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Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

Aims Norovirus remains the most significant virological risk that is transmitted via food and the environment to cause acute gastroenteritis. This study aimed to investigate the hypothesis that the contamination of the commercial food production environment with norovirus will be higher in premises that have recently reported a foodborne norovirus outbreak than those that have not. Methods Sampling of commercial food production environments was carried out across a 16-month period between January 2015 and April 2016 in the South East and the North West of England by local authority environmental health departments as part of routine surveillance visits to premises. A total of 2982 samples, 2038 virological and 944 bacteriological, were collected from 256 premises. Sixteen of these premises, six from South East and ten from North West England, were sampled as part of a public health outbreak investigation. Results & Conclusions Overall, 2038 swabs were submitted for norovirus testing, with an average of eight swabs per premises (range 4 to 23) and a median of seven. Of the premises sampled, 11.7% (30/256) yielded at least one norovirus-positive sample (environmental, and/or food handler hand swab), and 2.5% of the swabs were positive for norovirus. A peak in the positivity rate was seen in the South East in April 2016. No associations were found between norovirus positivity and bacteriology indicators, or between bacteriology indicators and hygiene ratings. Significance and impact of study This study demonstrates that food premises and food handlers remain a potential source of norovirus transmission and outbreaks.

Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).We measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 ( n = 39 and n = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing postacute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T-cell responses, as well as differences in the prevalence of PASC.Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T-cell responses as compared with a well matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8 + T cells ( P = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4 + T cells ( P = 0.007). Higher CD4 + /CD8 + ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8 + T cells (0.34-fold effect, P = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, P = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.We identified potentially important differences in SARS-CoV-2-specific CD4 + and CD8 + T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

Studies of comparative mRNA booster effectiveness among high-risk populations can inform mRNA booster-specific guidelines. The study emulated a target trial of COVID-19 vaccinated U.S. Veterans who received three doses of either mRNA-1273 or BNT162b2 vaccines. Participants were followed for up to 32 weeks between July 1, 2021 to May 30, 2022. Non-overlapping populations were average and high risk; high-risk sub-groups were age ≥65 years, high-risk co-morbid conditions, and immunocompromising conditions. Of 1,703,189 participants, 10.9 per 10,000 persons died or were hospitalized with COVID-19 pneumonia over 32 weeks (95% CI: 10.2, 11.8). Although relative risks of death or hospitalization with COVID-19 pneumonia were similar across at-risk groups, absolute risk varied when comparing three doses of BNT162b2 with mRNA-1273 (BNT162b2 minus mRNA-1273) between average-risk and high-risk populations, confirmed by the presence of additive interaction. The risk difference of death or hospitalization with COVID-19 pneumonia for high-risk populations was 2.2 (0.9, 3.6). Effects were not modified by predominant viral variant. In this work, the risk of death or hospitalization with COVID-19 pneumonia over 32 weeks was lower among high-risk populations who received three doses of mRNA-1273 vaccine instead of BNT162b2 vaccine; no difference was found among the average-risk population and age >65 sub-group.

Working in a hospital setting during a global health pandemic can lead to increased levels of anxiety, stress, burnout, and depression. Anecdotal evidence exists, but there is little research utilizing clinically validated tools to measure hospital staff psychological distress.In Summer 2021, 771 hospital staff in North Dakota responded to an electronic survey collecting demographic data and employing validated behavioral health screening tools to assess anxiety, depression, emotional distress, and work-related quality of life.Compassion satisfaction was significantly higher for those who worked in rural areas than urban [t(769) = -1.99, P = .0467]. The burnout rating was significantly higher for those who worked in urban areas than rural [t(769) = 2.23, P = .0261)]. There was no significant geographic variation in stress, anxiety, or depression. Anxiety, depression, burnout, and stress were all significantly higher for those who worked directly with COVID-19 patients than those who did not, regardless of hospital location.Hospital staff caring for COVID-19 patients experienced equitable (and high) levels of depression and anxiety. However, data indicate that rural providers experienced greater protective factors, resulting in lower rates of burnout and higher compassion satisfaction. Rural communities, hospitals, and health systems may have characteristics that could be duplicated in urban areas to support hospital staff well-being. Support and promotion of mental wellness must also come from the hospital system, and health care and policy leaders. If we do not care for our hospital staff, there will not be hospital staff left to care for the community.

ImportanceEvidence describing the incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines is needed, particularly for high-risk populations.ObjectiveTo describe the incidence of severe COVID-19 illness among a cohort that received vaccination plus a booster vaccine dose.Design, Setting, and ParticipantsRetrospective cohort study of adults receiving care at Veterans Health Administration facilities across the US who received a vaccination series plus 1 booster against SARS-CoV-2, conducted from July 1, 2021, to May 30, 2022. Patients were eligible if they had received a primary care visit in the prior 2 years and had documented receipt of all US Food and Drug Administration–authorized doses of the initial mRNA vaccine or viral vector vaccination series after December 11, 2020, and a subsequent documented booster dose between July 1, 2021, and April 29, 2022. The analytic cohort consisted of 1 610 719 participants.ExposuresReceipt of any combination of mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), and Ad26.COV2.S (Janssen/Johnson & Johnson) primary vaccination series and a booster dose.Main Outcomes and MeasuresOutcomes were breakthrough COVID-19 (symptomatic infection), hospitalization with COVID-19 pneumonia and/or death, and hospitalization with severe COVID-19 pneumonia and/or death. A subgroup analysis of nonoverlapping populations included those aged 65 years or older, those with high-risk comorbid conditions, and those with immunocompromising conditions.ResultsOf 1 610 719 participants, 1 100 280 (68.4%) were aged 65 years or older and 132 243 (8.2%) were female; 1 133 785 (70.4%) had high-risk comorbid conditions, 155 995 (9.6%) had immunocompromising conditions, and 1 467 879 (91.1%) received the same type of mRNA vaccine (initial series and booster). Over 24 weeks, 125.0 (95% CI, 123.3-126.8) per 10 000 persons had breakthrough COVID-19, 8.9 (95% CI, 8.5-9.4) per 10 000 persons were hospitalized with COVID-19 pneumonia or died, and 3.4 (95% CI, 3.1-3.7) per 10 000 persons were hospitalized with severe pneumonia or died. For high-risk populations, incidence of hospitalization with COVID-19 pneumonia or death was as follows: aged 65 years or older, 1.9 (95% CI, 1.4-2.6) per 10 000 persons; high-risk comorbid conditions, 6.7 (95% CI, 6.2-7.2) per 10 000 persons; and immunocompromising conditions, 39.6 (95% CI, 36.6-42.9) per 10 000 persons. Subgroup analyses of patients hospitalized with COVID-19 pneumonia or death by time after booster demonstrated similar incidence estimates among those aged 65 years or older and with high-risk comorbid conditions but not among those with immunocompromising conditions.Conclusions and RelevanceIn a US cohort of patients receiving care at Veterans Health Administration facilities during a period of Delta and Omicron variant predominance, there was a low incidence of hospitalization with COVID-19 pneumonia or death following vaccination and booster with any of BNT162b2, mRNA-1273, or Ad26.COV2.S vaccines.

BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).

Interferon (IFN)–specific autoantibodies have been implicated in severe coronavirus disease 2019 (COVID-19) and have been proposed as a potential driver of the persistent symptoms characterizing “long COVID,” a type of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We report that only 2 of 215 participants with convalescent SARS-CoV-2 infection tested over 394 time points, including 121 people experiencing long COVID symptoms, had detectable IFN-α2 antibodies. Both had been hospitalized during the acute phase of the infection. These data suggest that persistent anti-IFN antibodies, although a potential driver of severe COVID-19, are unlikely to contribute to long COVID symptoms in the postacute phase of the infection.

Background In 2018, the Democratic Republic of the Congo (DRC) declared its 9th and 10th Zaire ebolavirus (EBOV) outbreaks, in the Equateur province (end: July 2018), and in the eastern provinces including North Kivu (end: June 2020). The DRC Ministry of Health deployed the rVSV-vectored glycoprotein (VSV-EBOV) vaccine in response during both outbreaks. Methods A cohort of vaccinated and unvaccinated individuals from the Equateur province were enrolled and followed prospectively for 6 months. Among participants included in this analysis, 505 were vaccinated and 1,418 were unvaccinated. Differences in transmission behaviors pre- and post- outbreak were identified, along with associations between behaviors and vaccination. Results There was an overall increase in the proportion of both unvaccinated and vaccinated individuals in Mbandaka who participated in risky activities post-outbreak. Travel outside of the province pre-outbreak was associated with vaccination. Post-outbreak, vaccinated individuals were less likely to participate in funeral traditions than unvaccinated individuals. Conclusion A net increase in activities considered high risk was observed in both groups despite significant efforts to inform the population of risky behaviors. The absence of a reduction in transmission behavior post-outbreak should be considered for improving future behavior change campaigns in order to prevent recurrent outbreaks.

Aims: To explore younger adults' experiences of stroke rehabilitation to inform practice, education and future health policy. Design: Qualitative analysis of digital and other media sources on public platforms. Methods: Between March and June 2020, the experiences of younger adult stroke survivors aged 18 to 45 at the time of the stroke were collected. Data were gathered from publicly available sources, including social media, and from English-speaking users. In total, 117 accounts from 103 participants were identified from films, autobiographical books, blogs, websites, videos, Twitter and Instagram. Data analysis followed narrative and multimodal analysis with a focus on rehabilitation needs. Results: Younger adult stroke survivors make sense of their experience by reflecting on how stroke has impacted their lives. Accounts reflected an emotional journey between the past self, the present self and evolving self, as well as associated challenges such as the impact on relationships and careers. The majority of accounts presented transitions as problematic, including the receipt of the initial diagnosis, or sometimes misdiagnosis, to returning home and achieving long-term rehabilitation goals. Specialist stroke nurses were considered essential in the rehabilitation process. Conclusion: A complex process of recovery follows stroke for younger adult stroke populations. Challenges to the rehabilitation process need to be better understood and the role of nursing highlighted in future service provision. A series of age-related challenges were highlighted that require attention to improve the care and support offered. Impact: This article informs clinicians, educators, and policymakers of the age-related needs of young adult stroke survivors. Focusing on the individual and the development of age-appropriate person-centred stroke care is important. The study highlights the role of stroke nursing and challenges the current policy focus on older stroke populations as well as arguing for greater awareness of age-appropriate stroke rehabilitation in younger adults following stroke.

Evaluating cases of reinfection may offer some insight into areas for further investigation regarding durability of immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sixty cases of reinfection with viral sequencing were identified in PubMed, Embase, Web of Science, and medRxiv before May 1, 2021.Episodes of infection were separated by a median of 116 days. Severity of illness was greater among individuals reinfected within 90 days of initial infection, no asymptomatic initial cases developed severe reinfection, nearly half of cases had suspected escape variants, and nearly all individuals tested following reinfection were found to have detectable levels of anti-SARS-CoV-2 antibodies. This analysis is limited by the heterogeneous methods used among reports. Reinfection continues to be relatively rare. As the case rate presumably increases over time, this review will inform measurements to determine the natural history and causal determinants of reinfection in more rigorous observational cohort studies and other standardized surveillance approaches.

We aimed to characterize the variability in the illness experience and recovery process from COVID-19. We conducted in-depth individual interviews with participants enrolled in the Long-term Immunological Impact of Novel Coronavirus (LIINC) cohort study in San Francisco, California from June through October of 2020. Participants were adults who had a previously confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations at our clinical research center. We purposefully sampled 24 English- and Spanish-speaking adults with asymptomatic, mild and severe symptomatic infection, including those who were hospitalized, and those with HIV co-infection. Half of our sample (50.0%) identified as Latinx/Hispanic and most of the participants were men (62.5%). We used thematic analysis to characterize the illness experience, recovery process, and mental health impact of experiencing COVID-19 and present clinical data for each participant. Emergent themes were: (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress, (2) among participants with symptomatic infection, the illness experience was characterized by uncertainty in terms of managing symptoms and recovery, and (3) despite wide-ranging illness experiences, participants shared many common characteristics, including health information-seeking behavior facilitated by access to medical care, and uncertainty regarding the course of their illness and recovery. COVID-19 was associated with elevated levels of psychological distress, regardless of symptoms.

Before emergence in late 2021 of the highly transmissible B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19 (1,2), several studies demonstrated that SARS-CoV-2 was unlikely to be cultured from specimens with high cycle threshold (Ct) values

BackgroundHuman papillomavirus (HPV) vaccination offers protection against the virus responsible for cervical, oropharyngeal, anal, vulval and penile cancers. However, there is considerable variation across, and even within, countries as to how HPV vaccination is offered and accepted. This review aimed to identify what interventions exist to promote uptake and how effective they are.MethodsWe conducted an umbrella review using the JBI (Joanna Briggs Institute) methodology to evaluate routine or catch-up interventions to increase HPV vaccination uptake and/or intention for children aged 9 years and older, adolescents and young adults up to 26. Comprehensive searches for English language quantitative systematic reviews, published between January 2011 and July 2021, were conducted across five databases. After reviewing titles and abstract, relevant papers were independently assessed in detail.Main resultsFrom 1046 records identified, 10 articles were included in the review. They reported on 95 randomised controlled trials, 28 quasi-experimental studies, 14 cohort studies, 6 non-randomised pretest/post-test studies with control groups, 5 single-group pretest/post-test studies, 1 single-group post-test study and 1 randomised longitudinal study. Some interventions promoted change at the individual, community or organisational level, while others used a multicomponent approach. Face-to-face presentations, printed information and supplementing both strategies with additional components appear effective at increasing vaccination intention, while reminders and multicomponent strategies, especially ones that include some intervention aimed at provider level, appear effective at increasing vaccination uptake. Interventions that did not lead to an improvement in HPV vaccination intention or uptake varied in design and impacts were inconsistent across children/adolescents, young adults or parents.ConclusionThe evidence suggests that there is no single solution to increasing vaccination uptake and that different approaches may be better suited to certain populations. However, generalisations are limited by poor reporting and a paucity of studies beyond the USA. Further high-quality studies, therefore, are needed to understand how best to increase HPV vaccination uptake in different target populations.

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as β-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7–22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6–33, P, Patients with solid cancers have high rates of clonal haematopoiesis associated with increased risk of secondary leukemias. Here, by using peripheral blood sequencing data from patients with solid non-hematologic cancer, the authors profile the landscape of mosaic chromosomal alterations and gene mutations, defining patients at high risk of leukemia progression.

Background As of early 2022, the Omicron variants are the predominant circulating lineages globally. Understanding neutralizing antibody responses against Omicron BA.1 and BA.2 after vaccine breakthrough infections will provide insights into BA.2 infectivity and susceptibility to subsequent reinfection. Methods Live virus neutralization assays were used to study immunity against Delta and Omicron BA.1 and BA.2 variants in samples from 86 individuals, 24 unvaccinated (27.9%) and 62 vaccinated (72.1%), who were infected with Delta (n = 42, 48.8%) or BA.1 (n = 44, 51.2%). Among the 62 vaccinated individuals, 39 were unboosted (62.9%), whereas 23 were boosted (37.1%). Results In unvaccinated infections, neutralizing antibodies (nAbs) against the three variants were weak or undetectable, except against Delta for Delta-infected individuals. Both Delta and BA.1 breakthrough infections resulted in strong nAb responses against ancestral wild-type and Delta lineages, but moderate nAb responses against BA.1 and BA.2, with similar titers between unboosted and boosted individuals. Antibody titers against BA.2 were generally higher than those against BA.1 in breakthrough infections. Conclusions These results underscore the decreased immunogenicity of BA.1 compared to BA.2, insufficient neutralizing immunity against BA.2 in unvaccinated individuals, and moderate to strong neutralizing immunity induced against BA.2 in Delta and BA.1 breakthrough infections.

Background: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. Methods: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. Results: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 ( P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PaO2: FiO2) were significantly improved during days 4-7 (P < 0.05 for all). Conclusions: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated. Replicating results and scaling the intervention are important, but prone positioning may represent an additional therapeutic option in patients with ARDS due to COVID-19.

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) and both are prevalent in men with testosterone deficiency. Long-term effects of testosterone therapy (TTh) on NAFLD are not well studied. This observational, prospective, cumulative registry study assesses long-term effects of testosterone undecanoate (TU) on hepatic physiology and function in 505 hypogonadal men (T levels ≤350 ng/dL). Three hundred and twenty one men received TU 1000 mg/12 weeks for up to 12 years following an initial 6-week interval (T-group), while 184 who opted against TTh served as controls (C-group). T-group patients exhibited decreased fatty liver index (FLI, calculated according to Mayo Clinic guidelines) (83.6 ± 12.08 to 66.91 ± 19.38), γ-GT (39.31 ± 11.62 to 28.95 ± 7.57 U/L), bilirubin (1.64 ± 4.13 to 1.21 ± 1.89 mg/dL) and triglycerides (252.35 ± 90.99 to 213 ± 65.91 mg/dL) over 12 years. Waist circumference and body mass index were also reduced in the T-group (107.17 ± 9.64 to 100.34 ± 9.03 cm and 31.51 ± 4.32 to 29.03 ± 3.77 kg/m2). There were 25 deaths (7.8%) in the T-group of which 11 (44%) were cardiovascular related. In contrast, 28 patients (15.2%) died in C-group, and all deaths (100%) were attributed to CVD. These data suggest that long-term TTh improves hepatic steatosis and liver function in hypogonadal men. Improvements in liver function may have contributed to reduced CVD-related mortality.

More than 5 million patients are admitted to US intensive care units (ICUs) each year. Many of these patients have risk factors for dysphagia. Dysphagia must be promptly addressed and appropriately treated to avoid the deleterious impacts of aspiration and malnutrition. Therefore, clinicians must be aware of ways to identify and treat dysphagia. This review will highlight the risk factors, mechanisms, and impact of dysphagia in the ICU as well as provide screening, diagnostic, and management options.

Elimination of an infectious disease requires subcritical transmission, or a reproductive number less than one, and can be assessed with cross-sectional surveys conducted by neglected tropical disease programs. Here, we assess the distribution of onchocerciasis prevalence taken from surveys across sub-Saharan Africa before the initiation of ivermectin in mass drug administrations. Pre-intervention nodular palpation cross-sectional surveys were available from 15 countries in the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN) database. We determined whether the distribution of the prevalence over communities in an area was consistent with a geometric distribution, which previous studies have suggested indicates a subcritical disease. If not, we fitted a negative binominal distribution (hypothetically supercritical) or a mixture of two distributions: geometric (hypothetically subcritical) and Poisson (hypothetically supercritical). The overall distribution of community-level onchocerciasis prevalence estimates from the ESPEN dataset from 2005 to 2014 was not consistent with a geometric distribution. By contrast, data from several countries and parts of countries were consistent with the geometric distribution, for example, some areas within Nigeria and Angola. Even if the geometric distribution suggested pre-intervention subcriticality in more localized geographical areas, our model using pooled survey data of all geographic areas suggests that the entire pre-intervention prevalence does not fit a geometric distribution. Further work will be required to confirm the significance of a geometric distribution for onchocerciasis.

As SARS-CoV-2 is known to invade neural cell mitochondria, a plasma system for quantifying central nervous system proteins in living humans was used to investigate neuropathogenic mechanisms of long-COVID-19.SARS-CoV-2 proteins and mitochondrial proteins (MPs) in enriched plasma neuron-derived extracellular vesicles (NDEVs) and astrocyte-derived EVs (ADEVs) were quantified in resolved acute COVID-19 without post-acute sequelae of SARS-CoV-2 (PASC), PASC without neuropsychiatric manifestations (NP), PASC with NP and healthy controls.NDEV and ADEV mean levels of SARS-CoV-2 S1 and nucleocapsid (N) proteins were higher in all PASC sub-groups than controls, but only N levels were higher in PASC with than without NP. Exosome marker CD81-normalized NDEV mean levels of subunit 6 of MP respiratory chain complex I and subunit 10 of complex III, and neuroprotective MPs Humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were decreased significantly in PASC with NP but not in PASC without NP relative to controls. NDEV levels of MPs voltage-dependent anion-selective channel protein 1 (VDAC1) and N-methyl-D-aspartate receptor 1 (NMDAR1) were decreased in PASC without and with NP, whereas those of calcium channel MPs mitochondrial calcium uniporter (MCU), sodium/calcium exchanger (NCLX) and leucine zipper EF-hand containing transmembrane 1 protein (LETM1) were decreased only in PASC with NP. ADEV levels of MCU and NCLX only were increased in PASC without and with NP.Abnormal NDEV and ADEV levels of SARS-CoV-2 N and S1 protein and MPs correlate with NP and may be biomarkers for long-COVID prognostics and therapeutic trials. ANN NEUROL 2022;91:772-781.

Cognitive post-acute sequelae of SARS-CoV-2 (PASC) can occur after mild COVID-19. Detailed clinical characterizations may inform pathogenesis. We evaluated 22 adults reporting cognitive PASC and 10 not reporting cognitive symptoms after mild SARS-CoV-2 infection through structured interviews, neuropsychological testing, and optional cerebrospinal fluid (CSF) evaluations (53%). Delayed onset of cognitive PASC occurred in 43% and associated with younger age. Cognitive PASC participants had a higher number of pre-existing cognitive risk factors (2.5 vs. 0; p = 0.03) and higher proportion with abnormal CSF findings (77% vs. 0%; p = 0.01) versus controls. Cognitive risk factors and immunologic mechanisms may contribute to cognitive PASC pathogenesis.

Despite more than 300,000 rVSVΔG-ZEBOV-glycoprotein (GP) vaccine doses having been administered during Ebola virus disease (EVD) outbreaks in the Democratic Republic of the Congo (DRC) between 2018 and 2020, seroepidemiologic studies of vaccinated Congolese populations are lacking. This study examines the antibody response at 21 d and 6 mo postvaccination after single-dose rVSVΔG-ZEBOV-GP vaccination among EVD-exposed and potentially exposed populations in the DRC. We conducted a longitudinal cohort study of 608 rVSVΔG-ZEBOV-GP-vaccinated individuals during an EVD outbreak in North Kivu Province, DRC. Participants provided questionnaires and blood samples at three study visits (day 0, visit 1; day 21, visit 2; and month 6, visit 3). Anti-GP immunoglobulin G (IgG) antibody titers were measured in serum by the Filovirus Animal Nonclinical Group anti-Ebola virus GP IgG enzyme-linked immunosorbent assay. Antibody response was defined as an antibody titer that had increased fourfold from visit 1 to visit 2 and was above four times the lower limit of quantification at visit 2; antibody persistence was defined as a similar increase from visit 1 to visit 3. We then examined demographics for associations with follow-up antibody titers using generalized linear mixed models. A majority of the sample, 87.2%, had an antibody response at visit 2, and 95.6% demonstrated antibody persistence at visit 3. Being female and of young age was predictive of a higher antibody titer postvaccination. Antibody response and persistence after Ebola vaccination was robust in this cohort, confirming findings from outside of the DRC.

Understanding the complex interactions between virus and host that drive new strain evolution is key to predicting the emergence potential of variants and informing vaccine development. Under our hypothesis, future dominant human norovirus GII.4 variants with critical antigenic properties that allow them to spread are currently circulating undetected, having diverged years earlier. Through large-scale sequencing of GII.4 surveillance samples, we identified two variants with extensive divergence within domains that mediate neutralizing antibody binding. Subsequent serological characterization of these strains using temporally resolved adult and child sera suggests that neither candidate could spread globally in adults with multiple GII.4 exposures, yet young children with minimal GII.4 exposure appear susceptible. Antigenic cartography of surveillance and outbreak sera indicates that continued population exposure to GII.4 Sydney 2012 and antigenically related variants over a 6-year period resulted in a broadening of immunity to heterogeneous GII.4 variants, including those identified here. We show that the strongest antibody responses in adults exposed to GII.4 Sydney 2012 are directed to previously circulating GII.4 viruses. Our data suggest that the broadening of antibody responses compromises establishment of strong GII.4 Sydney 2012 immunity, thereby allowing the continued persistence of GII.4 Sydney 2012 and modulating the cycle of norovirus GII.4 variant replacement. Our results indicate a cycle of norovirus GII.4 variant replacement dependent upon population immunity. Young children are susceptible to divergent variants; therefore, emergence of these strains worldwide is driven proximally by changes in adult serological immunity and distally by viral evolution that confers fitness in the context of immunity.

Prostate cancer affects a significant proportion of men worldwide. Evidence from genetic and clinical studies suggests that there may be a causal association between prostate cancer and the human papilloma virus (HPV). As HPV is a vaccine-preventable pathogen, the possibility of a role in prostate cancer causation may reinforce the importance of effective HPV vaccination campaigns. This is of particular relevance in light of the COVID-19 pandemic, which may have considerable effects on HPV vaccine uptake and distribution.

Background:\ud The specific challenges experienced by the nursing and midwifery workforce in previous pandemics have exacerbated pre-existing professional and personal challenges, and triggered new issues. We aimed to determine the psychological impact of the COVID-19 pandemic on the UK nursing and midwifery workforce and identify potential factors associated with signs of post-traumatic stress disorder.\ud \ud Methods:\ud A United Kingdom national online survey was conducted at three time-points during the first wave of the COVID-19 pandemic between April and August 2020 (T1 and T2 during initial wave; T3 at three-months following the first wave). All members of the UK registered and unregistered nursing and midwifery workforce were eligible to participate. The survey was promoted via social media and through organisational email and newsletters.\ud \ud The primary outcome was an Impact of Events Scale-Revised score indicative of a post-traumatic stress disorder diagnosis (defined using the cut-off score ≥33). Multivariable logistic regression modelling was used to assess the association between explanatory variables and post-traumatic stress disorder.\ud \ud Results:\ud We received 7840 eligible responses (T1- 2040; T2- 3638; T3- 2162). Overall, 91.6% participants were female, 77.2% were adult registered nurses, and 28.7% were redeployed during the pandemic.\ud \ud An Impact of Events Scale-Revised score ≥33 (probable post-traumatic stress disorder) was observed in 44.6%, 37.1%, and 29.3% participants at T1, T2, and T3 respectively. At all three time-points, both personal and workplace factors were associated with probable post-traumatic stress disorder, although some specific associations changed over the course of the pandemic. Increased age was associated with reduced probable post-traumatic stress disorder at T1 and T2 (e.g. 41-50 years at T1 odds ratio (OR) 0.60, 95% confidence interval (CI) 0.42-0.86), but not at T3. Similarly, redeployment with inadequate/ no training was associated with increased probable post-traumatic stress disorder at T1 and T2, but not at T3 (T1 OR 1.37, 95% CI 1.06-1.77; T3 OR 1.17, 95% CI 0.89-1.55). A lack of confidence in infection prevention and control training was associated with increased probable post-traumatic stress disorder at all three time-points (e.g. T1 OR 1.48, 95% CI 1.11-1.97).\ud \ud Conclusion:\ud A negative psychological impact was evident 3-months following the first wave of the pandemic. Both personal and workplace are associated with adverse psychological effects linked to the COVID-19 pandemic.\ud \ud These findings will inform how healthcare organisations should respond to staff wellbeing needs both during the current pandemic, and in planning for future pandemics.

Mobility is an important factor in maintaining health and independence in an aging population. Facilitating community-dwelling older adults to independently identify signs of functional decline could help reduce disability and frailty development. Step-count from a body-worn sensor system was compared with a criterion measure in healthy young (n = 10) and healthy older adults (n = 10) during a Timed Up and Go test under different conditions. Spearman's rank correlation coefficient indicated strong agreement between the sensor-obtained step-count and that of the criterion measure in both age groups, in all mobility tests. A body-worn sensor system can provide objective, quantitative measures of step-count over short distances in older adults. Future research will examine if step-count alone can be used to identify functional decline and risk of frailty.Clinical Relevance-This demonstrates the correlation between step-count derived from a wearable sensor and a criterion measure over a short distance in older adults.

BackgroundWhether or not individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease develop clinical sequelae is unknown. We assessed current symptoms and physical examination findings among individuals with pauci-symptomatic or asymptomatic infection and unrecognised Ebola virus disease compared with Ebola virus disease survivors and uninfected contacts.MethodsBetween June 17, 2015, and June 30, 2017, we studied a cohort of Ebola virus disease survivors and their contacts in Liberia. Surveys, current symptoms and physical examination findings, and serology were used to characterise disease status of reported Ebola virus disease, unrecognised Ebola virus disease, pauci-symptomatic or asymptomatic Ebola virus infection, or no infection. We pre-specified findings known to be differentially prevalent among Ebola virus disease survivors versus their contacts (urinary frequency, headache, fatigue, muscle pain, memory loss, joint pain, neurological findings, chest findings, muscle findings, joint findings, abdominal findings, and uveitis). We estimated the prevalence and incidence of selected clinical findings by disease status.FindingsOur analytical cohort included 991 reported Ebola virus disease survivors and 2688 close contacts. The median time from acute Ebola virus disease onset to baseline was 317 days (IQR 271-366). Of 222 seropositive contacts, 115 had pauci-symptomatic or asymptomatic Ebola virus infection and 107 had unrecognised Ebola virus disease. At baseline, prevalent findings of joint pain, memory loss, muscle pain, and fatigue were lowest among those with pauci-symptomatic or asymptomatic infection or no infection, higher among contacts with unrecognised Ebola virus disease, and highest in reported survivors of Ebola virus disease. Joint pain was the most prevalent finding, and was reported in 434 (18%) of 2466 individuals with no infection, 14 (12%) of 115 with pauci-symptomatic or asymptomatic infection, 31 (29%) of 107 with unrecognised Ebola virus disease, and 476 (48%) of 991 with reported Ebola virus disease. In adjusted analyses, this pattern remained for joint pain and memory loss. Survivors had an increased odds of joint pain compared with unrecognised Ebola virus disease contacts (adjusted odds ratio [OR] 2·13, 95% CI 1·34-3·39); unrecognised Ebola virus disease contacts had an increased odds of joint pain compared with those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 1·89, 95% CI 1·21-2·97). The adjusted odds of memory loss was more than four-times higher among survivors than among unrecognised Ebola virus disease contacts (adjusted OR 4·47, 95% CI 2·41-8·30) and two-times higher among unrecognised Ebola virus disease contacts than in those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 2·05, 95% CI 1·10-3·84). By 12 months, prevalent findings had decreased in the three infected groups.InterpretationOur findings provide evidence of post-Ebola virus disease clinical sequelae among contacts with unrecognised Ebola virus disease but not in people with pauci-symptomatic or asymptomatic Ebola virus infection.FundingNational Cancer Institute and National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

As global demographics change, ageing is a global phenomenon which is increasingly of interest in our modern and rapidly changing society. Thus, the application of proper prognostic indices in clinical decisions regarding mortality prediction has assumed a significant importance for personalized risk management (i.e., identifying patients who are at high or low risk of death) and to help ensure effective healthcare services to patients. Consequently, prognostic modelling expressed as all-cause mortality prediction is an important step for effective patient management. Machine learning has the potential to transform prognostic modelling. In this paper, results on the development of machine learning models for all-cause mortality prediction in a cohort of healthy older adults are reported. The models are based on features covering anthropometric variables, physical and lab examinations, questionnaires, and lifestyles, as well as wearable data collected in free-living settings, obtained for the “Healthy Ageing Initiative” study conducted on 2291 recruited participants. Several machine learning techniques including feature engineering, feature selection, data augmentation and resampling were investigated for this purpose. A detailed empirical comparison of the impact of the different techniques is presented and discussed. The achieved performances were also compared with a standard epidemiological model. This investigation showed that, for the dataset under consideration, the best results were achieved with Random UnderSampling in conjunction with Random Forest (either with or without probability calibration). However, while including probability calibration slightly reduced the average performance, it increased the model robustness, as indicated by the lower 95% confidence intervals. The analysis showed that machine learning models could provide comparable results to standard epidemiological models while being completely data-driven and disease-agnostic, thus demonstrating the opportunity for building machine learning models on health records data for research and clinical practice. However, further testing is required to significantly improve the model performance and its robustness.

IntroductionThe introduction of multiparametric MRI (mpMRI) has improved almost every aspect of the prostate cancer diagnostic pathway. However, the novel imaging technique, prostate-specific membrane antigen positron emission tomography (PSMA PET) may have demonstrable accuracy in detecting and staging prostate cancer. Here, we describe a protocol for a systematic review and meta-analysis comparing mpMRI to PSMA PET for the diagnosis of suspected prostate cancer.Methods and analysisA systematic search of MEDLINE, EMBASE, PubMed and Cochrane databases will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed for screening, data extraction, statistical analysis and reporting. Included papers will be full-text articles providing original data, written in English articles and comparing the use of PSMA PET with mpMRI in the diagnosis of prostate cancer. All studies published between July 1977 and March 2021 will be eligible for inclusion. Study bias and quality will be assessed using Quadas-2 score. To ensure the quality of the reporting of studies, this protocol is written following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist.Ethics and disseminationEthical approval will not be required for this systematic review. Findings will be disseminated through peer-reviewed publications and presentations at both national and international conferences.PROSPERO registration numberCRD42021239296.

Background The biological processes associated with postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are unknown. Methods We measured soluble markers of inflammation in a SARS-CoV-2 recovery cohort at early (90 days) timepoints. We defined PASC as the presence of 1 or more coronavirus disease 2019 (COVID-19)–attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with and without PASC using mixed-effects models with terms for PASC and early and late recovery time periods. Results During early recovery, those who went on to develop PASC generally had higher levels of cytokine biomarkers including tumor necrosis factor–α (1.14-fold higher mean ratio [95% confidence interval {CI}, 1.01–1.28]; P = .028) and interferon-γ–induced protein 10 (1.28-fold higher mean ratio [95% CI, 1.01–1.62]; P = .038). Among those with PASC, there was a trend toward higher interleukin 6 levels during early recovery (1.29-fold higher mean ratio [95% CI, .98–1.70]; P = .07), which became more pronounced in late recovery (1.44-fold higher mean ratio [95% CI, 1.11–1.86]; P Conclusions Persistent immune activation may be associated with ongoing symptoms following COVID-19. Further characterization of these processes might identify therapeutic targets for those experiencing PASC.

