Navigating uncertain illness trajectories for young children with serious infectious illness: a mixed-methods modified grounded theory study

AbstractInfectious illness is the biggest cause of death in children due to a physical illness, particularly in children under five years. If mortality is to be reduced for this group of children, it is important to understand factors affecting their pathways to hospital.The aim of this study was to retrospectively identify organisational and environmental factors, and individual child, family, and professional factors affecting timing of admission to hospital for children under five years of age with a serious infectious illness (SII).MethodsAn explanatory modified grounded theory mixed methods design was used in collaboration with parents. Two stages of data collection were conducted: Stage 1, interviews with 22 parents whose child had recently been hospitalised with a SII and 14 health professionals (HPs) involved in their pre-admission trajectories; Stage 2, focus groups with 18 parents and 16 HPs with past experience of SII in young children. Constant comparative analysis generated the explanatory theory.FindingsThe core category was ‘navigating uncertain illness trajectories for young children with serious infectious illness’. Uncertainty was prevalent throughout the parents’ and HPs’ stories about their experiences of navigating social rules and overburdened health services for these children. The complexity of and lack of continuity within services, family lives, social expectations and hierarchies provided the context and conditions for children’s, often complex, illness trajectories. Parents reported powerlessness and perceived criticism leading to delayed help-seeking. Importantly, parents and professionals missed symptoms of serious illness. Risk averse services were found to refer more children to emergency departments.ConclusionsParents and professionals have difficulties recognising signs of SII in young children and can feel socially constrained from seeking help. The increased burden on services has made it more difficult for professionals to spot the seriously ill child.</jats:sec

Navigating uncertain illness trajectories for young children with serious infectious illness: a modified grounded theory study.

Background Infectious illness is the biggest cause of death in children due to a physical illness, particularly in children under five years. If mortality is to be reduced for this group of children, it is important to understand factors affecting their pathways to hospital. The aim of this study was to retrospectively identify organisational and environmental factors, and individual child, family, and professional factors affecting timing of admission to hospital for children under five years of age with a serious infectious illness (SII). Methods An explanatory modified grounded theory design was used in collaboration with parents. Two stages of data collection were conducted: Stage 1, interviews with 22 parents whose child had recently been hospitalised with a SII and 14 health professionals (HPs) involved in their pre-admission trajectories; Stage 2, focus groups with 18 parents and 16 HPs with past experience of SII in young children. Constant comparative analysis generated the explanatory theory

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Navigating uncertain illness trajectories for young children with serious infectious illness: a modified grounded theory study.

Files replaced (incorrect versions) on 12/8/2022 by KT (LDS).Background Infectious illness is the biggest cause of death in children due to a physical illness, particularly in children under five years. If mortality is to be reduced for this group of children, it is important to understand factors affecting their pathways to hospital. The aim of this study was to retrospectively identify organisational and environmental factors, and individual child, family, and professional factors affecting timing of admission to hospital for children under five years of age with a serious infectious illness (SII). Methods An explanatory modified grounded theory design was used in collaboration with parents. Two stages of data collection were conducted: Stage 1, interviews with 22 parents whose child had recently been hospitalised with a SII and 14 health professionals (HPs) involved in their pre-admission trajectories; Stage 2, focus groups with 18 parents and 16 HPs with past experience of SII in young children. Constant comparative analysis generated the explanatory theory. Results The core category was ‘navigating uncertain illness trajectories for young children with serious infectious illness’. Uncertainty was prevalent throughout the parents’ and HPs’ stories about their experiences of navigating social rules and overburdened health services for these children. The complexity of and lack of continuity within services, family lives, social expectations and hierarchies provided the context and conditions for children’s, often complex, illness trajectories. Parents reported powerlessness and perceived criticism leading to delayed help-seeking. Importantly, parents and professionals missed symptoms of serious illness. Risk averse services were found to refer more children to emergency departments. Conclusions Parents and professionals have difficulties recognising signs of SII in young children and can feel socially constrained from seeking help. The increased burden on services has made it more difficult for professionals to spot the seriously ill child

Impacts of AKST on development and sustainability goals

The International Assessment of Agricultural Knowledge, Science, and Technology for Development (IAASTD) looks realistically at how we could effectively use agriculture/AKST to help us meet development and sustainability goals. An unprecedented three-year collaborative effort, the IAASTD involved more than 400 authors in 110 countries and cost more than $11 million. It reports on the advances and setbacks of the past fifty years and offers options for the next fifty years. The results of the project are contained in seven reports: a Global Report, five regional Sub-Global Assessments, and a Synthesis Report. The Global Report gives the key findings of the Assessment, and the five Sub-Global Assessments address regional challenges. The volumes present options for action. All of the reports have been extensively peer-reviewed by governments and experts and all have been approved by a panel of participating governments. The Sub-Global Assessments all utilize a similar and consistent framework: examining and reporting on the impacts of AKST on hunger, poverty, nutrition, human health, and environmental/social sustainability. The IAASTD was initiated by the World Bank and the United Nations Food and Agricultural Organization, with support from the World Bank, the World Health Organization, and other sponsors. Its goal is to analyze the potential of agricultural knowledge, science, and technology (AKST) for reducing hunger and poverty, improving rural livelihoods, and working toward environmentally, socially, and economically sustainable development

Impacts of AKST on development and sustainability goals

The International Assessment of Agricultural Knowledge, Science, and Technology for Development (IAASTD) looks realistically at how we could effectively use agriculture/AKST to help us meet development and sustainability goals. An unprecedented three-year collaborative effort, the IAASTD involved more than 400 authors in 110 countries and cost more than $11 million. It reports on the advances and setbacks of the past fifty years and offers options for the next fifty years. The results of the project are contained in seven reports: a Global Report, five regional Sub-Global Assessments, and a Synthesis Report. The Global Report gives the key findings of the Assessment, and the five Sub-Global Assessments address regional challenges. The volumes present options for action. All of the reports have been extensively peer-reviewed by governments and experts and all have been approved by a panel of participating governments. The Sub-Global Assessments all utilize a similar and consistent framework: examining and reporting on the impacts of AKST on hunger, poverty, nutrition, human health, and environmental/social sustainability. The IAASTD was initiated by the World Bank and the United Nations Food and Agricultural Organization, with support from the World Bank, the World Health Organization, and other sponsors. Its goal is to analyze the potential of agricultural knowledge, science, and technology (AKST) for reducing hunger and poverty, improving rural livelihoods, and working toward environmentally, socially, and economically sustainable development

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc