Obesity is a leading comorbidity in psoriatic disease, including both psoriasis (PsO) and psoriatic arthritis (PsA), and is associated with adverse metabolic and cardiovascular (CV) outcomes. Anthropometric parameters, such as weight, body mass index (BMI) and waist-to-hip ratio, have been extensively reported in psoriatic disease. However, the associations of body composition and fat distribution with psoriasis have not yet been fully defined.To identify whether patients with psoriatic disease, including psoriatic arthritis, have altered body composition compared with the general population, and to review existing modalities for the assessment of body composition.®), Embase (Ovid®), Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria. The research question was answered with a systematic literature review and results were summarized narratively.Electronic searches of the literature were conducted in PubMed, Medline , dual energy X-ray absorptiometry (DXA) and computed tomography (CT). Few studies met all the quality assessment criteria. Clinical heterogeneity prevented meta-analysis.Patients with psoriatic disease reveal defined body composition changes that are independent of obesity and the customary metabolic syndrome, including higher overall body fat, visceral fat and sarcopenia. These findings emphasize that patients with psoriatic disease should be screened for abnormal adipose effects beyond their weight and body mass index (BMI). Our findings show that the last decade has seen an exciting expansion of research interest in the development and validation of new modalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group; hence there is a need for validation of existing modalities and standardization of assessment tools. Psoriasis (PsO) is an immune-mediated chronic inflammatory disease affecting the skin, entheses and joints, with an estimated prevalence in adults ranging from 0.5 to 11.4% and in children from 0 to 1.4% . In receThere is increasing recognition that psoriasis is more than skin deep and has important consequences beyond the skin. Proinflammatory molecules released during chronic inflammation are implicated in certain co-morbidities, such as obesity, hypertension, diabetes mellitus, cardiovascular disease and depression. Paradoxically, epidemiologic evidence infers that obesity, via pro-inflammatory pathways, predisposes to both development and progression of psoriasis . This asSustained inflammation due to psoriatic disease also leads to loss of muscle mass and muscle weakness termed sarcopenia; however, the reasons for these muscle changes in the context of inflammation are multifactorial and difficult to define. External factors, such as aging, decreased physical activity secondary to stiffness and pain, hormonal changes and disturbances in protein metabolism are likely to exert considerable influence on this process .Despite this knowledge about the associations between psoriatic disease, adipogenesis and metabolic dysfunction, there is less emphasis on body mass alterations and distribution between separate internal compartments: fat-free tissue (lean body mass), extracellular water and adipose tissue. Body composition, a measure of lean and fat mass proportions, provides a useful indicator of metabolic health , and itsOur principal aim was to determine the evidence for the association between psoriasis and abnormal patterns of fat  and muscle distribution. We also explored and compared different modalities used for assessment of fat distribution. We hope that this analysis may guide future clinical decision making with respect to risk assessment, screening and management of psoriatic patients in day-to-day practice, encouraging more individualized care and leading to better patient outcomes.This systematic review was performed following methodology recommended by the Cochrane Collaboration and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines , 14.The following inclusion and exclusion criteria were applied.Inclusion criteria:Types of studiesPublication date 2004 –present (inclusive)Studies from any geographical locationEnglish languagePublished studies (including conference papers)Grey literature  including dissertations/thesesAny quantitative study Studies using qualitative methods of analysis (to describe patterns or themes raised by studies) seeking to understand body composition phenotypes of psoriatic disease. This includes original qualitative studies, studies involving secondary analysis of data, and a qualitative study as part of a mixed methods study e.g. the study also has a quantitative componentThe reference lists of the final articles included for full data extraction were hand searched for further relevant articlesTypes of participantsAdults (>18 years)Diagnosed with psoriasis, psoriatic disease or psoriatic arthropathy/arthritisBeing treated in any ‘usual care’ setting: primary; secondary; tertiary care, e.g. in the hospital, hospice, community, home or rehabilitationReceiving care typical for that geographical locationTypes of outcome measuresUnderstanding and learning about body composition and metabolic phenotypes including measures of body fat and lean mass in men and women with psoriatic diseaseTo explore the metabolic, anthropometric and biochemical indices of psoriatic diseaseExclusion criteria:Non-English languagePublished pre-2004Any study where quantitative or qualitative data are not analyzed i.e. uninterpreted data; case reports; any editorial, meta-analysis or review Treatment guidelines and pathwaysCommentary articles, written to convey opinion or stimulate research/discussion, with no research componentTypes of participantsChildren or Young adults (<18 years)Diagnosis of Spondyloarthritis or Spondyloarthropathy, Ankylosing Spondylitis, other immune-mediated inflammatory diseases; studies that do not focus on psoriatic disease per seTypes of outcome measuresAnything that is not concerned with demonstrating either a metabolic, structural or functional relationship to psoriatic disease; studies focusing on individual components of metabolic syndrome  and any association with psoriatic disease®), Embase (Ovid®), Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar for reports published between 2004 to November 2019 using a sensitive methodologic filter for studies. A fifteen-year time frame was chosen to capture the most contemporary and innovative studies in this area. Search terms and criteria are shown in The search strategy was developed by two of the authors (TB and NG) and a librarian. Database searches were performed in PubMed, Medline  independently reviewed all titles/abstracts in the web-based software platform Covidence  and seleThe data extraction tool was designed by TB and included a Quality Assessment incorporating a Critical Appraisal Skills Programme (CASP) checklist  specificThe initial search yielded 5304 titles. After removing duplicates, 1848 titles and abstracts were screened, then 238 retained for full text review. A further 213 studies were excluded due to: incorrect outcomes (197), incorrect study design (9), duplicate material (3), incorrect intervention (3) and non-English language (1). A total of 25 studies from 25 publications met the inclusion criteria  with difTwenty-five studies represented a population of 2468 psoriatic patients from 10 countries: Belgium, Brazil, Denmark, France, Italy, Poland, Portugal, Spain, Turkey and UK. Demographics are shown in All studies included clinical anthropometric data to varying degrees for overall measurement of participant shape and size. In all but one study , particiIn general, 24 studies confirmed discrete biologic and body composition changes in patients with psoriatic disease, which correlated positively with other indicators of metabolic syndrome, including waist circumference, waist-to-hip ratio, weight, BMI, plasma concentrations of low-density lipoprotein (LDL)-cholesterol, leptin and apolipoprotein-B (apo-B).One study failed to reveal statistically significant differences between psoriatic patients and controls with respect to maximal aerobic capacity, resting metabolic rate, pulmonary function tests, body fatness, body fat distributions and quality of life . Moreove2) and demonstrated reductions for spondyloarthritis with no significant variation between psoriatic arthritis and ankylosing spondylitis patients. They identified a significant difference in mean MMI between patients and controls . MMI showed correlation with disease activity indices (BASDAI and BASMI) in the male AS patients only. However, their findings were not correlated with disease duration, function or radiological indices. A more recent study assessed sarcopenia and presarcopenia on the basis of European Working Group On Sarcopenia in Older People (EWGSOP) criteria and by using defined MMI cut-offs, and identified sarcopenia in 20.0% and presarcopenia in 25.7% of PsA patients. Their assessment did not include a sex- and age-matched control population [Three studies focused on muscle mass and reported levels of sarcopenia , 21, 22.P < 0.001), although this study included a low number of subjects.Ten techniques were used to describe body composition: BIA 10, DXA 6, CT 2, ultrasonography 1, transthoracic echocardiography 1 and other techniques 5 (including novel automated systems for measurement). Body composition outcomes by modality are shown in The following devices were used to derive body composition data for analysis in the 10 included BIA studies: BIA 101, Akern srl, Pontassieve, Florence, Italy ; single-All studies bar one  demonstrBalci et al.  identifiSix studies reported on cardiometabolic and body composition improvements on patient profiles after receiving specific interventions: hypocaloric diet with omega-3 supplementation , phosphoThe risk of bias quality assessment of included studies is presented in Sensitivity analysis was not feasible due to clinical heterogeneity preventing meta-analysis.To our knowledge, this is the first systematic review examining the relationship between psoriatic disease and whole-body composition as a distinct entity from metabolic syndrome. Strengths of the review include use of a high degree of rigor in its search strategy and screening procedures and using relevant standards for performing systematic reviews. We tried to reflect the complete picture of both published and unpublished literature on this topic including smaller studies and conference proceedings. Evidently, the last decade has seen an exciting expansion of interest in the development and validation of new modalities for the assessment of body composition. Our study provides evidence for a relationship between certain body composition phenotypes and the occurrence of psoriasis, including higher overall body fat, visceral fat and sarcopenia, that is similar, yet distinct, from the metabolic syndrome. Several aspects of body composition, specifically the amount and distribution of body fat and lean mass, are now understood to be important health outcomes in adults and should form an important part of the ongoing clinical assessment of patients with psoriasis. However, the issue of whether body compartment distribution is a result of severe psoriasis or a causative factor in its development remains contentious. It is likely that novel systems will eventually supplement less sophisticated bedside measurements and influence key aspects of risk assessment, prognostication and management.We found an increased prevalence of body composition derangements in psoriatic patients compared with controls. As expected, parameters associated with obesity, such as weight, body fat percentage, fat mass and degree of obesity, were higher in the psoriasis groups than in the control groups, irrespective of therapy. Such an association between obesity and psoriasis has been well documented, first described in 1986 . TraditiIn this review, treatment with anti-IL-12/23 or PDE4 inhibitors was associated with more favorable body composition profiles than anti-TNFα treatments, findings which mirror previous observations of increases in BMI seen with this drug class , 46. IL-Our review highlights that there are no data comparing and validating body composition techniques in a psoriatic population; therefore, drawing conclusions about the most precise or reliable technique is not possible. Due to its non-invasiveness, low cost and portability, it is easy to appreciate how BIA was adopted by most researchers. The technique relies on the assumption that the volume of fat-free tissue will be proportional to the electrical conductivity of the body. It employs a small electric current to measure the resistance and reactance at difference frequencies against various tissues in the body e.g. lipid has a high resistance to the flow of current, therefore shows a high impedance reading, whereas muscle, which stores most of our body water, has lower impedance. BIA assessment tools have been considered a promising approach for the quantitative measurement of tissue characteristics over time, as well as demonstrating the direct relativity between fluctuations in body composition and prognosis, clinical condition and quality of life . The tecPhA is thought to be one of the most clinically relevant parameters of BIA. It is defined as the ratio of resistance (intracellular and extracellular resistance) to reactance (cell membrane-specific resistance), expressed as an angle. It is considered an indicator of cellular health, where higher values reflect cell membrane integrity and better cell function. In healthy populations, increasing age bestows a lower PhA due to a reduction in reactance and a parallel loss of muscle mass and an increase in resistance due to the declining proportion of body water at the expense of fat mass. In disease, PhA is often reduced because of infection, inflammation or disease-specific determinants . Recent It is clear that there is no single method of body composition measurement that allows for the delineation of all tissues and organs, and there are pros and cons of all techniques. The seemingly unsophisticated measurements of skin thickness, BMI and waist circumference can provide simple longitudinal assessments of fatness and metabolic risk despite their poor accuracy and inability to differentiate fat and lean masses. The value of any approach in supporting clinical practice is enhanced by the availability of reference data. Recent developments include MRI for fat distribution.This systematic review should be interpreted in the context of the reported studies which were heterogeneous in several aspects. Firstly, the observational studies recruited different extents and subtypes of psoriatic disease, some with associated arthritis, and measured different aspects of body composition, making definitive conclusions problematic. Secondly, there was poor matching of patients and controls across all studies and little consideration for the potential confounding effects of key determinants of metabolism, e.g. physical activity, age and smoking. Finally, BIA-estimated percentage of body fat varies greatly with population and age and is directly and closely related to various health outcomes such as cardiovascular diseases. Despite its prognostic potential, BIA has not been validated in population studies or clinical practice due to lack of normal population reference limits for comparison and is also influenced by other factors such as age, sex and race . We aimeWe suggest that body composition indices should be analyzed in more detail using a broader range of techniques and imaging systems across the clinical spectrum of psoriatic patients in order to generate validated methods of assessment, particularly with regards to the prognostic ability of BIA and PhA. Further studies are needed to address the discrepancies in bioimpedance parameters within body compartments and between different devices and the deviation from health to disease. We hope that future studies will reveal insights into drug-specific alterations in body composition profiles in psoriatic disease, enabling clinicians to practice more stratified medicine and treat more effectively the metabolic components of patients’ disease that are so often neglected in clinical practice and associated with worse outcomes.In conclusion, this study provides evidence for a relationship between certain body composition phenotypes and the occurrence of psoriasis, including higher overall body fat, visceral fat and sarcopenia that are similar, albeit distinct, from the metabolic syndrome. Several aspects of body composition, specifically the amount and distribution of body fat and lean mass, are now understood to be important health outcomes in adults and should form an important part of the ongoing assessment of patients with psoriasis. However, the issue of whether body compartment distribution is a result of severe psoriasis or a causative factor in its development remains contentious. It is hoped that novel systems will eventually supplement less sophisticated bedside measurements and influence key aspects of risk assessment, prognostication and management.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.


To synthesize the current evidence for subcutaneous hydration and medication infusions from systematic reviews and to assess their methodological quality.Peripheral intravascular cannula/catheter insertion is a common invasive procedure for administering fluids and medications. Venous depletion is a growing concern for several patient populations. Subcutaneous access for the administration of isotonic solutions and medications is an alternative; however, vascular access assessment and planning guidelines rarely consider this route.Systematic review of systematic reviews (PROSPERO CRD42018046504). We searched 6 databases published in English language from 1990 to June 2020, identifying subcutaneous infusions an alternate route for fluids or medication. Methodological quality was evaluated using AMSTAR 2 criteria and data for mechanisms of infusion and outcomes related to effectiveness, safety, efficiency and acceptability extracted. The Johanna Briggs Institute’s grades of recommendation informed the strength of recommendation.The search yielded 1042 potential systematic reviews; 922 were excluded through abstract and duplicate screen. Of the remaining articles, 94 were excluded, and 26 were included. Overall, evidence is strong for recommending subcutaneous hydration infusions for older adults, weak for pediatric patients and inconclusive for palliative patients. There is strong evidence for 10 medications; weak evidence supporting 28 medications; however, there are eight medications with inconclusive evidence to make a recommendation and four medications not appropriate for subcutaneous delivery.Subcutaneous access should be considered alongside intravenous therapy for hydration in older adults, and several medications. There are additional benefits in terms of ease of use and cost-effectiveness of this mode. Inclusion of subcutaneous access in clinical guidelines may promote uptake of this route to help preserve vessel health of vulnerable patients. Further high-quality research is needed to inform subcutaneous infusion therapy in a variety of populations  and medications and clarifying the mechanism of delivery. Infusion therapy is a common treatment modality to deliver medications and fluids in the acute and home care settings and is gaining prevalence in the long-term care setting. Traditionally, these parenteral therapies have been delivered via the intravenous route. However, venous depletion is a growing concern with an increasing aging population and patients with long-term complex co-morbidities –3. The pThe Infusion Therapy Standards of Practice recommend consideration of subcutaneous access for the administration of isotonic solutions and for continuous opioid and other infusion therapies/medications  . SubcutaGiven the world’s aging population, health care systems rapidly changing, diversity in practice setting, and complexity of care and patient health conditions, the uptake and use of subcutaneous continuous infusions may help address these issues and challenges. The aim of our study is to determine the effectiveness, safety, acceptability and efficiency related to the use of subcutaneous infusion (SCI) as an alternate route to intravenous for the management of conditions or treatments such as dehydration and palliation, for children and adults in all care settings through a synthesis of systematic reviews of studies. A secondary objective is to identify the mechanisms of subcutaneous fluid and drug delivery that facilitated achieving these outcomes. This will provide an up-to-date and rigorous review of subcutaneous infusion therapy.We adopted the systematic review of systematic reviews  methodolWe considered all types of systematic reviews which included the following characteristics:A clearly stated set of objectives with an explicit, reproducible methodology;A systematic search that attempts to identify all studies that would meet the eligibility criteria;An assessment of the validity of the findings of the included studies ; andSystematic presentation, and synthesis, of the characteristics and findings of the included studies, +/- meta-analyses .Where some of the primary studies in the reviews were duplicated, we did not exclude the reviews, as they had different aims and objectives and thus added to the overall understanding of SCI to meet the aims of this current systematic review. We did however only include the primary studies’ findings once in our analysis and synthesis. Expert opinion/consensus and bench research, abstracts, and editorials/correspondence were excluded . No restWe included reviews that assessed interventions that used subcutaneous infusion (for a duration of around 2 hours or more) as an alternate route for fluid or medication therapy. Subcutaneous infusion is defined as the delivery of fluids or medication into the subcutaneous space for absorption into the circulation via “perfusion, diffusion, balance between hydrostatic/osmotic pressure and lymphatic drainage” .The primary outcomes of interest investigated included:Effectiveness: defined as clinical response to therapy ;Safety: defined as medication or vascular access adverse event , survival status  and complications related to treatment  and full copies of articles of potentially eligible reviews were obtained. Full texts of these reviews were then screened independently by two reviewers (MC and DB) against the review selection criteria. Disagreements were resolved by discussion between these reviewers and with consultation by a fourth reviewer and subject expert (BG).Data were extracted and assessed independently by the reviewers in pairs , with anomalies reconciled by agreement. Data were obtained primarily from the systematic reviews, although primary studies were consulted for critical missing data . Data extracted included author/year, aim, design and number of studies included, search strategy, population, intervention/comparator, quality appraisal of primary studies, infusion characteristics, outcomes as previously defined, key findings, study limitations, funding, and conclusions.Methodological rigour of each review was independently assessed by four reviewers in pairs as above, using the AMSTAR 2 tool . This isDue to the different interventions, outcomes and outcome measures, a meta-analysis was not feasible. Quantitative outcome data are provided and synthesized where possible. Only data from randomised controlled trials (RCTs) and prospective cohort studies were included to determine subcutaneous hydration outcomes; however, reviews exploring medications also included retrospective studies and case reports. The JBI grades of recommendation were used to derive the grading score to inform the strength of recommendation for the intervention  . Data syThe search strategy yielded 1042 potential systematic reviews , of whicThe systematic reviews incorporated a diversity of study designs and quality levels from case studies to systematic reviews and randomised controlled trials. However, only 9 reviews included only randomised controlled trials , 35–38. n = 12/26), while 5 only provided a narrative discussion of quality. Most review authors noted that results should be interpreted with caution due to study limitations.The AMSTAR 2 quality scores of the included reviews are described in Limited data were reported on the materials and techniques used to achieve subcutaneous access for hydration or medication therapy. Subcutaneous hydration has been primarily studied in the hospital sector (n = 6), palliative care and hospice setting (n = 3), long term care (n = 1) and one study discussed the home care setting as being appropriate  . One RCTTypical solutions in the elderly and palliative population were either sodium chloride (0.45% or 0.9%) or, more commonly, a dextrose/saline solution. Hyperosmolar, colloidal or hypertonic solutions without electrolytes are not recommended , 23. PotInfusion rates varied. Rochon et al.  acknowleIn a review of subcutaneous hydration at end of life, rates ranged from 20 mL/hour to 2400 mL/day, with the most commonly reported rate of ~75 mL/hour . In one Duration of treatment ranged from a mean of four to 21 days for SC hydration in 1 review with an average of 10.5 days , and as Study findings of the RCTs and prospective cohort studies support the recommendation that subcutaneous hydration is at least as effective as IV therapy and may be superior in certain circumstances for the treatment of dehydration in the pediatric and elderly population  and IV (90%) experienced at least one adverse event (no serious events) . There wThe most common, although rare, systemic reactions reported to be possibly related to SC therapy include hyponatremia in a total of 3 patients, cardiac failure in 2 patients, and fluid overload (mean 0.003 episodes per day of therapy), all of which were comparable rates to IV , 52, 53.Catheter dislodgments, in which the catheter/needle is pulled out, were more likely to occur with IV than SC in the elderly population  .Subcutaneous hydration is significantly favoured over IV hydration with regards to successful and ease of device placement, patient agitation, and patient/caregiver satisfaction . PatientIn an RCT of 96 elderly patients, 17 patients were switched to SC (from IV) due to lack of venous access (n = 8), removal of cannulae by patients (n = 5), or other causes not reported , 53. TheKer and colleagues  suggest Subcutaneous hydration is significant favoured over IV hydration in terms of cost effectiveness, in a few measured outcomes . Total tIdeal medications for subcutaneous administration are those that are hydro-soluble, and have neutral pH, low viscosity and low molecular weight . IrritatIn general, medications administered subcutaneously are absorbed slower than given IV; however, can reach similar plasma levels . MedicatFor pain management, SCI of morphine was compared with epidural infusions and found to be acceptable and effective with fewer hypotension concerns with subcutaneous than epidural , 60. FavTwo antibiotics (ceftriaxone and ertapenem) were found to have similar antimicrobial effect, although variances did occur with Tmax and Cmax values and need to be taken into consideration if time to maximal plasma concentration and serum concentration are important clinically , 44. ForMidazolam is considered the safest choice for SCI as it is the only water-soluble benzodiazepine and it has a fast onset, good tolerance and short half-life while still being reversible by antidote flumazenil even after administration . ChemothSC immunoglobulin (SCIG) infusion was found to achieve acceptable trough levels and reported effectiveness similar to IV infusion . SCIG waSCI of treprostinil for pulmonary hypertension was compared to placebo and found to be significantly more effective with minimal and tolerable side effects but no reviews included a comparison to intravenous . The revMost commonly reported adverse events were local tissue reactions including redness, pruritus, and itching at the administration site . OverallMedications contraindicated for subcutaneous infusion administration include severe irritants such as higher supplements of potassium chloride (contraindicated as bolus but slow rates may be tolerated), lipo-soluble drugs such as diazepam which can precipitate in the skin, and medications known to cause fat necrosis such as chlorpromazine and prochlorperazine .In cases of high osmolarity medications, such as subcutaneous immunoglobulins (SCIG), the subcutaneous route was considered safer as the infusion had less cardiovascular risks associated with the infusion. Reactions were more limited with the SCIG infusion versus the intravenous route with local skin whelps and irritation being the most frequent complaint. Specifically, in one review, 15 studies (376 patients) reported comparing adverse events during treatment for patients with Primary Antibody Deficiencies (PAD) with SCIG and IVIG, respectively . The calIn one large systemic review, 5 of 94 studies reported preference for subcutaneous over IV with reasons varying from less side effects, to less time involved, less pain with access/administration or overall comfort . SCIG paFew studies specifically reported on resource savings. In the review of clinical efficacy for diuretics, hospitalization of those patients with poor venous access was avoided in 83–93% cases . One repShifting from hospital based IVIG treatment to home based SCIG is reported as “25–33% of the annual costs  in Sweden, 50% of the annual costs (€17–77 million) in Germany, CA$2,000 per patient per year in Canada , 25–50% of the annual costs in France, and $2,000–5,000 per patient per year in the US” .This synthesis of systematic review data supports the overall strong recommendation for the use of subcutaneous hydration infusions in the older adult population, due to its strong safety, efficacy, and acceptability profiles as summarized in Overall ratings for medications were based on the success and strength of studies evaluating subcutaneous administration . Ten medSubcutaneous therapy has been shown to be safe, effective, acceptable and efficient as a treatment modality for mild to moderate dehydration in the older and pediatric population when oral therapy is not feasible or fails. This is in accordance with the Emergency Nurses Association recommendation of the use of SC hydration as an alternative to peripheral IV insertion for the mildly to moderately dehydrated pediatric and elderly patients  . Slesak Data is inconclusive yet to the use of SC hydration in the palliative care population. A small prospective study further explored SC hydration in palliative care, demonstrating that family caregivers and hospice nurses can administer SC hydration at end of life at home with minimal burden, equipment or technical support . A qualiRochon and colleagues  determinThe study data reveal the following advantages of SC hydration over intravenous therapy: reduced catheter dislodgements, infection, and phlebitis , clinical and biochemical improvements, less agitation related to the access device/infusion, increased patient/caregiver satisfaction, time and success in device placement, ease of use and number and cost of access devices and less staff time to start and maintain the infusion. A decision analytic model studying Spandorfer’s pediatric study  supportsIt has also been noted  that avoidance of IV venipunctures may help preserve peripheral veins and thus indirectly facilitate IV therapy . We therIndications of the most appropriate route may include the patient’s severity of dehydration, mentation, venous integrity, and preference; the volume and rate of the required therapy; clinician competency and training, resource availability, care setting, and healthcare costs. Hyaluronidase may help facilitate the absorption of fluids; however further study is required to determine its safety, efficacy and efficiency. We were unable to retrieve any studies comparing outcomes related to site selection.Limitations to the use of SC hydration include those who require high volumes or rapid rehydration or medications not appropriate for SC use. The maximum volume reported was two litres in a 24-hour period . While mGiven the evidence supporting the safety and efficacy of subcutaneous therapy, we concur with researchers who call for standardized policies and procedures to help optimize both study results and uptake of this practice . The InfLack of training and organizational protocols and unawareness of the subcutaneous route for the administration of fluids is a barrier to use , 66. In The investigation of the use of potassium chloride in hydration solutions was limited to three studies , 23, 43.The main strength of this study is that it has synthesized the evidence from a large number of systematic reviews that have investigated SC infusion for hydration and drug therapy to provide a comprehensive understanding of this intervention important to a wide range of healthcare professionals . A limitation of this study includes the potential for missing some systematic reviews. As our intervention was SC infusion there may have been drugs that would not have been captured as studies reported on the effectiveness of a specific medication, not how it was administered and therefore the title and abstract did not indicate SC as an administering route and thus excluded from full text review. It is also possible that the quality of evidence may be higher; however, the lack of reported methodological details led to downgrading of the overall confidence in results. Investigation of alternate routes was beyond the scope of this study; however, nasogastric and intraosseous rehydration has been shown to be effective in the pediatric population .The authors found it surprising that there were so few reported studies looking at subcutaneous administration of medication as an alternate route. A recently published narrative review of subcutaneously administered antibiotics, however, confirmed the acceptable pharmacokinetic and pharmacodynamics data supporting the administration of ceftriaxone, ertapenem, and teicoplanin . Of noteUnfortunately, limited studies have been reported and included in systematic reviews evaluating the use of medications as subcutaneous infusions. While some have been studies as injections, the data on infusions is very limited in scope with the reports often not providing detail on the mechanisms of administration such as duration, rates, dilutions, diluents, access devices, etc. Several medications were only studies in healthy volunteers, where disease specific concerns don’t exist or in the palliative care setting where advance illness may skew the assessment. Many of the medications reported in this review need further evaluation with more controlled studies, broader populations and stronger evaluations. Additionally, the strength of the evidence is lacking in most reviews. Many reports are limited to case studies or retrospective reviews and not well controlled.Limited studies included in systematic reviews looked at common therapies administered intravenous and subcutaneous including anti-emetics and treatments for pulmonary hypertension. While some studies did compare SC to oral or other therapies, the head to head comparison of the subcutaneous alternate route was lacking. The value of these studies shows safety and efficacy against placebo or oral but greater value would come from direct comparisons with intravenous so it would be easier to assess if intravenous and the associated risks could be avoided if oral is not an option.Subcutaneous administration of opioids can be advantageous. Subcutaneous, like intravenous, avoids the first-pass effect of hepatic metabolism experienced with oral administration, which often limits the effectiveness and increasing adverse events from metabolites.A trend was seen toward patient preference for subcutaneous infusions of chronic medications, such as SCIG. This appears to be influenced by ease of administration and low adverse events leading toward more patient independence and less interruption to schedule to receive the medication. Even when considering the additional doses required for SCIG, this preference was still found among many patients .The greatest strengths of SC therapy appear to be related to the ease of use and cost-effectiveness of this mode. Given the favourable outcomes in relation to effectiveness, safety, acceptability, and efficiency in the older and pediatric population, we suggest that subcutaneous access be considered alongside intravenous therapy as an alternative to oral hydration and some medications. Vascular access device selection algorithms do not currently include subcutaneous devices , 73, whiS1 Table(DOC)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S6 Table(DOCX)Click here for additional data file.


Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems.Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive  Salmonella enterica serovars Typhi or Paratyphi A, B, or C. Recent estimates suggest that these organisms cause 14.3 million infections  and 136 000 deaths  annually [Salmonella (iNTS) disease is caused by other Salmonella serovars, most frequently by Salmonella Typhimurium, Salmonella Enteritidis, or Salmonella Dublin. Invasive nontyphoidal Salmonella disease caused an estimated 535 000 infections  and 77 500 deaths  in 2017 [Salmonella infections, which include iNTS, remain a public health issue in many low- and lower-middle-income countries.Enteric fever, the collective term for typhoid and paratyphoid fevers, describes a systemic infection caused by Salmonella infections by the World Health Organization (WHO) [A major impediment to understanding the true burden of enteric fever and iNTS disease is the lack of appropriately sensitive diagnostics and inconsistent usage of existing tests. Bone marrow culture is considered the gold standard for diagnosis of typhoid and paratyphoid fever, but given the invasive and challenging nature of obtaining bone marrow aspirate, it is rarely performed . Often, on (WHO) , but theon (WHO) ; when thon (WHO) .Salmonella infections may be underestimated.Often, febrile patients will not present to healthcare facilities for diagnosis and treatment. Potential deterrents to healthcare seeking include distance to and accessibility of the closest healthcare facility, or costs associated with treatment and/or hospitalization, combined with ease of access and affordability of antimicrobials in the community. As a result, the true number of invasive Salmonella disease [In 2009, the WHO highlighted the need for additional data on the burden of invasive  disease . At that disease . A histo disease .To address the limitations of existing data sets, several surveillance studies have been established over the past decade, funded primarily by the Bill & Melinda Gates Foundation and the Wellcome Trust. One of the first studies funded was the Typhoid Fever Surveillance in Africa Program (TSAP), coordinated by the International Vaccine Institute (IVI). The TSAP study demonstrated higher overall incidence rates of typhoid fever in sub-Saharan Africa than previously suspected across both rural and urban sites, as well as high incidence rates of iNTS disease across multiple sites . In the Salmonella disease burden. In this article, we compare the methodological similarities and differences between these diverse and complementary studies. We also identify early lessons learned and outstanding data gaps, and issue recommendations for optimizing and sustaining surveillance systems going forward.Each of these studies has been conducted across mutliple distinct epidemiological settings and aims to address subtly different questions relating to invasive The SETA program builds on the infrastructure established as part of the TSAP study to characterize the severity and long-term effects of typhoid fever and iNTS disease across Africa. TSAP collected blood culture data between 2010 and 2014 and generated typhoid incidence rates from sites in 10 sub-Saharan African countries: Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania. The TSAP results showed a great deal of heterogeneity in typhoid incidence across sites, with crude rates ranging from 0 to 284 cases per 100 000 person-years, and that there is a high burden in both rural and urban sites . SETA suWithin each of the SETA study areas, patients were recruited at healthcare facilities across multiple tiers. Each site included a referral hospital, which, to be included in SETA, had to be equipped with imaging and surgical capacity to identify and treat intestinal perforations, as well as primary or secondary healthcare centers, which enrolled less severe febrile subjects using broader enrollment criteria . Each reSalmonella bacteremia detected in SETA laboratories from patients who were not enrolled in the study were also included, as well as patients with intestinal  perforation suspected to be due to typhoid, from referral hospitals. Intestinal perforation cases were recruited into the study regardless of whether or not the patient resided in the study catchment area. Upon enrollment, blood, stool, oropharyngeal, and urine samples were collected. Blood was subjected to conventional microbiological culture for detection and identification of bacterial pathogens as well as other immunological investigations; stool was cultured to assess acute carriage status, and urine was examined for antibiotic residues to determine patterns in antimicrobial pretreatment.Screening for study eligibility was systematically conducted at all study facilities, including inpatient, outpatient, surgical, and emergency wards at referral facilities. To augment case detection, Salmonella Typhi, Salmonella Paratyphi, and non-Typhi Salmonella serotype infections were recruited into the long-term follow-up component of the study. Two healthy household members and 4 healthy neighborhood controls were enrolled for each case, and the entire cohort was followed for 1 year with contact points at predefined intervals to collect clinical information, blood and stool samples, and cost-of-illness and quality-of-life assessments [Patients with blood culture–confirmed essments .Salmonella infections, and phase 2, a prospective surveillance study. Phase 1 showed that Salmonella Typhi and Paratyphoid A was isolated from 0.43% to 2% of blood cultures conducted at hospitals in Bangladesh, Nepal, Pakistan, and India [SEAP is a multicountry, multisite, population-based surveillance study aimed at characterizing the burden of enteric fever in South Asia. The project had two phases: phase 1, a retrospective clinical record review of invasive nd India .The prospective component of the study—initiated in October 2016—was conducted at urban and periurban sites in Bangladesh, Nepal, and Pakistan. Sites were selected to represent diverse communities in South Asia, but choices were constrained by the availability of laboratories capable of performing high-quality blood cultures. In addition to patients meeting the inclusion criteria at the hospital sites, the SEAP study also recruited enteric fever cases from laboratory networks beyond the site hospitals. Blood specimens were collected for culture, and a subsample of participants provided urine samples to test for residual antibiotic metabolites to understand antibiotic usage patterns. Data were collected on clinical manifestations, markers of severity of illness, complications of illness, and antimicrobial resistance. In addition, in collaboration with the US Centers for Disease Control and Prevention, an economic study of enteric illness was implemented at all 3 sites .SEAP used a hybrid surveillance approach, adapted from Luby et al , 14, comThere has been a lack of nationally representative enteric fever incidence data in India, as highlighted by a 2016 meta-analysis . To fillThe tier 1 surveillance for estimating the incidence of enteric fever in children consists of active, community-based surveillance in 1 rural and 3 urban sites, which were selected to be broadly representative of different geographic settings and population densities. At each of the 4 sites, 6000 children between 6 months and 15 years are followed each week for 2 years to estimate the age-specific incidence rates of enteric fever in children. At least 1 contact each month is in-person and the rest are either in-person or by telephone. Parents are also encouraged to reach out to the study team if a child has fever in between weekly follow-up points, and all participating families are given thermometers and diary cards. Any fever of 3 or more consecutive days is considered a suspected case, and the child is referred to a study facility on the fourth day of fever, where a blood culture is performed if the child has had fever in the past 12 hours. Risk factors and other demographic data are also collected from participating households to permit extrapolation of incidence estimates to other similar risk settings .Tier 2 is passive, hospital-based surveillance, which has been harmonized across 6 secondary-care facilities in 6 settings  with well-defined catchment populations between 100 000 and 400 000 each. All patients hospitalized at a study facility with a fever are considered eligible. Upon consent, a blood culture is collected irrespective of duration of fever or temperature. Those with blood culture–confirmed enteric fever are followed up for 28 days to capture costs and clinical complications. Biannual HCUSs are administered to 5000 randomly selected households in 100 clusters at each site. These are used to determine the probability of seeking healthcare at the study facility. The population denominators are estimated by projecting annual growth rates from the 2011 census for each village in the catchment area and validated by reviewing the population in the sampled clusters in the HCUS. The tier 2 surveillance system was designed to estimate the incidence of severe enteric fever  across all age groups.Salmonella Typhi or Paratyphi A and to characterize antimicrobial resistance patterns. Patients with nontraumatic ileal perforations are also enrolled in tier 2 and 3 surveillance and followed up for up to 90 days for clinical and health economic outcomes.Tier 3 surveillance is being conducted at 8 laboratories linked to tertiary care hospitals. The aims of this component of the surveillance system are to generate estimates of the proportion of blood cultures that are positive for The STRATAA consortium, which includes key partners from the University of Oxford’s Oxford Vaccine Group, the Malawi Liverpool Wellcome Trust Clinical Research Programme, the International Center for Diarrhoeal Disease Research, Bangladesh , and the Oxford University Clinical Research Unit , has conducted a prospective multicomponent epidemiological study in 3 densely populated urban sites in Bangladesh, Nepal, and Malawi . This stS. Typhi. After identifying individuals with a high anti-Vi antibody response, follow-up with stool collection and culture was performed to identify stool shedding.Passive surveillance was conducted from June 2016 in referral hospitals and primary health centers. Patients living within the population catchment area who presented to a study facility reporting fever of 2 days or longer or having a documented temperature of ≥ 38°C were enrolled and consented and blood cultures were taken . Age-strSalmonella isolates will be available from all studies. Cost-of-illness studies are embedded within each of these studies, as is screening for chronic typhoid carriage.There are important methodological similarities across these four studies. Each study includes passive, healthcare facility–based blood culture surveillance of febrile patients to generate crude age-stratified incidence rate estimates stratified by age. Each study team also conducts an HCUS and applies correction factors to these crude rates to account for the proportion of patients from within the catchment area or study population seeking care for febrile illness at a study facility. All 4 studies make an adjustment for eligible cases missed by the study , as well as an adjustment for blood culture sensitivity. Antimicrobial resistance patterns from sites in all 4 studies are being analyzed, and whole-genome sequencing of selected The SEAP and SETA studies employ similar methods to calculate incidence, owing in part to efforts coordinated by the Scientific Advisory Process for Optimal Research on Typhoid Burden of Disease Project  group to harmonize methods; therefore, the results are more easily compared. Both studies generate data on the incidence of severe disease and follow enteric fever patients for at least 6 weeks to characterize long-term sequelae. SEFI tier 2 surveillance processes also closely resemble that of SEAP and SETA, although enrollment criteria differ across all 3 studies.Each of the studies contributes data to advance broader enteric fever control objectives. Epidemiological data generated from all 4 have been shared with policymakers in relevant countries in support of decision-making around TCV introduction. The impact of TCV deployment is being evaluated or will be evaluated at site(s) from 3 of the 4 studies, although the designs of these studies and the delivery strategies under evaluation differ. A TCV impact assessment is being conducted through Kharadar General Hospital in Karachi, Pakistan (SEAP), in response to an extensively drug-resistant typhoid outbreak . The UniThere are several differences between the methodologies of these studies, which are important to consider when interpreting and comparing results. While there is some overlap, the objectives are not uniform across the 4 studies. Eligibility criteria differ, as do the type, number, and frequency of sample collections. The approach to estimating adjusted incidence rates differs between studies, and for SETA and SEFI, within study tiers as well. These and other general methodological differences are summarized in Each study generates both crude and adjusted incidence rates, but the approach to defining population denominators and the choice of adjustment factors used differ. Population denominators affect both crude and adjusted incidence rate calculations, so this distinction is important. The STRATAA approach to estimating the population denominator is different from the approach used by SEAP, SETA, and SEFI tier 2, as the demographic censuses provide precise population denominators. In SEAP, SETA, and SEFI tier 2, eligible cases come from predefined geographic catchment areas, which is arguably less precise but also less resource-intensive, and enables surveillance to cover larger catchment areas. Each study employs an adjustment for blood culture sensitivity, but STRATAA samples from probability distributions informed by a recent meta-analysis of blood culture sensitivity by volume of blood acquired per subject and reported prior antibiotic usage , whereasThere are also key differences between these studies based on the geographies under surveillance, which are illustrated in Salmonella infections, which will impact prioritization and targeting of combination vaccine development efforts. Having more broadly representative genomic data also facilitates monitoring the evolution and spread of different antimicrobial resistance genotypes, which also should inform more sophisticated targeting of interventions.There is value in the diversity of these study approaches. Some methodological differences are driven by rational, pragmatic choices made by study investigators that reflect differences between sites captured above. Each study addresses distinct data gaps, like potential transmission routes, prevalence of chronic carriers, and duration of immune response to natural infection, all of which will potentially inform optimal intervention strategies. Each study includes efforts to validate 1 or more low-cost alternatives to blood culture surveillance, which means that there is likely to be greater clarity in the near future about which approaches, if any, are viable, feasible, and cost-effective. The diversity of settings under surveillance broadens our understanding of the global incidence rates of typhoid fever and other invasive In a position paper from 2008, the WHO stated that the deployment of the then-available typhoid vaccines “should be based on detailed knowledge of the local epidemiological situation” while simultaneously acknowledging the limitations of the existing data, particularly for the African continent . In the Salmonella combination vaccine approaches. Methodological differences notwithstanding, each study has contributed important data to advance global typhoid control.The TSAP study demonstrated that there was a significant incidence of typhoid fever and iNTS disease in Africa. SETA, SEAP, SEFI, and STRATAA are generating data on disease transmission, risk factors, cost of illness, and incidence of severe disease in Africa and some parts of Asia. Furthermore, these studies have provided baseline data in support of ongoing or planned phase 3/4 TCV trials. Data from these studies are now being used to enable national stakeholders to make informed decisions on optimal TCV delivery strategies, and to direct the development and prioritization of future Each surveillance study will provide an estimate of disease burden for a particular setting at a particular point in time and will reflect transmission dynamics specific to a particular setting. We acknowledge that caution should be exercised when extrapolating these figures in an attempt to provide country-level estimates of disease burden, as the true distribution of disease is likely to display marked intra- and intercountry and temporal variation . FurtherS. Typhi in endemic and epidemic disease, before and after introduction of typhoid vaccines” [The updated 2018 WHO position paper on typhoid vaccination recommends that “endemic countries strengthen the surveillance of typhoid fever in all age groups, and monitor the presence of antimicrobial resistant strains of accines” . Neverth


Understanding public behavioral responses to the coronavirus disease (COVID-19) epidemic and the accompanying infodemic is crucial to controlling the epidemic.The aim of this study was to assess real-time public awareness and behavioral responses to the COVID-19 epidemic across 12 selected countries.Internet surveillance was used to collect real-time data from the general public to assess public awareness and rumors  and behavior responses . These indices measured the daily number of searches or purchases and were compared with the numbers of daily COVID-19 cases. The trend comparisons across selected countries were observed from December 1, 2019 (prepandemic baseline) to April 11, 2020 (at least one month after the governments of selected countries took actions for the pandemic).We identified missed windows of opportunity for early epidemic control in 12 countries, when public awareness was very low despite the emerging epidemic. China's epidemic and the declaration of a public health emergency of international concern did not prompt a worldwide public reaction to adopt health-protective measures; instead, most countries and regions only responded to the epidemic after their own case counts increased. Rumors and misinformation led to a surge of sales in herbal remedies in China and antimalarial drugs worldwide, and timely clarification of rumors mitigated the rush to purchase unproven remedies.Our comparative study highlights the urgent need for international coordination to promote mutual learning about epidemic characteristics and effective control measures as well as to trigger early and timely responses in individual countries. Early release of official guidelines and timely clarification of rumors led by governments are necessary to guide the public to take rational action. In early December 2019, the then-unnamed novel coronavirus disease (COVID-19) emerged in Wuhan City and spread rapidly across China . The WorDuring an epidemic, it is crucial to understand how critical information about the health threat is disseminated and how the public processes and responds to this information ,7. The rThe power of internet search data is being increasingly recognized in public health emergencies ,15. In cIn this study, we conducted internet surveillance in 12 countries. In addition to China, three countries in East and Southeast Asia that were affected by the first wave of the pandemic were selected, namely Japan, South Korea, and Singapore, followed by four European countries  and the United States. Additionally, Brazil, South Africa, and India, where internet surveillance data (Google Trends) are available, were selected from Latin America, Africa, and South Asia, respectively. All data are publicly available.Internet surveillance was used to collect real-time data from the general public to assess public awareness and rumors  and behavior responses . The data cover the period from December 1, 2019 (prepandemic baseline) to April 11, 2020 (at least one month after the governments of selected countries took actions to address the COVID-19 pandemic). coronavirus was used to assess the awareness of COVID-19 among the general public, whereas the Google Shopping indices on two topics, mask and hand sanitizer, were used to assess the adoption of personal protection measures. In countries where Google Shopping data were limited for assessing public purchasing behavior , Google web search data were used as an alternative. Google Trends presents relative search volumes ranging from 0 to 100 (the maximum daily search volume on specific terms is standardized as 100%).Google Trends can provide insight into the relative search volumes of search terms on Google on a daily basis . DependiThe antimalarial drugs chloroquine and hydroxychloroquine have been repeatedly mentioned by world-leading politicians as treatments for COVID-19 without clinical data to support their efficacy; these drugs have potentially deadly side effects ,22. By aThe Baidu search engine, which is Google’s equivalent in China, has more than 1 billion Chinese users. The Baidu Index, which stems from the frequency of searches using the Baidu search engine, is powered by Baidu statistics and exhibited as preset keywords. The Baidu Index reflects the daily number of searches on specific keywords, thereby assessing public awareness and intended behavior. We manually scanned and identified all Baidu Index keywords that included coronavirus, recommended personal protection measures, and rumors and misinformation. For comparison, we also gathered Baidu Index data from the same time period in the previous year as the baseline: December 1, 2018, to April 11, 2019.radix isatidis, Shuanghuanglian, and garlic. The Baidu Index on these terms was used to detect public behavioral responses regarding rumors and misinformation in China.Rumors and misinformation circulated widely in China regarding certain herbal medicines for personal health protection. From the Sina Weibo “Hot Search” ranking, we identified three keywords related to these rumors and misinformation: mask, hand sanitizer, disinfectant, and thermometer as keywords to reflect the above four measures. We employed these four keywords relevant to recommended personal protection measures to assess public behavioral responses to the COVID-19 epidemic (the Ali platform did not generate an index for rumor-related items).The Ali platform, Amazon’s equivalent in China, is a powerful and popular web-based electronic commerce marketplace with more than one billion users, and its purchasing index reflects the number of specific products purchased on the internet. The Ali Index was used to collect behavioral data during the epidemic. The National Health Commission of China issued a series of guidelines recommending that residents adopt personal protection measures consisting of four main aspects: respiratory protection, hand hygiene, home disinfection, and health monitoring . Accordimask and hand sanitizer and the numbers of new COVID-19 cases in the selected countries. The indices were input into charts to observe the trends along the period of observation and facilitate the trend comparisons across countries.Public awareness on the epidemic was assessed using the Baidu daily indices in China and Google Trends indices worldwide. We assessed the intentions (Baidu Index) and behaviors (Ali Index) regarding the adoption of recommended personal protection measures as well as rumors about ineffective treatments in China; Spearman rank correlation analyses between the Baidu and Ali indices were employed to detect the consistency of intention and behaviors. Google Trends was used to assess the intended behavior regarding personal protection measures and antimalarial drugs worldwide. These indices were used to measure the daily number of searches or purchases related to specific keywords, which we then compared with daily data on numbers of confirmed COVID-19 cases. The Spearman rank correlation was used to examine the correlations between Google Trends for coronavirus showed no results throughout most of December but jumped to 127,336 searches on December 31, 2019, when the Wuhan Health Commission first reported 27 patients with pneumonia of unknown cause. However, this number immediately decreased to 30,504 searches the next day and remained low between January 1 and 19, 2020. Starting on January 20, when the National Health Commission of China confirmed human-to-human transmission, this number increased sharply, and it peaked at 3,039,324 on January 25. Wuhan City implemented a series of quarantine measures starting January 23, followed by 30 provinces  across mainland China (excluding Tibet). After that, public searches steadily decreased with minor fluctuations. The first COVID-19 case emerged on December 8, 2019, and it was first announced by the Wuhan Health Commission on December 31. As shown in coronavirus began to decline on January 31, the day after the WHO declared the outbreak a PHEIC. This index continued to decline and remained at a low level until late February, when COVID-19 started to spread in Italy. Outside of China, although there was a slight increase in public searches following the confirmation of human-to-human transmission of COVID-19, the Google Trends index for thermometer, all started to increase sharply on January 21, with an exceptional drop on January 24 (Chinese New Year's Eve). The Ali Index of thermometer increased rapidly from January 25. The Baidu Index, which indicated an intention to adopt all four measures, increased earlier than the actual behaviors presented in the Ali Index. Both indices remained steadily low during the same period in the previous year (baseline). These results indicate that the Chinese public responded quickly to the issuing of specific guidelines, and both intended and actual purchasing behavior dramatically increased accordingly. Correlation analysis (P<.001).The National Health Commission of China first proposed respiratory protection and hand hygiene as protection guidelines on January 21, 2020, and the use of home disinfection and health monitoring on January 22 and 25, respectively . As showanalysis  showed smask and hand sanitizer in the three Asian countries were significantly correlated with new COVID-19 cases in China rather than local cases.hand sanitizer were highly correlated with the number of local cases, whereas the purchase of masks lagged behind the epidemic for 2 to 3 weeks ; it was not found in the United States, India, Brazil, or South Africa. Public searches on both drugs increased after mid-March and quickly peaked on March 20 after US President Donald Trump’s initial public remarks on the drugs at a briefing on March 19; this increase was observed in all countries.Using internet surveillance data, we conducted a cross-country comparison of real-time public awareness and behavioral responses to epidemic information during the first 100 days of the COVID-19 pandemic. We identified squandered windows of opportunity for early epidemic control in 12 countries. The epidemic in China and the PHEIC did not prompt a worldwide public reaction to adopt public health protective measures; instead, most countries and regions only responded to the epidemic after their own case counts mounted. Even if there was a worldwide reaction, the public response to the epidemic in other countries would quickly fall without government leadership and communication. The public responded quickly to official announcements and adopted personal protection behaviors such as buying hand sanitizers; however, rumors and misinformation were found to have led to a surge in sales of herbal remedies in China and antimalarial drugs worldwide. Chinese data showed that the timely governmental clarification of rumors mitigated the rush to buy unproven remedies to treat or prevent COVID-19. This comparative study highlighted the importance of governmental leadership and international coordination in directing epidemic control.The lack of transparent, timely, and effective risk communication by health authorities around an emerging infectious disease in its early stages failed to bring about appropriate levels of public awareness and behavioral responses, such as avoidance of mass gatherings and personal protection in China, Europe, and the United States. In China, the government did not provide actionable advice for personal protection until January 21. There were two missed windows of opportunity for early epidemic control in China. First, the first COVID-19 case emerged on December 8, 2019, more than three weeks before December 31, when the outbreak was first announced; second, between December 31, 2019, and January 19, 2020, the Wuhan Health Commission made four public announcements with no obvious evidence of human-to-human transmission ,24. DespFurther, due to variations in societal and cultural paradigms, face masks are commonly used as a hygienic practice in many Asian countries but are only used by the unwell in European and North American countries . In thesEvidence has proven that early implementation of containment measures can effectively control the COVID-19 epidemic . HoweverOur data showed that the public is highly responsive to governmental risk communication during epidemics, suggesting a need for real-time media surveillance. The early release of official guidelines by China’s National Health Commission was effective in guiding the Chinese public to take personal protection measures; however, rumors also triggered several incidents of panic buying , which were quickly calmed after official clarifications. Likewise, references to antimalarial drugs by US President Donald Trump triggered panic searches worldwide. Governments should engage early in public risk communication about epidemic control, detect misinformation, confront inaccurate messages, and clarify rumors in real time ,30. WorkCompared with traditional surveys, internet surveillance tools provide real-time, longitudinal, and dynamic data for capturing public awareness, rumors, and behavioral reactions, and they can be an effective means to evaluate public response towards epidemic information and rumors .This study has several limitations. First, Google Trends are not applicable in all countries, including China and most countries in Africa; therefore, we could only compare countries with available Google Trends data. For countries in which the volumes of Google Shopping data were low , we used Google web search data instead. This may have led to inconsistency in the measurements. Second, there is an inherent bias in internet data because the population may be skewed towards younger people. Moreover, Google Trends data related to personal protection measures represent intended behaviors instead of real shopping behaviors. Third, we are unable to conduct segmentation analysis these data to inform audience-tailored communication strategies.Our comparative study identified missed windows of opportunity for early epidemic control in 12 countries; it also highlighted the urgent need for international coordination to promote mutual learning regarding epidemic characteristics as well as effective control measures and to trigger early and timely responses in individual countries. During an epidemic, early release of official guidelines and timely governmental clarification of rumors are necessary to guide the public to make rational responses.


The Fire and Smoke Model Evaluation Experiment (FASMEE) is designed to collect integrated observations from large wildland fires and provide evaluation datasets for new models and operational systems. Wildland fire, smoke dispersion, and atmospheric chemistry models have become more sophisticated, and next-generation operational models will require evaluation datasets that are coordinated and comprehensive for their evaluation and advancement. Integrated measurements are required, including ground-based observations of fuels and fire behavior, estimates of fire-emitted heat and emissions fluxes, and observations of near-source micrometeorology, plume properties, smoke dispersion, and atmospheric chemistry. To address these requirements the FASMEE campaign design includes a study plan to guide the suite of required measurements in forested sites representative of many prescribed burning programs in the southeastern United States and increasingly common high-intensity fires in the western United States. Here we provide an overview of the proposed experiment and recommendations for key measurements. The FASMEE study provides a template for additional large-scale experimental campaigns to advance fire science and operational fire and smoke models. However, many models that currently drive operational systems are used without adequate validation and evaluation because of the lack of suitable data. As a consequence, the limits of applicability and expected errors are not defined, and results may not be realistic under certain conditions ,2. Accur3), and the resulting high computational demand precludes their routine use on large domains .Complex physics-based smoke models include, to different approximations, fire and atmosphere dynamics that drive buoyancy-induced plume rise and smoke transport. Currently fire weather forecast coupled models such as the Weather Research Forecasting – Spread FIRE ,4, MesoNThe Fire and Smoke Model Evaluation Experiment (FASMEE) is a proposed observational campaign to evaluate current operational fire and smoke modeling systems and support the advancement of newer models and systems into operational use. Integrated, large research campaigns are critical for making advances in wildland fire behavior, fire effects, and smoke science. An investment in coordinated sampling of fire–atmosphere interactions not only benefits fire and smoke science but also ultimately benefits fire and fuels managers, who rely on the best-available operational fire and smoke models to guide wildland fire management.The need for integrated, cross-discipline observations to support operational fire and smoke modeling has been highlighted in recent synthesis reports, including the Joint Fire Science Program (JFSP) Smoke Science Plan , the SmoHow do fuels, fire behavior, fire energy, and meteorology combine spatially to determine the development and dynamics of near-source plumes and the long-range transport of smoke and its chemical evolution?” To address this question, observational measurements of coupled fire–atmosphere dynamics are needed that are integrated over space and time to quantify a complex set of physical phenomena. To meet objectives that define a successful experiment, cross-scale measurements are necessary to adequately resolve buoyant emissions as well as plume development and smoke dispersion from sufficiently large fire events.The FASMEE study plan is guided by the overarching question, “FASMEE is conceived as part of a coordinated set of field campaigns on wildland fire and smoke, spanning a range of spatial scales . At the Among these campaigns, FASMEE provides a comprehensive, cross-scale perspective in that it specifically addresses the fuels, fire, and plume development that lead to smoke emissions and injection into the broader atmospheric circulation, as well as near-fire smoke chemistry and plume aging . DevelopAn additional aspect of FASMEE stems from extensive experimental planning performed by a team of scientists, covering all the main FASMEE scientific areas. With the active involvement of fire and smoke modelers, the measurement priorities and specifications have been defined in the context of particular modeling challenges and needs. Pre-burn weather analyses and numerical simulations performed during the planning stage of FASMEE delivers information on the desired burn conditions , definesThis paper reviews the motivation for integrated measurement campaigns, an overview of FASMEE measurement objectives by discipline, and the discussion of how large fire campaigns can inform model evaluation and development for both scientific understanding and operational application. The FASMEE study plan, abridged here, provides a template for additional large-scale campaigns that together can advance fire science and operational fire and smoke models . A work 2.The FASMEE campaign will target large fires with the potential for substantial plume development. An extensive search for field campaign options was undertaken to identify opportunities, including sites across the United States and Canada. In the initial phase of FASMEE, three measurement campaigns were identified based on their ability to meet identified needs and requirements for burns and measurements, host agency partners, cost estimates, and the range of anticipated fire behavior .With JFSP and USDA Forest Service support, the FASMEE planning team collaborated with the 2018 NSF Western Wildfire Experiment for Cloud Chemistry, Aerosol Absorption and Nitrogen (WE-CAN) and will participate in the 2019 Joint NASA and NOAA Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) campaigns. Coordination with these campaigns offers a rare opportunity to link aircraft smoke and satellite fire measurements with the characterization of wildfire and plume dynamics. These large aircraft campaigns, coordinated with FASMEE, will also provide a better understanding of the dynamics controlling near-source plumes and the resulting chemical composition, aging, and transport of smoke through measurements and observations of fuel, fire behavior, fire energy, and meteorology.−1) and high intensity surface and crown fires with dynamic long-range plumes relevant for smoke management. The potential to conduct measurements from prescribed crown fires presents a rare opportunity to sample the spectrum of fuel, fire behavior, and plume dynamics in a wildland fire that resembles a stand-replacing wildfire. Candidate host sites for the Southwestern Campaign have been identified as Fishlake National Forest (NF) in Utah and the North Kaibab Ranger District (RD) of the North Kaibab National Forest in Arizona due to their high fuel loadings, large burn units, and histories of prescribed burning (Populus tremuloides) stands in the mixed conifer forests using planned stand-replacement fires. Fishlake NF has been recently surveyed with aerial LiDAR, providing full coverage that FASMEE can use to enhance the characterization of canopy fuels. Fuels for all sites are mixed conifer and aspen forests with insect and disease damage following decades of fire exclusion. North Kaibab RD has an ambitious fuels management program and has established hundreds of permanent forest inventory and fuel plots throughout both ponderosa pine (Pinus ponderosa) and mixed conifer forests, including existing LiDAR coverage for much of the forest area. The district regularly conducts large (>500 ha) underburns of ponderosa pine and mixed conifer forests. The forest inventory and fuel data are available to FASMEE and will supplement the data collection planned for improving the representation of the fuels.The Southwestern FASMEE Campaign is intended to target prescribed, stand-replacement burns completed under heavy surface fuel loads (50–100 Mg ha burning . Fishlak−1.Fort Stewart in Georgia and the Department of Energy’s (DOE) Savannah River Site in South Carolina have been identified as candidate sites for the Southeastern Campaign because of their large burn units (>500 ha), smoke management relevancy, increased burn opportunities, prescribed burning history, and ability to host a large operational burn in older fuel complexes that will contribute to large plume development . Fort St3.Each field campaign will contain coordinated and interrelated measurements of fuels and fuel consumption, fire behavior and energy release, fire meteorology and plume dynamics, and smoke production and chemistry . ProduciThe following sections provide an overview of the sampling plan for each of the measurement disciplines: Fuels and Consumption, Fire Behavior and Energy Release, Plume Dynamics and Meteorology, and Smoke Chemistry and Transport. Any field campaign involving wildland fire must address a number of critical logistics, including safety and data quality. Ensuring safety throughout the project requires strict command structures, incident action plans, and aircraft safety plans, as well as site access and logistical staging plans. Detailed specifications and recommendations for operations, safety, and geospatial data management that synchronizes high-resolution spatial and temporal datasets are provided in the full study plan .3.1.Fuels are the primary independent variable for all other FASMEE disciplines. Specifically, the rate of fuel consumption determines the heat release rate and other aspects of fire behavior, plume dynamics, and the gaseous and particulate composition of smoke emissions. Fuel consumption is most explicitly linked to fire behavior at fine scales of variability, but it also drives plume dynamics at coarser scales and spatiotemporal variation in smoke near the source . BecauseFor each site, we will couple ground-based measurements  with remotely sensed 3D datasets to allow observations to be scaled from fine-scale inputs for physics-based, fire behavior models  to coarser-scale data collection required by traditionally used fire and smoke models . Ground-based field sampling is the most reliable method for collecting the pre- and post-fire fuel measurements, but to capture heterogeneous fuel distributions, terrestrial and airborne LiDAR and structure-from-motion (SfM) methods for complementary point cloud data are also needed –24. Key FASMEE also requires a high-resolution characterization of fuel consumption and heat release rates. The rate of fuel consumption per unit area relates more directly to combustion and heat release than fuel load, and consumption by combustion phase differs greatly by fuel component. Therefore, fuel consumption by type  will be mapped, using a combination of active fire infrared (IR) imagery and ground-based post-fire sampling, to provide more direct relationships to energy flux and emissions than maps of fuel loads and vegetation type . Charact3.2.The Fire Behavior and Energy (FBE) discipline will address key questions related to the transfer of mass and energy between the fire and plume. Together with fuels and meteorology, fire behavior and energy determine the heat source for plume rise . SpatialFire radiation mapping is foundational to understanding fire and plume development and to support plume modeling. Multiple measurements of fire radiation, using ground-based and airborne platforms, will be collected to derive spread rates and combined with in situ measurements, ground measurements, and modeling to derive flame-exit gas temperatures, velocities, and convective fluxes needed as inputs to plume models. The spatial and temporal characteristics of heat release is the most important determinant of plume dynamics and smoke transport . Cross-sCoordinated measurements will be stratified across their expected range of variability within and among fires, and heat release rate will be characterized across spatiotemporal scales. When surface fires are measured from beneath a forest canopy, airborne heat release measurements must include estimates of fire radiation attenuation ,37. With3.3.Coupled fire–atmosphere models are capable of resolving the spatial distribution and temporal dynamics of fire behavior, fuel combustion, and smoke production. However, a more thorough understanding of plume dynamics and meteorology is needed, as well as evaluation datasets that can be used to assess existing models and inform the development of new operational models . Fuel anPlume dynamics and meteorology measurements will be organized by four measurement platforms, including airborne, tower-mounted, ground-based in situ observations, and ground-based remote sensing. The atmospheric