Perceptions of parents on satisfaction with care in the pediatric intensive care unit: the EMPATHIC study

Abstract: PURPOSE: To identify parental perceptions on pediatric intensive care-related satisfaction items within the framework of developing a Dutch pediatric intensive care unit (PICU) satisfaction instrument. METHODS: Prospective cohort study in tertiary PICUs at seven university medical centers in The Netherlands. PARTICIPANTS: Parents of 1,042 children discharged from a PICU. RESULTS: A 78-item questionnaire was sent to 1,042 parents and completed by 559 (54%). Seventeen satisfaction items were rated with mean scores or =1.65, and thus considered of limited value. The empirical structure of the items was in agreement with the theoretically formulated domains: Information, Care a

Filarial Lymphedema Is Characterized by Antigen- Specific Th1 and Th17 Proinflammatory Responses and a Lack of Regulatory T Cells

Background: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Methods and Findings: To elucidate the role of CD4+ T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1–10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines—IFN-c and TNF-a—in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines—IL-17A, IL-17F, IL-21, and IL-23—was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFb, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls. Conclusion: Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema

Biochemical Properties of a Novel Cysteine Protease of Plasmodium vivax, Vivapain-4

Plasmodium vivax affects hundreds of millions each year and results in severe morbidity and mortality. Plasmodial cysteine proteases (CPs) play crucial roles during the progression of malaria since inhibition of these molecules impairs parasite growth. These CPs might be targeted for new antimalarial drugs. We characterized a novel P. vivax CP, vivapain-4 (VX-4), which appeared to evolve differentially among primate Plasmodium species. VX-4 showed highly unique substrate preference depending on surrounding micro-environmental pH. It effectively hydrolyzed benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA) and Z-Phe-Arg-MCA at acidic pH and Z-Arg-Arg-MCA at neutral pH. Three amino acids (Ala90, Gly157 and Glu180) that delineate the S2 pocket were found to be substituted in VX-4. Alteration of Glu180 abolished hydrolytic activity against Z-Arg-Arg-MCA at neutral pH, indicating Glu180 is intimately involved in the pH-dependent substrate preference. VX-4 hydrolyzed actin at neutral pH and hemoglobin at acidic pH, and participated in plasmepsin 4 activation at neutral/acidic pH. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of P. vivax. The differential substrate preferences depending on pH suggested a highly efficient mechanism to enlarge biological implications of VX-4, including hemoglobin degradation, maturation of plasmepsin, and remodeling of the parasite architecture during growth and development of P. vivax

Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO) : 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group

Background: Adhesive small bowel obstruction (ASBO) is a common surgical emergency, causing high morbidity and even some mortality. The adhesions causing such bowel obstructions are typically the footprints of previous abdominal surgical procedures. The present paper presents a revised version of the Bologna guidelines to evidence-based diagnosis and treatment of ASBO. The working group has added paragraphs on prevention of ASBO and special patient groups. Methods: The guideline was written under the auspices of the World Society of Emergency Surgery by the ASBO working group. A systematic literature search was performed prior to the update of the guidelines to identify relevant new papers on epidemiology, diagnosis, and treatment of ASBO. Literature was critically appraised according to an evidence-based guideline development method. Final recommendations were approved by the workgroup, taking into account the level of evidence of the conclusion. Recommendations: Adhesion formation might be reduced by minimally invasive surgical techniques and the use of adhesion barriers. Non-operative treatment is effective in most patients with ASBO. Contraindications for non-operative treatment include peritonitis, strangulation, and ischemia. When the adhesive etiology of obstruction is unsure, or when contraindications for non-operative management might be present, CT is the diagnostic technique of choice. The principles of non-operative treatment are nil per os, naso-gastric, or long-tube decompression, and intravenous supplementation with fluids and electrolytes. When operative treatment is required, a laparoscopic approach may be beneficial for selected cases of simple ASBO. Younger patients have a higher lifetime risk for recurrent ASBO and might therefore benefit from application of adhesion barriers as both primary and secondary prevention. Discussion: This guideline presents recommendations that can be used by surgeons who treat patients with ASBO. Scientific evidence for some aspects of ASBO management is scarce, in particular aspects relating to special patient groups. Results of a randomized trial of laparoscopic versus open surgery for ASBO are awaited.Peer reviewe

Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study

Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018. Methods: We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries. Findings: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1–190·6), 10·1 million influenza-virus-associated ALRI cases (6·8–15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000–1 415 000), 15 300 in-hospital deaths (5800–43 800), and up to 34 800 (13 200–97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries. Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries. Funding: WHO; Bill & Melinda Gates Foundation.Fil: Wang, Xin. University of Edinburgh; Reino UnidoFil: Li, You. University of Edinburgh; Reino UnidoFil: O'Brien, Katherine L.. University Johns Hopkins; Estados UnidosFil: Madhi, Shabir A.. University of the Witwatersrand; SudáfricaFil: Widdowson, Marc Alain. Centers for Disease Control and Prevention; Estados UnidosFil: Byass, Peter. Umea University; SueciaFil: Omer, Saad B.. Yale School Of Public Health; Estados UnidosFil: Abbas, Qalab. Aga Khan University; PakistánFil: Ali, Asad. Aga Khan University; PakistánFil: Amu, Alberta. Dodowa Health Research Centre; GhanaFil: Azziz-Baumgartner, Eduardo. Centers for Disease Control and Prevention; Estados UnidosFil: Bassat, Quique. University Of Barcelona; EspañaFil: Abdullah Brooks, W.. University Johns Hopkins; Estados UnidosFil: Chaves, Sandra S.. Centers for Disease Control and Prevention; Estados UnidosFil: Chung, Alexandria. University of Edinburgh; Reino UnidoFil: Cohen, Cheryl. National Institute For Communicable Diseases; SudáfricaFil: Echavarría, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Fasce, Rodrigo A.. Public Health Institute; ChileFil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gordon, Aubree. University of Michigan; Estados UnidosFil: Groome, Michelle. University of the Witwatersrand; SudáfricaFil: Heikkinen, Terho. University Of Turku; FinlandiaFil: Hirve, Siddhivinayak. Kem Hospital Research Centre; IndiaFil: Jara, Jorge H.. Universidad del Valle de Guatemala; GuatemalaFil: Katz, Mark A.. Clalit Research Institute; IsraelFil: Khuri Bulos, Najwa. University Of Jordan School Of Medicine; JordaniaFil: Krishnan, Anand. All India Institute Of Medical Sciences; IndiaFil: de Leon, Oscar. Universidad del Valle de Guatemala; GuatemalaFil: Lucero, Marilla G.. Research Institute For Tropical Medicine; FilipinasFil: McCracken, John P.. Universidad del Valle de Guatemala; GuatemalaFil: Mira-Iglesias, Ainara. Fundación Para El Fomento de la Investigación Sanitaria; EspañaFil: Moïsi, Jennifer C.. Agence de Médecine Préventive; FranciaFil: Munywoki, Patrick K.. No especifíca;Fil: Ourohiré, Millogo. No especifíca;Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rahi, Manveer. University of Edinburgh; Reino UnidoFil: Rasmussen, Zeba A.. National Institutes Of Health; Estados UnidosFil: Rath, Barbara A.. Vienna Vaccine Safety Initiative; AlemaniaFil: Saha, Samir K.. Child Health Research Foundation; BangladeshFil: Simões, Eric A.F.. University of Colorado; Estados UnidosFil: Sotomayor, Viviana. Ministerio de Salud de Santiago de Chile; ChileFil: Thamthitiwat, Somsak. Thailand Ministry Of Public Health; TailandiaFil: Treurnicht, Florette K.. University of the Witwatersrand; SudáfricaFil: Wamukoya, Marylene. African Population & Health Research Center; KeniaFil: Lay-Myint, Yoshida. Nagasaki University; JapónFil: Zar, Heather J.. University of Cape Town; SudáfricaFil: Campbell, Harry. University of Edinburgh; Reino UnidoFil: Nair, Harish. University of Edinburgh; Reino Unid

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions