PASQUALE - A long-term partnership to improve hand hygiene and capacity building in infection prevention and control in the Faranah region of Guinea.

Across the globe, hand hygiene (HH) is promoted to fight the spread of healthcare associated infections. Despite multiple ongoing HH campaigns and projects, the healthcare associated infection rates remain high especially in low- and middle-income countries. In the narrative overview presented here, we aim to share objectives, framework, successes and challenges of our long-term partnership in Guinea to offer guidance for other projects aiming to sustainably improve HH.

Whole blood stimulation as a tool for studying the human immune system.

The human immune system is best accessible via tissues and organs not requiring major surgical intervention, such as blood. In many circumstances, circulating immune cells correlate with an individual's health state and give insight into physiological and pathophysiological processes. Stimulating whole blood ex vivo is a powerful tool to investigate immune responses. In the context of clinical research, the applications of whole blood stimulation include host immunity, disease characterization, diagnosis, treatment, and drug development. Here, we summarize different setups and readouts of whole blood assays and discuss applications for preclinical research and clinical practice. Finally, we propose combining whole blood stimulation with high-throughput technologies, such as single-cell RNA-sequencing, to comprehensively analyze the human immune system for the identification of biomarkers, therapeutic interventions as well as companion diagnostics.

What should be done to combat misinformation about health products?

The increasing role of digital technology, social media, the wide range of channels and the volume of information, the role of medicine as a societal subject, public information that is insufficient and poorly suited to situations of uncertainty are all observations which led to the theme of this round table. After discussing the definition of disinformation, which is not limited to fake news, and talking about contributors who misinform, whether intentionally or not, the participants of this round table made nine recommendations (R) to combat disinformation about health products: create a collaborative platform, information/training on health products, a platform with five major characteristics, namely accessibility, flexibility, objectivity, transparency and independence, as well as media suited to the different targets (R1); promote basic knowledge on health products: education/training to restore the particularly poor image of medication, and teach the public how to use basic concepts appropriately (R2); improve communication to the public based on the observation that information is the main weapon against misinformation and entails, in particular, coordinating communication from the different institutions to make public information more audible, making institutional messages clearer, ensuring they are more factual and prioritising them (R3); know how to communicate using the correct codes and tools (R4), because, to be understood, the substance and the form are inseparable; develop research on communication in the field of health products (R5); acquire tools to identify and regulate as soon as possible (R6); keep check of content by developing critical thinking (R7); define quality criteria for information sources (R8); identify, assess and reference initiatives for the public that could be placed on the platform (R9).

Prevalence and risk factors for long COVID and post-COVID-19 condition in Africa: a systematic review.

BACKGROUND: An improved estimation of the clinical sequelae of SARS-CoV-2 infection is crucial in African countries, where the subject has received little attention despite more than 12 million reported cases and evidence that many more people were infected. We reviewed the evidence on prevalence, associated risk factors for long COVID, and systemic or sociocultural determinants of reporting long COVID. METHODS: We conducted a systematic review, searching PubMed, the Living OVerview of Evidence platform, and grey literature sources for publications from Dec 1, 2019, to Nov 23, 2022. We included articles published in English, French, Spanish, or Portuguese that reported on any study type in Africa with participants of any age who had symptoms for 4 weeks or more after an acute SARS-CoV-2 infection. We excluded secondary research, comments, and correspondence. Screening and data extraction were performed by two reviewers. Summary estimates were extracted, including sociodemographic factors, medical history, prevalence of persistent symptoms, and symptoms and associated factors. Results were analysed descriptively. The study was registered on the Open Science Framework platform. FINDINGS: Our search yielded 294 articles, of which 24 peer-reviewed manuscripts were included, reporting on 9712 patients from eight African countries. Only one study exclusively recruited children, and one other study included children as part of their study population. Studies indicated moderate to low risk of bias. Prevalence of long COVID varied widely, from 2% in Ghana to 86% in Egypt. Long COVID was positively associated with female sex, older age, non-Black ethnicity, low level of education, and the severity of acute infection and underlying comorbidity. HIV and tuberculosis were not identified as risk factors. Factors influencing reporting included absence of awareness, inadequate clinical data and diagnostics, and little access to health-care services. INTERPRETATION: In Africa, research on long COVID is scarce, particularly among children, who represent the majority of the population. However, existing studies show a substantial prevalence across settings, emphasising the importance of vaccination and other prevention strategies to avert the effects of long COVID on individual wellbeing, the increased strain on health systems, and the potential negative effects on economically vulnerable populations. At a global level, including African countries, tools for research on long COVID need to be harmonised to maximise the usefulness of the data collected. FUNDING: None.

Systems analysis of human innate immunity in COVID-19.

Recent developments in sequencing technologies, the computer and data sciences, as well as increasingly high-throughput immunological measurements have made it possible to derive holistic views on pathophysiological processes of disease and treatment effects directly in humans. We and others have illustrated that incredibly predictive data for immune cell function can be generated by single cell multi-omics (SCMO) technologies and that these technologies are perfectly suited to dissect pathophysiological processes in a new disease such as COVID-19, triggered by SARS-CoV-2 infection. Systems level interrogation not only revealed the different disease endotypes, highlighted the differential dynamics in context of disease severity, and pointed towards global immune deviation across the different arms of the immune system, but was already instrumental to better define long COVID phenotypes, suggest promising biomarkers for disease and therapy outcome predictions and explains treatment responses for the widely used corticosteroids. As we identified SCMO to be the most informative technologies in the vest to better understand COVID-19, we propose to routinely include such single cell level analysis in all future clinical trials and cohorts addressing diseases with an immunological component.

Qualitative assessment of hand hygiene knowledge, attitudes and practices among healthcare workers prior to the implementation of the WHO Hand Hygiene Improvement Strategy at Faranah Regional Hospital, Guinea.

Healthcare-associated infections are a serious burden globally. Few qualitative studies have explored healthcare workers' knowledge, attitudes and practices of hand hygiene. Prior to the implementation of the World Health Organization's Hand Hygiene Improvement Strategy at Faranah Regional Hospital in the Upper Region of Guinea in December 2018, we conducted a qualitative baseline assessment of knowledge, attitudes and practices of hand hygiene among healthcare workers to guide future hand hygiene interventions. The qualitative study consisted of direct observations, In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs). We found that the 2013-16 Ebola outbreak had had a pivotal impact on healthcare workers' knowledge, attitudes and practices. The severity of the disease and the training provided for infection control were responsible for their knowledge acquisition and adoption of good attitudes and practices. However, negligence, resulting in poor hand hygiene practices, rose after the outbreak, once the "cue of fear" that had motivated workers for their own self-protection had waned. Our results suggest that local capacity building through training and availability of hand hygiene materials would be a sustainable approach to enhance hand hygiene culture at the hospital. Our study suggests that there is a need for a high and long-term commitment of authorities and healthcare workers at all levels for a sustainable hand hygiene culture.

Comparative effectiveness of contact tracing interventions in the context of the COVID-19 pandemic: a systematic review.

Contact tracing is a non-pharmaceutical intervention (NPI) widely used in the control of the COVID-19 pandemic. Its effectiveness may depend on a number of factors including the proportion of contacts traced, delays in tracing, the mode of contact tracing (e.g. forward, backward or bidirectional contact training), the types of contacts who are traced (e.g. contacts of index cases or contacts of contacts of index cases), or the setting where contacts are traced (e.g. the household or the workplace). We performed a systematic review of the evidence regarding the comparative effectiveness of contact tracing interventions. 78 studies were included in the review, 12 observational (ten ecological studies, one retrospective cohort study and one pre-post study with two patient cohorts) and 66 mathematical modelling studies. Based on the results from six of the 12 observational studies, contact tracing can be effective at controlling COVID-19. Two high quality ecological studies showed the incremental effectiveness of adding digital contact tracing to manual contact tracing. One ecological study of intermediate quality showed that increases in contact tracing were associated with a drop in COVID-19 mortality, and a pre-post study of acceptable quality showed that prompt contact tracing of contacts of COVID-19 case clusters / symptomatic individuals led to a reduction in the reproduction number R. Within the seven observational studies exploring the effectiveness of contact tracing in the context of the implementation of other non-pharmaceutical interventions, contact tracing was found to have an effect on COVID-19 epidemic control in two studies and not in the remaining five studies. However, a limitation in many of these studies is the lack of description of the extent of implementation of contact tracing interventions. Based on the results from the mathematical modelling studies, we identified the following highly effective policies: (1) manual contact tracing with high tracing coverage and either medium-term immunity, highly efficacious isolation/quarantine and/ or physical distancing (2) hybrid manual and digital contact tracing with high app adoption with highly effective isolation/ quarantine and social distancing, (3) secondary contact tracing, (4) eliminating contact tracing delays, (5) bidirectional contact tracing, (6) contact tracing with high coverage in reopening educational institutions. We also highlighted the role of social distancing to enhance the effectiveness of some of these interventions in the context of 2020 lockdown reopening. While limited, the evidence from observational studies shows a role for manual and digital contact tracing in controlling the COVID-19 epidemic. More empirical studies accounting for the extent of contact tracing implementation are required.

Epigenetic regulation of T cell lineages in skin and blood following hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem-cell transplantation (HSCT) seeks to reconstitute the host's immune system from donor stem cells. The success of HSCT is threatened by complications including leukemia relapse or graft-versus-host-disease (GvHD). To investigate the underlying regulatory processes in central and peripheral T cell recovery, we performed sequential multi-omics analysis of T cells of the skin and blood during HSCT. We detected rapid effector T cell reconstitution, while emergence of regulatory T cells was delayed. Epigenetic and gene-regulatory programs were associated with recovering T cells and diverged greatly between skin and blood T cells. The BRG1/BRM-associated factor chromatin remodeling complex and histone deacetylases (HDACs) were epigenetic regulators involved in restoration of T cell homeostasis after transplantation. In isolated T cells of patients after HSCT, we observed class I HDAC-inhibitors to modulate their dysbalance. The present study highlights the importance of epigenetic regulation in the recovery of T cells following HSCT.

Tick feeding modulates the human skin immune landscape to facilitate tick-borne pathogen transmission.

During cutaneous tick attachment, the feeding cavity becomes a site of transmission for tick salivary compounds and tick-borne pathogens. However, the immunological consequences of tick feeding for human skin remain unclear. Here, we assessed human skin and blood samples upon tick bite and developed a human skin explant model mimicking Ixodes ricinus bites and tick-borne pathogen infection. Following tick attachment, we observed rapidly occurring patterns of immunomodulation, including increases in neutrophils and cutaneous B and T cells. T cells upregulated tissue residency markers, while lymphocytic cytokine production was impaired. In early stages of Borrelia burgdorferi model infections, we detected strain-specific immune responses and close spatial relationships between macrophages and spirochetes. Preincubation of spirochetes with tick salivary gland extracts hampered accumulation of immune cells and increased spirochete loads. Collectively, we showed that tick feeding exerts profound changes on the skin immune network that interfere with the primary response against tick-borne pathogens.

Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway.

BACKGROUND: Maintaining energy homeostasis is vital and supported by vagal signaling between digestive organs and the brain. Previous research has established a gastric network in the brain that is phase synchronized with the rhythm of the stomach, but tools to perturb its function were lacking. OBJECTIVE: To evaluate whether stomach-brain coupling can be acutely increased by non-invasively stimulating vagal afferent projections to the brain. METHODS: Using a single-blind randomized crossover design, we investigated the effect of acute right-sided transcutaneous auricular vagus nerve stimulation (taVNS) versus sham stimulation on stomach-brain coupling. RESULTS: In line with preclinical research, taVNS increased stomach-brain coupling in the nucleus of the solitary tract (NTS) and the midbrain while boosting coupling across the brain. Crucially, in the cortex, taVNS-induced changes in coupling occurred primarily in transmodal regions and were associated with changes in hunger ratings as indicators of the subjective metabolic state. CONCLUSIONS: taVNS increases stomach-brain coupling via an NTS-midbrain pathway that signals gut-induced reward, indicating that communication between the brain and the body is effectively modulated by vago-vagal signaling. Such insights may help us better understand the role of vagal afferents in orchestrating the recruitment of the gastric network which could pave the way for novel neuromodulatory treatments.