environment surrounding the burn unit and region is best characterized with a network of surface stations. Vertical atmospheric profilers will be placed around both the experimental burn unit and outside the experimental region to quantify local and mesoscale circulations and to provide measurements of atmospheric stability and wind shear. Key meteorological variables to characterize fire weather conditions and surface meteorology will include ambient air temperature, humidity, near-surface wind speed and direction of ambient and fire-induce wind fields . Plume r3.4.Over the past decade, comprehensive laboratory and field experiments have significantly increased our knowledge of the composition ,45 and pFull emissions characterization requires coordinated sampling of the plume and unlofted emissions from residual smoldering. Of the many emission studies of wildland fire conducted in the US, comprehensive ground measurements of emissions were lacking for all but a few of the units in the SCREAM study  and RxCA3), particulate matter (PM), and regional haze for scientific and regulatory assessments. Field and laboratory data from specific and well characterized wildland fires are important to improve emissions estimation approaches, and for assessing plume transport and chemical evolution in photochemical transport models [3, PM, haze, climate, and air toxics.The magnitude of pollutant emissions from wildland fires varies greatly depending on fire size (area burned), fire duration, fuel characteristics, combustion efficiency, and meteorological conditions ,51. Chemt models –57. ThisA comprehensive characterization of smoke emissions in FASMEE will require multiple instruments and techniques employed from both ground-based and airborne measurement platforms. To understand chemical evolution in the smoke plume, detailed precursor and chemical product measurements are needed in the near field to define emission rates of key precursors as well as at different downwind distances  extending over a multi-day period. Smoke and emissions measurements will be collected in three tasks, organized by vertical sampling range: Lofted plume sampled via manned aircraft, intermediate-level smoke sampled from UAS or tethered balloon (aerostat), and sub-canopy smoke collected with a ground-based instrumentation package and towers. Airborne chemical measurements from a manned aircraft are required to sample emissions in the lofted plume and to characterize the chemical processing of the emissions as the plume mixes with the ambient atmosphere and is transported downwind of the source. Flight profiles will provide intensive horizontal and vertical sampling of the near-field smoke plume (30 km from source).The primary purpose of the intermediate-level smoke measurements is to monitor fresh emissions while the manned aircraft is sampling downwind. Many of the factors that influence the combustion process (the mix of flaming and smoldering emissions), and the overall chemical composition of fresh smoke, may vary considerably over the lifetime of a fire. Although the manned aircraft will conduct pseudo-Lagrangian sampling e.g., ,58,59), ,59, 58,5Sub-canopy sampling will use ground-based platforms to characterize emissions over the life cycle of the burns. Direct emissions from biomass burning are a complex mixture of gases and aerosols. The emission factors measured must represent all phases of combustion, including flaming, near-term smoldering, and long-term smoldering phases. Four types of ground-based platforms will be used to measure buoyant smoke being entrained into the convective plume, unlofted smoke (drift smoke), and post-fire-front extended smoldering. The subcanopy plan includes instrumented towers erected within the burn unit, which will sample smoke forming and entraining into the bottom of buoyant plume and drift smoke. Unlofted drift smoke will be measured using fixed-site subcanopy instrument packages (SIP) located immediately downwind of the unit, flanking a mobile lab (ML). If available, a SIP will be located upwind of the burn unit to monitor background conditions. The post-fire-front sampling will use one or two mobile instrument packages . The post-fire-front sampling will measure emissions from independently smoldering fuel components . The SIP will also operate for an extended duration and sample smoke from extended smoldering that drifts across the sites.4.As wildland fire, smoke dispersion, atmospheric chemistry, and global climate models have become more sophisticated, there is an increasing need for complex datasets that are coordinated and comprehensive, from ground-based observations of fuels and fire behavior, to near-source plume dynamics and emissions, smoke trajectories, dispersion, and atmospheric chemistry. FASMEE is designed to provide these integrated observations and to serve as a template for other future campaigns that together will provide the evaluation datasets necessary to evaluate and develop next-generation, operational fire and smoke modeling systems. Many models that drive today’s operational systems need comprehensive validation and evaluation, as well as an understanding of a model’s predictive capability over the full range of wildland fire environments and weather conditions . ImproviOperational applications require that the models be executed rapidly enough to provide usable predictions and that the data needed for their executions are readily available. Existing models that predict area burned, fuel consumption (CONSUME and FOFEM),30, fireDue to the computational limitations of physics-based fire–atmosphere models, it remains challenging to implement them in operational systems useful to wildland fire managers. However, future operational systems may offer the ability to develop a new generation of models that are calibrated with fully dynamic models and provide superior accuracy across a wider range of conditions thanks to a combination of simplified physics and parameterizations. As the resolution of the weather forecasting models increases, these fire–atmosphere interactions and smoke plumes become explicitly resolvable on fine-model grids, which opens new avenues for development of new operational models explicitly resolving plume dynamics that inform operational models at coarser resolutions .4.1.Since the 1990s, a range of field-based large fire experiments have been conducted across major biomes and regions of the globe to study wildland fire behavior, fire–atmosphere interactions, including plume dynamics, and smoke dispersion. To compile lessons learned and legacy datasets, the FASMEE planning team synthesized these studies and source datasets of past studies that FASMEE observations will augment see .Pinus sylvestris) in north-central Siberia [One of the earliest integrated fire–atmosphere observational campaigns was the International Crown Fire Modeling Experiment (ICFME), initiated to evaluate fire propagation and spread in boreal landscapes and the role of boreal wildfires in ecosystem function and global climate change ,79. The  Siberia . This ex Siberia . Over 50In a project on sub-canopy transport and dispersion of smoke, five experimental units were burned as low-intensity surface fires in mature longleaf pine stands in the southeastern United States . This study evaluated sub-canopy emissions and smoke dispersion from low-intensity prescribed burns that are common in the southeastern US, and the results collectively contribute to better understanding of regional air quality issues . ObservaThe FireFlux I and II experiments collected field observations of fire–atmosphere interactions to evaluate coupled fire–atmosphere models including WRF-SFIRE  and MesoThe Prescribed Fire Combustion and Atmospheric Dynamics Research Experiment (RxCADRE) field campaign was conducted in the southeastern United States . The proBuilding on the success and lessons learned from RxCADRE, the FASMEE campaign was launched to provide integrated measurements of higher-intensity fire behavior and smoke. FASMEE takes advantage of lessons learned from past campaigns including the importance of involving fire scientists and model developers at the inception of measurement campaigns and the critical value of spatiotemporal synchronization of all measurements. Full funding for the FASMEE campaign has yet to be secured, but the study plan and conceptual promise of integrated measurements provides a compelling case for investment in large-scale, comprehensive measurement campaigns of fuels, fire and smoke production.The FASMEE team is closely collaborating with the 2018 Western Wildfire Experiment for Cloud Chemistry, Aerosol Absorption and Nitrogen experiment (WE-CAN) and the joint NASA and NOAA FIREX-AQ campaign planned for summer 2019 to provide source characterization for the planned airborne sampling campaigns to study emissions, chemical evolution, transport, and impacts of wildland fires. If possible, the timing of FASMEE prescribed burns will be coordinated with FIREX-AQ sampling to provide a detailed source characterization and greatly expand the information gained on emissions and smoke transport. The FASMEE burns will also offer unique opportunities for post-fire ecology research including tree mortality and vegetation response studies that make use of mapped fuels consumption and characterization of fine-scale fire behavior. Advances in remote sensing interpretation can also be made by pairing remotely sensed imagery such as Synthetic Aperture Radar and thermal infrared to assess fuel moisture, consumption, fire spread rates and energy release and hot-spot assessment.5.The past few decades have brought enormous advances in not only our understanding of fire and smoke dynamics but also our ability to observe and model fuel consumption, fire behavior, plume development, smoke production, and dispersion. Operationally, the adoption of fire and smoke models has been rapid. Advanced model output is now routinely available to managers; examples include the incorporation of fire models and the adoption of BlueSky-based smoke impact model runs within the Wildland Fire Decision Support System (WFDSS) and the Interagency Fuel Treatment Decision Support System .Although these systems provide value-added information, they are also relatively simplistic in their treatment of complex fire dynamics and therefore have issues in how well they can perform. More complex models, such as the coupled fire–atmosphere–chemistry models , are in testing to assess their ability for operational use. The advances to date offer the promise of capturing the underlying dynamics of fire–atmosphere interactions, but they also require greater input data. Unfortunately, a lack of observational data means substantial uncertainty about what the underlying dynamics are, and how well such systems can represent them. FASMEE is designed to facilitate the transition of more advanced modeling systems into operational use by supplying critical data necessary to facilitate improvements, testing, and adoption.The expected outcomes from the FASMEE project include (1) improved scientific knowledge of the physically coupled fuels–fire–smoke–chemistry system; (2) exportable methodologies for measuring fuels for fire spread, fuel consumption, and fire emissions models; (3) new insights concerning the processes that drive the spatial organization of fire energy and emissions that defines the transition between fires and plumes that impact air quality; and (4) improvement of existing operational fire and smoke models and the development of new, more advanced models based on the collection of an unprecedented dataset .The FASMEE campaigns are specifically planned to provide a full referenced set of synchronized fuels characteristics and fire behavior measurements for future campaigns and other related disciplines. For example, the proposed measurement campaigns offer a unique opportunity for related post-fire ecology studies that take advantage of highly resolved pre-burn vegetation and combustion mapping and associated datasets. Documentation of FASMEE burns will include spatiotemporal mapping of fuels, fuel consumption, fire behavior, and plume development to facilitate broad use of the datasets collected in the completed campaigns. The FASMEE data archive is being designed by a geospatial data manager and coordinated with partner agencies to ensure the development of a legacy dataset that can be amplified in subsequent coordinated field campaigns.Supporting Information