replacement therapy regardless of modality. Measurements and Main Results: Overall, 28-day mortality was similar between earlier and later renal replacement therapy initiation (38.43% vs 38.06%, respectively; risk ratio, 1.01; [95% CI, 0.94–1.09]; I2 = 0%). Earlier renal replacement therapy, however, shortened hospital length of stay (mean difference, –2.14 d; [95% CI, –4.13 to –0.14]) and ICU length of stay (mean difference, –1.18 d; [95% CI, –1.95 to –0.42]). In contrast, later renal replacement therapy decreased the use of renal replacement therapy (relative risk, 0.69; [95% CI, 0.58–0.82]) and lowered the risk of catheter-related blood stream infection (risk ratio, 0.50, [95% CI, 0.29–0.86). Among survivors, renal replacement therapy dependence at day 28 was similar between earlier and later renal replacement therapy initiation (risk ratio, 0.98; [95% CI, 0.66–1.40]). Conclusions: Earlier or later initiation of renal replacement therapy did not affect mortality. However, earlier renal replacement therapy was associated with significantly shorter ICU and hospital length of stay, whereas later renal replacement therapy was associated with decreased use of renal replacement therapy and decreased risk of catheter-related blood stream infection. These findings can be used to guide the management of critically ill patients with acute kidney injury. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Drs. Naorungroj, Neto, Eastwood, and Bellomo contributed to conceptualization and methodology. Drs. Naorungroj, Neto, Yanase, Bagshaw, and Wald contributed to material preparation and analysis. Dr. Naorungroj contributed to writing-original draft preparation. Drs. Naorungroj, Neto, Yanase, Bagshaw, Wald, and Bellomo contributed to writing-review and editing. Each author contributed important intellectual content during article drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Dr. Neto reported receiving lecture fee from Drager outside the submitted work. Dr. Yanase reported receiving scholarship for PhD course in Monash University from Japan Student Services Organization and Endeavour Scholarship. Dr. Wald reports receiving speaker fees and unrestricted research funding from Baxter. Dr. Bagshaw reported receiving fees for scientific advisory and grants from Baxter; he reported receiving fees for scientific advisory from Diagnostics and Spectral Medical, Canada, all outside the submitted work; he is supported by a Canada Research Chair in Critical Care Nephrology. Dr. Bellomo reported receiving grants from Baxter International outside the submitted work. The remaining authors have disclosed that they have no potential conflicts of interest. Registration: The study was registered with the Prospective Register of Systematic Reviews (CRD42020188951) on May 27, 2020. For information regarding this article, E-mail: rinaldo.bellomo@austin.org.au Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Nature Medicine, Published online: 12 April 2021; doi:10.1038/s41591-021-01301-0 Examination of the vaccine strategies and technical platforms used for the COVID-19 pandemic in the context of those used for previous emerging and reemerging infectious diseases and pandemics can offer critical lessons to prepare for future public health emergencies.

Tropical Medicine & International Health, Accepted Article.

Objective To identify theoretical and technical aspects regarding treatment, prevention of spread and protection of staff to inform the development of a comprehensive training curriculum on COVID-19 management. Design Cross-sectional study. Setting Nine hospitals caring for patients with COVID-19 in Wuhan, China. Participants 134 Chinese healthcare professionals (74 doctors and 60 nurses) who were deployed to Wuhan, China during the COVID-19 epidemic were included. A two-round Delphi process was initiated between March and May 2020. In the first round, the participants identified knowledge, technical and behavioural (ie, non-technical) skills that are needed to treat patients, prevent spread of the virus and protect healthcare workers. In round 2, the participants rated each item according to its importance to be included in a training curriculum on COVID-19. Consensus for inclusion in the final list was set at 80%. Primary outcome measures Knowledge, technical and behavioural (ie, non-technical) skills that could form the basis of a training curriculum for COVID-19 management. Results In the first round 1398 items were suggested by the doctors and reduced to 67 items after content analysis (treatment of patients: n=47; infection prevention and control: n=20). The nurses suggested 1193 items that were reduced to 70 items (treatment of patients: n=49; infection prevention and control: n=21). In round 2, the response rates were 82% in doctors and 93% in nurses. Fifty-eight items of knowledge, technical and behavioural skills were agreed on by the doctors to include in the final list. For the nurses, 58 items were agreed on. Conclusions This needs assessment process resulted in a comprehensive list of knowledge, technical and behavioural skills for COVID-19 management. Educators can use these to guide decisions regarding content of training curricula not only for COVID-19 management but also in preparation for future viral pandemic outbreaks.

The COVID-19 pandemic has accelerated the pace of digital innovation, in part thanks to unprecedented private–public and private–private collaborations. The pandemic has promoted collaboration between inventive and influential companies, universities, and public organisations. These institutions have worked together in vaccine development, in forecasting the spread of infection, and in sharing technology to build public health apps for general use. We must now build on this ability to work across boundaries to deliver results, not return to old silos.

New England Journal of Medicine, Ahead of Print.

Objective To report the clinical characteristics of patients hospitalised with COVID-19 in Southeast Michigan. Design Retrospective cohort study. Setting Eight hospitals in Southeast Michigan. Participants 3219 hospitalised patients with a positive SARS-CoV-2 infection by nasopharyngeal PCR test from 13 March 2020 until 29 April 2020. Main outcomes measures Outcomes were discharge from the hospital or in-hospital death. Examined predictors included patient demographics, chronic diseases, home medications, mechanical ventilation, in-hospital medications and timeframe of hospital admission. Multivariable logistic regression was conducted to identify risk factors for in-hospital mortality. Results During the study period, 3219 (90.4%) patients were discharged or died in the hospital. The median age was 65.2 (IQR 52.6–77.2) years, the median length of stay in the hospital was 6.0 (IQR 3.2–10.1) days, and 51% were female. Hypertension was the most common chronic disease, occurring in 2386 (74.1%) patients. Overall mortality rate was 16.0%. Blacks represented 52.3% of patients and had a mortality rate of 13.5%. Mortality was highest at 18.5% in the prepeak hospital COVID-19 volume, decreasing to 15.3% during the peak period and to 10.8% in the postpeak period. Multivariable regression showed increasing odds of in-hospital death associated with older age (OR 1.04, 95% CI 1.03 to 1.05, p<0.001) for every increase in 1 year of age and being male (OR 1.47, 95% CI 1.21 to 1.81, p<0.001). Certain chronic diseases increased the odds of in-hospital mortality, especially chronic kidney disease. Administration of vitamin C, corticosteroids and therapeutic heparin in the hospital was associated with higher odds of death. Conclusion In-hospital mortality was highest in early admissions and improved as our experience in treating patients with COVID-19 increased. Blacks were more likely to get admitted to the hospital and to receive mechanical ventilation, but less likely to die in the hospital than whites.

Journal Name: The American Journal of Tropical Medicine and HygieneVolume: 104Issue: 4Pages: 1495-1506…

Journal Name: The American Journal of Tropical Medicine and HygieneVolume: 104Issue: 4Pages: 1519-1525…

Introduction The COVID-19 pandemic and its control measures have impacted health and healthcare provision in various levels. Physical distancing measures, for instance, may affect sexual health, impacting access to HIV prevention supplies and changing sexual behaviour, as well as mental health, increasing feelings of unsafety and weakening community support ties. These effects can be worsened among socially marginalised groups, such as men who have sex with men (MSM) and transgender women (TGW). Brazil is among the countries most affected by COVID-19 in the world, where control measures have been inconsistently implemented. We aim to investigate the effects of the COVID-19 pandemic on the sexual and mental health of adolescent and adult MSM and TGW in Brazil. Methods Convergent mixed-method prospective cohort study, nested in two ongoing HIV pre-exposure prophylaxis (PrEP) cohorts in Brazil, named PrEP1519 and Combina. Participants will be invited to answer, at baseline and after 6 months, a questionnaire about the effects of the COVID-19 pandemic on sexual behaviour, HIV prevention and mental health. Data on HIV infection and sexually transmitted infections (STI) will be collected as part of routine follow-up from the cohorts. Main outcome measures (HIV infection, STI and depression symptoms) will be observed within 12 months after baseline. Sample size is estimated at 426 participants. Complementarily, 50 participants will be invited to in-depth interviews through video calls or interactive voice response, and 20 will be invited to chronicle their lives during the pandemic through digital diaries. Triangulation will be done across qualitative methods and with the quantitative data. Ethics and dissemination The study was approved by Research Ethics Committees from the Brazilian Universities coordinating the study. Findings will be published in scientific journals and presented at meetings. Informative flyers will be elaborated to communicate study findings to participants and key stakeholders.

Objectives We aimed to review SARS-CoV-2 seroprevalence studies conducted in Europe to understand how they may be used to inform ongoing control strategies for COVID-19. Design Scoping review of peer-reviewed publications and manuscripts on preprint servers from January 2020 to 15 September 2020. Primary measure Seroprevalence estimate (and lower and upper CIs). For studies conducted across a country or territory, we used the seroprevalence estimate and the upper and lower CIs and compared them to the total number of reported infections to calculate the ratio of reported to expected infections. Results We identified 23 population-based seroprevalence studies conducted in Europe. Among 12 general population studies, seroprevalence ranged from 0.42% among residual clinical samples in Greece to 13.6% in an area of high transmission in Gangelt, Germany. Of the eight studies in blood donors, seroprevalence ranged from 0.91% in North-Western Germany to 23.3% in a high-transmission area in Lombardy region, Italy. In three studies which recruited individuals through employment, seroprevalence ranged from 0.5% among factory workers in Frankfurt, Germany, to 10.2% among university employees in Milan, Italy. In comparison to nationally reported cases, the extent of infection, as derived from these seroprevalence estimates, is manyfold higher and largely heterogeneous. Conclusion Exposure to the virus in Europe has not reached a level of infection that would prevent further circulation of the virus. Effective vaccine candidates are urgently required to deliver the level of immunity in the population.

Background: PrEPX was an Australian HIV pre-exposure prophylaxis (PrEP) study conducted between 2016 and 2018. This analysis aimed to estimate hepatitis C (HCV) incidence and explore likely modes of transmission. Setting: Cohort study of PrEP users in Victoria, Australia. Methods: HCV tests were conducted at enrolment and every 12 months thereafter. HCV incident cases were identified from laboratory data. Likely modes of transmission were inferred from computer-assisted self-interviews (CASI), medical records, and interviews. Results: Among 3,202 PrEPX participants tested for HCV at baseline, HCV RNA-positive prevalence was 0.22% (95% CI 0.09–0.45). Among participants testing HCV antibody- or RNA-negative at baseline, 2,058 had at least one follow-up HCV test. Eight incident HCV cases were identified during 2,111 person-years of follow-up (incidence 0.38/100 person-years); all were primary infections in men who had sex with men (MSM). Clinical, laboratory and CASI data were available for all, and six cases were interviewed. Three cases were attributable to injecting drug use (IDU). A fourth case reported IDU, but his HCV was attributable to sexual transmission. Four other cases reported no IDU and probably acquired HCV sexually. Most cases reported anal trauma in the context of condomless receptive anal intercourse during group sex at sex-on-premises venues (SOPV). Conclusion: Incident HCV was uncommon in PrEPX compared to international PrEP studies, and most cases were transmitted sexually. Our findings highlight the need for HCV prevention messaging by clinicians, in SOPV and on digital platforms utilised to arrange group sex, and for HCV screening among some PrEP-using MSM. Corresponding Author: Dr Vincent Cornelisse, Kirketon Road Centre, 100 Darlinghurst Road, Kings Cross, NSW, Australia, Email: Vincent.cornelisse@health.nsw.gov.au Ph: +61478617179 Declaration of Interests: Gilead Sciences funded this analysis of Hepatitis C within the PrEPX study, however, Gilead did not have input into the study design or the analysis. VJC has received speaker’s fees and conference assistance from Gilead Sciences and advisory board fees from ViiV Healthcare. MWT received speaker’s fees from Gilead Sciences. EJW reports receipt of grants from the Victorian, Tasmanian and the South Australian governments for PrEPX; other from Gilead Sciences (free study drug for VicPrEP, compensation to her institution for chairing a nursing education session and for attending an advisory board meeting, and uncompensated attendance for attending 2 Gilead meetings regarding listing of Truvada on the Australian pharmaceutical benefits scheme); grants from, Gilead Science and Merck Sharp & Dohme outside the submitted work; and financial support from, Gilead Sciences, Abbott Laboratories, Janssen-Cilag, Boehringer Ingelheim, ViiV Healthcare, and Merck Sharp & Dohme. DM received grants from Alfred Health. MS received a research fellowship from the National Health and Medical Research Council, and investigator-initiated grants from Gilead Sciences and Bristol-Myers-Squibb. MH received grants from the Australian Department of Health, Gilead Sciences, Abbvie and Bristol-Myers-Squibb. JA received grants from the Australian Government’s Department of Health. JS has grant research funding from Gilead, Abbvie and Merck. He has also received speaker fees from Gilead Sciences. All other authors declare no potential conflicts of interest. Gilead Sciences donated study drug to the VicPrEP study (precursor to the PrEPX study). Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Background: The SEARCH study provided community-based HIV and multi-disease testing and antiretroviral therapy (ART) to 32 communities in East Africa and reported no statistically significant difference in three-year HIV incidence. We used mathematical modelling to estimate the effect of control arm viral suppression and community mixing on SEARCH trial outcomes. Setting: Uganda and Kenya. Methods: Using the individual-based HIV modeling software EMOD-HIV, we configured a new model of SEARCH communities. The model was parameterized using demographic, HIV prevalence, male circumcision, and viral suppression data, and calibrated to HIV prevalence, ART coverage, and population size. Using assumptions about ART scale-up in the control arm, degree of community mixing, and effect of baseline testing, we estimated comparative HIV incidence under multiple scenarios. Results: Prior to the trial results, we predicted that SEARCH would report a 4-40% reduction between arms, depending on control arm ART linkage rates and community mixing. With universal baseline testing followed by rapidly expanded ART eligibility and uptake, modelled effect sizes were smaller than the study was powered to detect. Using interim viral suppression data, we estimated three-year cumulative incidence would have been reduced by up to 27% in the control arm and 43% in the intervention arm compared to a counterfactual without universal baseline testing. Conclusions: Our model suggests that the active control arm substantially reduced expected effect size and power of the SEARCH study. However, compared to a counterfactual “true control” without increased ART linkage due to baseline testing, SEARCH reduced HIV incidence by up to 43%. Corresponding author: Britta L. Jewell (bljewell@berkeley.edu), Address: UC Berkeley School of Public Health, Room 5302, 2121 Berkeley Way, Berkeley, CA 94704, Telephone: +1 (510) 642-3241 Conflicts of interest and source of funding: BLJ, LBB, TDD, EDC, DK, MRK, DVH, and MLP have received grant funding paid to her institution from the NIH. AB declares no conflicts of interest. Research reported in this paper was supported by the Division of AIDS, NIAID of the National Institutes of Health under award number U01A1099959 and in part by the President’s Emergency Plan for AIDS Relief, the Bill and Melinda Gates Foundation, and Gilead Sciences. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

On Feb 24, 2021, 600 000 doses of the Oxford–AstraZeneca COVID-19 vaccine arrived in Ghana. 2 days later, 500 000 doses of the same vaccine landed in the Ivory Coast. The west African nations are the first countries to receive the product as part of the COVAX initiative, a joint endeavour between WHO, Gavi, and the Coalition for Epidemic Preparedness Innovations, which aims to ensure that the COVID-19 vaccines are equitably distributed around the world. Demand for the vaccines will far exceed supply this year and there are growing concerns that poorer countries will get left behind.

Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season’s severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season.

Introduction Youth with brain-based disabilities (BBDs), as well as their parents/caregivers, often feel ill-prepared for the transfer from paediatric to adult healthcare services. To address this pressing issue, we developed the MyREADY TransitionTM BBD App, a patient-facing e-health intervention. The primary aim of this randomised controlled trial (RCT) was to determine whether the App will result in greater transition readiness compared with usual care for youth with BBD. Secondary aims included exploring the contextual experiences of youth using the App, as well as the interactive processes of youth, their parents/caregivers and healthcare providers around use of the intervention. Methods and analysis We aimed to randomise 264 youth with BBD between 15 and 17 years of age, to receive existing services/usual care (control group) or to receive usual care along with the App (intervention group). Our recruitment strategy includes remote and virtual options in response to the current requirements for physical distancing due to the COVID-19 pandemic. We will use an embedded experimental model design which involves embedding a qualitative study within a RCT. The Transition Readiness Assessment Questionnaire will be administered as the primary outcome measure. Analysis of covariance will be used to compare change in the two groups on the primary outcome measure; analysis will be intention-to-treat. Interviews will be conducted with subsets of youth in the intervention group, as well as parents/caregivers and healthcare providers. Ethics and dissemination The study has been approved by the research ethics board of each participating site in four different regions in Canada. We will leverage our patient and family partnerships to find novel dissemination strategies. Study findings will be shared with the academic and stakeholder community, including dissemination of teaching and training tools through patient associations, and patient and family advocacy groups. Trial registration number NCT03852550.

by Sanne Kaelen, Wilma van den Boogaard, Umberto Pellecchia, Sofie Spiers, Caroline De Cramer, Gwennin Demaegd, Edouard Fouqueray, Rafael Van den Bergh, Stephanie Goublomme, Tom Decroo, Muriel Quinet, Elke Van Hoof, Bertrand Draguez Background Nursing homes (NH) for the elderly have been particularly affected by the Covid-19 pandemic mainly due to their hosted vulnerable populations and poor outbreak preparedness. In Belgium, the medical humanitarian organization Médecins Sans Frontières (MSF) implemented a support project for NH including training on infection prevention and control (IPC), (re)-organization of care, and psychosocial support for NH staff. As psychosocial and mental health needs of NH residents in times of Covid-19 are poorly understood and addressed, this study aimed to better understand these needs and how staff could respond accordingly. Methods A qualitative study adopting thematic content analysis. Eight focus group discussions with direct caring staff and 56 in-depth interviews with residents were conducted in eight purposively and conveniently selected NHs in Brussels, Belgium, June 2020. Results NH residents experienced losses of freedom, social life, autonomy, and recreational activities that deprived them of their basic psychological needs. This had a massive impact on their mental well-being expressed in feeling depressed, anxious, and frustrated as well as decreased meaning and quality of life. Staff felt unprepared for the challenges posed by the pandemic; lacking guidelines, personal protective equipment and clarity around organization of care. They were confronted with professional and ethical dilemmas, feeling ‘trapped’ between IPC and the residents’ wellbeing. They witnessed the detrimental effects of the measures imposed on their residents. Conclusion This study revealed the insights of residents’ and NH staff at the height of the early Covid-19 pandemic. Clearer outbreak plans, including psychosocial support, could have prevented the aggravated mental health conditions of both residents and staff. A holistic approach is needed in NHs in which tailor-made essential restrictive IPC measures are combined with psychosocial support measures to reduce the impact on residents’ mental health impact and to enhance their quality of life.

Abstract Background Galactomannan antigen (GM) testing is widely used in the diagnosis of invasive aspergillosis (IA). Digestive enzymes play an important role in enzyme substitution therapy in exocrine pancreatic insufficiency. As digestive enzymes of fungal origin like Nortase contain enzymes from Aspergillus, a false-positive result of the test might be possible because of cross-reacting antigens of the cell wall of the producing fungi. We, therefore, asked whether the administration of fungal enzymes is a relevant cause of false-positive GM antigen test results. Methods Patients with a positive GM antigen test between January 2016 and April 2020 were included in the evaluation and divided into two groups: group 1—Nortase-therapy, group 2—no Nortase-therapy. In addition, dissolved Nortase samples were analyzed in vitro for GM and β-1,3-D-glucan. For statistical analysis, the chi-squared and Mann‒Whitney U tests were used. Results Sixty-five patients were included in this evaluation (30 patients receiving Nortase and 35 patients not receiving Nortase). The overall false positivity rate of GM testing was 43.1%. Notably, false-positive results were detected significantly more often in the Nortase group (73.3%) than in the control group (17.1%, p < 0.001). While the positive predictive value of GM testing was 0.83 in the control group, there was a dramatic decline to 0.27 in the Nortase group. In vitro analysis proved that the Nortase enzyme preparation was highly positive for the fungal antigens GM and β-1,3-D-glucan. Conclusions Our data demonstrate that the administration of digestive enzymes of fungal origin like Nortase leads to a significantly higher rate of false-positive GM test results compared to that in patients without digestive enzyme treatment.

Background: The aim of this study was to evaluate the efficacy of a novel, brief two-session behavioral intervention to promote HIV pre-exposure prophylaxis (PrEP) uptake among men who have sex with men (MSM) who are behaviorally at risk for HIV. Setting: A pilot randomized controlled trial (RCT) was conducted at a sexually transmitted infection (STI) clinic to compare a brief motivational interviewing (MI) intervention to passive referral only for PrEP uptake. Methods: MSM who scored as “high-risk” on the HIV Incidence Risk Index for MSM (HIRI-MSM) were offered a brief (15-20 minutes) MI-based intervention at the time of STI testing to address barriers to PrEP uptake, including low risk perception, stigma, side-effects, and cost. The initial session was followed by a brief, telephone booster session that lasted…

Objective: Syndemic conditions have been linked to engagement in receptive condomless anal sex (CAS) and HIV seroconversion. However, little is known about the biological pathways whereby syndemics could amplify vulnerability to HIV and other sexually transmitted infections (STIs). Design: HIV-negative sexual minority men (i.e., gay, bisexual, and other men who have sex with men) were recruited from four STI clinics in South Florida for a cross-sectional study. Methods: Participants completed assessments for four syndemic conditions: depression, post-traumatic stress disorder, hazardous alcohol use, and any stimulant use (i.e., any self-reported use or reactive urine toxicology results). Cytokine and chemokine levels were measured using LEGENDplex from the rectal swabs of 92 participants reporting receptive CAS and no antibiotic use in the past three months. Results: After controlling for age, race/ethnicity, pre-exposure prophylaxis (PrEP) use, and number of receptive CAS partners, a greater number of syndemic conditions was associated with higher levels of rectal cytokines/chemokines relevant to immune activation, inflammation, and the expansion and maintenance of T-helper 17 target cells, including rectal interferon-gamma (β = 0.22; p = 0.047), CXCL-8 (β = 0.24; p = 0.025), and interleukin-23 (β = 0.22; p = 0.049). Elevations in rectal cytokine or chemokine levels were most pronounced among participants experiencing two or more syndemic conditions compared to those experiencing no syndemic conditions. PrEP use was independently associated with elevations in multiple rectal cytokines/chemokines. Conclusions: Syndemic conditions could increase biological vulnerability to HIV and other STIs in sexual minority men by potentiating rectal immune dysregulation. Correspondence to Adam W. Carrico, PhD, 1120 NW 14th St., Office 1010, Miami, FL 33136. Tel: +305-243-6947; e-mail: a.carrico@miami.edu Received 1 November, 2020 Revised 5 February, 2021 Accepted 18 February, 2021 Copyright © 2021 Wolters Kluwer Health, Inc.

We previously reported a higher incidence of non-albumin proteinuria and a small but significant decline in estimated glomerular filtration rate among HIV-negative adults randomized to emtricitabine/ tenofovir disoproxil fumarate pre-exposure prophylaxis (FTC/TDF PrEP) versus placebo. In a nested case-control study among participants randomized to FTC/TDF PrEP, established kidney injury biomarkers measured at 12 months were not significantly different between subjects who subsequently experienced one of these kidney endpoints and randomly selected controls who did not. Correspondence to Christina M. Wyatt, MD, Department of Medicine, Division of Nephrology, Duke University School of Medicine, Duke Clinical Research Institute, 200 Morris Street, Durham, NC 27705; USA. e-mail: christina.wyatt@duke.edu Received 7 August, 2020 Revised 24 September, 2020 Accepted 4 October, 2020 Copyright © 2021 Wolters Kluwer Health, Inc.