Low-grade mucinous neoplasms (LAMN) of the appendix in Germany between 2011 and 2018: a nationwide analysis based on data provided by the German Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI).

INTRODUCTION: Low-grade appendiceal mucinous neoplasms (LAMN) are semi-malignant tumors of the appendix which are incidentally found in up to 1% of appendectomy specimen. To this day, no valid descriptive analysis on LAMN is available for the German population. METHODS: Data of LAMN (ICD-10: D37.3) were collected from the population-based cancer registries in Germany, provided by the German Center for Cancer Registry Data (Zentrum für Krebsregisterdaten-ZfKD). Data was anonymized and included gender, age at diagnosis, tumor staging according to the TNM-classification, state of residence, information on the performed therapy, and survival data. RESULTS: A total of 612 cases were reported to the ZfKD between 2011 and 2018. A total of 63.07% were female and 36.93% were male. Great inhomogeneity in reporting cases was seen in the federal states of Germany including the fact that some federal states did not report any cases at all. Age distribution showed a mean age of 62.03 years (SD 16.15) at diagnosis. However, data on tumor stage was only available in 24.86% of cases (n = 152). A total of 49.34% of these patients presented with a T4-stage. Likewise, information regarding performed therapy was available in the minority of patients: 269 patients received surgery, 22 did not and for 312 cases no information was available. Twenty-four patients received chemotherapy, 188 did not, and for 400 cases, no information was available. Overall 5-year survival was estimated at 79.52%. Patients below the age of 55 years at time of diagnosis had a significantly higher 5-year survival rate compared to patients above the age of 55 years (85.77% vs. 73.27%). DISCUSSION: In this study, we observed an incidence of LAMN in 0.13% of all appendectomy specimen in 2018. It seems likely that not all cases were reported to the ZfKD; therefore, case numbers may be considered underestimated. Age and gender distribution goes in line with international studies with females being predominantly affected. Especially regarding tumor stage and therapy in depth information cannot be provided through the ZfKD-database. This data analysis emphasizes the need for further studies and the need for setting up a specialized registry for this unique tumor entity to develop guidelines for the appropriate treatment and follow-up.

Association between women's authorship and women's editorship in infectious diseases journals: a cross-sectional study.

BACKGROUND: Gender inequity is still pervasive in academic medicine, including journal publishing. We aimed to ascertain the proportion of women among first and last authors and editors in infectious diseases journals and assess the association between women's editorship and women's authorship while controlling for a journal's impact factor. METHODS: In this cross-sectional study, we randomly selected 40 infectious diseases journals (ten from each 2020 impact factor quartile), 20 obstetrics and gynaecology journals (five from each 2020 impact factor quartile), and 20 cardiology journals (five from each 2020 impact factor quartile) that were indexed in Journal Citation Reports, had an impact factor, had retrievable first and last author names, and had the name of more than one editor listed. We retrieved the names of the first and last authors of all citable articles published by the journals in 2018 and 2019 that counted towards their 2020 impact factor and collected the names of all the journals' editors-in-chief, deputy editors, section editors, and associate editors for the years 2018 and 2019. We used genderize.io to predict the gender of each first author, last author, and editor. The outcomes of interest were the proportions of women first authors and women last authors. We assessed the association between women's editorship and women's authorship by fitting quasi-Poisson regression models comprising the variables: the proportion of women last authors or women first authors; the proportion of women editors; the presence of a woman editor-in-chief; and journal 2020 impact factor. FINDINGS: We found 11 027 citable infectious diseases articles, of which 167 (1·5%) had an indeterminable first author gender, 155 (1·4%) had an indeterminable last author gender, and seven (0·1%) had no authors indexed. 5350 (49·3%) of 10 853 first authors whose gender could be determined were predicted to be women and 5503 (50·7%) were predicted to be men. Women accounted for 3788 (34·9%) of 10 865 last authors whose gender could be determined and men accounted for 7077 (65·1%). Of 577 infectious diseases journal editors, 190 (32·9%) were predicted to be women and 387 (67·1%) were predicted to be men. Of the 40 infectious diseases journals, 13 (32·5%) had a woman as editor-in-chief. For infectious diseases journals, the proportion of women editors had a significant effect on women's first authorship (incidence rate ratio 1·32, 95% CI 1·06-1·63; p=0·012) and women's last authorship (1·92, 1·45-2·55; p<0·0001). The presence of a woman editor-in-chief, the proportion of women last or first authors, and the journal's impact factor exerted no effect in these analyses. INTERPRETATION: The proportion of women editors appears to influence the proportion of women last and first authors in the analysed infectious diseases journals. These findings might help to explain gender disparities observed in publishing in academic medicine and suggest a need for revised policies towards increasing women's representation among editors. FUNDING: The European Society of Clinical Microbiology and Infectious Diseases.

Is the World Health Organization Multimodal Hand Hygiene Improvement Strategy applicable and effective at the primary care level in resource-limited settings? A quantitative assessment in healthcare centers of Faranah, Guinea.

Background: The World Health Organization Multimodal Hand Hygiene Improvement Strategy aims at reducing healthcare-associated infections; however, evidence of applicability and effectiveness at the primary care level is scarce, especially in healthcare centers in resource-limited settings. The objectives of this study were to improve hand hygiene knowledge and compliance at two healthcare centers in the region of Faranah, Guinea, to increase the availability of alcohol-based hand rub (ABHR), and to assess the effectiveness of the strategy at the primary care level. Methods: Knowledge, perceptions, and compliance were assessed prior to the intervention and compared to those of two follow-up assessments, immediately and 6 months after the intervention. The intervention consisted of training and the supply of ABHR. The monthly consumption of ABHR was monitored. Results: Baseline knowledge increased from a score of 11/25 at baseline to 16/25 at first follow-up; it then decreased to 15/25 at the second follow-up. Compliance showed an increase from 15.6% to 84.4% (P < 0.001) at the first follow-up. At the second follow-up, compliance was lower than at the first follow-up (53.2%, P < 0.001), but still more than two times higher than at baseline (P < 0.001). ABHR consumption averaged 0.77 ml per consultation. Conclusions: The World Health Organization hand hygiene strategy is an appropriate method to improve compliance and knowledge at the primary care level, but needs some adjustment: the inclusion of observation of the correctness of hand hygiene action, as well as training emphasizing the amount of ABHR to use.

Surgical Site Infection Following Single-Port Appendectomy: A Systematic Review of the Literature and Meta-Analysis.

Introduction: Surgical site infections (SSIs) are one of the most common postoperative complications after appendectomy leading to recurrent surgery, prolonged hospital stay, and the use of antibiotics. Numerous studies and meta-analyses have been published on the effect of open versus conventional laparoscopic appendectomy (CLA) reporting faster postoperative recovery and less postoperative pain for CLA. A development from CLA has been the single-port appendectomy (SPA), associated with a better cosmesis but seemingly having a higher risk of wound infections. The aim of this systematic literature review and meta-analysis is to investigate whether reduced port or SPA alters the ratio of SSIs. Methods: Pubmed, Embase, and Cochrane databases were screened for suitable articles. All articles published between January 1, 2002, and March 23, 2022, were included. Articles regarding children below the age of 18 were excluded as well as manuscripts that investigated solemnly open appendectomies. Articles were screened for inclusion criteria by two independent authors. Incidence of SSI was the primary outcome. Duration of operation and length of hospital stay were defined as secondary outcomes. Results: A total of 25 studies were found through a database search describing 5484 patients. A total of 2749 patients received SPA and 2735 received CLA. There was no statistical difference in the rate of SSI (P = 0.98). A total of 22 studies including 4699 patients reported the duration of operation (2223 SPA and 2476 CLA). There was a significantly shorter operation time seen in CLA. The length of hospital stay was reported in 23 studies (4735 patients: 2235 SPA and 2500 CLA). A shorter hospital stay was seen in the SPA group (P < 0.00001). Separately performed analysis of randomized controlled trials could not confirm this effect (P = 0.29). Discussion: SPA is an equally safe procedure considering SSI compared to CLA and does not lead to an increased risk of SSI. A longer operation time for SPA and a minor difference in the length of stay does lead to the use of SPA in selected patients only.

Effectiveness and sustainability of the WHO multimodal hand hygiene improvement strategy in the University Hospital Bouaké, Republic of Côte d'Ivoire in the context of the COVID-19 pandemic.

INTRODUCTION: The most frequent adverse events in healthcare are healthcare-associated infections, whose burden is highest in resource-limited settings. In addition, low resource settings often lack Hand Hygiene (HH) knowledge and reliable supply to disinfectant, a necessity emphasized by the past West African Ebola Epidemic and the ongoing COVID-19 pandemic. PASQUALE aims to increase patient safety by introducing the WHO multimodal HH strategy in the University Hospital Bouaké, Côte d'Ivoire. METHODS: Assessment of HH knowledge, perception and compliance was performed 12 months before, right after the intervention and at a ten months interval using questionnaires for knowledge and perception and direct observation for compliance. The intervention consisted of a HH training and the introduction of local production of alcohol-based hand-rub. In the absence of a control group, the effectiveness of the intervention was assessed by a before-and-after study. RESULTS: Baseline knowledge score was 14/25, increased significantly to 17/25 (p < 0.001) upon first and decreased to 13/25 in second follow-up. Compliance showed a significant increase from 12.7% to 36.8% (p < 0.001) in first and remained at 36.4% in second follow-up. Alcohol-based hand-rub production and consumption almost doubled after first confirmed COVID-19 case in Côte d'Ivoire. CONCLUSION: The WHO HH improvement strategy is an effective and pandemic-adaptable method to increase long-term HH compliance. This study emphasizes that the implementation of the strategy to build a robust system is of utmost importance.

[Temporal sequence of bile duct clearance with simultaneous cholecystolithiasis or choledocholithiasis-Preoperative, intraoperative or postoperative?] / Zeitliche Sequenz der Gallengangssanierung bei simultaner Cholezystocholedocholithiasis ­ prä-, intra- oder postoperativ?

Approximately 10% of patients with symptomatic cholecystolithiasis also have choledocholithiasis. The probability of this can be estimated on the basis of sonographic and laboratory chemistry parameters. If the probability is high, endoscopic retrograde cholangiography (ERC) or cholangiopancreatography (ERCP) should be performed and if the probability is low, cholecystectomy can be performed without further diagnostics. If the findings are equivocal, further work-up should be performed to detect or exclude choledocholithiasis by endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP). If choledocholithiasis is detected, it can be treated by ERC preoperatively, intraoperatively or postoperatively or alternatively by laparoscopic cholangiography. Regarding the temporal sequence, there is no clear advantage of a specific time point; however, considering the high availability of ERCP in German-speaking countries, preoperative clearance of choledocholithiasis seems reasonable. With respect to the time interval between clearance of choledocholithiasis and cholecystectomy, a number of multicenter studies and a meta-analysis have shown that a short time interval or a procedure during the same period of hospitalization is advantageous.

Prevention of risks associated with inappropriate use/unnecessary consumption of medicines.

In the code of public health, misuse is defined as intentional and inappropriate use of a medicine or product, which is not in accordance with the terms of the marketing authorisation or the registration as well as with good practice recommendations. Very often this involves an individual or the interaction of several individuals including the patient, his/her carers, prescriber(s) and/or dispensers. Misuse is common; it is the source of medicinal adverse effects for which a significant part is avoidable. Medicines initially prescribed or dispensed in the context of their marketing authorization (MA) can also be the subject of primary dependency and misappropriation. Companies which develop medicines nationally make declarations to the ANSM (French National Agency for the Safety of Medicines and Health Products) and implement measures to limit non-compliant use of their products. Recently, the coronavirus disease-2019 (COVID-19) pandemic has highlighted the influence and societal impact of drug misuse. The finding of the existence of systemic misuse, the impossibility of proposing simple solutions leads us to propose two main areas for improved information and the training of users and health professionals in medicines in the context of multi-faceted interventions: prevention of misuse on the one hand and its identification and treatment on the other hand.