Shortness of breath, chest pain, and palpitations occur as postacute sequelae of COVID-19, but whether symptoms are associated with echocardiographic abnormalities, cardiac biomarkers, or markers of systemic inflammation remains unknown. In a cross-sectional analysis, we assessed symptoms, performed echocardiograms, and measured biomarkers among adults more than 8 weeks after confirmed SARS-CoV-2 infection. We modeled associations between symptoms and baseline characteristics, echocardiographic findings, and biomarkers using logistic regression. We enrolled 102 participants at a median of 7.2 months following COVID-19 onset; 47 individuals reported dyspnea, chest pain, or palpitations. Median age was 52 years, and 41% of participants were women. Female sex, hospitalization, IgG antibody against SARS-CoV-2 receptor binding domain, and C-reactive protein were associated with symptoms. Regarding echocardiographic findings, 4 of 47 participants (9%) with symptoms had pericardial effusions compared with 0 of 55 participants without symptoms; those with effusions had a median of 4 symptoms compared with a median of 1 symptom in those without effusions. There was no strong evidence for a relationship between symptoms and echocardiographic functional parameters or other biomarkers. Among adults more than 8 weeks after SARS-CoV-2 infection, SARS-CoV-2 RBD antibodies, markers of inflammation, and, possibly, pericardial effusions are associated with cardiopulmonary symptoms. Investigation into inflammation as a mechanism underlying postacute sequelae of COVID-19 is warranted.

Cancer is an aggressive disease which imparts a tremendous socio-economic burden on the international community. Early detection is an important aspect in improving survival rates for cancer sufferers; however, very few studies have investigated the possibility of predicting which people have the highest risk to develop this disease, even years before the traditional symptoms first occur. In this paper, a dataset from a longitudinal study which was collected among 2291 70-year olds in Sweden has been analyzed to investigate the possibility for predicting 2-7 year cancer-specific mortality. A tailored ensemble model has been developed to tackle this highly imbalanced dataset. The performance with different feature subsets has been investigated to evaluate the impact that heterogeneous data sources may have on the overall model. While a full-features model shows an Area Under the ROC Curve (AUC-ROC) of 0.882, a feature subset which only includes demographics, self-report health and lifestyle data, and wearable dataset collected in free-living environments presents similar performance (AUC-ROC: 0.857). This analysis confirms the importance of wearable technology for providing unbiased health markers and suggests its possible use in the accurate prediction of 2-7 year cancer-related mortality in older adults.

BackgroundAs of 26 March 2021, the Africa CDC had reported 4,159,055 cases of COVID-19 and 111,357 deaths among the 55 African Union Member States; however, no country has published a nationally representative serosurvey as of May 2021. Such data are vital for understanding the pandemic’s progression on the continent, evaluating containment measures, and policy planning.MethodsWe conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on socio-demographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was was estimated after applying sampling weights.FindingsThe overall weighted seroprevalence was 2.6% (95% CI 1.9-3.4). This is 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0-2.5), and urban seropositivity was 4.2% (95% CI 2.6-5.7).InterpretationAlthough overall seroprevalence was low compared to countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone), our findings indicate enormous underreporting of active cases. This has ramifications for the country’s third wave (which started in June 2021), where the average number of daily reported cases was 87 by the end of the month—this could potentially be on the order of 3,700 actual infections, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant underreporting of incidence and mortality across the continent.FundingThis study was supported by NIAID K08 AI139361, the Sierra Leone Ministry of Health and Sanitation, and the Africa CDC.

ImportanceHerpes zoster infection after COVID-19 vaccination has been reported in numerous case studies. It is not known whether these cases represent increased reporting or a true increase in risk.ObjectiveTo assess whether COVID-19 vaccination is associated with an increased risk of herpes zoster infection.Design, Setting, and ParticipantsThis cohort study used a self-controlled risk interval (SCRI) design to compare the risk of herpes zoster in a risk interval of 30 days after COVID-19 vaccination or up to the date of the second vaccine dose with a control interval remote from COVID-19 vaccination (defined as 60-90 days after the last recorded vaccination date for each individual, allowing for a 30-day washout period between control and risk intervals). A supplemental cohort analysis was used to compare the risk of herpes zoster after COVID-19 vaccination with the risk of herpes zoster after influenza vaccination among 2 historical cohorts who received an influenza vaccine in the prepandemic period (January 1, 2018, to December 31, 2019) or the early pandemic period (March 1, 2020, to November 30, 2020). Data were obtained from Optum Labs Data Warehouse, a US national deidentified claims-based database. A total of 2 039 854 individuals who received any dose of a COVID-19 vaccine with emergency use authorization (BNT162b2 [Pfizer-BioNTech], mRNA-1273 [Moderna], or Ad26.COV2.S [Johnson & Johnson]) from December 11, 2020, through June 30, 2021, were eligible for inclusion. Individuals included in the SCRI analysis were a subset of the COVID-19–vaccinated cohort who had herpes zoster during either a risk or control interval.ExposuresAny dose of a COVID-19 vaccine.Main Outcomes and MeasuresIncident herpes zoster, defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and a prescription of a new antiviral medication or a dose increase in antiviral medication within 5 days of diagnosis.ResultsAmong 2 039 854 individuals who received any dose of a COVID-19 vaccine during the study period, the mean (SD) age was 43.2 (16.3) years; 1 031 149 individuals (50.6%) were female, and 1 344 318 (65.9%) were White. Of those, 1451 patients (mean [SD] age, 51.6 [12.6] years; 845 [58.2%] female) with a herpes zoster diagnosis were included in the primary SCRI analysis. In the SCRI analysis, COVID-19 vaccination was not associated with an increased risk of herpes zoster after adjustment (incidence rate ratio, 0.91; 95% CI, 0.82-1.01; P = .08). In the supplementary cohort analysis, COVID-19 vaccination was not associated with a higher risk of herpes zoster compared with influenza vaccination in the prepandemic period (first dose of COVID-19 vaccine: hazard ratio [HR], 0.78 [95% CI, 0.70-0.86; P P P = .05]; second dose: HR, 0.91 [95% CI, 0.81-1.02; P = .09]).Conclusions and RelevanceIn this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.

Visible signs of disease can evoke stigma while stigma contributes to depression and mental illness, sometimes manifesting as somatic symptoms. We assessed these hypotheses among Ebola virus disease (EVD) survivors, some of whom experienced clinical sequelae. Ebola virus disease survivors in Liberia were enrolled in an observational cohort study starting in June 2015 with visits every 6 months. At baseline and 18 months later, a seven-item index of EVD-related stigma was administered. Clinical findings (self-reported symptoms and abnormal findings) were obtained at each visit. We applied the generalized estimating equation method to assess the bidirectional concurrent and lagged associations between clinical findings and stigma, adjusting for age, gender, educational level, referral to medical care, and HIV serostatus as confounders. When assessing the contribution of stigma to later clinical findings, we restricted clinical findings to five that were also considered somatic symptoms. Data were obtained from 859 EVD survivors. In concurrent longitudinal analyses, each additional clinical finding increased the adjusted odds of stigma by 18% (95% CI: 1.11, 1.25), particularly palpitations, muscle pain, joint pain, urinary frequency, and memory loss. In lagged associations, memory loss (adjusted odds ratio [AOR]: 4.6; 95% CI: 1.73, 12.36) and anorexia (AOR: 4.17; 95% CI: 1.82, 9.53) were associated with later stigma, but stigma was not significantly associated with later clinical findings. Stigma was associated with select symptoms, not abnormal objective findings. Lagged associations between symptoms and later stigma substantiate the possibility of a pathway related to visible symptoms identified by community members and leading to fear of contagion.

Background Globally the population of older adults is increasing. It is estimated that by 2050 the number of adults over the age of 60 will represent over 21% of the world’s population. Frailty is a clinical condition associated with ageing resulting in an increase in adverse outcomes. It is considered the greatest challenge facing an ageing population affecting an estimated 16% of community-dwelling populations worldwide. Aim The aim of this systematic review is to explore how wearable sensors have been used to assess frailty in older adults. Method Electronic databases Medline, Science Direct, Scopus, and CINAHL were systematically searched March 2020 and November 2020. A search constraint of articles published in English, between January 2010 and November 2020 was applied. Papers included were primary observational studies involving; older adults aged > 60 years, used a wearable sensor to provide quantitative measurements of physical activity (PA) or mobility and a measure of frailty. Studies were excluded if they used non-wearable sensors for outcome measurement or outlined an algorithm or application development exclusively. The methodological quality of the selected studies was assessed using the Appraisal Tool for Cross-sectional Studies (AXIS). Results Twenty-nine studies examining the use of wearable sensors to assess and discriminate between stages of frailty in older adults were included. Thirteen different body-worn sensors were used in eight different body-locations. Participants were community-dwelling older adults. Studies were performed in home, laboratory or hospital settings. Postural transitions, number of steps, percentage of time in PA and intensity of PA together were the most frequently measured parameters followed closely by gait speed. All but one study demonstrated an association between PA and level of frailty. All reports of gait speed indicate correlation with frailty. Conclusions Wearable sensors have been successfully used to evaluate frailty in older adults. Further research is needed to identify a feasible, user-friendly device and body-location that can be used to identify signs of pre-frailty in community-dwelling older adults. This would facilitate early identification and targeted intervention to reduce the burden of frailty in an ageing population.

To explore the differences in perceived patient safety culture in cancer nurses working in Estonia, Germany, the Netherlands, and the United Kingdom.An exploratory cross-sectional survey.In 2018, 393 cancer nurses completed the 12 dimensions of the Hospital Survey on Patient Safety Culture.The mean score for the overall patient safety grade was 61.3. The highest rated dimension was "teamwork within units" while "staffing" was the lowest in all four countries. Nurses in the Netherlands and in the United Kingdom, scored higher on "communication openness", the "frequency of events reported", and "non-punitive response to errors", than nurses from Estonia or Germany. We found statistically significant differences between the countries for the association between five of the 12 dimensions with the overall patient safety grade: overall perception of patient safety, communication openness, staffing, handoffs and transitions and non-punitive response to errors.Patient safety culture, as reported by cancer nurses, varies between European countries and contextual factors, such as recognition of the nursing role and education have an impact on it. Cancer nurses' role in promoting patient safety is a key concern and requires better recognition on a European and global level.Cancer Nursing Societies in any country can use these data as an indication on how to improve patient care in their country. Recognition of cancer nursing as a distinct specialty in nursing will help to improve patient safety.目的: 探讨在爱沙尼亚、德国、荷兰和英国工作的癌症护士对病人安全文化的认知差异。 设计: 探索性横向调查。 方法: 2018年,393名癌症护士完成了医院患者安全文化调查的12个维度。 结果: 总体患者安全等级的平均分数为61.3。评分最高的维度是“单位内的团队合作”,而“人员配备”在所有四个国家中都是最低的。荷兰和英国的护士在“沟通开放性”、“事件报告频率”和“对错误的非惩罚性反应”方面得分高于爱沙尼亚和德国的护士。我们发现,在12个维度中,有5个维度与患者总体安全等级之间存在统计学上的显著差异:患者总体安全感知、沟通开放性、人员配备、交接和过渡以及对错误的非惩罚性反应。 结论: 癌症护士所报告的患者安全文化在欧洲国家之间存在差异,而护理角色的认知和教育等环境因素也会对其产生影响。癌症护士在促进患者安全方面的作用是一个关键问题,需要在欧洲和全球层面上得到更好的认识。 影响: 任何国家的癌症护理协会都可以利用这些数据作为改善本国患者护理的指示。认识到癌症护理是护理的一个独特的专业将有助于提高患者安全性。.

In a larger study where the aim was to investigate choice and control in decision making, the role of partners was significant. Reported here are the experiences of those partners of young people with cancer.A qualitative, exploratory case study approach was used.In the larger study, 22 participants were recruited including five adolescents and young adults with cancer, two sets of parents/carers and three individual parents, five healthcare professionals linked to the adolescent or young adult with cancer and five friends or partners. Data were collected between February 2014 and February 2015 and included interviews, non-participant observation and documentary analysis.Three themes were identified relating to partner experience derived from partner and patient interview data: "practical support", "putting your partner first" and "acting as a confidante/ally".These findings reveal new knowledge of partner experience when adolescents and young adults have cancer. Richer in-depth understandings of partner experience are required to improve the care of adolescents and young adults with cancer and those around them.These findings will inform the development of guidance and further research which will enhance the knowledge of partner experience for those involved in cancer care in the adolescent and young adult age group.目的: 研究的主要目的是研究决策中的选择和控制,服务者在决策中起很大作用。研究主要内容是患癌青年服务者的经历。 设计: 研究使用定性,案例探索研究方法。 方法: 研究参与者共有22位,包括5位患癌青少年和青年、两对父母/照顾者和3 位离异父母、5位患癌青少年和青年分别的健康护理专家和5位朋友。数据收集始于2014年2月到2015年2月截止,收集数据包括采访、局外观察、纪录片分析。 结果: 从服务者和病人采访数据中得出三类主题的服务患癌青少年和青年经历:“实际服务”“以服务者为第一位”“作为知己或盟友” 结论: 研究发现服务患癌青少年和青年的新经历。要提高对患癌青少年和青年的服务,首先需要对这些服务患癌青少年和青年的经历有深刻的丰富的理解。 影响: 这一发现将会促进指导政策的发展和更深入的研究,进一步促进人们对服务患癌青少年和青年经历的理解。.

Understanding antibiotic use may help predict emergence of antimicrobial resistance. We evaluated antibiotic prescription trends in rural Burkina Faso, where little is known about antibiotic consumption. Antibiotic prescription data for 20 communities were extracted through record review in six primary health-care facilities serving the communities. The number of antibiotic prescriptions per child-year was calculated using population-based census data from the communities. A total of 1,444 antibiotic prescriptions were made from March to June 2017 among 3,401 children in the communities. The frequency of antibiotic prescription was 1.70 prescriptions per child-year (95% CI: 1.61–1.79). Penicillins were the most common (1.04 prescriptions per child-year, 95% CI: 1.01–1.06), followed by sulfonamides (0.69 prescriptions per child-year, 95% CI: 0.67–0.71) and macrolides (0.38 prescriptions per child-year, 95% CI: 0.37–0.40). Continued monitoring of antibiotic consumption in diverse settings will be important to understand the potential for emergence of antibiotic resistance.

Aims and objectivesTo explore the role that Donor Transplant Co‐ordinators have played and the future potential of Specialist Nurses for Organ Donation (SN‐ODs), within organ donation strategies in the UK and other countries.BackgroundOrgan donation and transplantation rates vary extensively around the world. However, there is a universal shortage of deceased donors, prompting different approaches to increase transplantation rates. Within the UK, the Clinical Lead for Organ Donation and Specialist Nurse in Organ Donation undertake a key role in the implementation of the Organ Donation Strategy. The Human Transplantation (Wales) Act 2015 is a recent development which facilities a deemed (presumed) consent approach to organ donation, the Specialist Nurse in Organ Donation undertakes a major role identifying the potential donor in this situation by confirming the deemed consent status of the donor and supporting bereaved relatives. UK governments in England and Scotland are currently seeking legislative changes to an opt‐out system of organ donation, in line with the Wales change.DesignThis discursive paper explores the role from Donor Transplant Co‐ordinator to Specialist Nurse in Organ Donation (SN‐OD) within organ donation policy in different settings, but with a specific focus on the UK. The paper clarifies the current and future potential of nurses working with bereaved families when requesting authorisation for donation.Implications for nursingThe current scope and future potential of Donor Transplant Co‐ordinator and Specialist Nurse in Organ Donation roles need better recognition. Little empirical data exist about the key role that these nurses play in the organ donation process, especially in relation to gaining authorisation to proceed to donation.ConclusionThere is a need to clarify the role of the Specialist Nurse in Organ Donation and their impact on improving rates of organ donation.

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.Significance statementWe present longitudinal data on the magnitude, duration and decay rate of viral RNA and the magnitude and duration of infectious virus in nasal specimens from vaccinated and unvaccinated participants. On average, vaccinated participants (infected with the highly transmissible Delta variant) showed a lower probability of having infectious virus after 5 days of symptoms compared to unvaccinated participants (infected with mostly pre-delta viral lineages), even though both groups had a similar magnitude of infectious virus at or near the peak. These data help improve our understanding of the duration of the infectious period when infection occurs following vaccination and serves as a reference for future studies of shedding dynamics following infections with novel variants of concern.

The 690,000 cases of cancer caused worldwide each year by HPV (human papillomavirus) are among the easiest of all cancers to prevent. However, the actions so far taken in terms of both policy and practice by health systems in many European states have neither matched the scale of the problem nor seized the opportunities for disease prevention potentially offered by vaccination and screening. Treatments for HPV-caused cancers are also inequitably provided across the region and widespread misinformation about HPV undermines efforts to improve public health. The European Cancer Organisation's HPV Action Network has made the case for action for the elimination of all the cancers caused by HPV through gender-neutral vaccination, effective cervical cancer screening, better quality treatments, and public and professional education across Europe. The World Health Organisation's new global strategy for the elimination of cervical cancer (launched in November 2020), together with Europe's Beating Cancer Plan (February 2021), together provide a major opportunity to tackle decisively all the cancers caused by HPV. The Beating Cancer Plan, which was significantly influenced by evidence provided by the HPV Action Network, commits to supporting EU member states' efforts to extend routine vaccination of girls and boys and to creating a new EU-supported Cancer Screening Scheme to help Member States ensure that 90% of the EU population who qualify for cervical cancer screening are offered it by 2025. The goal of HPV cancer elimination is now both possible and achievable. The challenge is to ensure implementation and delivery by EU member states and more widely across the European region.

As the fight against the coronavirus disease 2019 (COVID-19) pandemic continues, the necessity for wide-scale, global vaccine rollout to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and slow its mutation rate remains unassailable. The COVID-19 Vaccines Global Access (COVAX) initiative’s campaign involves a proportional framework to finance and distribute SARS-CoV-2 vaccines in low- and middle-income countries. However, the COVAX framework has critical limitations, including limited funding and the failure to account for the special epidemic risks and needs of its participating nations, as recommended by the World Health Organization’s Strategic Advisory Group of Experts on Immunization framework. These drawbacks disproportionately impact Africa, where many nations rely on COVAX as their main source of vaccines. The current plan to vaccinate only up to 20% of participating nations’ populations is short-sighted from both epidemiologic and moral perspectives. COVAX must commit to vaccinating all of Africa and its initiative must be modified to account for the health and economic infrastructures in these countries. Lessons learned from successful vaccination campaigns, including the West African Ebola outbreak, have shown that vaccinating all of Africa is possible and feasible, and that infrastructure and human resources can support mass vaccination. To halt this global pandemic, global responsibility must be accepted to finance and equitably distribute SARS-CoV-2 vaccines to African nations. We urge COVAX to act swiftly to prevent Africa from becoming the new face of a persisting pandemic.

Context Focal therapy has emerged as a promising option to treat well-selected men with localised prostate cancer while preserving healthy prostate tissue and key structures, such as the urethral sphincter and neurovascular bundles. However, how this tissue preservation may translate into improved outcomes, particularly into improved sexual outcomes, is still an active research field. Objective We conducted a systematic review and meta-analysis of the literature to summarise the existing evidence, in order to provide patients with updated data on what to expect after treatment and help identify gaps in current knowledge that may warrant future research. Evidence acquisition A systematic literature search was conducted on Medline, EMBASE, Scopus, and Web of Science. The search strategy was defined using the “litsearchr” function in R based on a preliminary “naive” search using the following terms on Medline: ((“focal therapy” OR “focal treatment”) AND (“prostate cancer”) AND (“sexual function” OR “erectile function”)). A total of 42 studies, comprising 3117 patients treated and 2352 with available sexual outcomes, were included in the qualitative data synthesis and 26 in a random-effect meta-analysis. Evidence synthesis The five-item International Index of Erectile Function (IIEF-5) was the most frequently used questionnaire (30/42 studies), with completion rates ranging from 24% to 100% at 18–24 mo. A decrease was noted at 3 mo (IIEF-5 decrease estimate −3.70 [95% confidence interval −4.43, −2.96]), with improvements at 6 mo (−2.18 [−2.91, −1.46]) and 12 mo (−2.14 [−2.96, −1.32]). Studies in which patients had an altered baseline sexual function were more likely to report a significant and durable postoperative decrease in erectile function scores. The patient-reported outcome questionnaires used were not designed for a diverse population. Functional outcomes were not the primary endpoint and have not been reported consistently in most studies considered. Conclusions Focal therapy led to changes in erectile function in most cases under the significance threshold of the patient-reported outcome questionnaires used. However, patients should be counselled according to their baseline erectile function. More research is warranted to detail aspects other than erectile function, such as ejaculation or orgasm. The early postoperative period appears key to study sexual changes after focal therapy, while only a moderate decrease is expected at 12 mo. Patient summary We reviewed the published literature detailing the sexual consequences of focal therapy for localised prostate cancer using patient-reported outcome questionnaires. Patients were likely to describe a significant decrease in their erectile function at 3 mo, with improvements noted at 6 and 12 mo. The results obtained may not be reproducible in a more diverse population, and further research is warranted to better study aspects other than erectile function, such as ejaculation or orgasm.