No abstract available…

by Massab Umair, Aamer Ikram, Muhammad Salman, Adnan Khurshid, Masroor Alam, Nazish Badar, Rana Suleman, Faheem Tahir, Salmaan Sharif, Joel Montgomery, Shannon Whitmer, John Klena Since its emergence in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide including Pakistan. During the pandemic, whole genome sequencing has played an important role in understanding the evolution and genomic diversity of SARS-CoV-2. Although an unprecedented number of SARS-CoV-2 full genomes have been submitted in GISAID and NCBI, data from Pakistan is scarce. We report the sequencing, genomic characterization, and phylogenetic analysis of five SARS-CoV-2 strains isolated from patients in Pakistan. The oropharyngeal swabs of patients that were confirmed positive for SARS-CoV-2 through real-time RT-PCR at National Institute of Health, Pakistan, were selected for whole-genome sequencing. Sequencing was performed using NEBNext Ultra II Directional RNA Library Prep kit for Illumina (NEW ENGLAND BioLabs Inc., MA, US) and Illumina iSeq 100 instrument (Illumina, San Diego, US). Based on whole-genome analysis, three Pakistani SARS-CoV-2 strains clustered into the 20A (GH) clade along with the strains from Oman, Slovakia, United States, and Pakistani strain EPI_ISL_513925. The two 19B (S)-clade strains were closely related to viruses from India and Oman. Overall, twenty-nine amino acid mutations were detected in the current study genome sequences, including fifteen missense and four novel mutations. Notably, we have found a D614G (aspartic acid to glycine) mutation in spike protein of the sequences from the GH clade. The G614 variant carrying the characteristic D614G mutation has been shown to be more infectious that lead to its rapid spread worldwide. This report highlights the detection of GH and S clade strains and G614 variant from Pakistan warranting large-scale whole-genome sequencing of strains prevalent in different regions to understand virus evolution and to explore their genetic diversity.

Abstract Background Escherichia coli (E. coli) is one of the important causative pathogens of neonatal invasive infection. The epidemiological and clinical profile of invasive E. coli infection in Chinese newborns is not well characterized. Methods Ninety-four infants with invasive E. coli infection were categorized into E. coli early onset disease (EOD) group (onset ≤72 h after birth) (n = 46) and E. coli late onset disease (LOD) group (onset > 72 h) (n = 48). We compared and analyzed the clinical characteristics and drug sensitivity profile of early-onset and late-onset E. coli invasive infection in neonates. Results The incidence of E. coli-EOD and E.coli-LOD was 0.45/1000 live births (LBs) and 0.47/1000 LBs, respectively. The incidence of gestational diabetes mellitus, perinatal fever, urinary tract infection, chorioamnionitis, and positive E. coli culture among mothers in the E. coli-EOD group were significantly higher than that in E. coli-LOD group. The incidence of premature birth, low-birth-weight, nosocomial infection, and hospitalization time were significantly higher in the E. coli-LOD group. The main disease in E. coli-EOD group was pneumonia (main clinical manifestation: dyspnea). The main disease in E. coli-LOD group was sepsis (main clinical manifestation: fever). The sensitivity rates of E. coli strains to ampicillin and piperacillin were low (25.00–28.79%); sensitivity to cephalosporins was also low except ceftazidime (lowest sensitivity rate: 57.14%). Sensitivity to compound preparations containing β-lactamase inhibitors was high, even for extended spectrum β-lactamase-positive strains (nearly 100%). Conclusion E. coli is an important cause of invasive infection of newborns in Xiamen, China. E. coli-EOD was largely attributable to perinatal factors, while E. coli-LOD was largely related to nosocomial infection. Compound preparations containing β-lactamase inhibitor or carbapenem antibiotics should be preferred for neonatal invasive infection by E. coli.

This meta-analysis of randomized trials reported in medical journals, preprint servers, and press releases estimates associations between convalescent plasma treatment and clinical outcomes (all-cause mortality, length of stay, clinical improvement, clinical deterioration, mechanical ventilation use, serious adverse events) in patients with COVID-19.

In this issue of JAMA, Janiaud et al present a meta-analysis of randomized clinical trials (RCTs) of convalescent plasma for the treatment of patients with COVID-19. Based on an analysis of 1060 patients from 4 RCTs published in peer-reviewed journals and 10 722 patients from 6 RCTs (5 published as preprints and 1 as a press release), the authors found that treatment with convalescent plasma vs placebo or standard of care was not associated with a significant decrease in all-cause mortality (risk ratio, 0.93 [95% CI, 0.63-1.38] for the 4 peer-reviewed RCTs; risk ratio, 1.02 [95% CI, 0.92-1.12] for all 10 RCTs) or with benefit for other clinical outcomes, including length of hospital stay, mechanical ventilation use, and clinical improvement or deterioration.

Nature Medicine, Published online: 22 March 2021; doi:10.1038/s41591-021-01293-x Revisiting the challenges of the beginning of the COVID-19 pandemic, when doctors and patients had to make treatment decisions without the support of scientific evidence, can provide valuable clues on how to prepare for future pandemics.

Objective There is a lack of evidence addressing several important human factors questions pertaining to the quality of supportive information provided by commercial manufacturers that can affect the adoption and use of lateral flow serology assays in practice. We aimed to: (1) identify and assess the quality of information that commercial manufacturers provided for their point-of-care tests (POCTs) and (2) examine the implications of these findings on real-world settings. Design We used a content analysis methodology in two stages to systematically, code and analyse textual data from documents of commercial manufacturers. A deductive approach was applied using a coding guide based on the validated Point-of-Care Key Evidence Tool (POCKET) multidimensional checklist. An inductive approach was used to identify new patterns or themes generated from our textual analysis. Setting Publicly available supportive information documents by commercial manufacturers for lateral flow serology, were identified and gathered from online searches. Participants Supportive information documents retrieved from online searches over 3 months (March 2020 to June 2020). Results A total of 79 POCTs were identified that met the study inclusion criteria. Using the POCKET coding guide, we found that the quality of information varied significantly between the manufacturers and was often lacking in detail. Our inductive approach further examined these topics and found that several statements were vague and that significant variations in the level of details existed between manufacturers. Conclusions This study revealed significant concerns surrounding the supportive information reported by manufacturers for lateral flow serology assays. Information transparency was poor and human factor issues were not properly addressed to mitigate the risk of improper device use, although it should be noted that the results of our study are limited by the data that manufactures were prepared to disclose. Overall, commercial manufacturers should improve the quality and value of information presented in their supporting documentation.

The years 2020–21, designated by WHO as the International Year of the Nurse and Midwife, are characterised by unprecedented global efforts to contain and mitigate the COVID-19 pandemic. Lessons learned from successful pandemic response efforts in the past and present have implications for future efforts to leverage the global health-care workforce in response to outbreaks of emerging infectious diseases such as COVID-19. Given its scale, reach, and effectiveness, the response to the HIV/AIDS pandemic provides one such valuable example, particularly with respect to the pivotal, although largely overlooked, contributions of nurses and midwives.

Objective Access to health services and adequate care is influenced by sex, ethnicity, socioeconomic position (SEP) and the burden of comorbidities. Our study aimed to assess whether the COVID-19 pandemic further deepened these already existing health inequalities. Design Cross-sectional study. Setting Data were collected from five longitudinal age-homogenous British cohorts (born in 2000-2002, 1989-1990, 1970, 1958 and 1946). Participants A web survey was sent to the cohorts. Anybody who responded to the survey was included, resulting in 14 891 eligible participants. Main outcomes measured The survey provided data on cancelled surgical or medical appointments, and the number of care hours received in a week during the first UK COVID-19 national lockdown. Interventions Using binary or ordered logistic regression, we evaluated whether these outcomes differed by sex, ethnicity, SEP and having a chronic illness. Adjustment was made for study design, non-response weights, psychological distress, presence of children or adolescents in the household, COVID-19 infection, key worker status, and whether participants had received a shielding letter. Meta-analyses were performed across the cohorts, and meta-regression was used to evaluate the effect of age as a moderator. Results Women (OR 1.40, 95% CI 1.27 to 1.55) and those with a chronic illness (OR 1.84, 95% CI 1.65 to 2.05) experienced significantly more cancellations during lockdown (all p<0.0001). Ethnic minorities and those with a chronic illness required a higher number of care hours during the lockdown (both OR2.00, all p<0.002). SEP was not associated with cancellation or care hours. Age was not independently associated with either outcome in the meta-regression. Conclusion The UK government’s lockdown approach during the COVID-19 pandemic appears to have deepened existing health inequalities, impacting predominantly women, ethnic minorities and those with chronic illnesses. Public health authorities need to implement urgent policies to ensure equitable access to health and care for all in preparation for a fourthwave.

Abstract Background Neonatal ocular prophylaxis with silver nitrate does not prevent neonatal conjunctivitis due to Chlamydia trachomatis. The efficacy of antibiotic containing preparations for prevention of neonatal chlamydial conjunctivitis (NCC) has not been established. Objective To examine published literature to determine whether antibiotic containing preparation are efficacious for prevention of NCC and C. trachomatis in the nasopharynx. Methods A literature search of MEDLINE and EMBASE. Articles were selected for review if their content included 4 key criteria: (1) Prospective/comparative study. (2) Prenatal screening of mothers for C. trachomatis with results reported. (3) Follow-up of infants born to chlamydia-positive women. (4) Infants prospectively followed at regular intervals and tested for C. trachomatis in the eye/ nasopharynx (NP). Results The search yielded 159 studies; 11 were selected for full reviews, eight were excluded; three addressed the four criteria. Rates of C. trachomatis conjunctivitis in infants in included studies who received silver nitrate was 20–33%; positive NP, 1–28% and pneumonia, 3–8%. Rates of C. trachomatis conjunctivitis in neonates who received erythromycin or tetracycline prophylaxis did not differ from silver nitrate; 0–15 and 11%, respectively, who received erythromycin or tetracycline developed NCC. Similarly, 4–33 and 5% of infants who received erythromycin or tetracycline, respectively, had positive NP cultures; 0–4% developed chlamydial pneumonia. Conclusion Neonatal ocular prophylaxis with erythromycin or tetracycline ophthalmic ointments does not reduce incidence of neonatal chlamydial conjunctivitis or respiratory infection in infants born to mothers with C. trachomatis infection compared to silver nitrate.

Despite the importance of nucleic acid testing in managing the COVID-19 pandemic, current detection approaches remain limited due to their high complexity and extensive processing. Here, we describe a molecular nanotechnology that enables direct and sensitive detection of viral RNA targets in native clinical samples. The technology, termed catalytic amplification by transition-state molecular switch (CATCH), leverages DNA-enzyme hybrid complexes to form a molecular switch. By ratiometric tuning of its constituents, the multicomponent molecular switch is prepared in a hyperresponsive state—the transition state—that can be readily activated upon the binding of sparse RNA targets to turn on substantial enzymatic activity. CATCH thus achieves superior performance (~8 RNA copies/μl), direct fluorescence detection that bypasses all steps of PCR (<1 hour at room temperature), and versatile implementation (high-throughput 96-well format and portable microfluidic assay). When applied for clinical COVID-19 diagnostics, CATCH demonstrated direct and accurate detection in minimally processed patient swab samples.

Objectives To determine the extent and nature of changes in utilisation of healthcare services during COVID-19 pandemic. Design Systematic review. Eligibility Eligible studies compared utilisation of services during COVID-19 pandemic to at least one comparable period in prior years. Services included visits, admissions, diagnostics and therapeutics. Studies were excluded if from single centres or studied only patients with COVID-19. Data sources PubMed, Embase, Cochrane COVID-19 Study Register and preprints were searched, without language restrictions, until 10 August, using detailed searches with key concepts including COVID-19, health services and impact. Data analysis Risk of bias was assessed by adapting the Risk of Bias in Non-randomised Studies of Interventions tool, and a Cochrane Effective Practice and Organization of Care tool. Results were analysed using descriptive statistics, graphical figures and narrative synthesis. Outcome measures Primary outcome was change in service utilisation between prepandemic and pandemic periods. Secondary outcome was the change in proportions of users of healthcare services with milder or more severe illness (eg, triage scores). Results 3097 unique references were identified, and 81 studies across 20 countries included, reporting on >11 million services prepandemic and 6.9 million during pandemic. For the primary outcome, there were 143 estimates of changes, with a median 37% reduction in services overall (IQR –51% to –20%), comprising median reductions for visits of 42% (–53% to –32%), admissions 28% (–40% to –17%), diagnostics 31% (–53% to –24%) and for therapeutics 30% (–57% to –19%). Among 35 studies reporting secondary outcomes, there were 60 estimates, with 27 (45%) reporting larger reductions in utilisation among people with a milder spectrum of illness, and 33 (55%) reporting no difference. Conclusions Healthcare utilisation decreased by about a third during the pandemic, with considerable variation, and with greater reductions among people with less severe illness. While addressing unmet need remains a priority, studies of health impacts of reductions may help health systems reduce unnecessary care in the postpandemic recovery. PROSPERO registration number CRD42020203729.

by Chernet Tafere, Zewdu Yilma, Solomon Abrha, Adane Yehualaw Introduction Orally disintegrating tablet (ODT) is a dosage form that overcomes the problem of swallowing which is prevalent in about 35% of the general population. Co-trimoxazole (CTX) is given for patients with HIV for the prophylaxis of opportunistic infection (OI), commonly for pneumocystis carinii pneumonia. It was reported that CTX was associated with a 25–46% reduction in mortality among individuals infected with HIV in sub-Saharan Africa. Esophageal candidiasis which usually comes along with HIV/AIDS is one of AIDS defining illness affecting up to 1 in 5 of people with AIDS. This opportunistic illness is manifested by painful or difficulty of swallowing. In this respect, CTX ODT offer the advantages of both liquid dosage forms in terms of easy swallowing thereby improve patient compliance and solid dosage forms in terms of dose uniformity, stability, lower production, and transportation costs. The objective of this study was to formulate, characterize and optimize CTX ODT which could overcome swallowing problem and improve patient compliance. Co-trimoxazole ODTs were prepared by direct compression technique using a semi synthetic super disintegrant (crospovidone) along with other excipients. Two taste masking techniques were employed, addition of sweetening agent, and solid dispersion by using a pH sensitive polymer, Eudragit E-100 at different ratios (1:1, 1:2 and 1:3). Taste masking was determined by comparing taste threshold value and in vitro drug release. Preliminary study was used to investigate the effect of crospovidone, compression force (CF) and Hydroxypropyl cellulose (HPC) on disintegration time, friability and wetting time (WT). Factorial design was used as it enables simultaneous evaluation of formulation variables and their interaction effect. From the preliminary study, the factors that were found significant were further optimized using central composite design. Design-Expert 8.0.7.1 software was employed to carry out the experimental design. The bitterness threshold concentration of Trimethoprim was found to be 150 μg/ml and the in vitro drug release of the three batches of drug to polymer ratio (F1:1, 1:2 and 1:3) was 2.80±0.05, 2.77±0.00 and 2.63±0.00 respectively. From the optimization study, the optimal concentration for the superdisintegrant was 8.60% w/w and a CF of 11.25 KN which gave a rapid disintegration and WT of 13.79 and 23.19 seconds respectively and a friability of 0.666%. Conclusion In this study, co-trimoxazole ODT was formulated successfully. Central composite design was effectively used to model and optimize friability, DT and WT. The method was found effective for estimating the effect of independent variables on the dependent variables by using polynomial equation and surface plots. Optimization of the response variables was possible by using both numerical and graphical optimization and the predicted optimal conditions were confirmed experimentally and were found to be in good agreement within 5% of the predicted responses. The results of the study showed that CTX ODT had significantly rapid disintegration, less than 1% friability and enhanced dissolution profiles. The successful formulation of CTX ODT can solve difficulty of swallowing of conventional tablets for some group of patients which are unable to swallow solid oral dosage form.

It was not obvious when 2020 began what a grim year it would turn out to be. The first reported US case of coronavirus disease 2019 (COVID-19) was on January 19, 2020, in a man who had returned from Wuhan, China, 4 days earlier. The next day, the US Centers for Disease Control and Prevention started screening at 3 major airports hosting international travelers (John F. Kennedy International Airport, Los Angeles International Airport, and San Francisco International Airport). The first cases that were not related to travel were confirmed on February 26 and 28, 2020, signaling that COVID-19 was not limited to cases being “imported” by travelers from China and was thus much more of a threat to the US.

Abstract Background The African Union’s High-Level Panel on Emerging Technologies identified gene drive mosquitoes as a priority technology for malaria elimination. The first field trials are expected in 5–10 years in Uganda, Mali or Burkina Faso. In preparation, regional and international actors are developing risk governance guidelines which will delineate the framework for identifying and evaluating risks. Scientists and bioethicists have called for African stakeholder involvement in these developments, arguing the knowledge and perspectives of those people living in malaria-afflicted countries is currently missing. However, few African stakeholders have been involved to date, leaving a knowledge gap about the local social-cultural as well as ecological context in which gene drive mosquitoes will be tested and deployed. This study investigates and analyses Ugandan stakeholders’ hopes and concerns about gene drive mosquitoes for malaria control and explores the new directions needed for risk governance. Methods This qualitative study draws on 19 in-depth semi-structured interviews with Ugandan stakeholders in 2019. It explores their hopes for the technology and the risks they believed pertinent. Coding began at a workshop and continued through thematic analysis. Results Participants’ hopes and concerns for gene drive mosquitoes to address malaria fell into three themes: (1) ability of gene drive mosquitoes to prevent malaria infection; (2) impacts of gene drive testing and deployment; and, (3) governance. Stakeholder hopes fell almost exclusively into the first theme while concerns were spread across all three. The study demonstrates that local stakeholders are able and willing to contribute relevant and important knowledge to the development of risk frameworks. Conclusions International processes can provide high-level guidelines, but risk decision-making must be grounded in the local context if it is to be robust, meaningful and legitimate. Decisions about whether or not to release gene drive mosquitoes as part of a malaria control programme will need to consider the assessment of both the risks and the benefits of gene drive mosquitoes within a particular social, political, ecological, and technological context. Just as with risks, benefits—and importantly, the conditions that are necessary to realize them—must be identified and debated in Uganda and its neighbouring countries.

by Lidice Bernardo, Lucas Corallo, Judy Caterini, Jin Su, Lucy Gisonni-Lex, Beata Gajewska The microplate assay with Chinese Hamster Ovary (CHO) cells is currently used as a safety test to monitor the residual pertussis toxin (PT) amount in acellular pertussis antigens prior to vaccine formulation. The assay is based on the findings that the exposure of CHO cells to PT results in a concentration-dependent clustering response which can be used to estimate the amount of PT in a sample preparation. A major challenge with the current CHO cell assay methodology is that scoring of PT-induced clustering is dependent on subjective operator visual assessment using light microscopy. In this work, we have explored the feasibility of replacing the microscopy readout for the CHO cell assay with the xCELLigence Real-Time Cell Analysis system (ACEA BioSciences, a part of Agilent). The xCELLigence equipment is designed to monitor cell adhesion and growth. The electrical impedance generated from cell attachment and proliferation is quantified via gold electrodes at the bottom of the cell culture plate wells, which is then translated into a unitless readout called cell index. Results showed significant decrease in the cell index readouts of CHO cells exposed to PT compared to the cell index of unexposed CHO cells. Similar endpoint concentrations were obtained when the PT reference standard was titrated with either xCELLigence or microscopy. Testing genetically detoxified pertussis samples unspiked or spiked with PT further supported the sensitivity and reproducibility of the xCELLigence assay in comparison with the conventional microscopy assay. In conclusion, the xCELLigence RTCA system offers an alternative automated and higher throughput method for evaluating PT-induced clustering in CHO cells.

