COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Suicide prevention gatekeeper training in the Netherlands improves gatekeepers’ knowledge of suicide prevention and their confidence to discuss suicidality, an observational study

Abstract Background The gatekeeper training is designed to help identify suicidal individuals, respond to suicidal ideation and refer to help. The internationally widely used training shows promising results. This is the first study presenting its effectiveness in the Netherlands and the first study investigating the effect in different employment sectors. Methods In an observational study, 113 Suicide Prevention – the Dutch suicide prevention expertise centre and lifeline - trained 526 professionals as gatekeepers. Changes in gatekeepers’ identifying and referral behaviour, knowledge of suicide prevention and skills-confidence were studied, using a pre-post (6 weeks after training) self-report questionnaire. Outcomes were analyzed with General Linear Model (GLM) repeated measures with four employment sectors (healthcare-, educational-, socioeconomic and other sectors) as a between-subjects factor. Results Pre-post self-reports of 174 respondents showed no change in the identification of suicidal people, referrals to the general practitioner (GP) or lifeline 113, but significant improvement in professionals’ knowledge and confidence (p < .001). Results did not differ between employment sectors. Conclusions The gatekeeper training significantly increases suicide prevention knowledge and skills confidence in abilities to address suicidality. Healthcare, education, socioeconomic and other professionals (e.g. security, justice, transport, church workers) benefit similarly from the training. Increasing the number of gatekeeper training programs in all sectors is recommended

Additional file 1: of Suicide prevention gatekeeper training in the Netherlands improves gatekeepers’ knowledge of suicide prevention and their confidence to discuss suicidality, an observational study

Questionnaire Gatekeeper training. Data identifies people at risk of suicide, referral to GP, referral to 113 Suicide Prevention, knowledge and confidence. Personal data of participants and ordinal data on a 5 point scale. (DOCX 15 kb

Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis

Escherichia (E.) coli is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in cytotoxicity and, more recently, in the inflammatory response. We here sought to investigate the role of gzms in the host response to E. coli-induced peritonitis and sepsis in vivo. For this purpose, we used a murine model of E. coli intraperitoneal infection, resembling the clinical condition commonly associated with septic peritonitis by this bacterium, in wild-type and gzmA-deficient (gzmA(-/-) ), gzmB(-/-) , and gzmAxB(-/-) mice. GzmA and gzmB were predominantly expressed by natural killer cells, and during abdominal sepsis, the percentage of these cells expressing gzms in peritoneal lavage fluid decreased, while the amount of expression in the gzm(+) cells increased. Deficiency of gzmA and/or gzmB was associated with increased bacterial loads, especially in the case of gzmB at the primary site of infection at late stage sepsis. While gzm deficiency did not impact neutrophil recruitment into the abdominal cavity, it was accompanied by enhanced nucleosome release at the primary site of infection, earlier hepatic necrosis, and more renal dysfunction. These results suggest that gzms influence bacterial growth and the host inflammatory response during abdominal sepsis caused by E. col

Improving suicide prevention in dutch regions by creating local suicide prevention action networks (SUPRANET): A study protocol

The European Alliance against Depression (EAAD) program is to be introduced in The Netherlands from 2017 onwards. This program to combat suicide consists of interventions on four levels: (1) increasing the awareness of suicide by local media campaigns; (2) training local gatekeepers, such as teachers or police officers; (3) targeting high-risk persons in the community; and (4) training and support of professionals in primary care settings. The implementation starts in seven Dutch pilot regions. Each region is designated as a Suicide Prevention Action NETwork (SUPRANET). This paper describes the SUPRANET program components and the evaluation of its feasibility and impact. The findings will be used to facilitate the national implementation of EAAD in The Netherlands and to add new findings to the existing literature on EAAD

ASC and NLRP3 impair host defense during lethal pneumonia caused by serotype 3 Streptococcus pneumoniae in mice

Streptococcus (S.) pneumoniae is the most common cause of community-acquired pneumonia. The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, consisting of NLRP3, ASC (the adaptor apoptosis-associated speck-like protein containing a CARD) and caspase-1, has been implicated in protective immunity during pneumonia induced by high doses of S. pneumoniae serotype 2. Here we investigated the role of the NLRP3 inflammasome in the host response during lethal airway infection with a low dose of serotype 3 S. pneumoniae. Mice were euthanized at predefined endpoints for analysis or observed in survival studies. In additional studies, Tlr2(-/-)/Tlr4(-/-) mice and Myd88(-/-) mice incapable of Toll-like receptor signaling were studied. In stark contrast with existing literature, both Nlrp3(-/-) and Asc(-/-) mice showed a strongly improved host defense, as reflected by a markedly reduced mortality rate accompanied by diminished bacterial growth and dissemination. Host defense was unaltered in Tlr2(-/-)/Tlr4(-/-) mice and Myd88(-/-) mice. These results show that the NLRP3 inflammasome impairs host defense during lethal pneumonia caused by serotype 3 S. pneumoniae. Our findings challenge the current paradigm that proximal innate detection systems are indispensable for an adequate host immune response against bacteri

ASC and NLRP3 impair host defense during lethal pneumonia caused by serotype 3 Streptococcus pneumoniae in mice

Streptococcus (S.) pneumoniae is the most common cause of community-acquired pneumonia. The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, consisting of NLRP3, ASC (the adaptor apoptosis-associated speck-like protein containing a CARD) and caspase-1, has been implicated in protective immunity during pneumonia induced by high doses of S. pneumoniae serotype 2. Here we investigated the role of the NLRP3 inflammasome in the host response during lethal airway infection with a low dose of serotype 3 S. pneumoniae. Mice were euthanized at predefined endpoints for analysis or observed in survival studies. In additional studies, Tlr2(-/-)/Tlr4(-/-) mice and Myd88(-/-) mice incapable of Toll-like receptor signaling were studied. In stark contrast with existing literature, both Nlrp3(-/-) and Asc(-/-) mice showed a strongly improved host defense, as reflected by a markedly reduced mortality rate accompanied by diminished bacterial growth and dissemination. Host defense was unaltered in Tlr2(-/-)/Tlr4(-/-) mice and Myd88(-/-) mice. These results show that the NLRP3 inflammasome impairs host defense during lethal pneumonia caused by serotype 3 S. pneumoniae. Our findings challenge the current paradigm that proximal innate detection systems are indispensable for an adequate host immune response against bacteri