Nature Medicine, Published online: 15 March 2021; doi:10.1038/s41591-021-01291-z The COVID-19 pandemic has opened a window of opportunity for rethinking the way countries prepare for public-health crises. This window must not be wasted.

Nature Medicine, Published online: 15 March 2021; doi:10.1038/s41591-021-01269-x The COVID-19 pandemic provides an opportunity to reimagine preparedness for and responses to future pandemics.

Objectives: To investigate the incidence, characteristics, and outcomes of in-hospital cardiac arrest in patients with coronavirus disease 2019 and to describe the characteristics and outcomes for patients with in-hospital cardiac arrest within the ICU, compared with non-ICU patients with in-hospital cardiac arrest. Finally, we evaluated outcomes stratified by age. Data Sources: A systematic review of PubMed, EMBASE, and preprint websites was conducted between January 1, 2020, and December 10, 2020. Prospective Register of Systematic Reviews identification: CRD42020203369. Study Selection: Studies reporting on consecutive in-hospital cardiac arrest with a resuscitation attempt among patients with coronavirus disease 2019. Data Extraction: Two authors independently performed study selection and data extraction. Study quality was assessed with the Newcastle-Ottawa Scale. Data were synthesized according to the Preferred Reporting Items for Systematic Reviews guidelines. Discrepancies were resolved by consensus or through an independent third reviewer. Data Synthesis: Eight studies reporting on 847 in-hospital cardiac arrest were included. In-hospital cardiac arrest incidence varied between 1.5% and 5.8% among hospitalized patients and 8.0–11.4% among patients in ICU. In-hospital cardiac arrest occurred more commonly in older male patients. Most initial rhythms were nonshockable (83.9%, [asystole = 36.4% and pulseless electrical activity = 47.6%]). Return of spontaneous circulation occurred in 33.3%, with a 91.7% in-hospital mortality. In-hospital cardiac arrest events in ICU had higher incidence of return of spontaneous circulation (36.6% vs 18.7%; p < 0.001) and relatively lower mortality (88.7% vs 98.1%; p < 0.001) compared with in-hospital cardiac arrest in non-ICU locations. Patients greater than or equal to 60 years old had significantly higher in-hospital mortality than those less than 60 years (93.1% vs 87.9%; p = 0.019). Conclusions: Approximately, one in 20 patients hospitalized with coronavirus disease 2019 received resuscitation for an in-hospital cardiac arrest. Hospital survival after in-hospital cardiac arrest within the ICU was higher than non-ICU locations and seems comparable with prepandemic survival for nonshockable rhythms. Although the data provide guidance surrounding prognosis after in-hospital cardiac arrest, it should be interpreted cautiously given the paucity of information surrounding treatment limitations and resource constraints during the pandemic. Further research is into actual causative mechanisms is needed. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Lim has conceived the project idea, conducted the systematic review, statistical analysis, assisted with data analysis, wrote the initial drafts of the article, created tables and figures, and finalized the article. Dr. Reddy has conducted the systematic review, assisted with data analysis, wrote the initial drafts of the article, and finalized the article. Drs. Curtis, Jones, and Shekar have analyzed the data, edited, and critically evaluated the article and finalized the article. Drs. Afroz and Billah have conducted the statistical analysis, created the figures, and wrote the statistical section in methods. Drs. Sheth, Miles, Yuriditsky, and Shah have provided additional data to enable further analysis in this review. Drs. Hayek and Leaf have provided additional data to enable further analysis in this review and provided critical revisions to the article. Dr. Subramaniam has conducted the systematic review, statistical analysis, assisted with data analysis, wrote the initial drafts of the article, created tables and figures, and finalized the article. All authors critically reviewed the article and approved the final version prior to submission. Dr. Curtis reports grants from National Institutes of Health, grants from National Palliative Care Research Center, and grants from Cambia Health Foundation, outside of the submitted work. Dr. Hayek reports personal fees from Walden Biosciences, outside of the submitted work. The remaining authors have disclosed that they do not have any potential conflicts of interest. Data are available upon reasonable request. For information regarding this article, E-mail: zhengjie.lim@icloud.com Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background Plasmodium cynomolgi is a simian malaria parasite that has been reported as a naturally acquired human infection. The present study aims to systematically review reports on naturally acquired P. cynomolgi in humans, mosquitoes, and macaques to provide relevant data for pre-emptive surveillance and preparation in the event of an outbreak of zoonotic malaria in Southeast Asia. Methods The protocol of the systematic review was registered at PROSPERO with approval ID CRD42020203046. Three databases (Web of Science, Scopus, and MEDLINE) were searched for studies reporting the prevalence of P. cynomolgi infections in Southeast Asian countries between 1946 and 2020. The pooled prevalence or pooled proportion of P. cynomolgi parasitemia in humans, mosquitoes, and macaques was estimated using a random-effects model. Differences in the clinical characteristics of P. cynomolgi infections were also estimated using a random-effects model and presented as pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs). Results Thirteen studies reporting on the prevalence of naturally acquired P. cynomolgi in humans (3 studies, 21 cases), mosquitoes (3 studies, 28 cases), and macaques (7 studies, 334 cases) were included. The results demonstrated that the pooled proportion of naturally acquired P. cynomolgi in humans was 1% (95% CI, 0.1%, I2, 0%), while the pooled proportion of P. cynomolgi infecting mosquitoes was 18% (95% CI, 10–26%, I2, 32.7%). The pooled prevalence of naturally acquired P. cynomolgi in macaques was 47% (95% CI, 27–67%, I2, 98.3%). Most of the cases of naturally acquired P. cynomolgi in humans were reported in Cambodia (62%) and Malaysia (38%), while cases of P. cynomolgi in macaques were reported in Malaysia (35.4%), Singapore (23.2%), Indonesia (17.3%), Philippines (8.5%), Laos (7.93%), and Cambodia (7.65%). Cases of P. cynomolgi in mosquitoes were reported in Vietnam (76.9%) and Malaysia (23.1%). Conclusions This study demonstrated the occurrence of naturally acquired P. cynomolgi infection in humans, mosquitoes, and macaques. Further studies of P. cynomolgi in asymptomatic human cases in areas where vectors and natural hosts are endemic are extensively needed if human infections with P. cynomolgi do become public health problems.